Zika Virus Infects Early- and Midgestation Human Maternal Decidual Tissues, Inducing Distinct Innate Tissue Responses in the Maternal-Fetal Interface.

PubMed

Weisblum, Yiska; Oiknine-Djian, Esther; Vorontsov, Olesya M; Haimov-Kochman, Ronit; Zakay-Rones, Zichria; Meir, Karen; Shveiky, David; Elgavish, Sharona; Nevo, Yuval; Roseman, Moshe; Bronstein, Michal; Stockheim, David; From, Ido; Eisenberg, Iris; Lewkowicz, Aya A; Yagel, Simcha; Panet, Amos; Wolf, Dana G

2017-02-15

Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and a range of placenta-related abnormalities, highlighting the need to unveil the modes of maternal-fetal transmission. The most likely route of vertical ZIKV transmission is via the placenta. The earliest events of ZIKV transmission in the maternal decidua, representing the maternal uterine aspect of the chimeric placenta, have remained unexplored. Here, we show that ZIKV replicates in first-trimester human maternal-decidual tissues grown ex vivo as three-dimensional (3D) organ cultures. An efficient viral spread in the decidual tissues was demonstrated by the rapid upsurge and continued increase of tissue-associated ZIKV load and titers of infectious cell-free virus progeny, released from the infected tissues. Notably, maternal decidual tissues obtained at midgestation remained similarly susceptible to ZIKV, whereas fetus-derived chorionic villi demonstrated reduced ZIKV replication with increasing gestational age. A genome-wide transcriptome analysis revealed that ZIKV substantially upregulated the decidual tissue innate immune responses. Further comparison of the innate tissue response patterns following parallel infections with ZIKV and human cytomegalovirus (HCMV) revealed that unlike HCMV, ZIKV did not induce immune cell activation or trafficking responses in the maternal-fetal interface but rather upregulated placental apoptosis and cell death molecular functions. The data identify the maternal uterine aspect of the human placenta as a likely site of ZIKV transmission to the fetus and further reveal distinct patterns of innate tissue responses to ZIKV. Our unique experimental model and findings could further serve to study the initial stages of congenital ZIKV transmission and pathogenesis and evaluate the effect of new therapeutic interventions. In view of the rapid spread of the current ZIKV epidemic and the severe manifestations of congenital ZIKV infection, it is crucial to learn the fundamental mechanisms of viral transmission from the mother to the fetus. Our studies of ZIKV infection in the authentic tissues of the human maternal-fetal interface unveil a route of transmission whereby virus originating from the mother could reach the fetal compartment via efficient replication within the maternal decidual aspect of the placenta, coinhabited by maternal and fetal cells. The identified distinct placental tissue innate immune responses and damage pathways could provide a mechanistic basis for some of the placental developmental abnormalities associated with ZIKV infection. The findings in the unique model of the human decidua should pave the way to future studies examining the interaction of ZIKV with decidual immune cells and to evaluation of therapeutic interventions aimed at the earliest stages of transmission. Copyright © 2017 American Society for Microbiology.

Fetal-Maternal Interactions in the Synepitheliochorial Placenta Using the eGFP Cloned Cattle Model

PubMed Central

Mess, Andrea; Perecin, Felipe; Bressan, Fabiana Fernandes; Mesquita, Ligia Garcia; Miglino, Maria Angelica; Pimentel, José RodrigoValim; Neto, Paulo Fantinato; Meirelles, Flávio Vieira

2013-01-01

Background To investigate mechanisms of fetal-maternal cell interactions in the bovine placenta, we developed a model of transgenic enhanced Green Fluorescent Protein (t-eGFP) expressing bovine embryos produced by nuclear transfer (NT) to assess the distribution of fetal-derived products in the bovine placenta. In addition, we searched for male specific DNA in the blood of females carrying in vitro produced male embryos. Our hypothesis is that the bovine placenta is more permeable to fetal-derived products than described elsewhere. Methodology/Principal Findings Samples of placentomes, chorion, endometrium, maternal peripheral blood leukocytes and blood plasma were collected during early gestation and processed for nested-PCR for eGFP and testis-specific Y-encoded protein (TSPY), western blotting and immunohistochemistry for eGFP detection, as well as transmission electron microscopy to verify the level of interaction between maternal and fetal cells. TSPY and eGFP DNA were present in the blood of cows carrying male pregnancies at day 60 of pregnancy. Protein and mRNA of eGFP were observed in the trophoblast and uterine tissues. In the placentomes, the protein expression was weak in the syncytial regions, but intense in neighboring cells on both sides of the fetal-maternal interface. Ultrastructurally, our samples from t-eGFP expressing NT pregnancies showed to be normal, such as the presence of interdigitating structures between fetal and maternal cells. In addition, channels-like structures were present in the trophoblast cells. Conclusions/Significance Data suggested that there is a delivery of fetal contents to the maternal system on both systemic and local levels that involved nuclear acids and proteins. It not clear the mechanisms involved in the transfer of fetal-derived molecules to the maternal system. This delivery may occur through nonclassical protein secretion; throughout transtrophoblastic-like channels and/or by apoptotic processes previously described. In conclusion, the bovine synepitheliochorial placenta displays an intimate fetal-maternal interaction, similar to other placental types for instance human and mouse. PMID:23724045

Fetal-maternal interactions in the synepitheliochorial placenta using the eGFP cloned cattle model.

PubMed

Pereira, Flavia Thomaz Verechia; Oliveira, Lilian J; Barreto, Rodrigo da Silva Nunes; Mess, Andrea; Perecin, Felipe; Bressan, Fabiana Fernandes; Mesquita, Ligia Garcia; Miglino, Maria Angelica; Pimentel, José RodrigoValim; Fantinato Neto, Paulo; Meirelles, Flávio Vieira

2013-01-01

To investigate mechanisms of fetal-maternal cell interactions in the bovine placenta, we developed a model of transgenic enhanced Green Fluorescent Protein (t-eGFP) expressing bovine embryos produced by nuclear transfer (NT) to assess the distribution of fetal-derived products in the bovine placenta. In addition, we searched for male specific DNA in the blood of females carrying in vitro produced male embryos. Our hypothesis is that the bovine placenta is more permeable to fetal-derived products than described elsewhere. Samples of placentomes, chorion, endometrium, maternal peripheral blood leukocytes and blood plasma were collected during early gestation and processed for nested-PCR for eGFP and testis-specific Y-encoded protein (TSPY), western blotting and immunohistochemistry for eGFP detection, as well as transmission electron microscopy to verify the level of interaction between maternal and fetal cells. TSPY and eGFP DNA were present in the blood of cows carrying male pregnancies at day 60 of pregnancy. Protein and mRNA of eGFP were observed in the trophoblast and uterine tissues. In the placentomes, the protein expression was weak in the syncytial regions, but intense in neighboring cells on both sides of the fetal-maternal interface. Ultrastructurally, our samples from t-eGFP expressing NT pregnancies showed to be normal, such as the presence of interdigitating structures between fetal and maternal cells. In addition, channels-like structures were present in the trophoblast cells. Data suggested that there is a delivery of fetal contents to the maternal system on both systemic and local levels that involved nuclear acids and proteins. It not clear the mechanisms involved in the transfer of fetal-derived molecules to the maternal system. This delivery may occur through nonclassical protein secretion; throughout transtrophoblastic-like channels and/or by apoptotic processes previously described. In conclusion, the bovine synepitheliochorial placenta displays an intimate fetal-maternal interaction, similar to other placental types for instance human and mouse.

Acute Fetal Demise with First Trimester Maternal Infection Resulting from Listeria monocytogenes in a Nonhuman Primate Model

PubMed Central

Wolfe, Bryce; Wiepz, Gregory J.; Schotzko, Michele; Bondarenko, Gennadiy I.; Durning, Maureen; Simmons, Heather A.; Mejia, Andres; Faith, Nancy G.; Sampene, Emmanuel; Suresh, Marulasiddappa; Kathariou, Sophia; Czuprynski, Charles J.

2017-01-01

ABSTRACT Infection with Listeria monocytogenes during pregnancy is associated with miscarriage, preterm birth, and neonatal complications, including sepsis and meningitis. While the risk of these conditions is thought to be greatest during the third trimester of pregnancy, the determinants of fetoplacental susceptibility to infection, the contribution of gestational age, and the in vivo progression of disease at the maternal-fetal interface are poorly understood. We developed a nonhuman primate model of listeriosis to better understand antecedents of adverse pregnancy outcomes in early pregnancy. Four pregnant cynomolgus macaques (Macaca fascicularis) received a single intragastric inoculation between days 36 and 46 of gestation with 107 CFU of an L. monocytogenes strain isolated from a previous cluster of human listeriosis cases that resulted in adverse pregnancy outcomes. Fecal shedding, maternal bacteremia, and fetal demise were consistently noted within 7 to 13 days. Biopsy specimens of maternal liver, spleen, and lymph node displayed variable inflammation and relatively low bacterial burden. In comparison, we observed greater bacterial burden in the decidua and placenta and the highest burden in fetal tissues. Histopathology indicated vasculitis, fibrinoid necrosis, and thrombosis of the decidual spiral arteries, acute chorioamnionitis and villitis in the placenta, and hematogenous infection of the fetus. Vascular pathology suggests early impact of L. monocytogenes infection on spiral arteries in the decidua, which we hypothesize precipitates subsequent placentitis and fetal demise. These results demonstrate that L. monocytogenes tropism for the maternal reproductive tract results in infection of the decidua, placenta, and the fetus itself during the first trimester of pregnancy. PMID:28223455

Fetal HLA-G alleles and their effect on miscarriage.

PubMed

Koc, Altug; Kirbiyik, Ozgur; Kutbay, Yasar B; Ozyilmaz, Berk; Ozdemir, Taha R; Kaya, Ozge Ozer; Kubat, Gozde; Koc, Zeynep Peker

2018-05-29

Immunosuppression at the feto-maternal interface is crucial for a successful pregnancy outcome. Human leukocyte antigen-G (HLA-G) seems to be a major contributor to fetal tolerance. The HLA-G expression is seen in cytotrophoblasts and in maternal blood. Fetal HLA-G acts on decidual antigen-presenting cells (APCs), natural killers (NKs) and T cells. Recent findings revealed that defects in placentation and their consequences are associated with maternal HLA-G variants and their expression levels. The objective of this article is to investigate the relationship between fetal HLA-G alleles and miscarriage, which has not been investigated to date. The present study includes 204 recurrent miscarriage (RM) cases who were admitted to our clinic between 2012 and 2016. Twenty-eight miscarriage products without maternal cell contamination and any known pathology were analyzed by HLA-G typing. In addition, 3' untranslated region (UTR) 14-base pair (bp) insertion/deletion polymorphism was also investigated by Sanger sequencing. For our population, the most frequent HLA-G type was G*01:01, both in the study group (30.3%) and in the control group (47%). The study revealed that the G*01:04 allele was significantly associated with miscarriage (p = 0.007). The 3' UTR 14bp deletion was more frequent in the miscarriage group, but there was no significant correlation. HLA-G alleles seem to be related with miscarriage and should be considered in RM cases.

Involvement of galectin-1 in reproduction: past, present and future.

PubMed

Barrientos, Gabriela; Freitag, Nancy; Tirado-González, Irene; Unverdorben, Laura; Jeschke, Udo; Thijssen, Victor L J L; Blois, Sandra M

2014-01-01

After recognition of its pivotal contribution to fetomaternal tolerance, the study of galectin-1 (gal-1) functions in the context of pregnancy became an attractive topic in reproductive medicine. Despite considerable advances in the understanding of the immuno- and growth-regulatory properties of gal-1 at the fetal-maternal interface, many functional aspects of this lectin in reproduction are only emerging. The published literature was searched using Pubmed focusing on gal-1 signalling and functional properties at the maternal-fetal interface, including data on its implication in pregnancy disorders and malignancies of the female reproductive system. Papers discussing animal and human studies were included. This review provides an overview of gal-1 functions during pregnancy, such as modulation of maternal immune responses and roles in embryo implantation and placentation. We also emphasize the role of gal-1 in key regulatory processes, including trophoblast migration, invasion, syncytium formation and expression of non-classical MHC class I molecules (HLA-G). In addition, we argue in favour of gal-1 pro-angiogenic properties, as observed in tumourigenesis and other pathological settings, and its implication in the angiogenesis process associated with early gestation. The involvement of gal-1 in the regulation of different processes during the establishment, development and maintenance of pregnancy could be described as unique. Gal-1 has emerged as an important lectin with major functions in pregnancy.

Distinct pattern of Th17/Treg cells in pregnant women with a history of unexplained recurrent spontaneous abortion.

PubMed

Qian, Jinfeng; Zhang, Na; Lin, Jing; Wang, Caiyan; Pan, Xinyao; Chen, Lanting; Li, Dajin; Wang, Ling

2018-05-13

The aim of the current study was to determine the pattern of immune cells and related functional molecules in peripheral blood and at the maternal-fetal interface in women with unexplained recurrent spontaneous abortion (URSA). In part I, 155 women were included and divided into four groups: non-pregnant controls with no history of URSA (NPCs), pregnant controls with no history of URSA (PCs), non-pregnant women with a history of URSA (NPUs), and pregnant women with a history of URSA (PUs). Venous blood samples were collected and analyzed. In part II, 35 subjects with URSA and 40 subjects in the early stage of normal pregnancy who chose to undergo an abortion were recruited. Samples of the decidua were collected, and the proportion of immune cells and the expression of related molecules were evaluated. Peripheral regulatory T cells (Treg cells) increased in PCs compared to NPCs, but in women with URSA the flux of Treg cells disappeared when pregnancy occurred. Levels of interleukin-10 (IL-10), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and IL-17 and the ratio of Th17/Treg cells in peripheral blood remained stable among the four groups. At the maternal-fetal interface, the percentage of Treg cells, the level of CTLA-4 of CD4 + CD25 + CD127 lo cells and CD4 + Foxp3 + cells were significantly lower in women with URSA compared to controls, respectively. Levels of transforming growth factor-β1 (TGF-β1) mRNA and protein in the decidua significantly decreased in URSA while levels of IL-6 and tumor necrosis factor-ɑ (TNF-ɑ) and the Th17/Treg ratio significantly increased. In conclusion, peripheral Treg cells did not increase in pregnant women with URSA. The decrease in Treg cells and levels of CTLA-4 and TGF-β1 and as well as the increase in levels of IL-6 and TNF-ɑ, and the Th17/Treg ratio at the maternal-fetal interface might contribute to inappropriate maternal-fetal immune tolerance in URSA.

Impact of HIV-1 infection on the feto-maternal crosstalk and consequences for pregnancy outcome and infant health.

PubMed

Altfeld, Marcus; Bunders, Madeleine J

2016-11-01

Adaptation of the maternal immune system to establish maternal/fetal equilibrium is required for a successful pregnancy. Viral infections, including HIV-1 infection, can alter this maternal/fetal equilibrium, with significant consequences for pregnancy outcome, including miscarriages, impaired fetal growth, and premature delivery. Furthermore, maternal HIV-1 infection has been shown to have a long-term impact on the developing fetal immune system also when the infant is not infected with the virus. In this review, we discuss the consequences of maternal HIV-1 infection and antiretroviral therapy on pregnancy outcome and the health of the uninfected HIV-1-exposed infant.

Effects of Moderate Prenatal Alcohol Exposure during Early Gestation in Rats on Inflammation across the Maternal-Fetal-Immune Interface and Later-Life Immune Function in the Offspring

PubMed Central

Terasaki, Laurne S.; Schwarz, Jaclyn M.

2017-01-01

During early brain development, microglial activation can negatively impact long-term neuroimmune and cognitive outcomes. It is well-known that significant alcohol exposure during early gestation results in a number of cognitive deficits associated with fetal alcohol spectrum disorders (FASD). Additionally, microglia are activated following high levels of alcohol exposure in rodent models of FASD. We sought to examine whether moderate prenatal alcohol exposure (70 mg/dL blood alcohol concentration) activates microglia in the fetal rat brain, and whether moderate fetal alcohol exposure has long-term negative consequences for immune function and cognitive function in the rat. We also measured inflammation within the placenta and maternal serum following moderate alcohol exposure to determine whether either could be a source of cytokine production in the fetus. One week of moderate prenatal alcohol exposure produced a sex-specific increase in cytokines and chemokines within the fetal brain. Cytokines were also increased within the placenta, regardless of the sex of the fetus, and independent of the low levels of circulating cytokines within the maternal serum. Adult offspring exposed to alcohol prenatally had exaggerated cytokine production in the brain and periphery in response to lipopolysaccharide (25 μg/kg), as well as significant memory deficits precipitated by this low-level of inflammation. Thus the immune system, including microglia, may be a key link to understanding the etiology of fetal alcohol spectrum disorders and other unexplored cognitive or health risks associated with even low levels of fetal alcohol exposure. PMID:27318824

Maternal high-fat diet is associated with impaired fetal lung development

PubMed Central

Mayor, Reina S.; Finch, Katelyn E.; Zehr, Jordan; Morselli, Eugenia; Neinast, Michael D.; Frank, Aaron P.; Hahner, Lisa D.; Wang, Jason; Rakheja, Dinesh; Palmer, Biff F.; Rosenfeld, Charles R.; Savani, Rashmin C.

2015-01-01

Maternal nutrition has a profound long-term impact on infant health. Poor maternal nutrition influences placental development and fetal growth, resulting in low birth weight, which is strongly associated with the risk of developing chronic diseases, including heart disease, hypertension, asthma, and type 2 diabetes, later in life. Few studies have delineated the mechanisms by which maternal nutrition affects fetal lung development. Here, we report that maternal exposure to a diet high in fat (HFD) causes placental inflammation, resulting in placental insufficiency, fetal growth restriction (FGR), and inhibition of fetal lung development. Notably, pre- and postnatal exposure to maternal HFD also results in persistent alveolar simplification in the postnatal period. Our novel findings provide a strong association between maternal diet and fetal lung development. PMID:26092997

The parental non-equivalence of imprinting control regions during mammalian development and evolution.

PubMed

Schulz, Reiner; Proudhon, Charlotte; Bestor, Timothy H; Woodfine, Kathryn; Lin, Chyuan-Sheng; Lin, Shau-Ping; Prissette, Marine; Oakey, Rebecca J; Bourc'his, Déborah

2010-11-18

In mammals, imprinted gene expression results from the sex-specific methylation of imprinted control regions (ICRs) in the parental germlines. Imprinting is linked to therian reproduction, that is, the placenta and imprinting emerged at roughly the same time and potentially co-evolved. We assessed the transcriptome-wide and ontology effect of maternally versus paternally methylated ICRs at the developmental stage of setting of the chorioallantoic placenta in the mouse (8.5dpc), using two models of imprinting deficiency including completely imprint-free embryos. Paternal and maternal imprints have a similar quantitative impact on the embryonic transcriptome. However, transcriptional effects of maternal ICRs are qualitatively focused on the fetal-maternal interface, while paternal ICRs weakly affect non-convergent biological processes, with little consequence for viability at 8.5dpc. Moreover, genes regulated by maternal ICRs indirectly influence genes regulated by paternal ICRs, while the reverse is not observed. The functional dominance of maternal imprints over early embryonic development is potentially linked to selection pressures favoring methylation-dependent control of maternal over paternal ICRs. We previously hypothesized that the different methylation histories of ICRs in the maternal versus the paternal germlines may have put paternal ICRs under higher mutational pressure to lose CpGs by deamination. Using comparative genomics of 17 extant mammalian species, we show here that, while ICRs in general have been constrained to maintain more CpGs than non-imprinted sequences, the rate of CpG loss at paternal ICRs has indeed been higher than at maternal ICRs during evolution. In fact, maternal ICRs, which have the characteristics of CpG-rich promoters, have gained CpGs compared to non-imprinted CpG-rich promoters. Thus, the numerical and, during early embryonic development, functional dominance of maternal ICRs can be explained as the consequence of two orthogonal evolutionary forces: pressure to tightly regulate genes affecting the fetal-maternal interface and pressure to avoid the mutagenic environment of the paternal germline.

The Parental Non-Equivalence of Imprinting Control Regions during Mammalian Development and Evolution

PubMed Central

Bestor, Timothy H.; Woodfine, Kathryn; Lin, Chyuan-Sheng; Lin, Shau-Ping; Prissette, Marine; Oakey, Rebecca J.; Bourc'his, Déborah

2010-01-01

In mammals, imprinted gene expression results from the sex-specific methylation of imprinted control regions (ICRs) in the parental germlines. Imprinting is linked to therian reproduction, that is, the placenta and imprinting emerged at roughly the same time and potentially co-evolved. We assessed the transcriptome-wide and ontology effect of maternally versus paternally methylated ICRs at the developmental stage of setting of the chorioallantoic placenta in the mouse (8.5dpc), using two models of imprinting deficiency including completely imprint-free embryos. Paternal and maternal imprints have a similar quantitative impact on the embryonic transcriptome. However, transcriptional effects of maternal ICRs are qualitatively focused on the fetal-maternal interface, while paternal ICRs weakly affect non-convergent biological processes, with little consequence for viability at 8.5dpc. Moreover, genes regulated by maternal ICRs indirectly influence genes regulated by paternal ICRs, while the reverse is not observed. The functional dominance of maternal imprints over early embryonic development is potentially linked to selection pressures favoring methylation-dependent control of maternal over paternal ICRs. We previously hypothesized that the different methylation histories of ICRs in the maternal versus the paternal germlines may have put paternal ICRs under higher mutational pressure to lose CpGs by deamination. Using comparative genomics of 17 extant mammalian species, we show here that, while ICRs in general have been constrained to maintain more CpGs than non-imprinted sequences, the rate of CpG loss at paternal ICRs has indeed been higher than at maternal ICRs during evolution. In fact, maternal ICRs, which have the characteristics of CpG-rich promoters, have gained CpGs compared to non-imprinted CpG-rich promoters. Thus, the numerical and, during early embryonic development, functional dominance of maternal ICRs can be explained as the consequence of two orthogonal evolutionary forces: pressure to tightly regulate genes affecting the fetal-maternal interface and pressure to avoid the mutagenic environment of the paternal germline. PMID:21124941

Maternal and fetal metabonomic alterations in prenatal nicotine exposure-induced rat intrauterine growth retardation.

PubMed

Feng, Jiang-hua; Yan, You-e; Liang, Gai; Liu, Yan-song; Li, Xiao-jun; Zhang, Ben-jian; Chen, Liao-bin; Yu, Hong; He, Xiao-hua; Wang, Hui

2014-08-25

Prenatal nicotine exposure causes adverse birth outcome. However, the corresponding metabonomic alterations and underlying mechanisms of nicotine-induced developmental toxicity remain unclear. The aims of this study were to characterize the metabolic alterations in biofluids in nicotine-induced intrauterine growth retardation (IUGR) rat model. In the present study, pregnant Wistar rats were intragastrically administered with different doses of nicotine (0.5, 1.0 and 2.0 mg/kg d) from gestational day (GD) 11-20. The metabolic profiles of the biofluids, including maternal plasma, fetal plasma and amniotic fluid, were analyzed using (1)H nuclear magnetic resonance (NMR)-based metabonomic techniques. Prenatal nicotine exposure caused noticeably lower body weights, higher IUGR rates of fetal rats, and elevated maternal and fetal corticosterone (CORT) levels compared to the controls. The correlation analysis among maternal, fetal serum CORT levels and fetal bodyweight suggested that the levels of maternal and fetal serum CORT presented a positive correlation (r=0.356, n=32, P<0.05), while there was a negative correlation between fetal (r=-0.639, n=32, P<0.01) and maternal (r=-0.530, n=32, P<0.01) serum CORT level and fetal bodyweight. The fetal metabonome alterations included the stimulation of lipogenesis and the decreased levels of glucose and amino acids. The maternal metabonome alterations involved the enhanced blood glucose levels, fatty acid oxygenolysis, proteolysis and amino acid accumulation. These results suggested that prenatal nicotine exposure is associated with an altered maternal and fetal metabonome, which may be related to maternal increased glucocorticoid level induced by nicotine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Celecoxib restores angiogenic factor expression at the maternal-fetal interface in the BPH/5 mouse model of preeclampsia.

PubMed

Reijnders, Dorien; Liu, Chin-Chi; Xu, Xinjing; Zhao, Anna M; Olson, Kelsey N; Butler, Scott D; Douglas, Nataki C; Sones, Jenny L

2018-05-01

Preeclampsia (PE), a hypertensive disease of pregnancy, is a leading cause of fetal and maternal morbidity/mortality. Early angiogenic and inflammatory disturbances within the placenta are thought to underlie the development of the maternal PE syndrome and poor pregnancy outcomes. However, the exact etiology remains largely unknown. Here, we use the BPH/5 mouse model of PE to elucidate the way in which inflammation early in pregnancy contributes to abnormal expression of angiogenic factors at the maternal-fetal interface. We have previously described improvement in maternal hypertension and fetal growth restriction in this model after treatment with the anti-inflammatory cyclooxygenase-2 (Cox2) specific inhibitor celecoxib. To further characterize the mechanisms by which celecoxib improves poor pregnancy outcomes in BPH/5 mice, we determined expression of angiogenic factors and complement pathway components after celecoxib. In BPH/5 implantation sites there was increased hypoxia inducible factor-1α ( Hif1α), heme oxygenase-1 ( Ho-1), and stem cell factor ( Scf) mRNA concomitant with elevated prostaglandin synthase 2 ( Ptgs2), encoding Cox2, and elevated VEGF protein. Angiopoietin 1 ( Ang1), tunica interna endothelial cell kinase-2 receptor ( Tie2), complement factor 3 ( C3), and complement factor B ( CfB) were increased in midgestation BPH/5 placentae. Whereas BPH/5 expression levels of VEGF, Ang1, and Tie2 normalized after celecoxib, placental C3 and CfB mRNA remained unchanged. However, celecoxib did reduce the pregnancy-specific circulating soluble fms-like tyrosine kinase-1 (sFlt-1) rise in BPH/5 mice at midgestation. These data show that elevated Cox2 during implantation contributes to placental angiogenic factor imbalances in the BPH/5 mouse model of PE.

Amniocentesis for Fetal Lung Maturity: Will It Become Obsolete?

PubMed Central

Varner, Stephen; Sherman, Craig; Lewis, David; Owens, Sheri; Bodie, Frankie; McCathran, C Eric; Holliday, Nicolette

2013-01-01

Amniocentesis for fetal lung maturity has historically been performed for many reasons: uterine and placental complications, maternal comorbidities, fetal issues, and even obstetric problems. Even though the risks associated with third trimester amniocentesis are extremely low, complications have been documented, including preterm labor, placental abruptions, intrauterine rupture, maternal sepsis, fetal heart rate abnormalities, and fetal-maternal hemorrhage. This review presents the types of tests for fetal lung maturity, presents the indications and tests utilized, and discusses recommendations for when amniocentesis for fetal lung maturity may be appropriate. PMID:24826202

Amniocentesis for fetal lung maturity: will it become obsolete?

PubMed

Varner, Stephen; Sherman, Craig; Lewis, David; Owens, Sheri; Bodie, Frankie; McCathran, C Eric; Holliday, Nicolette

2013-01-01

AMNIOCENTESIS FOR FETAL LUNG MATURITY HAS HISTORICALLY BEEN PERFORMED FOR MANY REASONS: uterine and placental complications, maternal comorbidities, fetal issues, and even obstetric problems. Even though the risks associated with third trimester amniocentesis are extremely low, complications have been documented, including preterm labor, placental abruptions, intrauterine rupture, maternal sepsis, fetal heart rate abnormalities, and fetal-maternal hemorrhage. This review presents the types of tests for fetal lung maturity, presents the indications and tests utilized, and discusses recommendations for when amniocentesis for fetal lung maturity may be appropriate.

[Effects of shoutai pills on expression of Th1/Th2 cytokine in maternal-fetal interface and pregnancy outcome].

PubMed

Lai, Maohua; You, Zhaoling; Ma, Hongxia; Lei, Lei; Lu, Fangguo; He, Dongmei; Liu, Huiping; Yin, Sheng

2010-11-01

To evaluate its mechanism of inducing the maternal-fetal immune tolerance by studying the effects of Shoutai pills on the expression of Th1/Th2 cytokine and pregnancy in maternal-fetal interface of mice with recurrent spontaneous abortion (RSA). The normal pregnancy and RSA model were respectively induced with CBA/J x BALB/c and CBA/J x DBA/2. The mice with RSA were randomly divided into model group and low, middle and high dose groups of Shoutai pills. The mice were killed in 14 days after administration and embryo resorption rate was counted and their decidual and placental tissues were co-cultured to detect the expressions of IL-4, IL-10, IFN-gamma and TNF-alpha with ELISA. The embryo resorption rate of the model group was significantly higher than the normal pregnancy, middle and high dose groups of Shoutai pills could decreased the embryo resorption rate of the mice with RSA (P < 0.05). All the doses in 3 groups of Shoutai pills could decreased the expression of IFN-gamma and TNF-alpha (P < 0. 05) and there was no obvious difference between normal pregnancy group and all groups of Shoutai pills. Middle and high doses of Shoutai pills could increased the expression of IL-4 and IL-10 (P < 0.05) and there was no obvious differences between normal pregnancy and high dose group of Shoutai pills. The mechanism about Shoutai pills can change Th1 /Th2 cytokine towards Th2 bias, which induced the maternal-fetal immune tolerance.

Tracking fetal development through molecular analysis of maternal biofluids☆

PubMed Central

Edlow, Andrea G.; Bianchi, Diana W.

2015-01-01

Current monitoring of fetal development includes fetal ultrasonography, chorionic villus sampling or amniocentesis for chromosome analysis, and maternal serum biochemical screening for analytes associated with aneuploidy and open neural tube defects. Over the last 15 years, significant advances in noninvasive prenatal diagnosis (NIPD) via cell-free fetal (cff) nucleic acids in maternal plasma have resulted in the ability to determine fetal sex, RhD genotype, and aneuploidy. Cff nucleic acids in the maternal circulation originate primarily from the placenta. This contrasts with cff nucleic acids in amniotic fluid, which derive from the fetus, and are present in significantly higher concentrations than in maternal blood. The fetal origin of cff nucleic acids in the amniotic fluid permits the acquisition of real-time information about fetal development and gene expression. This review seeks to provide a comprehensive summary of the molecular analysis of cff nucleic acids in maternal biofluids to elucidate mechanisms of fetal development, physiology, and pathology. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure. PMID:22542507

Maternal influences on fetal microbial colonization and immune development

PubMed Central

Romano-Keeler, Joann; Weitkamp, Jörn-Hendrik

2014-01-01

While critical for normal development, the exact timing of establishment of the intestinal microbiome is unknown. For example, although preterm labor and birth have been associated with bacterial colonization of the amniotic cavity and fetal membranes for many years, the prevailing dogma of a sterile intrauterine environment during normal term pregnancies has been challenged more recently. While found to be a key contributor of evolution in the animal kingdom, maternal transmission of commensal bacteria may also constitute a critical process during healthy pregnancies in humans with yet unclear developmental importance. Metagenomic sequencing has elucidated a rich placental microbiome in normal term pregnancies likely providing important metabolic and immune contributions to the growing fetus. Conversely, an altered microbial composition during pregnancy may produce aberrant metabolites impairing fetal brain development and life-long neurological outcomes. Here we review the current understanding of microbial colonization at the feto-maternal interface and explain how normal gut colonization drives a balanced neonatal mucosal immune system, while dysbiosis contributes to aberrant immune function early in life and beyond. We discuss how maternal genetics, diet, medications, and probiotics inform the fetal microbiome in preparation for perinatal and postnatal bacterial colonization. PMID:25310759

Elsevier Trophoblast Research Award lecture: The multifaceted role of Nodal signaling during mammalian reproduction.

PubMed

Park, C B; Dufort, D

2011-03-01

Nodal, a secreted signaling protein in the transforming growth factor-beta (TGF-β) superfamily, has established roles in vertebrate development. However, components of the Nodal signaling pathway are also expressed at the maternal-fetal interface and have been implicated in many processes of mammalian reproduction. Emerging evidence indicates that Nodal and its extracellular inhibitor Lefty are expressed in the uterus and complex interactions between the two proteins mediate menstruation, decidualization and embryo implantation. Furthermore, several studies have shown that Nodal from both fetal and maternal sources may regulate trophoblast cell fate and facilitate placentation as both embryonic and uterine-specific Nodal knockout mouse strains exhibit disrupted placenta morphology. Here we review the established and prospective roles of Nodal signaling in facilitating successful pregnancy, including recent evidence supporting a potential link to parturition and preterm birth. Copyright © 2011 Elsevier Ltd. All rights reserved.

Fetal-maternal interface: a chronicle of allogeneic coexistence.

PubMed

Pujal, Josep-Maria; Roura, Santiago; Muñoz-Marmol, Ana M; Mate, Jose-Luis; Bayes-Genis, Antoni

2012-01-01

The existence of allogeneic cells within an individual has been demonstrated in multiple fields such as hematopoietic stem cell or solid organ transplantation, non-depleted blood transfusions and the most common form which is bidirectional maternal-fetal cell trafficking, whereby cells from the fetus pass through the placental barrier. In order to graphically illustrate this early natural phenomenon that initiates the journey of a child's cells within the mother's blood and other tissues, we used a new procedure in microscopy imaging generating Large Scale Panoramic Pictures (LSPP). This technique can also be extended to explore a broad diversity of experimental models.

High Tumor Volume to Fetal Weight Ratio Is Associated with Worse Fetal Outcomes and Increased Maternal Risk in Fetuses with Sacrococcygeal Teratoma.

PubMed

Gebb, Juliana S; Khalek, Nahla; Qamar, Huma; Johnson, Mark P; Oliver, Edward R; Coleman, Beverly G; Peranteau, William H; Hedrick, Holly L; Flake, Alan W; Adzick, N Scott; Moldenhauer, Julie S

2018-03-01

Tumor volume to fetal weight ratio (TFR) > 0.12 before 24 weeks has been associated with poor outcome in fetuses with sacrococcygeal teratoma (SCT). We evaluated TFR in predicting poor fetal outcome and increased maternal operative risk in our cohort of SCT pregnancies. This is a retrospective, single-center review of fetuses seen with SCT from 1997 to 2015. Patients who chose termination of pregnancy (TOP), delivered elsewhere, or had initial evaluation at > 24 weeks were excluded. Receiver operating characteristic (ROC) analysis determined the optimal TFR to predict poor fetal outcome and increased maternal operative risk. Poor fetal outcome included fetal demise, neonatal demise, or fetal deterioration warranting open fetal surgery or delivery < 32 weeks. Increased maternal operative risk included cases necessitating open fetal surgery, classical cesarean delivery, or ex utero intrapartum treatment (EXIT). Of 139 pregnancies with SCT, 27 chose TOP, 14 delivered elsewhere, and 40 had initial evaluation at > 24 weeks. Thus, 58 fetuses were reviewed. ROC analysis revealed that at ≤24 weeks, TFR > 0.095 was predictive of poor fetal outcome and TFR > 0.12 was predictive of increased maternal operative risk. This study supports the use of TFR at ≤24 weeks for risk stratification of pregnancies with SCT. © 2018 S. Karger AG, Basel.

Nonclassical MHC-E (Mamu-E) expression in the rhesus monkey placenta

PubMed Central

Dambaeva, Svetlana V.; Bondarenko, Gennadiy I.; Grendell, Richard L.; Kravitz, Rachel H.; Durning, Maureen; Golos, Thaddeus G.

2009-01-01

The aim of this study was to characterize the expression of the rhesus HLA-E ortholog Mamu-E, particularly at the maternal-fetal interface. Mamu-E expression was confirmed by locus-specific RT-PCR in the placenta as well as in peripheral blood mononuclear cells (PBMC) and other organs. We evaluated the utility of antibodies recognizing HLA-E (MEM-E/06 against native HLA-E, MEM-E/02 against denatured HLA-E) to detect Mamu-E by flow cytometry/immunofluorescence, Western blot, and immunohistochemistry (IHC). Western blot analysis of cells and selected transfectants confirmed the recognition of Mamu-E but not Mamu-AG by antibodies MEM-E/06 and HC10 but not MEM-E/02. Immunohistochemical staining of frozen sections of rhesus placenta with the MEM-E/06 antibody demonstrated expression in most populations of rhesus monkey trophoblast cells, including villous cytotrophoblasts (strong positive staining), apical membrane of syncytiotrophoblasts (light to moderate staining) and extravillous cytotrophoblasts (moderate to strong staining, especially endovascular trophoblasts in early pregnancy). Expression was not trophoblast cell-specific, especially at term, when endothelial cells in both the chorionic plate and placental villi showed strong staining for Mamu-E. Staining of rhesus extravillous trophoblast cells suggested the co-expression of Mamu-E and Mamu-AG (the rhesus HLA-G homolog) on these cells. MEM-E/06 was shown also to react with differentiating rhesus placental syncytiotrophoblasts in primary culture, detecting intracellular and weak surface expression of Mamu-E. We conclude that the gestation-dependent co-expression of Mamu-E with Mamu-AG in villous and extravillous trophoblast cells suggests important and perhaps complementary but distinct roles of these two nonclassical MHC class I loci in pregnancy at the maternal-fetal interface. In addition, the MEM-E/06 antibody will be useful for the detection of Mamu-E at the maternal-fetal interface in the rhesus monkey. PMID:17996936

Natural Killer Cells Promote Fetal Development through the Secretion of Growth-Promoting Factors.

PubMed

Fu, Binqing; Zhou, Yonggang; Ni, Xiang; Tong, Xianhong; Xu, Xiuxiu; Dong, Zhongjun; Sun, Rui; Tian, Zhigang; Wei, Haiming

2017-12-19

Natural killer (NK) cells are present in large populations at the maternal-fetal interface during early pregnancy. However, the role of NK cells in fetal growth is unclear. Here, we have identified a CD49a + Eomes + subset of NK cells that secreted growth-promoting factors (GPFs), including pleiotrophin and osteoglycin, in both humans and mice. The crosstalk between HLA-G and ILT2 served as a stimulus for GPF-secreting function of this NK cell subset. Decreases in this GPF-secreting NK cell subset impaired fetal development, resulting in fetal growth restriction. The transcription factor Nfil3, but not T-bet, affected the function and the number of this decidual NK cell subset. Adoptive transfer of induced CD49a + Eomes + NK cells reversed impaired fetal growth and rebuilt an appropriate local microenvironment. These findings reveal properties of NK cells in promoting fetal growth. In addition, this research proposes approaches for therapeutic administration of NK cells in order to reverse restricted nourishments within the uterine microenvironment during early pregnancy. Copyright © 2017 Elsevier Inc. All rights reserved.

Fetal optimization during maternal sepsis: relevance and response of the obstetric anesthesiologist.

PubMed

Chau, Anthony; Tsen, Lawrence C

2014-06-01

In many labor and delivery units, the obstetric anesthesiologist is often responsible for managing and stabilizing the acutely septic parturient. The management of maternal sepsis has been summarized previously; this study will focus on the implications of maternal sepsis on the fetus, and ways to optimize fetal outcomes. Although the complex pathophysiology of sepsis is being better understood, the incidence of maternal severe sepsis and deaths continues to increase. The differential sensitivities of systemic and uterine vasculature to catecholamines during pregnancy and the role of fetal inflammatory responses have recently been further elucidated. Additional investigations on methods of fetal monitoring are needed to assist in early identification of the compromised fetus. Despite decades of research, management of a septic parturient and her fetus, including the most appropriate resuscitation fluids, vasopressors and hemodynamic monitoring systems to maximize maternal and fetal outcomes, remain controversial. In the setting of maternal sepsis, fetal optimization is frequently best accomplished by meeting maternal hemodynamic, oxygenization, and infection treatment goals. Understanding the circulatory and pathophysiologic changes that occur within the uteroplacental unit and fetus is essential to identifying and resolving potential conflicts between maternal and fetal management goals.

STUDIES IN FETAL BEHAVIOR: REVISITED, RENEWED, AND REIMAGINED.

PubMed

DiPietro, Janet A; Costigan, Kathleen A; Voegtline, Kristin M

2015-09-01

Among the earliest volumes of this monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodrmal activity and fetal heartrate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include:within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physio-logical processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship.We pose a number of open questions for future research. Although the human fetus remains just out of reach, new technologies portend an era of accelerated discovery of the earliest period of development

Studies in Fetal Behavior: Revisited, Renewed, and Reimagined

PubMed Central

DiPietro, Janet A.; Costigan, Kathleen A.; Voegtline, Kristin M.

2016-01-01

Among the earliest volumes of this Monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodermal activity and fetal heart rate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include: within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physiological processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship. We pose a number of open questions for future research. Although the human fetus remains just out of reach, new technologies portend an era of accelerated discovery of the earliest period of development. PMID:26303396

Excessively delayed maternal reaction after their perception of decreased fetal movements in stillbirths: Population-based study in Japan.

PubMed

Koshida, Shigeki; Ono, Tetsuo; Tsuji, Shunichiro; Murakami, Takashi; Arima, Hisatomi; Takahashi, Kentaro

2017-12-01

Fetal movement is the most common method to evaluate fetal well-being. Furthermore, maternal perception of decreased fetal movements is associated with perinatal demise. Previously, we showed that perception of decreased fetal movements was the most common reason for mothers visiting the outpatient department among those who had stillbirths in our region. Further investigation of stillbirths with decreased fetal movements is essential to find a possible way of preventing stillbirth. To investigate maternal reaction time after their perceiving decreased fetal movements among stillbirths in our region of Japan. This is a population-based study of stillbirths in Shiga Prefecture, Japan conducted from 2007 to 2011. We sent a questionnaire to each obstetrician who had submitted the stillbirth certificate. We reviewed and evaluated the questionnaires returned from the obstetricians. There were 66 cases (35%) with decreased fetal movements among 188 stillbirths in Shiga during the study period. The number of maternal visits to outpatient department after perception of decreased fetal movements within 24h was only seven (11%) among 64 stillbirths diagnosed at outpatient department. We conclude that delayed maternal visit after perceiving decreased fetal movements is frequently observed in stillbirths. Promoting more thorough maternal education on fetal movements, including emphasizing earlier visitation after perceiving decreased fetal movements, may prevent stillbirths. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The influence of physical activity during pregnancy on maternal, fetal or infant heart rate variability: a systematic review.

PubMed

Dietz, Pavel; Watson, Estelle D; Sattler, Matteo C; Ruf, Wolfgang; Titze, Sylvia; van Poppel, Mireille

2016-10-26

Physical activity (PA) during pregnancy has been shown to be associated with several positive effects for mother, fetus, and offspring. Heart rate variability (HRV) is a noninvasive and surrogate marker to determine fetal overall health and the development of fetal autonomic nervous system. In addition, it has been shown to be significantly influenced by maternal behavior. However, the influence of maternal PA on HRV has not yet been systematically reviewed. Therefore, the aim of this systematic review was to assess the influence of regular maternal PA on maternal, fetal or infant HRV. A systematic literature search following a priori formulated criteria of studies that examined the influence of regular maternal PA (assessed for a minimum period of 6 weeks) on maternal, fetal or infant HRV was performed in the databases Pubmed and SPORTDiscus. Quality of each study was assessed using the standardized Quality Assessment Tool for Quantitative Studies (QATQS). Nine articles were included into the present systematic review: two intervention studies, one prospective longitudinal study, and six post-hoc analysis of subsets of the longitudinal study. Of these articles four referred to maternal HRV, five to fetal HRV, and one to infant HRV. The overall global rating for the standardized quality assessment of the articles was moderate to weak. The articles regarding the influence of maternal PA on maternal HRV indicated contrary results. Five of five articles regarding the influence of maternal PA on fetal HRV showed increases of fetal HRV on most parameters depending on maternal PA. The article referring to infant HRV (measured one month postnatal) showed an increased HRV. Based on the current evidence available, our overall conclusion is that the hypothesis that maternal PA influences maternal HRV cannot be supported, but there is a trend that maternal PA might increase fetal and infant HRV (clinical conclusion). Therefore, we recommend that further, high quality studies addressing the influence of maternal PA on HRV should be performed (methodological conclusion).

Noninvasive fetal RhCE genotyping from maternal blood.

PubMed

Geifman-Holtzman, O; Grotegut, C A; Gaughan, J P; Holtzman, E J; Floro, C; Hernandez, E

2009-01-01

The successful prevention of RhD disease has brought attention to other red blood cells' antigens causing alloimmunisation including RhC/c and RhE/e. Prenatal diagnosis of fetal Rh genotype from maternal blood is in clinical use in Europe but not in the USA. To estimate the collective reported diagnostic accuracy of fetal RhCE genotyping from peripheral maternal blood and compare the results of genotyping when fetal cells and free fetal DNA (FfDNA) are used. English-written literature describing fetal RhCE determination from maternal blood using fetal cells or FfDNA was performed using medical subject headings and text words. The sources included Pubmed (1966-2007), Ovid (1966-2007), CINAHL, The Cochrane Library, ACP Journal Club and OCLC. Key words were prenatal diagnosis, fetal RhCE, fetal DNA in maternal blood and alloimmunisation. A study was considered eligible if it described fetal RhCE type determination using maternal peripheral blood reported in the English literature. Abstracts were excluded. From each study, we determined the number of samples tested, fetal RhCE genotype, the source of the fetal DNA, gestational age, presence of alloimmunisation and confirmation of fetal RhCE type. Exclusions and inclusions were noted. We calculated composite estimates of accuracy using a weighted random effects model. We assessed the papers against an international quality, STARD checklist which is standards for reporting studies of diagnostic accuracy. We identified 20 protocols in six English-written publications reporting fetal RhC/c (seven protocols) and/or E/e (13 protocols) genotyping using DNA obtained from maternal blood for a total of 369 samples. For RhC/c, 176 samples were tested and for RhE/e, 193 samples were tested. Accuracy was determined for each study and for all studies. The combined accuracy of fetal genotype was 96.3% for RhC/c and 98.2% for RhE/e. Only a few samples of the sorted cells were found to be a source for accurate diagnosis, but plasma was consistently the best source of fetal RhCE genotyping in 147/147 (100%) for RhC/c and 168/168 (100%) for RhE/e. The combined accuracy of noninvasive fetal RhC/c or RhE/e determination using maternal peripheral blood is 96.3% and 98.2%, respectively. FfDNA in maternal plasma is a better source for genotyping reported to be 100% correct for both RHCE genotypes. Further studies and reports of accuracy from laboratories performing the tests are required before prenatal determination of fetal RhC/c or RhE/e genotypes from maternal blood can safely replace the current methods used in the management of the RhC/c or RhE alloimmunised pregnancies.

Reproductive corticotropin releasing hormone, implantation, and fetal immunotolerance.

PubMed

Kalantaridou, Sophia N; Zoumakis, Emmanouil; Weil, Stacie; Lavasidis, Lazaros G; Chrousos, George P; Makrigiannakis, Antonis

2007-01-01

The fundamental process of implantation involves a series of steps leading to effective cross-talk between invasive trophoblast cells and the maternal endometrium. The molecular interactions at the embryo-maternal interface during the time of blastocyst adhesion and subsequent invasion are not fully understood. Embryonic trophoblast and maternal decidual cells produce corticotropin-releasing hormone (CRH) and express Fas ligand (FasL), a proapoptotic cytokine. Fas and its ligand are pivotal in the regulation of immune tolerance. Trophoblast and decidual CRH play crucial roles in implantation, as well as in the anti-rejection process that protects the fetus from the maternal immune system, primarily by killing activated T cells through Fas-FasL interaction. The potential use of CRH antagonists is presently under intense investigation. CRH antagonists have been used experimentally to elucidate the role of CRH in blastocyst implantation and invasion, early fetal immunotolerance, and premature labor.

Antigen-presenting cells and materno-fetal tolerance: an emerging role for dendritic cells.

PubMed

Laskarin, Gordana; Kämmerer, Ulrike; Rukavina, Daniel; Thomson, Angus W; Fernandez, Nelson; Blois, Sandra M

2007-09-01

During pregnancy, a delicate balance of innate and adaptive immune responses at the maternal-fetal interface promotes survival of the semi-allogeneic embryo and, at the same time, allows effective immunity to protect the mother from environmental pathogens. As in other tissues, antigen handling and processing in the decidualized endometrium constitutes a primary event in the onset of immune responses and is therefore likely to determine their stimulatory or tolerogenic nature. Maternal antigen-presenting cells [macrophages and dendritic cells (DCs)] are scattered throughout the decidualized endometrium during all stages of pregnancy and appear to be important players in this feto-maternal immune adjustment. This review focuses on the characterization of decidual macrophages and DCs, as well as their involvement in cell-cell interactions within the decidual leukocyte network, which are likely to influence uterine and placental homeostasis as well as the local maternal immune responses to the fetus during pregnancy.

Role of dendritic cells in the regulation of maternal immune responses to the fetus during mammalian gestation.

PubMed

Kammerer, Ulrike; Kruse, Andrea; Barrientos, Gabriela; Arck, Petra C; Blois, Sandra M

2008-01-01

Successful mammalian pregnancy relies on the action of sophisticated regulatory mechanisms that allow the fetus (a semi-allograft) to grow and develop in the uterus in spite of being recognized by maternal immune cells. Among several immunocompetent cells present at the maternal fetal interface, dendritic cells (DC) seem to be of particular relevance for pregnancy maintenance given their unique ability to induce both antigen-specific immunity and tolerance. Thus, these cells would be potentially suitable candidates for the regulation of local immune responses within the uterus necessary to meet the difficult task of protecting the mother from infection without compromising fetal survival. Current evidence on decidual DC phenotype and function, and their role in the regulation of the maternal immune system during mouse and human pregnancy are discussed and reviewed herein; highlighting novel DC functions that seem to be of great importance for a successful pregnancy outcome.

Correlation between pre-pregnancy body mass index and maternal visceral adiposity with fetal biometry during the second trimester.

PubMed

Lopes, Karina R M; Souza, Alex Sandro R; Figueiroa, José N; Alves, João Guilherme B

2017-08-01

To determine the correlation between pre-pregnancy body mass index (BMI) and maternal visceral adiposity with fetal biometry during the second trimester. A cross-sectional observational study was conducted among pregnant women who received prenatal care at a center in Recife, Brazil, between October 3, 2011, and September 27, 2013. Pre-pregnancy BMI was determined at the first prenatal care visit. Maternal visceral adiposity and fetal biometry were measured at the same ultrasonography session. The associations between maternal and fetal variables were evaluated using the Pearson correlation coefficient (R). The Student t test was used to test the null hypothesis of adjusted correlation coefficients. Overall, 740 women were included. No correlation was found between pre-pregnancy BMI and any of the fetal biometric variables assessed. By contrast, maternal visceral adiposity positively correlated with fetal abdominal circumference (R=0.529), estimated fetal weight (R=0.524), head circumference (R=0.521), femur length (R=0.521), and biparietal diameter (R=0.524; P<0.001 for all fetal variables). These findings remained statistically significant after controlling for pregnancy length. Maternal visceral adiposity, but not pre-pregnancy BMI, positively correlated with fetal biometry during the second trimester. © 2017 International Federation of Gynecology and Obstetrics.

The relation between social support, anxiety and distress symptoms and maternal fetal attachment.

PubMed

Hopkins, Joyce; Miller, Jennifer L; Butler, Kristina; Gibson, Lynda; Hedrick, Laura; Boyle, Deborah Anne

2018-05-04

The aims of this study were to: (1) examine the relation between social support, trait anxiety, symptoms of maternal distress (including stress, depression and anxiety) and maternal-fetal attachment; and (2) to determine if social support buffers the relation between trait anxiety, symptoms of distress and maternal-fetal attachment. Ninety-four pregnant women completed five self-report questions. Two hierarchical regression analyses were conducted to examine the influence of trait anxiety, symptoms of distress, and social support on two factors of maternal-fetal attachment, quality and intensity/frequency. In the first model with the dependent measure as the maternal-fetal attachment quality score, trait anxiety (β = -.24, p < .05) and social support (β = .30, p < .01) were significant predictors, accounting for 18% of the variance. In the second model with the dependent measure as the maternal-fetal attachment intensity/frequency score, trait anxiety (β = -.23, p < .05) and social support (β = .32, p < .01) were significant predictors, accounting for 23% of the variance. In addition, the interaction term contributed a significant 4% of the variance, indicating that when social support is high, the relation between anxiety and maternal-fetal attachment intensity/frequency is attenuated. This study demonstrates that prenatal attachment is related to trait anxiety and social support. These findings suggest that interventions to decrease anxiety and increase social support could enhance maternal-fetal attachment.

Correlation of maternal-fetal attachment and health practices during pregnancy with neonatal outcomes.

PubMed

Maddahi, Maryam Sadat; Dolatian, Mahrokh; Khoramabadi, Monirsadat; Talebi, Atefeh

2016-07-01

Low birth weight due to preterm delivery or intrauterine growth restriction (IUGR) is the strongest factor contributing to prenatal, neonatal, and postnatal mortality. Maternal-fetal attachment plays a significant role in maternal and fetal health. Health practices performed by the mother during pregnancy constitute one of the factors that may affect neonatal outcomes. The present study was conducted to identify the relationship between maternal-fetal attachment and health practices during pregnancy with neonatal outcomes. This cross-sectional study was conducted on 315 pregnant women with a gestational age of 33-41 weeks who presented to hospitals in Sirjan (Iran) between December 2014 and February 2015. The data collection tools used included the Health Practices in Pregnancy Questionnaire and the Maternal Fetal Attachment Scale. Data were analyzed using IBM-SPSS version 20, focusing on the Pearson product-moment correlation and the logistic regression model. Statistical significance was set to p<0.05. The mean score of maternal-fetal attachment was 60.34, and the mean score of health practices was 123.57. The mean birth weight of the neonates was 3052.38 g. Health practices (p<0.05, r=0.11) and maternal-fetal attachment (p<0.01, r=0.23) were positively and significantly correlated with neonatal outcomes. A significant positive relationship was also observed between maternal-fetal attachment and neonatal outcomes. No significant relationships were observed between health practices during pregnancy and neonatal outcomes. Maternal-fetal attachment and health practices during pregnancy are positively and significantly correlated with neonatal outcomes.

Rab11 family expression in the human placenta: Localization at the maternal-fetal interface

PubMed Central

Artemiuk, Patrycja A.; Hanscom, Sara R.; Lindsay, Andrew J.; Wuebbolt, Danielle; Breathnach, Fionnuala M.; Tully, Elizabeth C.; Khan, Amir R.; McCaffrey, Mary W.

2017-01-01

Rab proteins are a family of small GTPases involved in a variety of cellular processes. The Rab11 subfamily in particular directs key steps of intracellular functions involving vesicle trafficking of the endosomal recycling pathway. This Rab subfamily works through a series of effector proteins including the Rab11-FIPs (Rab11 Family-Interacting Proteins). While the Rab11 subfamily has been well characterized at the cellular level, its function within human organ systems is still being explored. In an effort to further study these proteins, we conducted a preliminary investigation of a subgroup of endosomal Rab proteins in a range of human cell lines by Western blotting. The results from this analysis indicated that Rab11a, Rab11c(Rab25) and Rab14 were expressed in a wide range of cell lines, including the human placental trophoblastic BeWo cell line. These findings encouraged us to further analyse the localization of these Rabs and their common effector protein, the Rab Coupling Protein (RCP), by immunofluorescence microscopy and to extend this work to normal human placental tissue. The placenta is a highly active exchange interface, facilitating transfer between mother and fetus during pregnancy. As Rab11 proteins are closely involved in transcytosis we hypothesized that the placenta would be an interesting human tissue model system for Rab investigation. By immunofluorescence microscopy, Rab11a, Rab11c(Rab25), Rab14 as well as their common FIP effector RCP showed prominent expression in the placental cell lines. We also identified the expression of these proteins in human placental lysates by Western blot analysis. Further, via fluorescent immunohistochemistry, we noted abundant localization of these proteins within key functional areas of primary human placental tissues, namely the outer syncytial layer of placental villous tissue and the endothelia of fetal blood vessels. Overall these findings highlight the expression of the Rab11 family within the human placenta, with novel localization at the maternal-fetal interface. PMID:28922401

The formation and transformation of hormones in maternal, placental and fetal compartments: biological implications.

PubMed

Pasqualini, Jorge R; Chetrite, Gérard S

2016-07-01

The fetal endocrine system constitutes the earliest system developing in fetal life and operates during all the steps of gestation. Its regulation is in part dependent on the secretion of placental and/or maternal precursors emanating across the feto-maternal interface. Human fetal and placental compartments possess all the enzymatic systems necessary to produce steroid hormones. However, their activities are different and complementary: the fetus is very active in converting acetate into cholesterol, in transforming pregnanes to androstanes, various hydroxylases, sulfotransferases, while all these transformations are absent or very limited in the placenta. This compartment can transform cholesterol to C21-steroids, convert 5-ene to 4-ene steroids, and has a high capacity to aromatize C19 precursors and to hydrolyze sulfates. Steroid hormone receptors are present at an early stage of gestation and are functional for important physiological activities. The production rate of some steroids greatly increases with fetal evolution (e.g. estriol increases 500-1000 times in relation to non-pregnant women). Other hormones, such as glucocorticoids, in particular the stress hormone cortisol, adipokines (e.g. leptin, adiponectin), insulin-like growth factors, are also a key factor for regulating reproduction, metabolism, appetite and may be significant in programming the fetus and its growth. We can hypothesize that the fetal and placental factors controlling hormonal levels in the fetal compartment can be of capital importance in the normal development of extra-uterine life.

Infectious Prions in the Pregnancy Microenvironment of Chronic Wasting Disease-Infected Reeves' Muntjac Deer

PubMed Central

Nalls, Amy V.; McNulty, Erin; Hoover, Clare E.; Pulscher, Laura A.; Hoover, Edward A.

2017-01-01

ABSTRACT Ample evidence exists for the presence of infectious agents at the maternal-fetal interface, often with grave outcomes to the developing fetus (i.e., Zika virus, brucella, cytomegalovirus, and toxoplasma). While less studied, pregnancy-related transmissible spongiform encephalopathies (TSEs) have been implicated in several species, including humans. Our previous work has shown that prions can be transferred from mother to offspring, resulting in the development of clinical TSE disease in offspring born to muntjac dams infected with chronic wasting disease (CWD) (1). We further demonstrated protein misfolding cyclic amplification (PMCA)-competent prions within the female reproductive tract and in fetal tissues harvested from CWD experimentally and naturally exposed cervids (1, 2). To assess whether the PMCA-competent prions residing at the maternal-fetal interface were infectious and to determine if the real-time quaking-induced conversion (RT-QuIC) methodology may enhance our ability to detect amyloid fibrils within the pregnancy microenvironment, we employed a mouse bioassay and RT-QuIC. In this study, we have demonstrated RT-QuIC seeding activity in uterus, placentome, ovary, and amniotic fluid but not in allantoic fluids harvested from CWD-infected Reeves' muntjac dams showing clinical signs of infection (clinically CWD-infected) and in some placentomes from pre-clinically CWD-infected dams. Prion infectivity was confirmed within the uterus, amniotic fluid, and the placentome, the semipermeable interface that sustains the developing fetus, of CWD-infected dams. This is the first report of prion infectivity within the cervid pregnancy microenvironment, revealing a source of fetal CWD exposure prior to the birthing process, maternal grooming, or encounters with contaminated environments. IMPORTANCE The facile dissemination of chronic wasting disease within captive and free-range cervid populations has led to questions regarding the transmission dynamics of this disease. Direct contact with infected animals and indirect contact with infectious prions in bodily fluids and contaminated environments are suspected to explain the majority of this transmission. A third mode of transmission, from mother to offspring, may be underappreciated. The presence of pregnancy-related prion infectivity within the uterus, amniotic fluid, and the placental structure reveals that the developing fetus is exposed to a source of prions long before exposure to the infectious agent during and after the birthing process or via contact with contaminated environments. These findings have impact on our current concept of CWD disease transmission. PMID:28539446

Zika Virus Infection in Pregnancy, Microcephaly, and Maternal and Fetal Health: What We Think, What We Know, and What We Think We Know.

PubMed

Alvarado, Maria Gabriela; Schwartz, David A

2017-01-01

-The global epidemic of Zika virus (ZIKV) infection has emerged as an important public health problem affecting pregnant women and their infants. -To review the causal association between ZIKV infection during pregnancy and intrauterine fetal infection, microcephaly, brain damage, congenital malformation syndrome, and experimental laboratory models of fetal infection. Many questions remain regarding the risk factors, pathophysiology, epidemiology, and timing of maternal-fetal transmission and disease. These include mechanisms of fetal brain damage and microcephaly; the role of covariables, such as viral burden, duration of viremia, and host genetics, on vertical transmission; and the clinical and pathologic spectrum of congenital Zika syndrome. Additional questions include defining the potential long-term physical and neurobehavioral outcomes for infected infants, whether maternal or fetal host genetics influence the clinical outcome, and whether ZIKV infection can cause maternal morbidity. Finally, are experimental laboratory and animal models of ZIKV infection helpful in addressing maternal-fetal viral transmission and the development of congenital microcephaly? This communication provides current information and attempts to address some of these important questions. -Comprehensive review of published scientific literature. -Recent advances in epidemiology, clinical medicine, pathology, and experimental studies have provided a great amount of new information regarding vertical ZIKV transmission and the mechanisms of congenital microcephaly, brain damage, and congenital Zika syndrome in a relatively short time. However, much work still needs to be performed to more completely understand the maternal and fetal aspects of this new and emerging viral disease.

Selection and validation of reference genes for miRNA expression studies during porcine pregnancy.

PubMed

Wessels, Jocelyn M; Edwards, Andrew K; Zettler, Candace; Tayade, Chandrakant

2011-01-01

MicroRNAs comprise a family of small non-coding RNAs that modulate several developmental and physiological processes including pregnancy. Their ubiquitous presence is confirmed in mammals, worms, flies and plants. Although rapid advances have been made in microRNA research, information on stable reference genes for validation of microRNA expression is still lacking. Real time PCR is a widely used tool to quantify gene transcripts. An appropriate reference gene must be chosen to minimize experimental error in this system. A small difference in miRNA levels between experimental samples can be biologically meaningful as these entities can affect multiple targets in a pathway. This study examined the suitability of six commercially available reference genes (RNU1A, RNU5A, RNU6B, SNORD25, SCARNA17, and SNORA73A) in maternal-fetal tissues from healthy and spontaneously arresting/dying conceptuses from sows were separately analyzed at gestation day 20. Comparisons were also made with non-pregnant endometrial tissues from sows. Spontaneous fetal loss is a prime concern to the commercial pork industry. Our laboratory has previously identified deficits in vasculature development at maternal-fetal interface as one of the major participating causes of fetal loss. Using this well-established model, we have extended our studies to identify suitable microRNA reference genes. A methodical approach to assessing suitability was adopted using standard curve and melting curve analysis, PCR product sequencing, real time PCR expression in a panel of gestational tissues, and geNorm and NormFinder analysis. Our quantitative real time PCR analysis confirmed expression of all 6 reference genes in maternal and fetal tissues. All genes were uniformly expressed in tissues from healthy and spontaneously arresting conceptus attachment sites. Comparisons between tissue types (maternal/fetal/non-pregnant) revealed significant differences for RNU5A, RNU6B, SCARNA17, and SNORA73A expression. Based on our methodical assessment of all 6 reference genes, results suggest that RNU1A is the most stable reference gene for porcine pregnancy studies.

Histologic Changes Associated With Placental Separation in Gilts Infected with Porcine Reproductive and Respiratory Syndrome Virus.

PubMed

Novakovic, Predrag; Detmer, Susan E; Suleman, Muhammad; Malgarin, Carol M; MacPhee, Daniel J; Harding, John C S

2018-07-01

The placenta is a vital organ providing the developing fetus with nutrient and gas exchange, thermoregulation, and waste elimination necessary for fetal development, as well as producing hormones to maintain pregnancy. It is hypothesized that fetal pig death in porcine reproductive and respiratory syndrome may be attributed to pathology of the maternal-fetal interface leading to premature placental separation. This study was designed to evaluate the chronologic progression of porcine reproductive and respiratory syndrome virus (PRRSV)-induced lesions at the maternal-fetal interface, with particular focus on placental separation in experimentally challenged third-trimester gilts. Fifteen gilts were inoculated with a virulent strain of PRRSV-2 on gestation day 86 ± 0.4. On multiple days postinoculation, 3 gilts along with 1 sham-inoculated control per time point were euthanized, and uterine and fetal placental tissues corresponding to each fetus were collected for histopathologic evaluation. The presence of any fetal lesion was 23 times more likely in compromised (meconium-stained and decomposed) compared with viable fetuses ( P < .001). In PRRSV-infected gilts, endometritis was more severe than placentitis, and the severity of endometrial inflammation and vasculitis increased progressively from 2 to 14 days postinoculation. Neither placental vasculitis nor a chronologic progression in the severity of placental detachment was observed. Severe placental detachment was more frequently present in PRRSV-infected compared with noninfected samples and was most significantly associated with placental inflammation, compared with other uterine lesions, viral load, or termination day. The results of this study suggest that placental separation by itself is not sufficient to significantly compromise fetal viability in reproductive porcine reproductive and respiratory syndrome.

Natural killer cells and regulatory T cells in early pregnancy loss

PubMed Central

SHARMA, SURENDRA

2015-01-01

Survival of the allogeneic embryo in the uterus depends on the maintenance of immune tolerance at the maternal-fetal interface. The pregnant uterus is replete with activated maternal immune cells. How this immune tolerance is acquired and maintained has been a topic of intense investigation. The key immune cells that predominantly populate the pregnant uterus are natural killer (NK) cells. In normal pregnancy, these cells are not killers, but rather provide a microenvironment that is pregnancy compatible and supports healthy placentation. In placental mammals, an array of highly orchestrated immune elements to support successful pregnancy outcome has been incorporated. This includes active cooperation between maternal immune cells, particularly NK cells, and trophoblast cells. This intricate process is required for placentation, immune regulation and to remodel the blood supply to the fetus. During the past decade, various types of maternal immune cells have been thought to be involved in cross-talk with trophoblasts and in programming immune tolerance. RegulatoryT cells (Tregs) have attracted a great deal of attention in promoting implantation and immune tolerance beyond implantation. However, what has not been fully addressed is how this immune-trophoblast axis breaks down during adverse pregnancy outcomes, particularly early pregnancy loss, and in response to unscheduled inflammation. Intense research efforts have begun to shed light on the roles of NK cells and Tregs in early pregnancy loss, although much remains to be unraveled in order to fully characterize the mechanisms underlying their detrimental activity. An increased understanding of host-environment interactions that lead to the cytotoxic phenotype of these otherwise pregnancy compatible maternal immune cells is important for prediction, prevention and treatment of pregnancy maladies, particularly recurrent pregnancy loss. In this review, we discuss relevant information from experimental and human models that may explain the pregnancy disrupting roles of these pivotal sentinel cells at the maternal-fetal interface. PMID:25023688

Effects of estrogen coadministration on epoxiconazole toxicity in rats.

PubMed

Stinchcombe, Stefan; Schneider, Steffen; Fegert, Ivana; Rey Moreno, Maria Cecilia; Strauss, Volker; Gröters, Sibylle; Fabian, Eric; Fussell, Karma C; Pigott, Geoffrey H; van Ravenzwaay, Bennard

2013-06-01

Epoxiconazole (EPX; CAS-No. 133855-98-8) is a triazole class-active substance of plant protection products. At a dose level of 50 mg/kg bw/day, it causes a significantly increased incidence of late fetal mortality when administered to pregnant rats throughout gestation (gestation day [GD] 7-18 or 21), as reported previously (Taxvig et al., 2007, 2008) and confirmed in these studies. Late fetal resorptions occurred in the presence of significant maternal toxicity such as clear reduction of corrected body weight gain, signs of anemia, and, critically, a marked reduction of maternal estradiol plasma levels. Furthermore, estradiol supplementation at dose levels of 0.5 or 1.0 μg/animal/day of estradiol cyclopentylpropionate abolished the EPX-mediated late fetal resorptions. No increased incidences of external malformations were found in rats cotreated with 50 mg/kg bw/day EPX and estradiol cyclopentylpropionate, indicating that the occurrence of malformations was not masked by fetal mortality under the study conditions. Overall, the study data indicate that fetal mortality observed in rat studies with EPX is not the result of direct fetal toxicity but occurs indirectly via depletion of maternal estradiol levels. The clarification of the human relevance of the estrogen-related mechanism behind EPX-mediated late fetal resorptions in rats warrants further studies. In particular, this should involve investigation of the placenta (Rey Moreno et al., 2013), since it is the materno-fetal interface and crucial for fetal maintenance. The human relevance is best addressed in a species which is closer to humans with reference to placentation and hormonal regulation of pregnancy, such as the guinea pig (Schneider et al., 2013). © 2013 Wiley Periodicals, Inc.

Prenatal Depression Restricts Fetal Growth

PubMed Central

Diego, Miguel A.; Field, Tiffany; Hernandez-Reif, Maria; Schanberg, Saul; Kuhn, Cynthia; Gonzalez-Quintero, Victor Hugo

2009-01-01

Objective To identify whether prenatal depression is a risk factor for fetal growth restriction. Methods Midgestation (18-20 weeks GA) estimated fetal weight and urine cortisol and birth weight and gestational age at birth data were collected on a sample of 40 depressed and 40 non-depressed women. Estimated fetal weight and birthweight data were then used to compute fetal growth rates. Results Depressed women had a 13% greater incidence of premature delivery (Odds Ratio (OR) = 2.61) and 15% greater incidence of low birthweight (OR = 4.75) than non-depressed women. Depressed women also had elevated prenatal cortisol levels (p = .006) and fetuses who were smaller (p = .001) and who showed slower fetal growth rates (p = .011) and lower birthweights (p = .008). Mediation analyses further revealed that prenatal maternal cortisol levels were a potential mediator for the relationship between maternal symptoms of depression and both gestational age at birth and the rate of fetal growth. After controlling for maternal demographic variables, prenatal maternal cortisol levels were associated with 30% of the variance in gestational age at birth and 14% of the variance in the rate of fetal growth. Conclusion Prenatal depression was associated with adverse perinatal outcomes, including premature delivery and slower fetal growth rates. Prenatal maternal cortisol levels appear to play a role in mediating these outcomes. PMID:18723301

Telomere length and fetal programming: A review of recent scientific advances.

PubMed

Whiteman, Valerie E; Goswami, Anjali; Salihu, Hamisu M

2017-05-01

We sought to synthesize a comprehensive literature review comprising recent research linking fetal programming to fetal telomere length. We also explored the potential effects fetal telomere length shortening has on fetal phenotypes. Utilizing the PubMed database as our primary search engine, we retrieved and reviewed 165 articles of published research. The inclusion criteria limited the articles to those that appeared within the last ten years, were pertinent to humans, and without restriction to language of publication. Our results showed that socio-demographic factors like age, sex, genetic inheritance, and acquired disease impact telomere length. Further, we found several maternal characteristics to be associated with fetal telomere length shortening, and these include maternal chemical exposure (eg, tobacco smoke), maternal stress during pregnancy, maternal nutritional and sleeping disorders during pregnancy as well as maternal disease status. Due to paucity of data, our review could not synthesize evidence directly linking fetal phenotypes to telomere length shortening. Although the research summarized in this review shows some association between determinants of intrauterine programming and fetal telomere length, there is still significant work that needs to be done to delineate the direct relationship of telomere attrition with specific fetal phenotypes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The up side of decidual natural killer cells: new developments in immunology of pregnancy.

PubMed

Jabrane-Ferrat, Nabila; Siewiera, Johan

2014-04-01

Early phases of human pregnancy are associated with the accumulation of a unique subset of natural killer (NK) cells in the maternal decidua. Decidual NK (dNK) cells that are devoid of cytotoxicity play a pivotal role in successful pregnancy. By secreting large amounts of cytokines/chemokines and angiogenic factors, dNK cells participate in all steps of placentation including trophoblast invasion into the maternal endometrium and vascular remodelling. In this review, we summarize some of dNK cell features and discuss more recent exciting data that challenge the conventional view of these cells. Our new data demonstrate that dNK cells undergo fine tuning or even subvert their classical inhibitory machinery and turn into a real defence force in order to prevent the spread of viruses to fetal tissue. Today it is not clear how these phenotypic and functional adaptations impact cellular cross-talk at the fetal-maternal interface and tissue homeostasis. Ultimately, precise understanding of the molecular mechanisms that govern dNK cell plasticity during congenital human cytomegalovirus infection should lead to the design of more robust strategies to reverse immune escape during viral infection and cancer. © 2013 John Wiley & Sons Ltd.

Maternal obesity and neurodevelopmental and psychiatric disorders in offspring

PubMed Central

Edlow, Andrea G.

2017-01-01

There is a growing body of evidence from both human epidemiologic and animal studies that prenatal and lactational exposure to maternal obesity and high-fat diet are associated with neurodevelopmental and psychiatric disorders in offspring. These disorders include cognitive impairment, autism spectrum disorders, attention deficit hyperactivity disorder, cerebral palsy, anxiety and depression, schizophrenia, and eating disorders. This review synthesizes human and animal data linking maternal obesity and high-fat diet consumption to abnormal fetal brain development and neurodevelopmental and psychiatric morbidity in offspring. In addition, it highlights key mechanisms by which maternal obesity and maternal diet might impact fetal and offspring neurodevelopment, including neuroinflammation; increased oxidative stress, dysregulated insulin, glucose, and leptin signaling; dysregulated serotonergic and dopaminergic signaling; and perturbations in synaptic plasticity. Finally, the review summarizes available evidence regarding investigational therapeutic approaches to mitigate the harmful effects of maternal obesity on fetal and offspring neurodevelopment. PMID:27684946

Interaction between dendritic cells and natural killer cells during pregnancy in mice.

PubMed

Blois, Sandra M; Barrientos, Gabriela; Garcia, Mariana G; Orsal, Arif S; Tometten, Mareike; Cordo-Russo, Rosalia I; Klapp, Burghard F; Santoni, Angela; Fernández, Nelson; Terness, Peter; Arck, Petra C

2008-07-01

A complex regulation of innate and adaptive immune responses at the maternal fetal interface promotes tolerance of trophoblast cells carrying paternally derived antigens. Such regulatory functions involve uterine dendritic cells (uDC) and natural killer (uNK) cells. The existence of a NK and DC "cross talk" has been revealed in various experimental settings; its biological significance ranging from cooperative stimulation to cell lysis. Little is known about the presence or role of NK and DC cross talk at the maternal fetal interface. The present study shows that mouse NK and DC interactions are subject to modulation by trophoblast cells in vitro. This interaction promotes a tolerogenic microenvironment characterized by downregulation of the expression of activation markers on uNK cells and uDC and dominance of Th2 cytokines. NK and DC interactions would also influence uterine cell proliferation and this process would be strongly modulated by trophoblast-derived signals. Indeed; while low proliferation rates were observed upon regular coculture allowing direct contact between uterine cells and trophoblasts, incubation in a transwell culture system markedly increased uterine cell proliferation suggesting that soluble factors are key mediators in the molecular "dialog" between the mother and the conceptus during the establishment of mouse pregnancy. Our data further reveal that the regulatory functions of trophoblast cells associated with tolerance induction are impaired in high abortion murine matings. Interestingly, we observed that secretion of interleukin-12p70 by uDC is dramatically abrogated in the presence of uNK cells. Taken together, our results provide the first evidence that a delicate balance of interactions involving NK cells, DC, and trophoblasts at the mouse maternal fetal interface supports a successful pregnancy outcome.

Women with Recurrent Miscarriage Have Decreased Expression of 25-Hydroxyvitamin D3-1α-Hydroxylase by the Fetal-Maternal Interface.

PubMed

Wang, Li-Qin; Yan, Xiao-Ting; Yan, Chun-Fang; Zhang, Xin-Wen; Hui, Ling-Yun; Xue, Mingzhan; Yu, Xue-Wen

2016-01-01

Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1) is integral to the vitamin D metabolic pathway. The enzyme catalyzes localized conversion of pro-hormone 25-hydroxyvitamin D3 to active 1,25-dihydroxyvitamin D3. Our aim was to investigate the expression of CYP27B1 at the fetal-maternal interface in the first trimester pregnancy and to determine whether CYP27B1 was associated with recurrent miscarriage (RM). Expressions of CYP27B1 mRNA and protein in villi and decidua from 20 women undergoing primary miscarriage, 20 women with RM and 20 women with normal pregnancy were evaluated by western blot, and quantitative real-time PCR. The co-localization of CYP27B1 and certain cytokines including IL-10, IFN-γ, TNF-α, and IL-2 expression were examined using immunohistochemistry and confocal microscopy. Women with RM had a significantly lower expression of CYP27B1 mRNA and protein in villous and decidual tissues compared with the normal pregnant women (P = 0.000 in villus, P = 0.002 in decidua for mRNA; P = 0.036 in villus, P = 0.007 in decidua for protein.). Compared with the normal pregnancy, immunostaining for CYP27B1 was significantly decreased in villous trophoblasts and decidual glandular epithelial cells in RM women. No significant differences in the localization of CYP27B1, IL-10, IFN-γ, TNF-α, and IL-2 expression were identified between the normal pregnant and RM women. Women with RM have a lower level of CYP27B1 expression in chorionic villi and decidua compared with normal pregnant women, suggesting that reduced CYP27B1 expression may be associated with RM. The consistent localization of CYP27B1 and IL-10, IFN-γ, TNF-α, and IL-2 expression in villous and decidual tissues suggests the importance of the local production of 1,25(OH)2D3 at the fetal-maternal interface to regulate cytokine responses.

Fetal sex chromosome testing by maternal plasma DNA sequencing: clinical laboratory experience and biology.

PubMed

Bianchi, Diana W; Parsa, Saba; Bhatt, Sucheta; Halks-Miller, Meredith; Kurtzman, Kathryn; Sehnert, Amy J; Swanson, Amy

2015-02-01

To describe the clinical experience with noninvasive prenatal testing for fetal sex chromosomes using sequencing of maternal plasma cell-free DNA in a commercial laboratory. A noninvasive prenatal testing laboratory data set was examined for samples in which fetal sex chromosomes were reported. Available clinical outcomes were reviewed. Of 18,161 samples with sex chromosome results, no sex chromosome aneuploidy was detected in 98.9% and the fetal sex was reported as XY (9,236) or XX (8,721). In 4 of 32 cases in which the fetal sex was reportedly discordant between noninvasive prenatal testing and karyotype or ultrasonogram, a potential biological reason for the discordance exists, including two cases of documented co-twin demise, one case of a maternal kidney transplant from a male donor, and one case of fetal ambiguous genitalia. In the remaining 204 samples (1.1%), one of four sex chromosome aneuploidies (monosomy X, XXX, XXY, or XYY) was detected. The frequency of false positive results for sex chromosome aneuploidies is a minimum of 0.26% and a maximum of 1.05%. All but one of the discordant sex chromosome aneuploidy results involved the X chromosome. In two putative false-positive XXX cases, maternal XXX was confirmed by karyotype. For the false-positive cases, mean maternal age was significantly higher in monosomy X (P<.001) and lower in XXX (P=.008). Noninvasive prenatal testing results for sex chromosome aneuploidy can be confounded by maternal or fetal biological phenomena. When a discordant noninvasive prenatal testing result is encountered, resolution requires additional maternal history, detailed fetal ultrasonography, and determination of fetal and possibly maternal karyotypes.

Regulatory T cells and the immune pathogenesis of prenatal infection

PubMed Central

Rowe, Jared H.; Ertelt, James M.; Xin, Lijun; Way, Sing Sing

2013-01-01

Pregnancy in placental mammals offers exceptional comprehensive benefits of in utero protection, nutrition, and elimination of metabolic waste for the developing fetus. However, these advantages also require durable strategies to mitigate maternal rejection of fetal tissue expressing foreign paternal antigens. Since the initial postulate of expanded maternal immune tolerance by Sir Peter Medawar 60 years ago, an amazingly elaborate assortment of molecular and cellular modifications acting both locally at the maternal placental interface and systemically have been shown to silence potentially detrimental maternal immune responses. In turn, simultaneously maintaining host defense against the infinite array of potential pathogens during pregnancy is equally important. Fortunately, resistance against most infections is preserved seamlessly throughout gestation. On the other hand, recent studies on pathogens with unique predisposition for prenatal infection have uncovered distinctive holes in host defense associated with the reproductive process. Using these infections to probe the response during pregnancy, the immune suppressive regulatory subset of maternal CD4 T cells has been increasingly shown to dictate the inter-workings between prenatal infection susceptibility and pathogenesis of ensuing pregnancy complications. Herein, the recent literature suggesting a necessity for maternal regulatory T cells in pregnancy induced immunological shifts that sustain fetal tolerance is reviewed. Additional discussion is focused on how expansion of maternal regulatory T cell suppression may become exploited by pathogens that cause prenatal infection, and the perilous potential of infection induced immune activation that may mitigate fetal tolerance and inadvertently inject hostility into the protective in utero environment. PMID:23929902

Innate Immune System at the Maternal-Fetal Interface: Mechanisms of Disease and Targets of Therapy in Pregnancy Syndromes.

PubMed

Triggianese, Paola; Perricone, Carlo; Chimenti, Maria Sole; De Carolis, Caterina; Perricone, Roberto

2016-10-01

The maternal-fetal interface is an immunologically unique site that allows the tolerance to the allogenic fetus and maintains host defense against possible pathogens. Balanced immune responses are required for the maintenance of successful pregnancy. It has been demonstrated that innate immune disturbances may be responsible for some adverse pregnancy outcomes such as preeclampsia (PE); hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome; intrauterine growth restriction (IUGR); and recurrent spontaneous abortion (RSA). Observational studies suggest that immunomodulatory treatments in pregnancy-specific complications may improve both the hematological/biochemical features in the mother and the perinatal outcomes. The following review will discuss how recent and relevant findings in the field of the innate immunity have advanced our understanding of the role of inflammation and innate immune system in the pathogenesis of pregnancy failure and will discuss the therapeutic outcomes of the existing studies and clinical trials in light of these new insights. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The relationship of maternal and fetal toxicity in developmental toxicology bioassays with notes on the biological significance of the "no observed adverse effect level".

EPA Science Inventory

Standard developmental toxicology bioassays are designed to identify agents with the potential to induce adverse effects and include dose levels that induce maternal toxicity. The work reported here was undertaken to evaluate the relationship of maternal and fetal toxicity. It co...

Type 2 porcine reproductive and respiratory syndrome virus infection increases apoptosis at the maternal-fetal interface in late gestation pregnant gilts

PubMed Central

Harding, John C. S.; Al-Dissi, Ahmad N; Detmer, Susan E.

2017-01-01

The pathogenesis of fetal death associated with porcine reproductive and respiratory syndrome (PRRS) is hypothesized to be a consequence of PRRS virus-induced apoptosis at the maternal-fetal interface (MFI). The objectives of this study were to evaluate distribution and degree of apoptosis in the uterine and fetal placental tissues during the experimental type 2 PRRS virus (PRRSV) infection and determine associations between apoptosis at the MFI, PRRSV RNA concentration and antigen staining intensity, PRRSV-induced microscopic lesions, and fetal preservation status. A total of 114 naïve, high-health pregnant gilts were inoculated with type 2 PRRSV on gestation day 85±1 with euthanasia 21 days later; 19 sham-inoculated gilts served as controls. Two hundred and fifty samples of uterine tissue with fetal placenta were selected based on negative, low PRRSV RNA, and high PRRSV RNA concentration (0, < or > 2.7 log10 copies/mg, respectively). TUNEL assay was used to detect apoptosis in the endometrium and at the MFI. PRRSV RNA concentration and numbers of PRRSV immunopositive cells in uterine and placental tissue were positively associated with the severity of apoptosis in the endometrium and the MFI (P<0.001, P<0.05 and P<0.001, respectively). The number of TUNEL positive cells at the MFI was also positively associated with the severity (P<0.001) of vasculitis, but not total numbers of inflammatory cells in the endometrium. Increased numbers of TUNEL positive cells at the MFI were associated with PRRSV load in the fetal thymus, and greater odds of meconium staining of the fetus at 21 days post infection (P<0.001 for both). These findings suggest an important role of apoptosis in the pathogenesis of uterine epithelial and trophoblastic cell death at the MFI. Moreover, apoptosis at the MFI is significantly associated with fetal demise during in utero type 2 PRRSV infection. PMID:28253336

A role for xanthine oxidase in the control of fetal cardiovascular function in late gestation sheep

PubMed Central

Herrera, E A; Kane, A D; Hansell, J A; Thakor, A S; Allison, B J; Niu, Y; Giussani, D A

2012-01-01

Virtually nothing is known about the effects on fetal physiology of xanthine oxidase inhibition. This is despite maternal treatment with the xanthine oxidase inhibitor allopurinol being considered in human complicated pregnancy to protect the infant's brain from excessive generation of ROS. We investigated the in vivo effects of maternal treatment with allopurinol on fetal cardiovascular function in ovine pregnancy in late gestation. Under anaesthesia, pregnant ewes and their singleton fetus were instrumented with vascular catheters and flow probes around an umbilical and a fetal femoral artery at 118 ± 1 dGA (days of gestational age; term ca. 145 days). Five days later, mothers were infused i.v. with either vehicle (n= 11) or allopurinol (n= 10). Fetal cardiovascular function was stimulated with increasing bolus doses of phenylephrine (PE) following maternal vehicle or allopurinol. The effects of maternal allopurinol on maternal and fetal cardiovascular function were also investigated following fetal NO blockade (n= 6) or fetal β1-adrenergic antagonism (n= 7). Maternal allopurinol led to significant increases in fetal heart rate, umbilical blood flow and umbilical vascular conductance, effects abolished by fetal β1-adrenergic antagonism but not by fetal NO blockade. Maternal allopurinol impaired fetal α1-adrenergic pressor and femoral vasopressor responses and enhanced the gain of the fetal cardiac baroreflex. These effects of maternal allopurinol were restored to control levels during fetal NO blockade. Maternal treatment with allopurinol induced maternal hypotension, tachycardia and acid–base disturbance. We conclude that maternal treatment with allopurinol alters in vivo maternal, umbilical and fetal vascular function via mechanisms involving NO and β1-adrenergic stimulation. The evidence suggests that the use of allopurinol in clinical practice should be approached with caution. PMID:22331413

Effects of Maternal Obesity on Fetal Programming: Molecular Approaches

PubMed Central

Neri, Caterina; Edlow, Andrea G.

2016-01-01

Maternal obesity has become a worldwide epidemic. Obesity and a high-fat diet have been shown to have deleterious effects on fetal programming, predisposing offspring to adverse cardiometabolic and neurodevelopmental outcomes. Although large epidemiological studies have shown an association between maternal obesity and adverse outcomes for offspring, the underlying mechanisms remain unclear. Molecular approaches have played a key role in elucidating the mechanistic underpinnings of fetal malprogramming in the setting of maternal obesity. These approaches include, among others, characterization of epigenetic modifications, microRNA expression, the gut microbiome, the transcriptome, and evaluation of specific mRNA expression via quantitative reverse transcription polmerase chain reaction (RT-qPCR) in fetuses and offspring of obese females. This work will review the data from animal models and human fluids/cells regarding the effects of maternal obesity on fetal and offspring neurodevelopment and cardiometabolic outcomes, with a particular focus on molecular approaches. PMID:26337113

Physiological reactivity of pregnant women to evoked fetal startle

PubMed Central

DiPietro, Janet A.; Voegtline, Kristin M.; Costigan, Kathleen A.; Aguirre, Frank; Kivlighan, Katie; Chen, Ping

2013-01-01

Objective The bidirectional nature of mother-child interaction is widely acknowledged during infancy and childhood. Prevailing models during pregnancy focus on unidirectional influences exerted by the pregnant woman on the developing fetus. Prior work has indicated that the fetus also affects the pregnant woman. Our objective was to determine whether a maternal psychophysiological response to stimulation of the fetus could be isolated. Methods Using a longitudinal design, an airborne auditory stimulus was used to elicit a fetal heart rate and motor response at 24 (n = 47) and 36 weeks (n = 45) gestation. Women were blind to condition (stimulus versus sham). Maternal parameters included cardiac (heart rate) and electrodermal (skin conductance) responses. Multilevel modeling of repeated measures with 5 data points per second was used to examine fetal and maternal responses. Results As expected, compared to a sham condition, the stimulus generated a fetal motor response at both gestational ages, consistent with a mild fetal startle. Fetal stimulation was associated with significant, transient slowing of maternal heart rate coupled with increased skin conductance within 10 s of the stimulus at both gestational ages. Nulliparous women showed greater electrodermal responsiveness. The magnitude of the fetal motor response significantly corresponded to the maternal skin conductance response at 5, 10, 15, and 30 s following stimulation. Conclusion Elicited fetal movement exerts an independent influence on the maternal autonomic nervous system. This finding contributes to current models of the dyadic relationship during pregnancy between fetus and pregnant woman. PMID:24119937

Comparison of maternal and fetal complications in elective and emergency cesarean section: a systematic review and meta-analysis.

PubMed

Yang, Xiao-Jing; Sun, Shan-Shan

2017-09-01

Though the same types of complication were found in both elective cesarean section (ElCS) and emergence cesarean section (EmCS), the aim of this study is to compare the rates of maternal and fetal morbidity and mortality between ElCS and EmCS. Full-text articles involved in the maternal and fetal complications and outcomes of ElCS and EmCS were searched in multiple database. Review Manager 5.0 was adopted for meta-analysis, sensitivity analysis, and bias analysis. Funnel plots and Egger's tests were also applied with STATA 10.0 software to assess possible publication bias. Totally nine articles were included in this study. Among these articles, seven, three, and four studies were involved in the maternal complication, fetal complication, and fetal outcomes, respectively. The combined analyses showed that both rates of maternal complication and fetal complication in EmCS were higher than those in ElCS. The rates of infection, fever, UTI (urinary tract infection), wound dehiscence, DIC (disseminated intravascular coagulation), and reoperation of postpartum women with EmCS were much higher than those with ElCS. Larger infant mortality rate of EmCS was also observed. Emergency cesarean sections showed significantly more maternal and fetal complications and mortality than elective cesarean sections in this study. Certain plans should be worked out by obstetric practitioners to avoid the post-operative complications.

Effect of Fetal Sex on Maternal and Obstetric Outcomes.

PubMed

Al-Qaraghouli, Mohammed; Fang, Yu Ming Victor

2017-01-01

Fetal sex plays an important role in modifying the course and complications related to pregnancy and may also have an impact on maternal health and well-being both during and after pregnancy. The goal of this article is to review and summarize the findings from published research on physiologic and pathologic changes that may be affected by fetal sex and the effect of these changes on the maternal and obstetrical outcomes. This will help create awareness that fetal sex is not just a random chance event but an interactive process between the mother, the placenta, and the fetus. The reported effects of male sex on the course of pregnancy and delivery include higher incidence of preterm labor in singletons and twins, failure of progression in labor, true umbilical cord knots, cord prolapse, nuchal cord, higher cesarean section rate, higher heart rate variability with increased frequency, and duration of decelerations without acidemia and increased risk of gestational diabetes mellitus through the poor beta cells function. Similarly, female fetal sex has been reported to modify pregnancy and delivery outcomes including altered fetal cardiac hemodynamics, increased hypertensive diseases of pregnancy, higher vulnerability of developing type 2 DM after pregnancy possibly because of influences on increased maternal insulin resistance. Placental function is also influenced by fetal sex. Vitamin D metabolism in the placenta varies by fetal sex; and the placenta of a female fetus is more responsive to the relaxing action of magnesium sulfate. Male and female feto-placental units also vary in their responses to environmental toxin exposure. The association of fetal sex with stillbirths is controversial with many studies reporting higher risk of stillbirth in male fetuses; although some smaller and limited studies have reported more stillbirths with female fetus pregnancies. Maternal status such as BMI may in turn also affect the fetus and the placenta in a sex-specific manner. There is probably a sex-specific maternal-placental-fetal interaction that has significant biological implications of which the mechanisms may be genetic, epigenetic, or hormonal. Determination of fetal sex may therefore be an important consideration in management of pregnancy and childbirth.

Maternal perception of fetal activity and late stillbirth risk: findings from the Auckland Stillbirth Study.

PubMed

Stacey, Tomasina; Thompson, John M D; Mitchell, Edwin A; Ekeroma, Alec; Zuccollo, Jane; McCowan, Lesley M E

2011-12-01

  Maternal perception of decreased fetal movements has been associated with adverse pregnancy outcomes, including stillbirth. Little is known about other aspects of perceived fetal activity. The objective of this study was to explore the relationship between maternal perception of fetal activity and late stillbirth (≥28 wk gestation) risk.   Participants were women with a singleton, late stillbirth without congenital abnormality, born between July 2006 and June 2009 in Auckland, New Zealand. Two control women with ongoing pregnancies were randomly selected at the same gestation at which the stillbirth occurred. Detailed demographic and fetal movement data were collected by way of interview in the first few weeks after the stillbirth, or at the equivalent gestation for control women.   A total of 155/215 (72%) women who experienced a stillbirth and 310/429 (72%) control group women consented to participate in the study. Maternal perception of increased strength and frequency of fetal movements, fetal hiccups, and frequent vigorous fetal activity were all associated with a reduced risk of late stillbirth. In contrast, perception of decreased strength of fetal movement was associated with a more than twofold increased risk of late stillbirth (aOR: 2.37; 95% CI: 1.29-4.35). A single episode of vigorous fetal activity was associated with an almost sevenfold increase in late stillbirth risk (aOR: 6.81; 95% CI: 3.01-15.41) compared with no unusually vigorous activity.   Our study suggests that maternal perception of increasing fetal activity throughout the last 3 months of pregnancy is a sign of fetal well-being, whereas perception of reduced fetal movements is associated with increased risk of late stillbirth. © 2011, Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc.

Dietary Iron Fortification Normalizes Fetal Hematology, Hepcidin, and Iron Distribution in a Rat Model of Prenatal Alcohol Exposure.

PubMed

Huebner, Shane M; Helfrich, Kaylee K; Saini, Nipun; Blohowiak, Sharon E; Cheng, Adrienne A; Kling, Pamela J; Smith, Susan M

2018-06-01

Prenatal alcohol exposure (PAE) causes neurodevelopmental disability. Clinical and animal studies show gestational iron deficiency (ID) exacerbates PAE's behavioral and growth deficits. In rat, PAE manifests an inability to establish iron homeostasis, increasing hepcidin (maternal and fetal), and fetal liver iron while decreasing brain iron and promoting anemia. Here, we hypothesize dietary iron fortification during pregnancy may mitigate alcohol's disruption of fetal iron homeostasis. Pregnant Long-Evans rats, fed iron-sufficient (100 ppm iron) or iron-fortified (IF; 500 ppm iron) diets, received either 5 g/kg alcohol (PAE) or isocaloric maltodextrin daily on gestational days (GD) 13.5 through 19.5. Maternal and fetal outcomes were evaluated on GD20.5. PAE reduced mean fetal weight (p < 0.001) regardless of maternal iron status, suggesting iron fortification did not improve fetal growth. Both PAE (p < 0.01) and IF (p = 0.035) increased fetal liver iron. In fetal brain, PAE (p = 0.015) affected total (p < 0.001) and nonheme iron (p < 0.001) such that iron fortification normalized (p = 0.99) the alcohol-mediated reductions in brain iron and nonheme iron. Iron fortification also improved fetal hematologic indices in PAE including hemoglobin, hematocrit, and mean cell volume (ps<0.001). Iron fortification also normalized hepcidin expression in alcohol-exposed maternal and fetal liver. Neither diet nor PAE affected transferrin (Tf) and ferritin (FTN) content in fetal liver, nor Tf or transferrin receptor in fetal brain. However, IF-PAE fetal brains trended to less FTN content (p = 0.074), suggesting greater availability of nonstorage iron. In PAE, hepcidin levels were linearly related to increased liver iron stores and decreased red blood cell count and brain iron. Maternal oral iron fortification mitigated PAE's disruption of fetal iron homeostasis and improved brain iron content, hematologic indices, and hepcidin production in this rat PAE model. Clinical studies show maternal ID substantially enhances fetal vulnerability to PAE, and our work supports increased maternal dietary iron intake may improve fetal iron status in alcohol-exposed pregnancies. Copyright © 2018 by the Research Society on Alcoholism.

Maternal risk factors predicting child physical characteristics and dysmorphology in fetal alcohol syndrome and partial fetal alcohol syndrome.

PubMed

May, Philip A; Tabachnick, Barbara G; Gossage, J Phillip; Kalberg, Wendy O; Marais, Anna-Susan; Robinson, Luther K; Manning, Melanie; Buckley, David; Hoyme, H Eugene

2011-12-01

Previous research in South Africa revealed very high rates of fetal alcohol syndrome (FAS), of 46-89 per 1000 among young children. Maternal and child data from studies in this community summarize the multiple predictors of FAS and partial fetal alcohol syndrome (PFAS). Sequential regression was employed to examine influences on child physical characteristics and dysmorphology from four categories of maternal traits: physical, demographic, childbearing, and drinking. Then, a structural equation model (SEM) was constructed to predict influences on child physical characteristics. Individual sequential regressions revealed that maternal drinking measures were the most powerful predictors of a child's physical anomalies (R² = .30, p < .001), followed by maternal demographics (R² = .24, p < .001), maternal physical characteristics (R²=.15, p < .001), and childbearing variables (R² = .06, p < .001). The SEM utilized both individual variables and the four composite categories of maternal traits to predict a set of child physical characteristics, including a total dysmorphology score. As predicted, drinking behavior is a relatively strong predictor of child physical characteristics (β = 0.61, p < .001), even when all other maternal risk variables are included; higher levels of drinking predict child physical anomalies. Overall, the SEM model explains 62% of the variance in child physical anomalies. As expected, drinking variables explain the most variance. But this highly controlled estimation of multiple effects also reveals a significant contribution played by maternal demographics and, to a lesser degree, maternal physical and childbearing variables. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The Effect of Very Advanced Maternal Age on Maternal and Neonatal Outcomes: A Systematic Review.

PubMed

Leader, Jordana; Bajwa, Amrit; Lanes, Andrea; Hua, Xiaolin; Rennicks White, Ruth; Rybak, Natalie; Walker, Mark

2018-04-19

To summarize information on the maternal and perinatal outcomes among pregnant women with a maternal age greater or equal to 45 years old compared with women with a maternal age of less than 45. A comprehensive systematic search of online databases from January 1946 through June 2015 was completed. The maternal outcomes were: fetal loss, preterm birth, full-term birth, complications of pregnancy, the type of delivery, and periconception hemorrhage. The fetal outcomes were: intrauterine growth restriction/LGA, fetal anomalies, APGAR score, and neonatal death. Twenty articles were included in the systematic review and 15 included in the meta-analysis. There was a 2.60 greater likelihood of fetal loss (I 2  = 99%). Newborns of women of a very advanced maternal age were 2.49 more likely to have a concerning 5-minute APGAR score. Very advanced maternal age women had a 3.32 greater likelihood of pregnancy complications (I 2  = 91%). There was a 1.96 greater likelihood of preterm birth at very advanced maternal age (I 2  = 91%) and a 4 times greater likelihood of having to deliver through Caesarean section (I 2  = 97%). This systematic review showed an increased risk of adverse maternal and perinatal outcomes. The large amount of heterogeneity among most outcomes that were investigated suggest results must be interpreted with caution. Copyright © 2017 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

A new biosensor for noninvasive determination of fetal RHD status in maternal blood of RhD negative pregnant women.

PubMed

Dündar Yenilmez, Ebru; Kökbaş, Umut; Kartlaşmış, Kezban; Kayrın, Levent; Tuli, Abdullah

2018-01-01

Prenatal detection of the fetal RHD status can be useful in the management of RhD incompatibility to identify fetuses at risk of hemolytic disease. Hemolytic disease causes morbidity and mortality of the fetus in the neonatal period. The routine use of antenatal and postnatal anti-D prophylaxis has reduced the incidence of hemolytic disease of the fetus and newborn. This study describe the detection of fetal RhD antigens in blood of RhD negative pregnant women using a nanopolymer coated electrochemical biosensor for medical diagnosis. Cell free fetal DNA in maternal plasma was also used to genotyping fetal RHD status using multiplex real-time PCR. Twenty-six RhD negative pregnant women in different gestational ages were included in the study. RhD positive fetal antibodies detected with a developed biosensor in maternal blood of RhD negative mothers. The electrochemical measurements were performed on a PalmSens potentiostat, and corundum ceramic based screen printed gold electrode combined with the reference Ag/AgCl electrode, and the auxiliary Au/Pd (98/2%) electrode. Fetal RHD genotyping performed using fluorescence-based multiplex real-time PCR exons 5 and 7 of the RHD gene. The fetal RHD status of 26 RhD negative cases were detected 21 as RhD positive and 5 as RhD negative with electrochemical biosensor. Fetal RHD status confirmed with extracted fetal DNA in maternal plasma using multiplex real-time PCR RHD genotyping and by serological test after delivery. The new method for fetal RhD detection in early pregnancy is useful and can be carry out rapidly in clinical diagnosis. Using automated biosensors are reproducible, quick and results can be generated within a few minutes compared to noninvasive fetal RHD genotyping from maternal plasma with real-time PCR-based techniques. We suggest the biosensor techniques could become an alternative part of fetal RHD genotyping from maternal plasma as a prenatal screening in the management of RhD incompatibility.

Placental angiogenesis in sheep models of compromised pregnancy

PubMed Central

Reynolds, Lawrence P; Borowicz, Pawel P; Vonnahme, Kimberly A; Johnson, Mary Lynn; Grazul-Bilska, Anna T; Redmer, Dale A; Caton, Joel S

2005-01-01

Because the placenta is the organ that transports nutrients, respiratory gases and wastes between the maternal and fetal systems, development of its vascular beds is essential to normal placental function, and thus in supporting normal fetal growth. Compromised fetal growth and development have adverse health consequences during the neonatal period and throughout adult life. To establish the role of placental angiogenesis in compromised pregnancies, we first evaluated the pattern of placental angiogenesis and expression of angiogenic factors throughout normal pregnancy. In addition, we and others have established a variety of sheep models to evaluate the effects on fetal growth of various factors including maternal nutrient excess or deprivation and specific nutrients, maternal age, maternal and fetal genotype, increased numbers of fetuses, environmental thermal stress, and high altitude (hypobaric) conditions. Although placental angiogenesis is altered in each of these models in which fetal growth is adversely affected, the specific effect on placental angiogenesis depends on the type of ‘stress’ to which the pregnancy is subjected, and also differs between the fetal and maternal systems and between genotypes. We believe that the models of compromised pregnancy and the methods described in this review will enable us to develop a much better understanding of the mechanisms responsible for alterations in placental vascular development. PMID:15760944

Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model

PubMed Central

Niu, Jing; Venkatasubramanian, Raja; Vinks, Alexander A.; Sadhasivam, Senthilkumar

2016-01-01

Background Measuring fetal drug concentrations is extremely difficult in humans. We conducted a study in pregnant sheep to simultaneously describe maternal and fetal concentrations of propofol, a common intravenous anesthetic agent used in humans. Compared to inhalational anesthesia, propofol supplemented anesthesia lowered the dose of desflurane required to provide adequate uterine relaxation during open fetal surgery. This resulted in better intraoperative fetal cardiac outcome. This study describes maternal and fetal propofol pharmacokinetics (PK) using a chronically instrumented maternal-fetal sheep model. Methods Fetal and maternal blood samples were simultaneously collected from eight mid-gestational pregnant ewes during general anesthesia with propofol, remifentanil and desflurane. Nonlinear mixed-effects modeling was performed by using NONMEM software. Total body weight, gestational age and hemodynamic parameters were tested in the covariate analysis. The final model was validated by bootstrapping and visual predictive check. Results A total of 160 propofol samples were collected. A 2-compartment maternal PK model with a third fetal compartment appropriately described the data. Mean population parameter estimates for maternal propofol clearance and central volume of distribution were 4.17 L/min and 37.7 L, respectively, in a typical ewe with a median heart rate of 135 beats/min. Increase in maternal heart rate significantly correlated with increase in propofol clearance. The estimated population maternal-fetal inter-compartment clearance was 0.0138 L/min and the volume of distribution of propofol in the fetus was 0.144 L. Fetal propofol clearance was found to be almost negligible compared to maternal clearance and could not be robustly estimated. Conclusions For the first time, a maternal-fetal PK model of propofol in pregnant ewes was successfully developed. This study narrows the gap in our knowledge in maternal-fetal PK model in human. Our study confirms that maternal heart rate has an important influence on the pharmacokinetics of propofol during pregnancy. Much lower propofol concentration in the fetus compared to maternal concentrations explain limited placental transfer in in-vivo paired model, and less direct fetal cardiac depression we observed earlier with propofol supplemented inhalational anesthesia compared to higher dose inhalational anesthesia in humans and sheep. PMID:26752560

Hemodynamic effects of intravenous nicardipine in severely pre-eclamptic women with a hypertensive crisis.

PubMed

Cornette, J; Buijs, E A B; Duvekot, J J; Herzog, E; Roos-Hesselink, J W; Rizopoulos, D; Meima, M; Steegers, E A P

2016-01-01

Nicardipine permits rapid control of blood pressure in women with severe pre-eclampsia (PE) and hypertensive crisis. Our objective was to investigate its maternal and fetal hemodynamic effects. Ten severely pre-eclamptic pregnant women who required intravenous nicardipine for severe hypertension were included in this prospective observational trial. Maternal macrocirculation was assessed by transthoracic echocardiography. Maternal microcirculatory perfusion was examined sublingually with the sidestream dark field imaging technique. Fetal hemodynamics were assessed by Doppler examinations of the uteroplacental and fetal circulations. Maternal cardiac output, total vascular resistance, mitral E/A ratio and capillary heterogeneity index, uterine artery pulsatility index and fetal cerebroplacental ratio were considered primary outcomes. Paired measurements, obtained before administration of nicardipine infusion and after stabilization of blood pressure, were compared. Administration of nicardipine significantly reduced the mean arterial blood pressure (median difference, 26 mmHg; P = 0.002) and total vascular resistance (median difference, 791 dynes × s/cm(5) ; P = 0.002) in all included women. This induced a reflex tachycardia with consequent increase in cardiac output of 1.55 L/min (P  =  0.004). There were no significant changes in the other determinants of maternal or fetal hemodynamic parameters. Nicardipine effectively reduces blood pressure through selective afterload reduction that triggers an increase in cardiac output, without affecting maternal diastolic function, or microcirculatory, uteroplacental or fetal perfusion. This hemodynamic response is uniform and predictable. Fetomaternal cardiovascular profiling can be achieved by combining transthoracic echocardiography with obstetric Doppler. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Anesthesia for fetal surgery.

PubMed

Hoagland, Monica A; Chatterjee, Debnath

2017-04-01

Fetal therapy is an exciting and growing field of medicine. Advances in prenatal imaging and continued innovations in surgical and anesthetic techniques have resulted in a wide range of fetal interventions including minimally invasive, open mid-gestation, and ex-utero intrapartum treatment procedures. The potential for maternal morbidity is significant and must be carefully weighed against claimed benefits to the fetus. Appropriate patient selection is critical, and a multidisciplinary team-based approach is strongly recommended. The anesthetic management should focus on maintaining uteroplacental circulation, achieving profound uterine relaxation, optimizing surgical conditions, monitoring fetal hemodynamics, and minimizing maternal and fetal risk. © 2017 John Wiley & Sons Ltd.

Membrane Vesicles of Group B Streptococcus Disrupt Feto-Maternal Barrier Leading to Preterm Birth

PubMed Central

Sthanam, Lakshmi Kavitha; Srivastava, Rohit; Basu, Bhakti; Dutta, Suryendu; Sen, Shamik; Modi, Deepak

2016-01-01

Infection of the genitourinary tract with Group B Streptococcus (GBS), an opportunistic gram positive pathogen, is associated with premature rupture of amniotic membrane and preterm birth. In this work, we demonstrate that GBS produces membrane vesicles (MVs) in a serotype independent manner. These MVs are loaded with virulence factors including extracellular matrix degrading proteases and pore forming toxins. Mice chorio-decidual membranes challenged with MVs ex vivo resulted in extensive collagen degradation leading to loss of stiffness and mechanical weakening. MVs when instilled vaginally are capable of anterograde transport in mouse reproductive tract. Intra-amniotic injections of GBS MVs in mice led to upregulation of pro-inflammatory cytokines and inflammation mimicking features of chorio-amnionitis; it also led to apoptosis in the chorio-decidual tissue. Instillation of MVs in the amniotic sac also resulted in intrauterine fetal death and preterm delivery. Our findings suggest that GBS MVs can independently orchestrate events at the feto-maternal interface causing chorio-amnionitis and membrane damage leading to preterm birth or fetal death. PMID:27583406

The multiple roles of EG-VEGF/PROK1 in normal and pathological placental angiogenesis.

PubMed

Alfaidy, Nadia; Hoffmann, Pascale; Boufettal, Houssine; Samouh, Naima; Aboussaouira, Touria; Benharouga, Mohamed; Feige, Jean-Jacques; Brouillet, Sophie

2014-01-01

Placentation is associated with several steps of vascular adaptations throughout pregnancy. These vascular changes occur both on the maternal and fetal sides, consisting of maternal uterine spiral arteries remodeling and placental vasculogenesis and angiogenesis, respectively. Placental angiogenesis is a pivotal process for efficient fetomaternal exchanges and placental development. This process is finely controlled throughout pregnancy, and it involves ubiquitous and pregnancy-specific angiogenic factors. In the last decade, endocrine gland derived vascular endothelial growth factor (EG-VEGF), also called prokineticin 1 (PROK1), has emerged as specific placental angiogenic factor that controls many aspects of normal and pathological placental angiogenesis such as recurrent pregnancy loss (RPL), gestational trophoblastic diseases (GTD), fetal growth restriction (FGR), and preeclampsia (PE). This review recapitulates EG-VEGF mediated-angiogenesis within the placenta and at the fetomaternal interface and proposes that its deregulation might contribute to the pathogenesis of several placental diseases including FGR and PE. More importantly this paper argues for EG-VEGF clinical relevance as a potential biomarker of the onset of pregnancy pathologies and discusses its potential usefulness for future therapeutic directions.

High Resolution Size Analysis of Fetal DNA in the Urine of Pregnant Women by Paired-End Massively Parallel Sequencing

PubMed Central

Tsui, Nancy B. Y.; Jiang, Peiyong; Chow, Katherine C. K.; Su, Xiaoxi; Leung, Tak Y.; Sun, Hao; Chan, K. C. Allen; Chiu, Rossa W. K.; Lo, Y. M. Dennis

2012-01-01

Background Fetal DNA in maternal urine, if present, would be a valuable source of fetal genetic material for noninvasive prenatal diagnosis. However, the existence of fetal DNA in maternal urine has remained controversial. The issue is due to the lack of appropriate technology to robustly detect the potentially highly degraded fetal DNA in maternal urine. Methodology We have used massively parallel paired-end sequencing to investigate cell-free DNA molecules in maternal urine. Catheterized urine samples were collected from seven pregnant women during the third trimester of pregnancies. We detected fetal DNA by identifying sequenced reads that contained fetal-specific alleles of the single nucleotide polymorphisms. The sizes of individual urinary DNA fragments were deduced from the alignment positions of the paired reads. We measured the fractional fetal DNA concentration as well as the size distributions of fetal and maternal DNA in maternal urine. Principal Findings Cell-free fetal DNA was detected in five of the seven maternal urine samples, with the fractional fetal DNA concentrations ranged from 1.92% to 4.73%. Fetal DNA became undetectable in maternal urine after delivery. The total urinary cell-free DNA molecules were less intact when compared with plasma DNA. Urinary fetal DNA fragments were very short, and the most dominant fetal sequences were between 29 bp and 45 bp in length. Conclusions With the use of massively parallel sequencing, we have confirmed the existence of transrenal fetal DNA in maternal urine, and have shown that urinary fetal DNA was heavily degraded. PMID:23118982

Infectious Prions in the Pregnancy Microenvironment of Chronic Wasting Disease-Infected Reeves' Muntjac Deer.

PubMed

Nalls, Amy V; McNulty, Erin; Hoover, Clare E; Pulscher, Laura A; Hoover, Edward A; Mathiason, Candace K

2017-08-01

Ample evidence exists for the presence of infectious agents at the maternal-fetal interface, often with grave outcomes to the developing fetus (i.e., Zika virus, brucella, cytomegalovirus, and toxoplasma). While less studied, pregnancy-related transmissible spongiform encephalopathies (TSEs) have been implicated in several species, including humans. Our previous work has shown that prions can be transferred from mother to offspring, resulting in the development of clinical TSE disease in offspring born to muntjac dams infected with chronic wasting disease (CWD) (1). We further demonstrated protein misfolding cyclic amplification (PMCA)-competent prions within the female reproductive tract and in fetal tissues harvested from CWD experimentally and naturally exposed cervids (1, 2). To assess whether the PMCA-competent prions residing at the maternal-fetal interface were infectious and to determine if the real-time quaking-induced conversion (RT-QuIC) methodology may enhance our ability to detect amyloid fibrils within the pregnancy microenvironment, we employed a mouse bioassay and RT-QuIC. In this study, we have demonstrated RT-QuIC seeding activity in uterus, placentome, ovary, and amniotic fluid but not in allantoic fluids harvested from CWD-infected Reeves' muntjac dams showing clinical signs of infection (clinically CWD-infected) and in some placentomes from pre-clinically CWD-infected dams. Prion infectivity was confirmed within the uterus, amniotic fluid, and the placentome, the semipermeable interface that sustains the developing fetus, of CWD-infected dams. This is the first report of prion infectivity within the cervid pregnancy microenvironment, revealing a source of fetal CWD exposure prior to the birthing process, maternal grooming, or encounters with contaminated environments. IMPORTANCE The facile dissemination of chronic wasting disease within captive and free-range cervid populations has led to questions regarding the transmission dynamics of this disease. Direct contact with infected animals and indirect contact with infectious prions in bodily fluids and contaminated environments are suspected to explain the majority of this transmission. A third mode of transmission, from mother to offspring, may be underappreciated. The presence of pregnancy-related prion infectivity within the uterus, amniotic fluid, and the placental structure reveals that the developing fetus is exposed to a source of prions long before exposure to the infectious agent during and after the birthing process or via contact with contaminated environments. These findings have impact on our current concept of CWD disease transmission. Copyright © 2017 American Society for Microbiology.

Males are from Mars, females are from Venus: sex-specific fetal brain gene expression signatures in a mouse model of maternal diet-induced obesity

PubMed Central

EDLOW, Andrea G.; GUEDJ, Faycal; PENNINGS, Jeroen L.A.; SVERDLOV, Deanna; NERI, Caterina; BIANCHI, Diana W.

2016-01-01

BACKGROUND Maternal obesity is associated with adverse neurodevelopmental outcomes in children, including autism spectrum disorders, developmental delay, and attention deficit hyperactivity disorder. The underlying mechanisms remain unclear. We previously identified second trimester amniotic fluid and term cord blood gene expression patterns suggesting dysregulated brain development in fetuses of obese compared to lean women. OBJECTIVES We sought to investigate the biological significance of these findings in a mouse model of maternal diet-induced obesity. We evaluated sex-specific differences in fetal growth, brain gene expression signatures and associated pathways. STUDY DESIGN Female C57BL/6J mice were fed a 60% high-fat diet or 10% fat control diet for 12–14 weeks prior to mating. During pregnancy, obese dams continued on the high-fat diet (HFD/HFD), or transitioned to the CD (HFD/CD). Lean dams stayed on the control diet. On embryonic day 17.5, embryos were weighed and fetal brains were snap frozen. RNA was extracted from male and female forebrains (10/diet group/sex) and hybridized to whole genome expression arrays. Significantly differentially expressed genes were identified using Welch’s t-test with the Benjamini-Hochberg correction. Functional analyses were performed using Ingenuity Pathways Analysis and Gene Set Enrichment Analysis. RESULTS Embryos of HFD/HFD dams were significantly smaller than controls, with males more severely affected than females (p=0.01). Maternal obesity and maternal obesity with dietary change in pregnancy resulted in significantly more dysregulated genes in male versus female fetal brains (386 vs 66, p<0.001). Maternal obesity with and without dietary change in pregnancy was associated with unique brain gene expression signatures for each sex, with overlap of only one gene. Changing obese dams to a control diet in pregnancy resulted in more differentially expressed genes in the fetal brain than maternal obesity alone. Functional analyses identified common dysregulated pathways in both sexes, but maternal obesity and maternal dietary change affected different aspects of brain development in males compared to females. CONCLUSIONS Maternal obesity is associated with sex-specific differences in fetal size and fetal brain gene expression signatures. Male fetal growth and brain gene expression may be more sensitive to environmental influences during pregnancy. Maternal diet during pregnancy significantly impacts the embryonic brain transcriptome. It is important to consider both fetal sex and maternal diet when evaluating the effects of maternal obesity on fetal neurodevelopment. PMID:26945603

Males are from Mars, and females are from Venus: sex-specific fetal brain gene expression signatures in a mouse model of maternal diet-induced obesity.

PubMed

Edlow, Andrea G; Guedj, Faycal; Pennings, Jeroen L A; Sverdlov, Deanna; Neri, Caterina; Bianchi, Diana W

2016-05-01

Maternal obesity is associated with adverse neurodevelopmental outcomes in children, including autism spectrum disorders, developmental delay, and attention-deficit hyperactivity disorder. The underlying mechanisms remain unclear. We previously identified second-trimester amniotic fluid and term cord blood gene expression patterns suggesting dysregulated brain development in fetuses of obese compared with lean women. We sought to investigate the biological significance of these findings in a mouse model of maternal diet-induced obesity. We evaluated sex-specific differences in fetal growth, brain gene expression signatures, and associated pathways. Female C57BL/6J mice were fed a 60% high-fat diet or 10% fat control diet for 12-14 weeks prior to mating. During pregnancy, obese dams continued on the high-fat diet or transitioned to the control diet. Lean dams stayed on the control diet. On embryonic day 17.5, embryos were weighed and fetal brains were snap frozen. RNA was extracted from male and female forebrains (10 per diet group per sex) and hybridized to whole-genome expression arrays. Significantly differentially expressed genes were identified using a Welch's t test with the Benjamini-Hochberg correction. Functional analyses were performed using ingenuity pathways analysis and gene set enrichment analysis. Embryos of dams on the high-fat diet were significantly smaller than controls, with males more severely affected than females (P = .01). Maternal obesity and maternal obesity with dietary change in pregnancy resulted in significantly more dysregulated genes in male vs female fetal brains (386 vs 66, P < .001). Maternal obesity with and without dietary change in pregnancy was associated with unique brain gene expression signatures for each sex, with an overlap of only 1 gene. Changing obese dams to a control diet in pregnancy resulted in more differentially expressed genes in the fetal brain than maternal obesity alone. Functional analyses identified common dysregulated pathways in both sexes, but maternal obesity and maternal dietary change affected different aspects of brain development in males compared with females. Maternal obesity is associated with sex-specific differences in fetal size and fetal brain gene expression signatures. Male fetal growth and brain gene expression may be more sensitive to environmental influences during pregnancy. Maternal diet during pregnancy has a significant impact on the embryonic brain transcriptome. It is important to consider both fetal sex and maternal diet when evaluating the effects of maternal obesity on fetal neurodevelopment. Copyright © 2016 Elsevier Inc. All rights reserved.

Anesthesia For In Utero Repair of Myelomeningocele

PubMed Central

Ferschl, Marla; Ball, Robert; Lee, Hanmin; Rollins, Mark D.

2013-01-01

Recently published results suggest that prenatal repair of fetal myelomeningocele is a potentially preferable alternative when compared to postnatal repair. In this article, the pathology of myelomeningocele, unique physiologic considerations, perioperative anesthetic management, and ethical considerations of open fetal surgery for prenatal myelomeningocele repair are discussed. Open fetal surgeries have many unique anesthetic issues such as inducing profound uterine relaxation, vigilance for maternal or fetal blood loss, fetal monitoring, and possible fetal resuscitation. Postoperative management, including the requirement for postoperative tocolysis and maternal analgesia are also reviewed. The success of intrauterine myelomeningocele repair relies on a well-coordinated multidisciplinary approach. Fetal surgery is an important topic for anesthesiologists to understand, as the number of fetal procedures is likely to increase as new fetal treatment centers are opened across the United States. PMID:23508219

Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development.

PubMed

Dunford, Louise J; Sinclair, Kevin D; Kwong, Wing Y; Sturrock, Craig; Clifford, Bethan L; Giles, Tom C; Gardner, David S

2014-11-01

This paper identifies a common nutritional pathway relating maternal through to fetal protein-energy malnutrition (PEM) and compromised fetal kidney development. Thirty-one twin-bearing sheep were fed either a control (n=15) or low-protein diet (n=16, 17 vs. 8.7 g crude protein/MJ metabolizable energy) from d 0 to 65 gestation (term, ∼ 145 d). Effects on the maternal and fetal nutritional environment were characterized by sampling blood and amniotic fluid. Kidney development was characterized by histology, immunohistochemistry, vascular corrosion casts, and molecular biology. PEM had little measureable effect on maternal and fetal macronutrient balance (glucose, total protein, total amino acids, and lactate were unaffected) or on fetal growth. PEM decreased maternal and fetal urea concentration, which blunted fetal ornithine availability and affected fetal hepatic polyamine production. For the first time in a large animal model, we associated these nutritional effects with reduced micro- but not macrovascular development in the fetal kidney. Maternal PEM specifically impacts the fetal ornithine cycle, affecting cellular polyamine metabolism and microvascular development of the fetal kidney, effects that likely underpin programming of kidney development and function by a maternal low protein diet. © FASEB.

Macrosomia Predictors in Infants Born to Cuban Mothers with Gestational Diabetes.

PubMed

Cruz, Jeddú; Grandía, Raiden; Padilla, Liset; Rodríguez, Suilbert; Hernández García, Pilar; Lang Prieto, Jacinto; Márquez-Guillén, Antonio

2015-07-01

INTRODUCTION Fetal macrosomia is the most important complication in infants of women with diabetes, whether preconceptional or gestational. Its occurrence is related to certain maternal and fetal conditions and negatively affects maternal and perinatal outcomes. The definitive diagnosis is made at birth if a newborn weighs >4000 g. OBJECTIVE Identify which maternal and fetal conditions could be macrosomia predictors in infants born to Cuban mothers with gestational diabetes. METHODS A case-control study comprising 236 women with gestational diabetes who bore live infants (118 with macrosomia and 118 without) was conducted in the América Arias University Maternity Hospital, Havana, Cuba, during 2002-2012. The dependent variable was macrosomia (birth weight >4000 g). Independent maternal variables included body mass index at pregnancy onset, overweight or obesity at pregnancy onset, gestational age at diabetes diagnosis, pregnancy weight gain, glycemic control, triglycerides and cholesterol. Fetal variables examined included third-semester fetal abdominal circumference, estimated fetal weight at ≥28 weeks (absolute and percentilized by Campbell and Wilkin, and Usher and McLean curves). Chi square was used to compare continuous variables (proportions) and the student t test (X ± SD) for categorical variables, with significance threshold set at p <0.05. ORs and their 95% CIs were calculated. RESULTS Significant differences between cases and controls were found in most variables studied, with the exception of late gestational diabetes diagnosis, total fasting cholesterol and hypercholesterolemia. The highest OR for macrosomia were for maternal hypertriglyceridemia (OR 4.80, CI 2.34-9.84), third-trimester fetal abdominal circumference >75th percentile (OR 7.54, CI 4.04-14.06), and estimated fetal weight >90th percentile by Campbell and Wilkin curves (OR 4.75, CI 1.42-15.84) and by Usher and McLean curves (OR 8.81, CI 4.25-18.26). CONCLUSIONS Most variables assessed were predictors of macrosomia in infants of mothers with gestational diabetes. They should therefore be taken into account for future studies and for patient management. Wide confidence intervals indicate uncertainty about the magnitude of predictive power. KEYWORDS Fetal macrosomia, fetal diseases, gestational diabetes, risk factors, risk prediction, Cuba.

Fetal heart rate and motor activity associations with maternal organochlorine levels: Results of an exploratory study

PubMed Central

DiPietro, Janet A.; Davis, Meghan F.; Costigan, Kathleen A; Barr, Dana Boyd

2015-01-01

Contemporaneous associations between circulating maternal organochlorines and measures of fetal heart rate and motor activity were evaluated. A panel of 47 organochlorines (OCs), including pesticides and polychlorinated biphenyls (PCBs), was analyzed from serum of 50 pregnant women at 36 weeks gestation. Data were empirically reduced into four factors and six individual compounds. All participants had detectable concentrations of at least one-quarter of the assayed OCs and, in general, higher socioeconomic level was associated with higher OC concentrations. Fetal heart rate measures were not consistently associated with maternal OCs. In contrast, one or more indicators of greater fetal motor activity were significantly associated with higher levels of the DDT and low chlorinated OC factors and five of the six individual compounds (heptachlor epoxide, trans nonachlor, oxychlordane, and PCBs 18 and 52). This preliminary demonstration of associations between fetal motor activity and maternal concentrations of persistent and pervasive environmental contaminants suggests that fetal assessment may be useful in ascertaining the potential early effects of these compounds on development. PMID:23591698

Prenatal diagnosis and management of fetal goiter caused by maternal Grave's disease.

PubMed

Hadi, H A; Strickland, D

1995-07-01

We present a case of maternal Grave's disease associated with fetal goitrous hyperthyroidism. Fetal goiter was diagnosed by ultrasound and diagnosis of fetal hyperthyroidism was established by umbilical blood sampling. Fetus was successfully treated by increasing maternal propylthiouracil dosage. Fetal thyroid status was normal at birth. Role of sonography and umbilical blood sampling in management of fetal goiter complicated with maternal Grave's disease is discussed.

Maternal Azithromycin Therapy for Ureaplasma Intra-Amniotic Infection Delays Preterm Delivery and Reduces Fetal Lung Injury in a Primate Model

PubMed Central

Grigsby, Peta L.; Novy, Miles J.; Sadowsky, Drew W.; Morgan, Terry K.; Long, Mary; Acosta, Ed; Duffy, Lynn B; Waites, Ken B.

2012-01-01

Objective We assessed the efficacy of a maternal multi–dose azithromycin (AZI) regimen, with and without anti–inflammatory agents to delay preterm birth and to mitigate fetal lung injury associated with Ureaplasma parvum intra–amniotic infection (IAI). Study Design Long–term catheterized rhesus monkeys (n=16) received intra–amniotic inoculation of U. parvum (107 CFU/ml, serovar 1). After contraction onset, rhesus monkeys received either no treatment (n=6); AZI (12.5mg/kg, q12h, IV for 10 days; n=5); or AZI plus dexamethasone (DEX) and indomethacin (INDO; n=5). Outcomes included amniotic fluid pro–inflammatory mediators, U. parvum cultures & PCR, AZI pharmacokinetics and the extent of fetal lung inflammation. Results Maternal AZI therapy eradicated U. parvum IAI from the amniotic fluid within 4 days. Placenta and fetal tissues were 90% culture negative at delivery. AZI therapy significantly delayed preterm delivery and prevented advanced fetal lung injury, although residual acute chorioamnionitis persisted. Conclusions Specific maternal antibiotic therapy can eradicate U. parvum from the amniotic fluid and key fetal organs, with subsequent prolongation of pregnancy which provides a therapeutic window of opportunity to effectively reduce the severity of fetal lung injury. PMID:23111115

Maternal-fetal cholesterol transport in the second half of mouse pregnancy does not involve LDL receptor-related protein 2.

PubMed

Zwier, M V; Baardman, M E; van Dijk, T H; Jurdzinski, A; Wisse, L J; Bloks, V W; Berger, R M F; DeRuiter, M C; Groen, A K; Plösch, T

2017-08-01

LDL receptor-related protein type 2 (LRP2) is highly expressed on both yolk sac and placenta. Mutations in the corresponding gene are associated with severe birth defects in humans, known as Donnai-Barrow syndrome. We here characterized the contribution of LRP2 and maternal plasma cholesterol availability to maternal-fetal cholesterol transport and fetal cholesterol levels in utero in mice. Lrp2 +/- mice were mated heterozygously to yield fetuses of all three genotypes. Half of the dams received a 0.5% probucol-enriched diet during gestation to decrease maternal HDL cholesterol. At E13.5, the dams received an injection of D7-labelled cholesterol and were provided with 1- 13 C acetate-supplemented drinking water. At E16.5, fetal tissues were collected and maternal cholesterol transport and fetal synthesis quantified by isotope enrichments in fetal tissues by GC-MS. The Lrp2 genotype did not influence maternal-fetal cholesterol transport and fetal cholesterol. However, lowering of maternal plasma cholesterol levels by probucol significantly reduced maternal-fetal cholesterol transport. In the fetal liver, this was associated with increased cholesterol synthesis rates. No indications were found for an interaction between the Lrp2 genotype and maternal probucol treatment. Maternal-fetal cholesterol transport and endogenous fetal cholesterol synthesis depend on maternal cholesterol concentrations but do not involve LRP2 in the second half of murine pregnancy. Our results suggest that the mouse fetus can compensate for decreased maternal cholesterol levels. It remains a relevant question how the delicate system of cholesterol transport and synthesis is regulated in the human fetus and placenta. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Immunology of term and preterm labor

PubMed Central

Peltier, Morgan R

2003-01-01

During pregnancy there is an alteration in maternal immunity within the uterus where innate, proinflammatory immune responses are tightly regulated to prevent immunological rejection of the fetal allograft. Disruption of the delicate balance of cytokines by bacteria or other factors increases the production of proinflammatory cytokines at the maternal-fetal interface and activates the parturition mechanism prematurely. Despite years of searching, there is still no broadly effective strategy for preventing preterm labor and most therapies are directed at inhibiting myometrial contractions and improving neonatal outcome. Recent studies with progestins and interleukin-10 (IL-10), however, are showing promise in randomized clinical trials and animal studies. Furthermore, the identification of the Toll-like receptors as upstream mediators of inflammation may offer alternative therapeutic targets for preventing this common pregnancy complication. PMID:14651749

Postpartum acute kidney injury: a review of 99 cases.

PubMed

Eswarappa, Mahesh; Madhyastha, P Rakesh; Puri, Sonika; Varma, Vijay; Bhandari, Aneesh; Chennabassappa, Gurudev

2016-07-01

Postpartum acute kidney injury (PPAKI) constitutes an important cause of obstetric AKI. It is associated with high maternal and fetal mortality in developing nations. The aim of this study is to survey the etiology and outcomes of PPAKI in a tertiary care Indian hospital. Ninety-nine patients, without prior comorbidities, treated for PPAKI, between 2005-2014 at M.S. Ramaiah Medical College, were included for analysis in this retrospective, observational study. AKI was analyzed in terms of maximal stage of renal injury attained as per RIFLE criteria. Outcomes included requirement for renal replacement therapy (RRT), maternal and fetal outcomes. PPAKI constituted 60% of all obstetric AKI cases. Median maternal age was 23 years and 52% of patients were primigravidas. Mean serum creatinine was 4.1 mg/dL. Failure (33%) and injury (31%) were the major categories as per RIFLE criteria. Thirty-nine percent of cases required RRT. Sepsis, particularly puerperal sepsis, was the leading causes of PPAKI (75% of cases) and maternal mortality (94% of deaths). Maternal and fetal mortality were 19% and 22% respectively. The incidence of cortical necrosis was 10.3%. Three patients required long-term RRT. In conclusion, consistent with other Indian literature, we report a high incidence of PPAKI. We found incremental mortality on moving from "Risk" to "Failure" category of RIFLE. PPAKI was associated with high maternal and fetal mortality with sepsis being the leading cause. Our study highlights the need for provision of better quality of maternal care and fetal monitoring to decrease mortality associated with PPAKI in developing countries.

Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol

PubMed Central

Sawant, Onkar B.; Ramadoss, Jayanth; Hankins, Gary D.; Wu, Guoyao

2014-01-01

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75–2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid–base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid–base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy. PMID:24810329

Effects of L-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol.

PubMed

Sawant, Onkar B; Ramadoss, Jayanth; Hankins, Gary D; Wu, Guoyao; Washburn, Shannon E

2014-08-01

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and L-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75-2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal L-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. L-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid-base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, L-glutamine supplementation mitigates alcohol-induced acid-base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy.

Non-invasive prenatal testing using cell-free fetal DNA in maternal circulation.

PubMed

Liao, Gary J W; Gronowski, Ann M; Zhao, Zhen

2014-01-20

The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible. Maternal plasma cell free DNA is a mixture of maternal and fetal DNA, of which, fetal DNA represents a minor population in maternal plasma. Therefore, methods with high sensitivity and precision are required to detect and differentiate fetal DNA from the large background of maternal DNA. In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future. This review briefly summarizes the technical aspects of the NIPT and application of NIPT in clinical practice.

The relationship of maternal-fetal attachment and depression with social support in pregnant women referring to health centers of Tabriz-Iran, 2016.

PubMed

Delavari, Mina; Mirghafourvand, Mojgan; Mohammad-Alizadeh-Charandabi, Sakineh

2018-09-01

The objective of this study was to determine the relationship of maternal-fetal attachment and depression during pregnancy with social support. This cross-sectional study was done on 287 primipara women. The data collection tools used included a demographic characteristics questionnaire, Maternal-Fetal Attachment Scale, the Edinburgh Postnatal Depression Scale and the Social Support Scale. Pearson's correlation test and general linear model were used for data analysis. The mean maternal-fetal attachment score was 90.0 (SD: 10.3). The highest score was obtained in the "role taking" domain and the lowest in the "interaction with the fetus" domain. The mean depression score was 8.5 (SD: 4.0). The score of perceived social support was 135.5 (SD: 15.6). Pearson's correlation test showed a significant positive correlation between social support and maternal-fetal attachment (r = 0.36, p < .001) and a significant negative correlation between social support and depression (r= -0.14, p = .018). The present study found a significant relationship between maternal-fetal attachment, depression and social support. It is recommended to devise plans for increasing the support given to women and to improve the society's and families' awareness about these issues in the attempt to have healthy mothers and thereby healthy families and communities.

Severe hydramnios and preterm delivery in association with transient maternal diabetes insipidus.

PubMed

Weinberg, Lori E; Dinsmoor, Mara J; Silver, Richard K

2010-08-01

Diabetes insipidus is rare in pregnancy. It is characterized by hypoosmolar polyuria and may be central, nephrogenic, or transient in etiology; the latter is presumably related to excess placental vasopresinase production. In theory, fetal effects of this endocrine condition may include hydramnios secondary to fetal polyuria. A pregnant patient developed rapid-onset second-trimester hydramnios that prompted a thorough fetal and maternal evaluation. She ultimately was diagnosed with transient diabetes insipidus of pregnancy because of an abrupt change in her voiding pattern at 20 weeks of gestation, significant polydipsia, and laboratory studies that revealed a hypoosmolar polyuria with normal serum and urine electrolytes. Transient neonatal polyuria also was confirmed in association with this unique maternal endocrine syndrome. The most likely cause of hydramnios in this case is transient maternal diabetes insipidus of pregnancy from excessive secretion of placental vasopressinase resulting in fetal polyuria. In cases of hydramnios of unknown etiology, if a history of maternal polyuria is elicited and confirmed, diabetes insipidus of pregnancy may play a role in some cases.

Correlation between maternal and umbilical cord blood in pregnant women of Pokhara Valley: a cross sectional study.

PubMed

Timilsina, Sameer; Karki, Sirisa; Gautam, Aajeevan; Bhusal, Pujan; Paudel, Gita; Sharma, Deepak

2018-03-21

Complete blood count is one of the routinely advised blood investigation during pregnancy. It is also utilized as a diagnostic tool for neonatal anemia, sepsis and determining hemostatic status of the newborn. The present study aims at estimating the complete blood count of maternal and umbilical cord blood at the time of delivery and to establish its correlation. This cross sectional study included 114 mothers and their healthy neonates born through normal vaginal delivery. Complete blood count of umbilical cord blood and maternal blood was estimated using automatic hematology analyzer. The mean maternal and neonatal hemoglobin concentration was 11.14 ± 1.39 g/dL and 16.34 ± 2.01 g/dL respectively. A significant positive correlation was found between maternal and fetal hemoglobin concentration (p < 0.001 and Pearson R = 0.496). The correlation between maternal and fetal WBC, RBC and Platelet count was not statistically significant. A significant positive correlation was found between maternal and fetal MCV and MCH while PCV showed a non-significant positive correlation. There was moderately positive correlation between maternal and fetal hemoglobin, MCV and MCH. The cord blood hemoglobin was lower in babies born to anemic mothers. The decrease in hemoglobin followed the severity of anemia, however, the correlation did not exist in anemic mothers. It suggested that fetal hematological parameters are not reflective of maternal hemogram.

The relationship between maternal-fetal attachment and cigarette smoking over pregnancy

PubMed Central

Magee, Susanna R.; Bublitz, Margaret H.; Orazine, Christina; Brush, Bridget; Salisbury, Amy; Niaura, Raymond; Stroud, Laura R.

2014-01-01

Background Cigarette smoking during pregnancy is one of the most preventable causes of infant morbidity and mortality, yet 80% of women who smoked prior to pregnancy continue to smoke during pregnancy. Past studies have found that lower maternal-fetal attachment predicts smoking status in pregnancy, yet past research has not examined whether maternal-fetal attachment predicts patterns or quantity of smoking among pregnant smokers. The aim of this study was to examine the relationship between maternal-fetal attachment and patterns of maternal smoking among pregnant smokers. We used self-reported and biochemical markers of cigarette smoking in order to better understand how maternal-fetal attachment relates to the degree of fetal exposure to nicotine. Methods Fifty-eight pregnant smokers participated in the current study. Women completed the Maternal-Fetal Attachment scale, reported weekly smoking behaviors throughout pregnancy using the Timeline Follow Back interview, and provided a saliva sample at 30 and 35 weeks gestation and 1 day postpartum to measure salivary cotinine concentrations. Results Lower maternal-fetal attachment scores were associated with higher salivary cotinine at 30 weeks gestation and 1 day postpartum. As well, women who reported lower fetal attachment reported smoking a greater maximum number of cigarettes per day, on average, over pregnancy. Conclusion Lower maternal-fetal attachment is associated with greater smoking in pregnancy. Future research might explore whether successful smoking cessation programs improve maternal assessments of attachment to their infants. PMID:23892790

The relationship between maternal-fetal attachment and cigarette smoking over pregnancy.

PubMed

Magee, Susanna R; Bublitz, Margaret H; Orazine, Christina; Brush, Bridget; Salisbury, Amy; Niaura, Raymond; Stroud, Laura R

2014-05-01

Cigarette smoking during pregnancy is one of the most preventable causes of infant morbidity and mortality, yet 80 % of women who smoked prior to pregnancy continue to smoke during pregnancy. Past studies have found that lower maternal-fetal attachment predicts smoking status in pregnancy, yet past research has not examined whether maternal-fetal attachment predicts patterns or quantity of smoking among pregnant smokers. The aim of this study was to examine the relationship between maternal-fetal attachment and patterns of maternal smoking among pregnant smokers. We used self-reported and biochemical markers of cigarette smoking in order to better understand how maternal-fetal attachment relates to the degree of fetal exposure to nicotine. Fifty-eight pregnant smokers participated in the current study. Women completed the Maternal-Fetal Attachment Scale, reported weekly smoking behaviors throughout pregnancy using the Timeline Follow Back interview, and provided a saliva sample at 30 and 35 weeks gestation and 1 day postpartum to measure salivary cotinine concentrations. Lower maternal-fetal attachment scores were associated with higher salivary cotinine at 30 weeks gestation and 1 day postpartum. As well, women who reported lower fetal attachment reported smoking a greater maximum number of cigarettes per day, on average, over pregnancy. Lower maternal-fetal attachment is associated with greater smoking in pregnancy. Future research might explore whether successful smoking cessation programs improve maternal assessments of attachment to their infants.

Fetal Allostimulation of Maternal Cells: A Potential Mechanism for Perinatal HIV Transmission following Obstetrical Hemorrhage

PubMed Central

Wang, Guangwu; Izadpanah, Nazanin; Kitchen, Christina M.R.

2008-01-01

Abstract Our aim was to elucidate the mechanism by which HIV transmission is increased following obstetrical hemorrhage. We investigated whether fetal allostimulation of maternal cells, which could occur following fetal-to-maternal hemorrhage, increases proliferation, HIV replication, and cellular activation. Peripheral blood mononuclear cells (PBMCs) were collected from HIV-infected mothers and their infants to assess maternal-fetal allostimulation. Responses were compared to allostimulation with unrelated donors. Maternal and fetal cells were cocultured to assess allogeneic stimulation. Cell proliferation was measured by [3H]thymidine incorporation and cell activation was assessed via fluorochrome-labeled antibody staining and flow cytometric analysis. Virus production from HIV-infected maternal cells was quantitated by p24 enzyme-linked immunosorbent assay or by branched chain DNA assay. Allostimulation with fetal cells led to maternal cell proliferation. In women with unsuppressed viral loads, virus release was also enhanced following allostimulation of maternal cells with fetal cells. Fetal cells are capable of allogeneically stimulating maternal cells, with responses comparable to those seen following allostimulation with unrelated donors. Allostimulation of maternal cells by fetal cells results in statistically significant increases in proliferation and enhanced HIV replication, suggesting a possible physiological mechanism for mother-to-child transmission of HIV in women with obstetrical hemorrhage. PMID:19102686

Quercetin and Bornyl Acetate Regulate T-Lymphocyte Subsets and INF-γ/IL-4 Ratio In Utero in Pregnant Mice.

PubMed

Wang, Xiaodan; Ma, Aituan; Shi, Wanyu; Geng, Meiying; Zhong, Xiuhui; Zhao, Yantao

2011-01-01

The objective of this study is to investigate the antiabortive effects of Quercetin and Bornvl Acetate and their immunological modulation at maternal-fetal interface. Lipopolysaccharide (LPS) was injected via tail vein to induce abortion in mice which received Quercetin and Bornvl Acetate at days 4-7 of gestation. Uterine CD4+/CD8+ T lymphocytes and IFN-γ/IL-4 of each group (n = 10) were detected by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The ratio of CD4+/CD8+ increased significantly (P < .01) in the uterus of LPS-induced abortion mice. In the Quercetin and Bornvl Acetate pretreated mice followed by LPS administration, the ratio of CD4+/CD8+ dropped to 0.562 ± 0.021, lower than that of LPS-abortion group (P < .01). The mean value of IFN-γ/IL-4 in LPS-treated mice was 0.310 ± 0.066, higher than that of Quercetin and Bornyl Acetate group. The results indicate that Quercetin and Bornyl Acetate have an antiabortive effect through modulation of immunological balance at maternal-fetal interface.

Microbial ecology and host-microbiota interactions during early life stages

PubMed Central

Collado, Maria Carmen; Cernada, Maria; Baüerl, Christine; Vento, Máximo; Pérez-Martínez, Gaspar

2012-01-01

The role of human microbiota has been redefined during recent years and its physiological role is now much more important than earlier understood. Intestinal microbial colonization is essential for the maturation of immune system and for the developmental regulation of the intestinal physiology. Alterations in this process of colonization have been shown to predispose and increase the risk to disease later in life. The first contact of neonates with microbes is provided by the maternal microbiota. Moreover, mode of delivery, type of infant feeding and other perinatal factors can influence the establishment of the infant microbiota. Taken into consideration all the available information it could be concluded that the exposure to the adequate microbes early in gestation and neonatal period seems to have a relevant role in health. Maternal microbial environment affects maternal and fetal immune physiology and, of relevance, this interaction with microbes at the fetal-maternal interface could be modulated by specific microbes administered to the pregnant mother. Indeed, probiotic interventions aiming to reduce the risk of immune-mediated diseases may appear effective during early life. PMID:22743759

Investigating attachment, caregiving, and mental health: a model of maternal-fetal relationships.

PubMed

Walsh, Judi; Hepper, Erica G; Marshall, Benjamin J

2014-11-19

Maternal-fetal relationships have been associated with psychosocial outcomes for women and children, but there has been a lack of conceptual clarity about the nature of the maternal relationship with the unborn child, and inconsistent findings assessing its predictors. We proposed and tested a model whereby maternal-fetal relationship quality was predicted by factors relating to the quality of the couple relationship and psychological health. We hypothesized that the contribution of individual differences in romantic attachment shown in past research would be mediated by romantic caregiving responsiveness, as maternal-fetal relationships reflect the beginnings of the caregiving system. 258 women in pregnancy (13, 23, and 33-weeks gestation) completed online measures of attachment to partner, caregiving responsiveness to partner, mental health, and thoughts about their unborn baby. Structural equation modeling was used to test a model of maternal-fetal relationships. Maternal-fetal relationship quality was higher for women at 23-weeks than 13-weeks gestation. Women in first pregnancies had higher self-reported scores of psychological functioning and quality of maternal-fetal relationships than women in subsequent pregnancies. Structural equation models indicated that the quality of the maternal-fetal relationship was best predicted by romantic caregiving responsiveness to partner and women's own psychological health, and that the association between adult romantic attachment avoidance and maternal-fetal relationships was fully mediated by caregiving responsiveness to partner, even after controlling for other factors. These data support the hypothesis that maternal-fetal relationships better reflect the operation of the caregiving system than the care-seeking (i.e., attachment) system. Models of maternal-fetal relationships and interventions with couples should consider the role of caregiving styles of mothers to partners and the relationship between expectant parents alongside other known predictors, particularly psychological health.

NODAL in the Uterus Is Necessary for Proper Placental Development and Maintenance of Pregnancy1

PubMed Central

Park, Craig B.; DeMayo, Francesco J.; Lydon, John P.; Dufort, Daniel

2012-01-01

Preterm birth is the single leading cause of perinatal mortality in developed countries, affecting approximately 12% of pregnancies and accounting for 75% of neonatal loss in the United States. Despite the prevalence and severity of premature delivery, the causes and mechanisms that underlie spontaneous and idiopathic preterm birth remain unknown. Our inability to elucidate these fundamental causes has been attributed to a poor understanding of the signaling pathways associated with the premature induction of parturition and a lack of suitable animal models available for preterm birth research. In this study, we describe the generation and analysis of a novel conditional knockout of the transforming growth factor beta (TGFB) superfamily member, Nodal, from the maternal reproductive tract of mice. Strikingly, uterine Nodal knockout females exhibited a severe malformation of the maternal decidua basalis during placentation, leading to significant intrauterine growth restriction, and ultimately preterm birth and fetal loss on Day 17.5 of gestation. Using several approaches, we characterized aberrant placental development and demonstrated that reduced proliferation combined with increased apoptosis resulted in a diminished decidua basalis and compromised maternal-fetal interface. Last, we evaluated various components of the established parturition cascade and determined that preterm birth derived from the maternal Nodal knockout occurs prior to PTGS2 (COX-2) upregulation at the placental interface. Taken together, the results presented in this study highlight an in vivo role for maternal NODAL during placentation, present an interesting link between disrupted decidua basalis formation and premature parturition, and describe a potentially valuable model toward elucidating the complex processes that underlie preterm birth. PMID:22378764

Placental Glucose Transfer: A Human In Vivo Study

PubMed Central

Holme, Ane M.; Roland, Marie Cecilie P.; Lorentzen, Bjørg; Michelsen, Trond M.; Henriksen, Tore

2015-01-01

Objectives The placental transfer of nutrients is influenced by maternal metabolic state, placenta function and fetal demands. Human in vivo studies of this interplay are scarce and challenging. We aimed to establish a method to study placental nutrient transfer in humans. Focusing on glucose, we tested a hypothesis that maternal glucose concentrations and uteroplacental arterio-venous difference (reflecting maternal supply) determines the fetal venous-arterial glucose difference (reflecting fetal consumption). Methods Cross-sectional in vivo study of 40 healthy women with uncomplicated term pregnancies undergoing planned caesarean section. Glucose and insulin were measured in plasma from maternal and fetal sides of the placenta, at the incoming (radial artery and umbilical vein) and outgoing vessels (uterine vein and umbilical artery). Results There were significant mean (SD) uteroplacental arterio-venous 0.29 (0.23) mmol/L and fetal venous-arterial 0.38 (0.31) mmol/L glucose differences. The transplacental maternal-fetal glucose gradient was 1.22 (0.42) mmol/L. The maternal arterial glucose concentration was correlated to the fetal venous glucose concentration (r = 0.86, p<0.001), but not to the fetal venous-arterial glucose difference. The uteroplacental arterio-venous glucose difference was neither correlated to the level of glucose in the umbilical vein, nor fetal venous-arterial glucose difference. The maternal-fetal gradient was correlated to fetal venous-arterial glucose difference (r = 0.8, p<0.001) and the glucose concentration in the umbilical artery (r = −0.45, p = 0.004). Glucose and insulin concentrations were correlated in the mother (r = 0.52, p = 0.001), but not significantly in the fetus. We found no significant correlation between maternal and fetal insulin values. Conclusions We did not find a relation between indicators of maternal glucose supply and the fetal venous-arterial glucose difference. Our findings indicate that the maternal-fetal glucose gradient is significantly influenced by the fetal venous-arterial difference and not merely dependent on maternal glucose concentration or the arterio-venous difference on the maternal side of the placenta. PMID:25680194

Placental expression of 2,3 bisphosphoglycerate mutase in IGF-II knock out mouse: correlation of circulating maternal 2,3 bisphosphoglycerate and fetal growth.

PubMed

Gu, M; Pritlove, D C; Boyd, C A R; Vatish, M

2009-10-01

Bisphosphoglycerate mutase (BPGM) catalyses the formation of 2,3 bisphosphoglycerate (BPG) a ligand of haemoglobin. BPG facilitates liberation of oxygen from haemoglobin at low oxygen tension enabling efficient delivery of oxygen to tissues. We describe expression of BPGM in mouse labyrinthine trophoblasts, located at the maternal-placental interface. Expression is lower in placentae of igf2(+/-) knockout mice, a widely used model of growth restriction, compared to wild type placentae. Circulating maternal BPG increased throughout gestation but this increase was less in wt mothers carrying igf2(+/-) pups than in those carrying exclusively wt pups. This reduction was observed well before term and may contribute to the low birth weight of igf2(+/-) pups. Strikingly, we also measured reductions of fetal and placental weight in wt littermates of igf2(+/-) pups compared to pups developing in an exclusively wt environment. These data suggest that placental expression of BPGM can influence maternal BPG concentrations and supports a hypothesis under which BPG synthesized in the placenta may act on maternal haemoglobin to enhance delivery of oxygen to the developing fetus.

Effect of Fetal Sex on Maternal and Obstetric Outcomes

PubMed Central

Al-Qaraghouli, Mohammed; Fang, Yu Ming Victor

2017-01-01

Fetal sex plays an important role in modifying the course and complications related to pregnancy and may also have an impact on maternal health and well-being both during and after pregnancy. The goal of this article is to review and summarize the findings from published research on physiologic and pathologic changes that may be affected by fetal sex and the effect of these changes on the maternal and obstetrical outcomes. This will help create awareness that fetal sex is not just a random chance event but an interactive process between the mother, the placenta, and the fetus. The reported effects of male sex on the course of pregnancy and delivery include higher incidence of preterm labor in singletons and twins, failure of progression in labor, true umbilical cord knots, cord prolapse, nuchal cord, higher cesarean section rate, higher heart rate variability with increased frequency, and duration of decelerations without acidemia and increased risk of gestational diabetes mellitus through the poor beta cells function. Similarly, female fetal sex has been reported to modify pregnancy and delivery outcomes including altered fetal cardiac hemodynamics, increased hypertensive diseases of pregnancy, higher vulnerability of developing type 2 DM after pregnancy possibly because of influences on increased maternal insulin resistance. Placental function is also influenced by fetal sex. Vitamin D metabolism in the placenta varies by fetal sex; and the placenta of a female fetus is more responsive to the relaxing action of magnesium sulfate. Male and female feto-placental units also vary in their responses to environmental toxin exposure. The association of fetal sex with stillbirths is controversial with many studies reporting higher risk of stillbirth in male fetuses; although some smaller and limited studies have reported more stillbirths with female fetus pregnancies. Maternal status such as BMI may in turn also affect the fetus and the placenta in a sex-specific manner. There is probably a sex-specific maternal–placental–fetal interaction that has significant biological implications of which the mechanisms may be genetic, epigenetic, or hormonal. Determination of fetal sex may therefore be an important consideration in management of pregnancy and childbirth. PMID:28674684

A system for counting fetal and maternal red blood cells.

PubMed

Ge, Ji; Gong, Zheng; Chen, Jun; Liu, Jun; Nguyen, John; Yang, Zongyi; Wang, Chen; Sun, Yu

2014-12-01

The Kleihauer-Betke (KB) test is the standard method for quantitating fetal-maternal hemorrhage in maternal care. In hospitals, the KB test is performed by a certified technologist to count a minimum of 2000 fetal and maternal red blood cells (RBCs) on a blood smear. Manual counting suffers from inherent inconsistency and unreliability. This paper describes a system for automated counting and distinguishing fetal and maternal RBCs on clinical KB slides. A custom-adapted hardware platform is used for KB slide scanning and image capturing. Spatial-color pixel classification with spectral clustering is proposed to separate overlapping cells. Optimal clustering number and total cell number are obtained through maximizing cluster validity index. To accurately identify fetal RBCs from maternal RBCs, multiple features including cell size, roundness, gradient, and saturation difference between cell and whole slide are used in supervised learning to generate feature vectors, to tackle cell color, shape, and contrast variations across clinical KB slides. The results show that the automated system is capable of completing the counting of over 60,000 cells (versus ∼2000 by technologists) within 5 min (versus ∼15 min by technologists). The throughput is improved by approximately 90 times compared to manual reading by technologists. The counting results are highly accurate and correlate strongly with those from benchmarking flow cytometry measurement.

Evaluation of single-nucleotide polymorphisms as internal controls in prenatal diagnosis of fetal blood groups.

PubMed

Doescher, Andrea; Petershofen, Eduard K; Wagner, Franz F; Schunter, Markus; Müller, Thomas H

2013-02-01

Determination of fetal blood groups in maternal plasma samples critically depends on adequate amplification of fetal DNA. We evaluated the routine inclusion of 52 single-nucleotide polymorphisms (SNPs) as internal reference in our polymerase chain reaction (PCR) settings to obtain a positive internal control for fetal DNA. DNA from 223 plasma samples of pregnant women was screened for RHD Exons 3, 4, 5, and 7 in a multiplex PCR including 52 SNPs divided into four primer pools. Amplicons were analyzed by single-base extension and the GeneScan method in a genetic analyzer. Results of D screening were compared to standard RHD genotyping of amniotic fluid or real-time PCR of fetal DNA from maternal plasma. The vast majority of all samples (97.8%) demonstrated differences in maternal and fetal SNP patterns when tested with four primer pools. These differences were not observed in less than 2.2% of the samples most probably due to an extraction failure for adequate amounts of fetal DNA. Comparison of the fetal genotypes with independent results did not reveal a single false-negative case among samples (n = 42) with positive internal control and negative fetal RHD typing. Coamplification of 52 SNPs with RHD-specific sequences for fetal blood group determination introduces a valid positive control for the amplification of fetal DNA to avoid false-negative results. This new approach does not require a paternal blood sample. It may also be applicable to other assays for fetal genotyping in maternal blood samples. © 2012 American Association of Blood Banks.

Impact of maternal steroids during pregnancy.

PubMed

Reynolds, Rebecca M

2016-12-01

Increased fetal exposure to glucocorticoids is a key mechanism thought to underlie the early life programming of later life disease. There is substantial experimental data in animal models in support of this hypothesis. Emerging evidence suggests glucocorticoid programming may also occur in humans with some studies now linking maternal endogenous cortisol levels with size at birth and gestation at delivery. The dramatic changes to the maternal hypothalamic-pituitary-adrenal axis during pregnancy mean that large-scale studies in humans are challenging to conduct. One of the key regulators of fetal glucocorticoid exposure is the activity of placental "barrier" enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD2) which converts active cortisol to inactive cortisone. In animal models, this enzyme is down-regulated by various influences including maternal malnutrition, inflammation or stress but it is not known whether this is a major factor in regulation of human fetal glucocorticoid exposure. More studies are needed to understand the mechanisms whereby altered fetal glucocorticoid exposure may alter fetal growth trajectories and whether changes in the maternal hypothalamic-pituitary-adrenal axis in pregnancy could be suitable as a biomarker to identify those pregnancies most at risk. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Obesity Disrupts the Rhythmic Profiles of Maternal and Fetal Progesterone in Rat Pregnancy.

PubMed

Crew, Rachael C; Mark, Peter J; Clarke, Michael W; Waddell, Brendan J

2016-09-01

Maternal obesity increases the risk of abnormal fetal growth, but the underlying mechanisms remain unclear. Because steroid hormones regulate fetal growth, and both pregnancy and obesity markedly alter circadian biology, we hypothesized that maternal obesity disrupts the normal rhythmic profiles of steroid hormones in rat pregnancy. Obesity was established by cafeteria (CAF) feeding for 8 wk prior to mating and throughout pregnancy. Control (CON) animals had ad libitum access to chow. Daily profiles of plasma corticosterone, 11-dehydrocorticosterone, progesterone, and testosterone were measured at Days 15 and 21 of gestation (term = 23 days) in maternal (both days) and fetal (Day 21) plasma. CAF mothers exhibited increased adiposity relative to CON and showed fetal and placental growth restriction. There was no change, however, in total fetal or placental mass due to slightly larger litter sizes in CAF. Nocturnal declines in progesterone were observed in maternal (39% lower) and fetal (45% lower) plasma in CON animals, but these were absent in CAF animals. CAF mothers were hyperlipidemic at both days of gestation, but this effect was isolated to the dark period at Day 21. CAF maternal testosterone was slightly lower at Day 15 (8%) but increased above CON by Day 21 (16%). Despite elevated maternal testosterone, male fetal testosterone was suppressed by obesity on Day 21. Neither maternal nor fetal glucocorticoid profiles were affected by obesity. In conclusion, obesity disrupts rhythmic profiles of maternal and fetal progesterone, preventing the normal nocturnal decline. Obesity subtly changed testosterone profiles but did not alter maternal and fetal glucocorticoids. © 2016 by the Society for the Study of Reproduction, Inc.

Avoidance of Maternal Cell Contamination and Overgrowth in Isolating Fetal Chorionic Villi Mesenchymal Stem Cells from Human Term Placenta

PubMed Central

Sardesai, Varda S.; Shafiee, Abbas; Fisk, Nicholas M.

2017-01-01

Abstract Human placenta is rich in mesenchymal stem/stromal cells (MSC), with their origin widely presumed fetal. Cultured placental MSCs are confounded by a high frequency of maternal cell contamination. Our recent systematic review concluded that only a small minority of placental MSC publications report fetal/maternal origin, and failed to discern a specific methodology for isolation of fetal MSC from term villi. We determined isolation conditions to yield fetal and separately maternal MSC during ex vivo expansion from human term placenta. MSCs were isolated via a range of methods in combination; selection from various chorionic regions, different commercial media, mononuclear cell digest and/or explant culture. Fetal and maternal cell identities were quantitated in gender‐discordant pregnancies by XY chromosome fluorescence in situ hybridization. We first demonstrated reproducible maternal cell contamination in MSC cultures from all chorionic anatomical locations tested. Cultures in standard media rapidly became composed entirely of maternal cells despite isolation from fetal villi. To isolate pure fetal cells, we validated a novel isolation procedure comprising focal dissection from the cotyledonary core, collagenase/dispase digestion and explant culture in endothelial growth media that selected, and provided a proliferative environment, for fetal MSC. Comparison of MSC populations within the same placenta confirmed fetal to be smaller, more osteogenic and proliferative than maternal MSC. We conclude that in standard media, fetal chorionic villi‐derived MSC (CV‐MSC) do not grow readily, whereas maternal MSC proliferate to result in maternal overgrowth during culture. Instead, fetal CV‐MSCs require isolation under specific conditions, which has implications for clinical trials using placental MSC. Stem Cells Translational Medicine 2017;6:1070–1084 PMID:28205414

Antenatal management of recurrent fetal goitrous hyperthyroidism associated with fetal cardiac failure in a pregnant woman with persistent high levels of thyroid-stimulating hormone receptor antibody after ablative therapy.

PubMed

Matsumoto, Tadashi; Miyakoshi, Kei; Saisho, Yoshifumi; Ishii, Tomohiro; Ikenoue, Satoru; Kasuga, Yoshifumi; Kadohira, Ikuko; Sato, Seiji; Momotani, Naoko; Minegishi, Kazuhiro; Yoshimura, Yasunori

2013-01-01

High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease could cause fetal hyperthyroidism during pregnancy. Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth restriction, advanced bone maturation, cardiomegaly, and fetal death. The recognition and treatment of fetal hyperthyroidism are believed to be important to optimize growth and intellectual development in affected fetuses. We herein report a case of fetal treatment in two successive siblings showing in utero hyperthyroid status in a woman with a history of ablative treatment for Graves' disease. The fetuses were considered in hyperthyroid status based on high levels of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac failure was observed in the second fetus. With intrauterine treatment using potassium iodine and propylthiouracil, fetal cardiac function improved. A high level of TRAb was detected in the both neonates. To the best of our knowledge, this is the first report on the changes of fetal cardiac function in response to fetal treatment in two siblings showing in utero hyperthyroid status. This case report illustrates the impact of prenatal medication via the maternal circulation for fetal hyperthyroidism and cardiac failure.

Fetal Genotype for the Xenobiotic Metabolizing Enzyme "NQO1" Influences Intrauterine Growth among Infants Whose Mothers Smoked during Pregnancy

ERIC Educational Resources Information Center

Price, Thomas S.; Grosser, Tilo; Plomin, Robert; Jaffee, Sara R.

2010-01-01

Maternal smoking during pregnancy retards fetal growth and depresses infant birth weight. The magnitude of these effects may be moderated by fetal genotype. The current study investigated maternal smoking, fetal genotype, and fetal growth in a large population sample of dizygotic twins. Maternal smoking retarded fetal growth in a dose-dependent…

Management of hyperthyroidism in pregnancy

PubMed Central

Cezar, C; Grigoras, M; Horhoianu, I; Parau, C; Virtej, P; Lungu, A; Horhoianu, V; Poiana, C

2008-01-01

Maternal hypertiroidism is a relative rare disorder, which can seriously complicate pregnancy in each of its periods. There are several maternal and fetal complications during pregnancy, delivery and postpartum period. Correct management includes an accurate diagnosis, rigorous individualized treatment and minutious follow–up. We are presenting a retrospective study of 38 pregnant women who delivered in the Obstetric Unit of the University Emergency Bucharest Hospital in the past five years. We established a follow–up protocol in collaboration with endocrinologists. Precocious diagnosis of pregnancy is, in our opinion, mandatory. Accurate diagnosis of hormonal status beginning from the first week of pregnancy is of great importance. Maternal (weight, BP, TSH, thyroid hormones, ECG, etc.) and fetal (ultrasound, non–stress test, Doppler study) evaluation during pregnancy were rigorous performed. Results: abortion rate was 5%; 15% of pregnant women delivered prematurely; cesarean section rate was 22%; fetal outcome was excellent. Treatment adjustment during pregnancy was frequent, 28% of pregnant women had no hormonal treatment in the last trimester of pregnancy. Maternal complications were rare (poor weight gain, tachycardia). Fetal complications included low birth weight (24%), fetal respiratory distress (10%). Conclusions: team work with experienced endocrinologists and understanding of versatility of disease leads to good prognosis of mother and fetus in presence of hypertiroidism. PMID:20108518

Programming the offspring through altered uteroplacental hemodynamics: how maternal environment impacts uterine and umbilical blood flow in cattle, sheep and pigs.

PubMed

Vonnahme, Kimberly A; Lemley, Caleb O

2011-01-01

As placental growth and vascularity precedes exponential fetal growth, not only is proper establishment of the placenta important, but also a continual plasticity of placental function throughout gestation. Inadequate maternal environment, such as nutritional plane, has been documented to alter fetal organogenesis and growth, thus leading to improper postnatal growth and performance in many livestock species. The timing and duration of maternal nutritional restriction appears to influence the capillary vascularity, angiogenic profile and vascular function of the placenta in cattle and sheep. In environments where fetal growth and/or fetal organogenesis are compromised, potential therapeutics may augment placental nutrient transport capacity and improve offspring performance. Supplementation of specific nutrients, including protein, as well as hormone supplements, such as indolamines, during times of nutrient restriction may assist placental function. Current use of Doppler ultrasonography has allowed for repeated measurements of uterine and umbilical blood flow including assessment of uteroplacental hemodynamics in cattle, sheep and swine. Moreover, these variables can be monitored in conjugation with placental capacity and fetal growth at specific time points of gestation. Elucidating the consequences of inadequate maternal intake on the continual plasticity of placental function will allow us to determine the proper timing and duration for intervention.

Maternal–Fetal Nutrient Transport in Pregnancy Pathologies: The Role of the Placenta

PubMed Central

Brett, Kendra Elizabeth; Ferraro, Zachary Michael; Yockell-Lelievre, Julien; Gruslin, Andrée; Adamo, Kristi Bree

2014-01-01

Appropriate in utero growth is essential for offspring development and is a critical contributor to long-term health. Fetal growth is largely dictated by the availability of nutrients in maternal circulation and the ability of these nutrients to be transported into fetal circulation via the placenta. Substrate flux across placental gradients is dependent on the accessibility and activity of nutrient-specific transporters. Changes in the expression and activity of these transporters is implicated in cases of restricted and excessive fetal growth, and may represent a control mechanism by which fetal growth rate attempts to match availability of nutrients in maternal circulation. This review provides an overview of placenta nutrient transport with an emphasis on macro-nutrient transporters. It highlights the changes in expression and activity of these transporters associated with common pregnancy pathologies, including intrauterine growth restriction, macrosomia, diabetes and obesity, as well as the potential impact of maternal diet. Molecular signaling pathways linking maternal nutrient availability and placenta nutrient transport are discussed. How sexual dimorphism affects fetal growth strategies and the placenta’s response to an altered intrauterine environment is considered. Further knowledge in this area may be the first step in the development of targeted interventions to help optimize fetal growth. PMID:25222554

Maternal bisphenol A alters fetal endocrine system: Thyroid adipokine dysfunction.

PubMed

Ahmed, R G

2016-09-01

Because bisphenol A (BPA) has been detected in animals, the aim of this study was to investigate the possible effects of maternal BPA exposure on the fetal endocrine system (thyroid-adipokine axis). BPA (20 or 40 μg/kg body weight) was orally administered to pregnant rats from gestation day (GD) 1-20. In both treated groups, the dams and their fetuses had lower serum thyroxine (T4) and triiodothyronine (T3) levels, and higher thyrotropin (TSH) level than control dams and fetuses at GD 20. Some histopathological changes in fetal thyroid glands were observed in both maternal BPA groups at embryonic day (ED) 20, including fibroblast proliferation, hyperplasia, luminal obliteration, oedema, and degeneration. These disorders resulted in the suppression of fetal serum growth hormone (GH), insulin growth factor-1 (IGF1) and adiponectin (ADP) levels, and the elevation of fetal serum leptin, insulin and tumor necrosis factor-alpha (TNFα) levels in both treated groups with respect to control. The depraved effects of both treated groups were associated with reduced maternal and fetal body weight compared to the control group. These alterations were dose dependent. Thus, BPA might penetrate the placental barrier and perturb the fetal thyroid adipokine axis to influence fat metabolism and the endocrine system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maternal exposure to nanosized titanium dioxide suppresses embryonic development in mice.

PubMed

Hong, Fashui; Zhou, Yingjun; Zhao, Xiaoyang; Sheng, Lei; Wang, Ling

2017-01-01

Although nanoscale titanium dioxide (nano-TiO 2 ) has been extensively used in industrial food applications and daily products for pregnant women, infants, and children, its potential toxicity on fetal development has been rarely studied. The main objective of this investigation was to establish the effects of maternal exposure of nano-TiO 2 on developing embryos. Female imprinting control region mice were orally administered nano-TiO 2 from gestational day 0 to 17. Our findings showed that Ti concentrations in maternal serum, placenta, and fetus were increased in nano-TiO 2 -exposed mice when compared to controls, which resulted in reductions in the contents of calcium and zinc in maternal serum, placenta, and fetus, maternal weight gain, placental weight, fetal weight, number of live fetuses, and fetal crown-rump length as well as cauda length, and caused an increase in the number of both dead fetuses and resorptions. Furthermore, maternal nano-TiO 2 exposure inhibited development of the fetal skeleton, suggesting a significant absence of cartilage, reduced or absent ossification, and an increase in the number of fetuses with dysplasia, including exencephaly, spina bifida, coiled tail, scoliosis, rib absence, and sternum absence. These findings indicated that nano-TiO 2 can cross the blood-fetal barrier and placental barrier, thereby delaying the development of fetal mice and inducing skeletal malformation. These factors may be associated with reductions in both calcium and zinc in maternal serum and the fetus, and both the placenta and embryos may be major targets of developmental toxicity following maternal exposure to nano-TiO 2 during the prenatal period. Therefore, the application of nano-TiO 2 should be carried out with caution.

Maternal exposure to nanosized titanium dioxide suppresses embryonic development in mice

PubMed Central

Hong, Fashui; Zhou, Yingjun; Zhao, Xiaoyang; Sheng, Lei; Wang, Ling

2017-01-01

Although nanoscale titanium dioxide (nano-TiO2) has been extensively used in industrial food applications and daily products for pregnant women, infants, and children, its potential toxicity on fetal development has been rarely studied. The main objective of this investigation was to establish the effects of maternal exposure of nano-TiO2 on developing embryos. Female imprinting control region mice were orally administered nano-TiO2 from gestational day 0 to 17. Our findings showed that Ti concentrations in maternal serum, placenta, and fetus were increased in nano-TiO2-exposed mice when compared to controls, which resulted in reductions in the contents of calcium and zinc in maternal serum, placenta, and fetus, maternal weight gain, placental weight, fetal weight, number of live fetuses, and fetal crown–rump length as well as cauda length, and caused an increase in the number of both dead fetuses and resorptions. Furthermore, maternal nano-TiO2 exposure inhibited development of the fetal skeleton, suggesting a significant absence of cartilage, reduced or absent ossification, and an increase in the number of fetuses with dysplasia, including exencephaly, spina bifida, coiled tail, scoliosis, rib absence, and sternum absence. These findings indicated that nano-TiO2 can cross the blood–fetal barrier and placental barrier, thereby delaying the development of fetal mice and inducing skeletal malformation. These factors may be associated with reductions in both calcium and zinc in maternal serum and the fetus, and both the placenta and embryos may be major targets of developmental toxicity following maternal exposure to nano-TiO2 during the prenatal period. Therefore, the application of nano-TiO2 should be carried out with caution. PMID:28883729

Effect of uterine contractions on fetal heart rate in pregnancy: a prospective observational study.

PubMed

Sletten, Julie; Kiserud, Torvid; Kessler, Jörg

2016-10-01

The new Holter monitoring technology enables long-term electrocardiographic recording of the fetal heart rate without discomfort for the mother. The aim of the study was to assess the feasibility of a fetal Holter monitor. This technology was further used to study fetal heart rate outside the hospital setting during normal daily activities and to test the hypothesis that uterine activity during pregnancy influences fetal heart rate. Prospective observational study including 12 healthy pregnant women at 20-40 weeks of gestation. Data were collected using the Monica AN24 system. Outcome measures were fetal heart rate, maternal heart rate, and uterine activity categorized according to the strength of the electrohysterographic signal. The recordings had a median length of 18.8 h, and fetal heart rate and maternal heart rate were obtained with success rates of 73.1 and 99.9%, respectively. Uterine activity was found to affect fetal heart rate in all participants. Compared with the basal tone and mild levels of uterine activity, moderate and strong levels of uterine activity were associated with increases in fetal heart rate of 4.0 and 5.7 beats/min, respectively. At night, the corresponding increases were 4.9 and 7.6 beats/min. Linear correlations were found between maternal heart rate and fetal heart rate in 11 of the 12 cases, with a mean coefficient beta of 0.189. Both maternal heart rate and fetal heart rate exhibited a diurnal pattern, with lower heart rates being recorded at night. Uterine activity during pregnancy is associated with a graded response in fetal heart rate and may represent a physiological challenge for the development and adaptation of the fetal cardiovascular system. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Timing of induction of labor.

PubMed

Bacak, Stephen J; Olson-Chen, Courtney; Pressman, Eva

2015-10-01

Determining the optimal timing for induction of labor is critical in minimizing the risks to maternal and fetal health. While data are available to guide us in some clinical situations, such as hypertension and diabetes, many gaps in knowledge still exist in others, including cholestasis of pregnancy, fetal anomalies, and placental abruption. This review of the currently available literature assesses the risks and benefits of preterm and early term induction in a wide variety of maternal and fetal conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

[Maternal and fetal outcome in Mexican women with rheumatoid arthritis].

PubMed

Saavedra, Miguel A; Sánchez, Antonio; Bustamante, Reyna; Miranda-Hernández, Dafhne; Soliz-Antezana, Jimena; Cruz-Domínguez, Pilar; Morales, Sara; Jara, Luis J

2015-01-01

To report our experience in maternal-fetal outcome in women with RA in a national medical referral center. A retrospective analysis of the records of pregnant women with rheumatoid arthritis attending at a Pregnancy and Autoimmune Rheumatic Diseases Clinic was performed. Maternal-fetal outcomes such as disease activity, preclampsia/eclampsia, rate of live births, abortions, stillbirths, preterm birth, weeks of gestation, birth weight, congenital malformations and use of anti-rheumatic drugs were studied. We included 73 pregnancies in 72 patients. Disease activity was documented in 47.2% of patients during pregnancy and/or postpartum and 87.7% of patients received some antirheumatic drug. Preclampsia developed in 8.2% of cases. The live birth rate was 98.6%, with preterm delivery in 15.9% and low weight at term in 17.6% of cases. Cesarean section was performed in 77.1% of cases. The disease activity was not associated with a higher percentage of maternal-fetal complications. Our study showed that most patients do not experience significant activity of RA during pregnancy, fetal outcome is satisfactory and disease activity did not appear to influence significantly the obstetric outcome.

The Association Between Maternal Subclinical Hypothyroidism and Growth, Development, and Childhood Intelligence: A Meta-analysis

PubMed

Liu, Yahong; Chen, Hui; Jing, Chen; Li, FuPin

2018-06-01

To explore the association between maternal subclinical hypothyroidism (SCH) in pregnancy and the somatic and intellectual development of their offspring. Using RevMan 5.3 software, a meta-analysis of cohort studies published from inception to May 2017, focusing on the association between maternal SCH in pregnancy and childhood growth, development and intelligence, was performed. Sources included the Cochrane Library, Pub-Med, Web of Science, China National Knowledge Infrastructure and Wan Fang Data. Analysis of a total of 15 cohort studies involving 1.896 pregnant women with SCH revealed that SCH in pregnancy was significantly associated with the intelligence (p=0.0007) and motor development (p<0.00001) of the offspring. SCH was also significantly associated with the child’s weight in four studies involving 222 women (p=0.02). Maternal SCH in pregnancy was identified as a risk factor for fetal growth restriction with a combined relative risk (RR) value of 2.4 [95% confidence interval (CI): 1.56, 3.7]. Meta-analysis of 10 studies that provided numbers of preterm infants revealed a significant association between maternal SCH in pregnancy and premature delivery, with a combined RR of 1.96 (95% CI: 1.34, 2.88). There was a significant effect of maternal SCH in pregnancy on fetal distress in utero (p=0.003). Maternal SCH in pregnancy is associated with increased risk of adverse neonatal outcomes, including delayed intellectual and motor development, low birth weight, premature delivery, fetal distress and fetal growth restriction.

Prediction of Fetal Darunavir Exposure by Integrating Human Ex-Vivo Placental Transfer and Physiologically Based Pharmacokinetic Modeling.

PubMed

Schalkwijk, Stein; Buaben, Aaron O; Freriksen, Jolien J M; Colbers, Angela P; Burger, David M; Greupink, Rick; Russel, Frans G M

2017-07-25

Fetal antiretroviral exposure is usually derived from the cord-to-maternal concentration ratio. This static parameter does not provide information on the pharmacokinetics in utero, limiting the assessment of a fetal exposure-effect relationship. The aim of this study was to incorporate placental transfer into a pregnancy physiologically based pharmacokinetic model to simulate and evaluate fetal darunavir exposure at term. An existing and validated pregnancy physiologically based pharmacokinetic model of maternal darunavir/ritonavir exposure was extended with a feto-placental unit. To parameterize the model, we determined maternal-to-fetal and fetal-to-maternal darunavir/ritonavir placental clearance with an ex-vivo human cotyledon perfusion model. Simulated maternal and fetal pharmacokinetic profiles were compared with observed clinical data to qualify the model for simulation. Next, population fetal pharmacokinetic profiles were simulated for different maternal darunavir/ritonavir dosing regimens. An average (±standard deviation) maternal-to-fetal cotyledon clearance of 0.91 ± 0.11 mL/min and fetal-to-maternal clearance of 1.6 ± 0.3 mL/min was determined (n = 6 perfusions). Scaled placental transfer was integrated into the pregnancy physiologically based pharmacokinetic model. For darunavir 600/100 mg twice a day, the predicted fetal maximum plasma concentration, trough concentration, time to maximum plasma concentration, and half-life were 1.1, 0.57 mg/L, 3, and 21 h, respectively. This indicates that the fetal population trough concentration is higher or around the half-maximal effective darunavir concentration for a resistant virus (0.55 mg/L). The results indicate that the population fetal exposure after oral maternal darunavir dosing is therapeutic and this may provide benefits to the prevention of mother-to-child transmission of human immunodeficiency virus. Moreover, this integrated approach provides a tool to prevent fetal toxicity or enhance the development of more selectively targeted fetal drug treatments.

Gene promoter DNA methylation patterns have a limited role in orchestrating transcriptional changes in the fetal liver in response to maternal folate depletion during pregnancy.

PubMed

McKay, Jill A; Adriaens, Michiel; Evelo, Chris T; Ford, Dianne; Mathers, John C

2016-09-01

Early-life exposures are critical in fetal programming and may influence function and health in later life. Adequate maternal folate consumption during pregnancy is essential for healthy fetal development and long-term offspring health. The mechanisms underlying fetal programming are poorly understood, but are likely to involve gene regulation. Epigenetic marks, including DNA methylation, regulate gene expression and are modifiable by folate supply. We observed transcriptional changes in fetal liver in response to maternal folate depletion and hypothesized that these changes are concomitant with altered gene promoter methylation. Female C57BL/6J mice were fed diets containing 2 or 0.4 mg folic acid/kg for 4 wk before mating and throughout pregnancy. At 17.5-day gestation, genome-wide gene expression and promoter methylation were measured by microarray analysis in male fetal livers. While 989 genes were differentially expressed, 333 promoters had altered methylation (247 hypermethylated, 86 hypomethylated) in response to maternal folate depletion. Only 16 genes had both expression and methylation changes. However, most methylation changes occurred in genomic regions neighboring expression changes. In response to maternal folate depletion, altered expression at the mRNA level was not associated with altered promoter methylation of the same gene in fetal liver. © 2016 The Authors. Molecular Nutrition & Food Research Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transfer of repaglinide in the dually perfused human placenta and the role of organic anion transporting polypeptides (OATPs).

PubMed

Tertti, Kristiina; Petsalo, Aleksanteri; Niemi, Mikko; Ekblad, Ulla; Tolonen, Ari; Rönnemaa, Tapani; Turpeinen, Miia; Heikkinen, Tuija; Laine, Kari

2011-10-09

Our aim was to investigate the placental transfer of repaglinide by ex vivo placental perfusion experiment. In addition, the involvement of the active organic anion transporters (OATP1B1, OATP1B3 and OATP2B1) was studied by assessing the single nucleotide polymorphisms (SNPs) in genes (SLCO1B1, SLCO1B3 and SLCO2B1) encoding OATPs. Fifteen placentas were obtained after delivery and a 2-h non-recirculating perfusion of a single placental cotyledon was performed to study maternal-to-fetal and fetal-to-maternal transport of repaglinide by using antipyrine as a reference of passive-diffusion transfer compound. Genotyping was performed for all placentas. Maternal-to-fetal transfer of repaglinide and antipyrine were 1.5% and 13.2%, respectively, and fetal-to-maternal transfers were 6.7% and 40.3%, respectively. Fetal-to-maternal transfer of repaglinide was statistically significantly higher than maternal-to-fetal transfer (P<0.0001). The number of placentas was not sufficient for proper statistical analysis, but the fetal-to-maternal transfer seemed to be affected by the SLCO1B3 polymorphism. The placental transfer of repaglinide from mother to fetus was low. Since a higher transfer rate of repaglinide was observed in fetal-to-maternal than maternal-to-fetal direction, active transport by OATP-transporters may be an important factor in fetal exposure to repaglinide. Copyright © 2011 Elsevier B.V. All rights reserved.

Near-term fetal response to maternal spoken voice

PubMed Central

Voegtline, Kristin M.; Costigan, Kathleen A.; Pater, Heather A.; DiPietro, Janet A.

2013-01-01

Knowledge about prenatal learning has been largely predicated on the observation that newborns appear to recognize the maternal voice. Few studies have examined the process underlying this phenomenon; that is, whether and how the fetus responds to maternal voice in situ. Fetal heart rate and motor activity were recorded at 36 weeks gestation (n = 69) while pregnant women read aloud from a neutral passage. Compared to a baseline period, fetuses responded with a decrease in motor activity in the 10-seconds following onset of maternal speech and a trend level decelerative heart rate response, consistent with an orienting response. Subsequent analyses revealed that the fetal response was modified by both maternal and fetal factors. Fetuses of women who were previously awake and talking (n = 40) showed an orienting response to onset of maternal reading aloud, while fetuses of mothers who had previously been resting and silent (n = 29) responded with elevated heart rate and increased movement. The magnitude of the fetal response was further dependent on baseline fetal heart rate variability such that largest response was demonstrated by fetuses with low variability of mothers who were previously resting and silent. Results indicate that fetal responsivity is affected by both maternal and fetal state and have implications for understanding fetal learning of the maternal voice under naturalistic conditions. PMID:23748167

State of the science: does the theory of maternal role attainment apply to African American motherhood?

PubMed

Fouquier, Katherine Ferrell

2013-01-01

This article reviews the current state of knowledge of the theory of maternal role attainment (MRA) and its relevance in describing African American motherhood. EBSCOhost Research Databases that included PubMed, CINAHL plus, MEDLINE, PsycINFO, SCOPUS, and Web of Science were searched for journal articles that examined maternal identity and MRA. Keyword searches included maternal identity, maternal role attainment, becoming a mother, prenatal attachment, maternal-fetal attachment, and maternal-infant attachment. Inclusion criteria for this review were published journal articles of studies conducted in the United States, with a clear delineation of the theoretical framework of MRA. Journal articles that measured MRA among women with depression or medically fragile infants were excluded. Two hundred and twelve studies were reviewed; 25 studies, published between 1975 and 2007, met the inclusion criteria. Nine articles described the theory of MRA, 11 articles measured variables thought to influence MRA, and 6 articles described maternal-fetal attachment, a construct of MRA. Studies were reviewed, categorized, and analyzed to determine current knowledge of how the theory of MRA describes African American motherhood. Categories included studies describing the theoretical framework of maternal identity and MRA, studies measuring key variables thought to impact MRA, and studies measuring maternal-fetal attachment and maternal-infant attachment. The studies were limited by homogenous samples of upper-middle-class white women and low-income, single, African American adolescents. Study results of MRA cannot be generalized to African American women. Further research is essential to identify attributes influencing MRA, specifically among larger samples of African American women with demographics similar to that of the white populations that have been included in studies thus far. © 2013 by the American College of Nurse-Midwives.

Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.

PubMed

Beaumont, Robin N; Warrington, Nicole M; Cavadino, Alana; Tyrrell, Jessica; Nodzenski, Michael; Horikoshi, Momoko; Geller, Frank; Myhre, Ronny; Richmond, Rebecca C; Paternoster, Lavinia; Bradfield, Jonathan P; Kreiner-Møller, Eskil; Huikari, Ville; Metrustry, Sarah; Lunetta, Kathryn L; Painter, Jodie N; Hottenga, Jouke-Jan; Allard, Catherine; Barton, Sheila J; Espinosa, Ana; Marsh, Julie A; Potter, Catherine; Zhang, Ge; Ang, Wei; Berry, Diane J; Bouchard, Luigi; Das, Shikta; Hakonarson, Hakon; Heikkinen, Jani; Helgeland, Øyvind; Hocher, Berthold; Hofman, Albert; Inskip, Hazel M; Jones, Samuel E; Kogevinas, Manolis; Lind, Penelope A; Marullo, Letizia; Medland, Sarah E; Murray, Anna; Murray, Jeffrey C; Njølstad, Pål R; Nohr, Ellen A; Reichetzeder, Christoph; Ring, Susan M; Ruth, Katherine S; Santa-Marina, Loreto; Scholtens, Denise M; Sebert, Sylvain; Sengpiel, Verena; Tuke, Marcus A; Vaudel, Marc; Weedon, Michael N; Willemsen, Gonneke; Wood, Andrew R; Yaghootkar, Hanieh; Muglia, Louis J; Bartels, Meike; Relton, Caroline L; Pennell, Craig E; Chatzi, Leda; Estivill, Xavier; Holloway, John W; Boomsma, Dorret I; Montgomery, Grant W; Murabito, Joanne M; Spector, Tim D; Power, Christine; Järvelin, Marjo-Ritta; Bisgaard, Hans; Grant, Struan F A; Sørensen, Thorkild I A; Jaddoe, Vincent W; Jacobsson, Bo; Melbye, Mads; McCarthy, Mark I; Hattersley, Andrew T; Hayes, M Geoffrey; Frayling, Timothy M; Hivert, Marie-France; Felix, Janine F; Hyppönen, Elina; Lowe, William L; Evans, David M; Lawlor, Debbie A; Feenstra, Bjarke; Freathy, Rachel M

2018-02-15

Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 × 10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights. © The Author(s) 2018. Published by Oxford University Press.

Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics

PubMed Central

Beaumont, Robin N; Warrington, Nicole M; Cavadino, Alana; Tyrrell, Jessica; Nodzenski, Michael; Horikoshi, Momoko; Geller, Frank; Myhre, Ronny; Richmond, Rebecca C; Paternoster, Lavinia; Bradfield, Jonathan P; Kreiner-Møller, Eskil; Huikari, Ville; Metrustry, Sarah; Lunetta, Kathryn L; Painter, Jodie N; Hottenga, Jouke-Jan; Allard, Catherine; Barton, Sheila J; Espinosa, Ana; Marsh, Julie A; Potter, Catherine; Zhang, Ge; Ang, Wei; Berry, Diane J; Bouchard, Luigi; Das, Shikta; Hakonarson, Hakon; Heikkinen, Jani; Helgeland, Øyvind; Hocher, Berthold; Hofman, Albert; Inskip, Hazel M; Jones, Samuel E; Kogevinas, Manolis; Lind, Penelope A; Marullo, Letizia; Medland, Sarah E; Murray, Anna; Murray, Jeffrey C; Njølstad, Pål R; Nohr, Ellen A; Reichetzeder, Christoph; Ring, Susan M; Ruth, Katherine S; Santa-Marina, Loreto; Scholtens, Denise M; Sebert, Sylvain; Sengpiel, Verena; Tuke, Marcus A; Vaudel, Marc; Weedon, Michael N; Willemsen, Gonneke; Wood, Andrew R; Yaghootkar, Hanieh; Muglia, Louis J; Bartels, Meike; Relton, Caroline L; Pennell, Craig E; Chatzi, Leda; Estivill, Xavier; Holloway, John W; Boomsma, Dorret I; Montgomery, Grant W; Murabito, Joanne M; Spector, Tim D; Power, Christine; Järvelin, Marjo-Ritta; Bisgaard, Hans; Grant, Struan F A; Sørensen, Thorkild I A; Jaddoe, Vincent W; Jacobsson, Bo; Melbye, Mads; McCarthy, Mark I; Hattersley, Andrew T; Hayes, M Geoffrey; Frayling, Timothy M; Hivert, Marie-France; Felix, Janine F; Hyppönen, Elina; Lowe, William L; Evans, David M; Lawlor, Debbie A; Feenstra, Bjarke

2018-01-01

Abstract Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother–child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 × 10−8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights. PMID:29309628

Differential expression of genes in fetal brain as a consequence of maternal protein deficiency and nematode infection.

PubMed

Haque, Manjurul; Starr, Lisa M; Koski, Kristine G; Scott, Marilyn E

2018-01-01

Maternal dietary protein deficiency and gastrointestinal nematode infection during early pregnancy have negative impacts on both maternal placental gene expression and fetal growth in the mouse. Here we used next-generation RNA sequencing to test our hypothesis that maternal protein deficiency and/or nematode infection also alter the expression of genes in the developing fetal brain. Outbred pregnant CD1 mice were used in a 2×2 design with two levels of dietary protein (24% versus 6%) and two levels of infection (repeated sham versus Heligmosomoides bakeri beginning at gestation day 5). Pregnant dams were euthanized on gestation day 18 to harvest the whole fetal brain. Four fetal brains from each treatment group were analyzed using RNA Hi-Seq sequencing and the differential expression of genes was determined by the edgeR package using NetworkAnalyst. In response to maternal H. bakeri infection, 96 genes (88 up-regulated and eight down-regulated) were differentially expressed in the fetal brain. Differentially expressed genes were involved in metabolic processes, developmental processes and the immune system according to the PANTHER classification system. Among the important biological functions identified, several up-regulated genes have known neurological functions including neuro-development (Gdf15, Ing4), neural differentiation (miRNA let-7), synaptic plasticity (via suppression of NF-κβ), neuro-inflammation (S100A8, S100A9) and glucose metabolism (Tnnt1, Atf3). However, in response to maternal protein deficiency, brain-specific serine protease (Prss22) was the only up-regulated gene and only one gene (Dynlt1a) responded to the interaction of maternal nematode infection and protein deficiency. In conclusion, maternal exposure to GI nematode infection from day 5 to 18 of pregnancy may influence developmental programming of the fetal brain. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The Role of Placental Nutrient Sensing in Maternal-Fetal Resource Allocation1

PubMed Central

Díaz, Paula; Powell, Theresa L.; Jansson, Thomas

2014-01-01

ABSTRACT The placenta mediates maternal-fetal exchange and has historically been regarded as a passive conduit for nutrients. However, emerging evidence suggests that the placenta actively responds to nutritional and metabolic signals from the mother and the fetus. We propose that the placenta integrates a multitude of maternal and fetal nutritional cues with information from intrinsic nutrient-sensing signaling pathways to match fetal demand with maternal supply by regulating maternal physiology, placental growth, and nutrient transport. This process, which we have called placental nutrient sensing, ensures optimal allocation of resources between the mother and the fetus to maximize the chances for propagation of parental genes without jeopardizing maternal health. We suggest that these mechanisms have evolved because of the evolutionary pressures of maternal undernutrition, which result in decreased placental growth and down-regulation of nutrient transporters, thereby limiting fetal growth to ensure maternal survival. These regulatory loops may also function in response to maternal overnutrition, leading to increased placental growth and nutrient transport in cases of maternal obesity or gestational diabetes. Thus, placental nutrient sensing modulates maternal-fetal resource allocation to increase the likelihood of reproductive success. This model implies that the placenta plays a critical role in mediating fetal programming and determining lifelong health. PMID:25122064

Fetal and maternal outcomes in pregnancies complicated with fetal macrosomia.

PubMed

Alsammani, Mohamed Alkahatim; Ahmed, Salah Roshdy

2012-06-01

Fetal macrosomia remains a considerable challenge in current obstetrics due to the fetal and maternal complications associated with this condition. This study was designed to determine the prevalence of fetal macrosomia and associated fetal and maternal morbidity and mortality in the Al Qassim Region of Saudi Arabia. This register-based study was conducted from January 1, 2011 through December 30, 2011 at the Maternity and Child Hospital, Qassim, Saudi Arabia. Macrosomia was defined as birth weight of 4 kg or greater. Malformed babies and those born dead were excluded. The total number of babies delivered was 9241; of these, 418 were macrosomic. Thus, the prevalence of fetal macrosomia was 4.5%. The most common maternal complications were postpartum hemorrhage (5 cases, 1.2%), perineal tear (7 cases, 1.7%), cervical lacerations (3 cases, 0.7%), and shoulder dystocia (40 cases, 9.6%) that resulted in 4 cases of Erb's palsy (0.96%), and 6 cases of bone fractures (1.4%). The rate of cesarean section among women delivering macrosomic babies was 47.6% (199), while 52.4% (219) delivered vaginally. Despite extensive efforts to reduce fetal and maternal complications associated with macrosomia, considerable fetal and maternal morbidity remain associated with this condition.

Effects of maternal subtotal nephrectomy on the development of the fetal kidney: A morphometric study.

PubMed

Kondo, Tomohiro; Kitano-Amahori, Yoko; Nagai, Hiroaki; Mino, Masaki; Takeshita, Ai; Kusakabe, Ken Takeshi; Okada, Toshiya

2015-11-01

The present study was designed to explore if maternal subtotal (5/6) nephrectomy affects the development of fetal rat kidneys using morphometric methods and examining whether there are any apoptotic changes in the fetal kidney. To generate 5/6 nephrectomized model rats, animals underwent 2/3 left nephrectomy on gestation day (GD) 5 and total right nephrectomy on GD 12. The fetal kidneys were examined on GDs 16 and 22. A significant decrease in fetal body weight resulting from maternal 5/6 nephrectomy was observed on GD 16, and a significant decrease in fetal renal weight and fetal body weight caused by maternal nephrectomy was observed on GD 22. Maternal 5/6 nephrectomy induced a significant increase in glomerular number, proximal tubular length, and total proximal tubular volume of fetuses on GD 22. Maternal 5/6 nephrectomy resulted in an increase in the number of apoptotic cells in the metanephric mesenchyme of the kidney on GD 16, and in the collecting tubules on GD 22. These findings suggest that maternal 5/6 nephrectomy stimulates the development of the fetal kidney while suppressing fetal growth. © 2015 Japanese Teratology Society.

2011 and 2012 Early Careers Achievement Awards: Placental programming: how the maternal environment can impact placental function.

PubMed

Vonnahme, K A; Lemley, C O; Shukla, P; O'Rourke, S T

2013-06-01

Proper establishment of the placenta is important for fetal survival; however, placental adaptations to inadequate maternal nutrition or other stressors are imperative for fetal growth to be optimal. The effects of maternal nutritional status and activity level on placental vascular function and uteroplacental blood flows are important to understand as improper placental function leads to reduced growth of the fetus. In environments where fetal growth can be compromised, potential therapeutics may augment placental function and delivery of nutrients to improve offspring performance during postnatal life. Factors that could enhance placental function include supplementation of specific nutrients, such as protein, hormone supplements, such as indolamines, and increased activity levels of the dam. To understand the mechanism of how the maternal environment can impact uterine or umbilical blood flows, assessment of placental vascular reactivity has been studied in several large animal models. As we begin to understand how the maternal environment impacts uterine and umbilical blood flows and other uteroplacental hemodynamic parameters, development of management methods and therapeutics for proper fetal growth can be achieved.

Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations.

PubMed

Visentin, Carly E; Masih, Shannon; Plumptre, Lesley; Malysheva, Olga; Nielsen, Daiva E; Sohn, Kyoung-Jin; Ly, Anna; Lausman, Andrea Y; Berger, Howard; Croxford, Ruth; El-Sohemy, Ahmed; Caudill, Marie A; O'Connor, Deborah L; Kim, Young-In

2015-07-01

Choline deficiency during pregnancy can lead to adverse birth outcomes, including impaired neurodevelopment and birth defects. Genetic variants of choline and one-carbon metabolism may also influence birth outcomes by altering plasma choline concentrations. The effects of maternal ad libitum choline intake during pregnancy and fetal genetic variants on maternal and cord concentrations of choline and its metabolites are unknown. This prospective study sought to assess the effect of 1) maternal dietary choline intake on maternal and cord plasma concentrations of choline and its metabolites, and 2) fetal genetic polymorphisms on cord plasma concentrations. The dietary choline intake of 368 pregnant Canadian women was assessed in early (0-16 wk) and late (23-37 wk) pregnancy with the use of a food frequency questionnaire. Plasma concentrations of free choline and its metabolites were measured in maternal samples at recruitment and delivery, and in the cord blood. Ten fetal genetic variants in choline and one-carbon metabolism were assessed for their association with cord plasma concentrations of free choline and its metabolites. Mean maternal plasma free choline, dimethylglycine, and trimethylamine N-oxide (TMAO) concentrations increased during pregnancy by 49%, 17%, and 13%, respectively (P < 0.005), whereas betaine concentrations decreased by 21% (P < 0.005). Cord plasma concentrations of free choline, betaine, dimethylglycine, and TMAO were 3.2, 2.0, 1.3, and 0.88 times corresponding maternal concentrations at delivery, respectively (all P < 0.005). Maternal plasma concentrations of betaine, dimethylglycine, and TMAO (r(2) = 0.19-0.51; P < 0.0001) at delivery were moderately strong, whereas maternal concentrations of free choline were not significant (r(2) = 0.12; P = 0.06), predictors of cord plasma concentrations of these metabolites. Neither maternal dietary intake nor fetal genetic variants predicted maternal or cord plasma concentrations of choline and its metabolites. These data collectively indicate that maternal choline status, but not fetal genotype, influences cord plasma concentrations of choline metabolites. This trial was registered at clinicaltrials.gov as NCT02244684. © 2015 American Society for Nutrition.

[Per partum acidosis: Interest and feasibility of cerebral Doppler during labor].

PubMed

Barrois, M; Chartier, M; Lecarpentier, E; Goffinet, F; Tsatsaris, V

2016-09-01

To evaluate feasibility and interest of fetal cerebral Doppler during labor and the link with fetal pH to predict perinatal fetal asphyxia. Our prospective study in a university perinatal center, included patients during labor. There were no risk factors during pregnancy and patients were included after 37 weeks of pregnancy. For each patient an ultrasound with cerebral Doppler was done concomitant to a fetal scalp blood sample. We collected maternal and fetal characteristics as well as cervix dilatation, fetal heart rate analysis and fetal presentation. Among 49 patients included over a period of 4 months, cerebral Doppler failed in 7 cases (11%). Majority of failure occurred at 10cm of dilatation (P=0.007, OR=14.1 [1.483; 709.1275]). Others factors like: maternal age, body mass index, parity, history of C-Section were not associated with higher rate of failure. We did not found either significant correlation between cerebral fetal Doppler and pH on fetal scalp blood sample (r=0.15) nor pH at cord blood sample (r=0.13). No threshold of cerebral Doppler is significant for fetal asphyxia prediction. Fetal cerebral Doppler is feasible during labor with a low rate of failure but not a good exam to predict fetal acidosis and asphyxia. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The placenta: a multifaceted, transient organ

PubMed Central

Burton, Graham J.; Fowden, Abigail L.

2015-01-01

The placenta is arguably the most important organ of the body, but paradoxically the most poorly understood. During its transient existence, it performs actions that are later taken on by diverse separate organs, including the lungs, liver, gut, kidneys and endocrine glands. Its principal function is to supply the fetus, and in particular, the fetal brain, with oxygen and nutrients. The placenta is structurally adapted to achieve this, possessing a large surface area for exchange and a thin interhaemal membrane separating the maternal and fetal circulations. In addition, it adopts other strategies that are key to facilitating transfer, including remodelling of the maternal uterine arteries that supply the placenta to ensure optimal perfusion. Furthermore, placental hormones have profound effects on maternal metabolism, initially building up her energy reserves and then releasing these to support fetal growth in later pregnancy and lactation post-natally. Bipedalism has posed unique haemodynamic challenges to the placental circulation, as pressure applied to the vena cava by the pregnant uterus may compromise venous return to the heart. These challenges, along with the immune interactions involved in maternal arterial remodelling, may explain complications of pregnancy that are almost unique to the human, including pre-eclampsia. Such complications may represent a trade-off against the provision for a large fetal brain. PMID:25602070

Uptake and release of amino acids in the fetal-placental unit in human pregnancies.

PubMed

Holm, Maia Blomhoff; Bastani, Nasser Ezzatkhah; Holme, Ane Moe; Zucknick, Manuela; Jansson, Thomas; Refsum, Helga; Mørkrid, Lars; Blomhoff, Rune; Henriksen, Tore; Michelsen, Trond Melbye

2017-01-01

The current concepts of human fetal-placental amino acid exchange and metabolism are mainly based on animal-, in vitro- and ex vivo models. We aimed to determine and assess the paired relationships between concentrations and arteriovenous differences of 19 amino acids on the maternal and fetal sides of the human placenta in a large study sample. This cross-sectional in vivo study included 179 healthy women with uncomplicated term pregnancies. During planned cesarean section, we sampled blood from incoming and outgoing vessels on the maternal (radial artery and uterine vein) and fetal (umbilical vein and artery) sides of the placenta. Amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry. We calculated paired arteriovenous differences and performed Wilcoxon signed-rank tests and Spearman's correlations. In the umbilical circulation, we observed a positive venoarterial difference (fetal uptake) for 14 amino acids and a negative venoarterial difference (fetal release) for glutamic acid (p<0.001). In the maternal circulation, we observed a positive arteriovenous difference (uteroplacental uptake) for leucine (p = 0.005), isoleucine (p = 0.01), glutamic acid (p<0.001) and arginine (p = 0.04) and a negative arteriovenous difference (uteroplacental release) for tyrosine (p = 0.002), glycine (p = 0.01) and glutamine (p = 0.02). The concentrations in the maternal artery and umbilical vein were correlated for all amino acids except tryptophan, but we observed no correlations between the uteroplacental uptake and the fetal uptake or the umbilical vein concentration. Two amino acids showed a correlation between the maternal artery concentration and the fetal uptake. Our human in vivo study expands the current insight into fetal-placental amino acid exchange, and discloses some differences from what has been previously described in animals. Our findings are consistent with the concept that the fetal supply of amino acids in the human is the result of a dynamic interplay between fetal and placental amino acid metabolism and interconversions.

Maternal anemia effects during pregnancy on male and female fetuses: are there any differences?

PubMed

Orlandini, Cinzia; Torricelli, Michela; Spirito, Nicoletta; Alaimo, Lucia; Di Tommaso, Mariarosaria; Severi, Filiberto Maria; Ragusa, Antonio; Petraglia, Felice

2017-07-01

Sideropenic anemia is a common pregnancy disorder. The relationship between anemia and adverse pregnancy outcome are contradictory, and it is related to the severity of the hemoglobin deficit. The aim of the study was to evaluate the relationship between maternal mild anemia at third trimester of pregnancy, fetal birth weight and fetal gender. A retrospective study including 1131 single physiological term pregnancies was conducted. According to maternal Hb levels during the third trimester, pregnant women enrolled were divided in two groups: Group A (n = 156) with Hb ≤ 11 g/dl and Group B (n = 975) with Hb ≥ 11,1 g/dl. Maternal characteristics, gestational age at delivery, Apgar score and post-partum hemorrhage were similar between groups. However, when neonatal sex was considerate, female newborns of anemic women had a higher birth weight (p = 0.01). Moreover, anemic women showed a significantly higher rate of emergency cesarean section (p = 0.006), in particular when the newborn was a male (p= 0.03). Maternal mild anemia in third trimester of pregnancy correlates with fetal birth weight, influencing fetal growth and delivery outcome on the basis of fetal gender. Even though the reason of this phenomenon is still unknown, these new data may represent a novel parameter to add significant prognostic information in relation to maternal mild anemia and neonatal outcome.

What do we know about maternal-fetal attachment?

PubMed

Shieh, C; Kravitz, M; Wang, H H

2001-09-01

A review of the literature suggests that there are three critical attributes related to the concept of maternal-fetal attachment, including cognitive, affective, and altruistic attachment. Cognitive attachment is the desire to know the baby. Affective attachment is the pleasure associated with thoughts of or interaction with the fetus. Altruistic attachment refers to a desire to protect the unborn child. Existing measurements on maternal-fetal attachment are developed based on low-risk and white pregnant women and previous research has not yet resulted in a consistent theoretical model. Future research should focus on development of culturally sensitive instruments and combining qualitative and quantitative measures to broaden theoretical understanding of the concept. Nursing assessment of maternal-fetal attachment is an on-going process. The nurse's role is to reassure those who have developed attachment to their fetuses and to motivate those who are unaware of or unconcerned about their attachment to their fetuses. Collecting data from different attributes of attachment helps nurses identify each woman's attachment patterns and areas of concern.

Fetal programming by maternal stress: Insights from a conflict perspective.

PubMed

Del Giudice, Marco

2012-10-01

Maternal stress during pregnancy has pervasive effects on the offspring's physiology and behavior, including the development of anxious, reactive temperament and increased stress responsivity. These outcomes can be seen as the result of adaptive developmental plasticity: maternal stress hormones carry useful information about the state of the external world, which can be used by the developing fetus to match its phenotype to the predicted environment. This account, however, neglects the inherent conflict of interest between mother and fetus about the outcomes of fetal programming. The aim of this paper is to extend the adaptive model of prenatal stress by framing mother-fetus interactions in an evolutionary conflict perspective. In the paper, I show how a conflict perspective provides many new insights in the functions and mechanisms of fetal programming, with particular emphasis on human pregnancy. I then take advantage of those insights to make sense of some puzzling features of maternal and fetal physiology and generate novel empirical predictions. Copyright © 2012 Elsevier Ltd. All rights reserved.

QF2011: a protocol to study the effects of the Queensland flood on pregnant women, their pregnancies, and their children's early development.

PubMed

King, Suzanne; Kildea, Sue; Austin, Marie-Paule; Brunet, Alain; Cobham, Vanessa E; Dawson, Paul A; Harris, Mark; Hurrion, Elizabeth M; Laplante, David P; McDermott, Brett M; McIntyre, H David; O'Hara, Michael W; Schmitz, Norbert; Stapleton, Helen; Tracy, Sally K; Vaillancourt, Cathy; Dancause, Kelsey N; Kruske, Sue; Reilly, Nicole; Shoo, Laura; Simcock, Gabrielle; Turcotte-Tremblay, Anne-Marie; Yong Ping, Erin

2015-05-06

Retrospective studies suggest that maternal exposure to a severe stressor during pregnancy increases the fetus' risk for a variety of disorders in adulthood. Animal studies testing the fetal programming hypothesis find that maternal glucocorticoids pass through the placenta and alter fetal brain development, particularly the hypothalamic-pituitary-adrenal axis. However, there are no prospective studies of pregnant women exposed to a sudden-onset independent stressor that elucidate the biopsychosocial mechanisms responsible for the wide variety of consequences of prenatal stress seen in human offspring. The aim of the QF2011 Queensland Flood Study is to fill this gap, and to test the buffering effects of Midwifery Group Practice, a form of continuity of maternity care. In January 2011 Queensland, Australia had its worst flooding in 30 years. Simultaneously, researchers in Brisbane were collecting psychosocial data on pregnant women for a randomized control trial (the M@NGO Trial) comparing Midwifery Group Practice to standard care. We invited these and other pregnant women to participate in a prospective, longitudinal study of the effects of prenatal maternal stress from the floods on maternal, perinatal and early childhood outcomes. Data collection included assessment of objective hardship and subjective distress from the floods at recruitment and again 12 months post-flood. Biological samples included maternal bloods at 36 weeks pregnancy, umbilical cord, cord blood, and placental tissues at birth. Questionnaires assessing maternal and child outcomes were sent to women at 6 weeks and 6 months postpartum. The protocol includes assessments at 16 months, 2½ and 4 years. Outcomes include maternal psychopathology, and the child's cognitive, behavioral, motor and physical development. Additional biological samples include maternal and child DNA, as well as child testosterone, diurnal and reactive cortisol. This prenatal stress study is the first of its kind, and will fill important gaps in the literature. Analyses will determine the extent to which flood exposure influences the maternal biological stress response which may then affect the maternal-placental-fetal axis at the biological, biochemical, and molecular levels, altering fetal development and influencing outcomes in the offspring. The role of Midwifery Group Practice in moderating effects of maternal stress will be tested.

Examining the transplacental passage of apixaban using the dually perfused human placenta.

PubMed

Bapat, P; Pinto, L S R; Lubetsky, A; Aleksa, K; Berger, H; Koren, G; Ito, S

2016-07-01

Essentials Apixaban is a novel oral anticoagulant that has not been studied in pregnant patients. Our objective was to determine the rate and extent of the placental transfer of apixaban. Apixaban rapidly crosses the ex vivo term human placenta from maternal to fetal circulation. Fetal apixaban levels in vivo are estimated to be 35-90% of the corresponding maternal levels. Background Apixaban is a novel oral anticoagulant that is increasingly being prescribed to women of reproductive age. However, information regarding its placental transfer is non-existent. Objective To determine the rate and extent of placental transfer of apixaban, using the human placenta ex vivo. Methods Placentae collected after Caesarean or vaginal delivery of healthy term infants were perfused in the respective maternal and fetal circulation. At the start of the experiment, apixaban was added to the maternal circulation at a concentration of 150 ng mL(-1) , and samples from maternal and fetal reservoirs were collected over 3 h. Results There was a rapid decline of apixaban in the maternal compartment, followed by emergence in the fetal compartment with a median fetal-to-maternal drug concentration ratio of 0.77 (interquartile range [IQR], 0.76-0.81) and fetal concentration of 39.0 ng mL(-1) (IQR, 36.8-40.6) after 3 h (n = 5). The perfusion results were subsequently adjusted to account for differences in the concentration of plasma proteins in maternal and fetal blood, as apixaban remains highly bound to albumin and alpha-1 acid glycoprotein. After the adjustment, the predicted fetal-to-maternal ratio of total (bound plus unbound) apixaban concentrations in vivo ranged from 0.35 to 0.90. Conclusions We conclude that unbound apixaban rapidly crosses from the maternal to fetal circulation. We further predict that total apixaban concentrations in cord blood in vivo are 35-90% of the corresponding maternal levels, suggesting that apixaban could have a possible adverse effect on fetal and neonatal coagulation. © 2016 International Society on Thrombosis and Haemostasis.

Maternal-fetal transfer of selenium in the mouse

PubMed Central

Burk, Raymond F.; Olson, Gary E.; Hill, Kristina E.; Winfrey, Virginia P.; Motley, Amy K.; Kurokawa, Suguru

2013-01-01

Selenoprotein P (Sepp1) is taken up by receptor-mediated endocytosis for its selenium. The other extracellular selenoprotein, glutathione peroxidase-3 (Gpx3), has not been shown to transport selenium. Mice with genetic alterations of Sepp1, the Sepp1 receptors apolipoprotein E receptor-2 (apoER2) and megalin, and Gpx3 were used to investigate maternal-fetal selenium transfer. Immunocytochemistry (ICC) showed receptor-independent uptake of Sepp1 and Gpx3 in the same vesicles of d-13 visceral yolk sac cells, suggesting uptake by pinocytosis. ICC also showed apoER2-mediated uptake of maternal Sepp1 in the d-18 placenta. Thus, two selenoprotein-dependent maternal-fetal selenium transfer mechanisms were identified. Selenium was quantified in d-18 fetuses with the mechanisms disrupted. Maternal Sepp1 deletion, which lowers maternal whole-body selenium, decreased fetal selenium under selenium-adequate conditions but deletion of fetal apoER2 did not. Fetal apoER2 deletion did decrease fetal selenium, by 51%, under selenium-deficient conditions, verifying function of the placental Sepp1-apoER2 mechanism. Maternal Gpx3 deletion decreased fetal selenium, by 13%, but only under selenium-deficient conditions. These findings indicate that the selenoprotein uptake mechanisms ensure selenium transfer to the fetus under selenium-deficient conditions. The failure of their disruptions (apoER2 deletion, Gpx3 deletion) to affect fetal selenium under selenium-adequate conditions indicates the existence of an additional maternal-fetal selenium transfer mechanism.—Burk, R. F., Olson, G. E., Hill, K. E., Winfrey, V. P., Motley, A. K., and Kurokawa, S. Maternal-fetal transfer of selenium in the mouse. PMID:23651543

Bovine fetal DNA in the maternal circulation: Applications and implications.

PubMed

Lemos, D C; Takeuchi, P L; Rios, A F L; Araújo, A; Lemos, H C; Ramos, E S

2011-11-01

The main aim of the present study was to detect bovine fetal DNA in the maternal circulation, a relatively unexplored subject in the literature. DNA was extracted from blood of 84 primipara cows (Bos indicus) at different gestational ages (30-270 days) and from 100 adult animals (50 males and 50 non-pregnant cows). The samples were analyzed using PCR with primers for TSPY gene. Molecular results matched the fetal phenotypic gender in all 47 male and 37 female fetuses, including early pregnancy, and in control animals. These results evidence a bovine transplacental fetal DNA passage. Copyright © 2011 Elsevier Ltd. All rights reserved.

Maternal-fetal transfer of selenium in the mouse.

PubMed

Burk, Raymond F; Olson, Gary E; Hill, Kristina E; Winfrey, Virginia P; Motley, Amy K; Kurokawa, Suguru

2013-08-01

Selenoprotein P (Sepp1) is taken up by receptor-mediated endocytosis for its selenium. The other extracellular selenoprotein, glutathione peroxidase-3 (Gpx3), has not been shown to transport selenium. Mice with genetic alterations of Sepp1, the Sepp1 receptors apolipoprotein E receptor-2 (apoER2) and megalin, and Gpx3 were used to investigate maternal-fetal selenium transfer. Immunocytochemistry (ICC) showed receptor-independent uptake of Sepp1 and Gpx3 in the same vesicles of d-13 visceral yolk sac cells, suggesting uptake by pinocytosis. ICC also showed apoER2-mediated uptake of maternal Sepp1 in the d-18 placenta. Thus, two selenoprotein-dependent maternal-fetal selenium transfer mechanisms were identified. Selenium was quantified in d-18 fetuses with the mechanisms disrupted. Maternal Sepp1 deletion, which lowers maternal whole-body selenium, decreased fetal selenium under selenium-adequate conditions but deletion of fetal apoER2 did not. Fetal apoER2 deletion did decrease fetal selenium, by 51%, under selenium-deficient conditions, verifying function of the placental Sepp1-apoER2 mechanism. Maternal Gpx3 deletion decreased fetal selenium, by 13%, but only under selenium-deficient conditions. These findings indicate that the selenoprotein uptake mechanisms ensure selenium transfer to the fetus under selenium-deficient conditions. The failure of their disruptions (apoER2 deletion, Gpx3 deletion) to affect fetal selenium under selenium-adequate conditions indicates the existence of an additional maternal-fetal selenium transfer mechanism.

Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy

PubMed Central

Feng, Xiaodi; Wood, Charles E.; Richards, Elaine; Anthony, Russell V.; Dahl, Geoffrey E.; Tao, Sha

2014-01-01

In normal pregnancy, cortisol increases; however, further pathological increases in cortisol are associated with maternal and fetal morbidities. These experiments were designed to test the hypothesis that increased maternal cortisol would increase maternal glucose concentrations, suppress fetal growth, and impair neonatal glucose homeostasis. Ewes were infused with cortisol (1 mg·kg−1·day−1) from day 115 of gestation to term; maternal glucose, insulin, ovine placental lactogen, estrone, progesterone, nonesterified free fatty acids (NEFA), β-hydroxybutyrate (BHB), and electrolytes were measured. Infusion of cortisol increased maternal glucose concentration and slowed the glucose disappearance after injection of glucose; maternal infusion of cortisol also increased the incidence of fetal death at or near parturition. The design of the study was altered to terminate the study prior to delivery, and post hoc analysis of the data was performed to test the hypothesis that maternal metabolic factors predict the fetal outcome. In cortisol-infused ewes that had stillborn lambs, plasma insulin was increased relative to control ewes or cortisol-infused ewes with live lambs. Maternal cortisol infusion did not alter maternal food intake or plasma NEFA, BHB, estrone, progesterone or placental lactogen concentrations, and it did not alter fetal body weight, ponderal index, or fetal organ weights. Our study suggests that the adverse effect of elevated maternal cortisol on pregnancy outcome may be related to the effects of cortisol on maternal glucose homeostasis, and that chronic maternal stress or adrenal hypersecretion of cortisol may create fetal pathophysiology paralleling some aspects of maternal gestational diabetes. PMID:24920731

Maternal perception of fetal movements in late pregnancy is affected by type and duration of fetal movement.

PubMed

Brown, Rebecca; Higgins, Lucy E; Johnstone, Edward D; Wijekoon, Jayawan H; Heazell, Alexander E P

2016-01-01

A reduction in fetal movements has been proposed to identify pregnancies at risk of stillbirth. The utility of this approach is limited by variability in maternal perception of fetal movements. We aimed to determine the proportion of fetal movements observed by ultrasound that were maternally perceived and identify factors that affected maternal perception. During 30-min recordings, women (n = 21) depressed a trigger upon perception of a fetal movement, while an ultrasound operator recorded observed movements according to the fetal parts involved. Women perceived between 2.4% and 81.0% (median 44.8%) of movements observed on scan. Synchronous movement of the fetal trunk and limbs was more likely to be recognized than either part in isolation (60.5% versus 37.5% and 30%, respectively). The ultrasound operator judged the fetus to be moving for a significantly greater proportion of the time than mothers (median 1.5% of total recording time versus 0.7%). There was no significant relationship between the ability to perceive fetal activity and placental site, parity, amniotic fluid index or maternal body mass index. Variations in maternal perception of fetal movements may affect detection of a clinically significant reduction in fetal movements for some women.

Fetal Genotype and Maternal Glucose Have Independent and Additive Effects on Birth Weight.

PubMed

Hughes, Alice E; Nodzenski, Michael; Beaumont, Robin N; Talbot, Octavious; Shields, Beverley M; Scholtens, Denise M; Knight, Bridget A; Lowe, William L; Hattersley, Andrew T; Freathy, Rachel M

2018-05-01

Maternal glycemia is a key determinant of birth weight, but recent large-scale genome-wide association studies demonstrated an important contribution of fetal genetics. It is not known whether fetal genotype modifies the impact of maternal glycemia or whether it acts through insulin-mediated growth. We tested the effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for birth weight on birth weight and fetal insulin in 2,051 European mother-child pairs from the Exeter Family Study of Childhood Health (EFSOCH) and the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The fetal genetic score influenced birth weight independently of maternal FPG and impacted growth at all levels of maternal glycemia. For mothers with FPG in the top tertile, the frequency of large for gestational age (birth weight ≥90th centile) was 31.1% for offspring with the highest tertile genetic score and only 14.0% for those with the lowest tertile genetic score. Unlike maternal glucose, the fetal genetic score was not associated with cord insulin or C-peptide. Similar results were seen for HAPO participants of non-European ancestry ( n = 2,842 pairs). This work demonstrates that for any level of maternal FPG, fetal genetics has a major impact on fetal growth and acts predominantly through independent mechanisms. © 2018 by the American Diabetes Association.

Fetal cell-free DNA fraction in maternal plasma for the prediction of hypertensive disorders of pregnancy.

PubMed

Suzumori, Nobuhiro; Sekizawa, Akihiko; Ebara, Takeshi; Samura, Osamu; Sasaki, Aiko; Akaishi, Rina; Wada, Seiji; Hamanoue, Haruka; Hirahara, Fumiki; Izumi, Haruna; Sawai, Hideaki; Nakamura, Hiroaki; Yamada, Takahiro; Miura, Kiyonori; Masuzaki, Hideaki; Yamashita, Takahiro; Okai, Takashi; Kamei, Yoshimasa; Namba, Akira; Murotsuki, Jun; Tanemoto, Tomohiro; Fukushima, Akimune; Haino, Kazufumi; Tairaku, Shinya; Matsubara, Keiichi; Maeda, Kazutoshi; Kaji, Takashi; Ogawa, Masanobu; Osada, Hisao; Nishizawa, Haruki; Okamoto, Yoko; Kanagawa, Takeshi; Kakigano, Aiko; Kitagawa, Michihiro; Ogawa, Masaki; Izumi, Shunichiro; Katagiri, Yukiko; Takeshita, Naoki; Kasai, Yasuyo; Naruse, Katsuhiko; Neki, Reiko; Masuyama, Hisashi; Hyodo, Maki; Kawano, Yukie; Ohba, Takashi; Ichizuka, Kiyotake; Nagamatsu, Takeshi; Watanabe, Atsushi; Shirato, Nahoko; Yotsumoto, Junko; Nishiyama, Miyuki; Hirose, Tatsuko; Sago, Haruhiko

2018-05-01

The purpose of this study is to compare the fetal fractions during non-invasive prenatal testing (NIPT) in singleton pregnancies according to gestational age and maternal characteristics to evaluate the utility of this parameter for the prediction of pregnancy complications including gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). This study was a multicenter prospective cohort study. The present data were collected from women whose NIPT results were negative. The relationships between the fetal fractions and the gestational age, maternal weight and height, and incidences of miscarriage, preterm delivery, and pregnancy complications including GDM, HDP and placental abruption were assessed. A total of 5582 pregnant women with verified NIPT negative results were registered in the study. The demographic characteristics of the study populations were statistically analyzed, and the women with HDP tended to have a low fetal fraction in samples taken during early gestation. The area under the curve (AUC) in a receiver operating characteristic curve (ROC) analysis was 0.608 for women with HDP. A low fetal fraction on NIPT might be correlated with future HDP. However, predicting HDP during early pregnancy in women with a low fetal fraction might be difficult. Copyright © 2018 Elsevier B.V. All rights reserved.

THE EFFECTS OF SPINAL ANESTHESIA ON THE FETAL HEART RATE

PubMed Central

Downs, Howard S.; Morrison, Philip H.

1963-01-01

The effect of spinal anesthesia on fetal heart rate is due to maternal hypotension and subsequent fetal hypoxia. Maternal hypotension of 80 mm of mercury for five minutes almost always results in hypoxic fetal bradycardia. This bradycardia is gradual in onset, and may be preceded by a short period of fetal tachycardia. There is a lag in the return of fetal heart rate to normal after maternal blood pressure has normalized. Similar bradycardia has been observed in maternal syncope unassociated with anesthesia. Maternal hypotension should be prevented, and if it occurs should be corrected early. Administration of a vasopressor drug is the treatment of choice, with oxygen and fluids as indicated. ImagesFigure 1.Figure 3.Figure 4.Figure 5. PMID:14084683

Congenital toxoplasmosis: continued parasite proliferation in the fetal brain despite maternal immunological control in other tissues.

PubMed

Ferguson, David J P; Bowker, Colene; Jeffery, Katie J M; Chamberlain, Paul; Squier, Waney

2013-01-01

Congenital toxoplasmosis is a serious condition but little is known of the natural history of parasite development and associated fetal tissue destruction. Two cases identified by ultrasound underwent induced abortion at 21 and 30 weeks' gestation. At autopsy, the placenta and fetal organs were examined by histology and immunocytochemistry employing anti-Toxoplasma stage-specific antibodies to confirm diagnosis and also provide information on the stage of parasite development. In both cases, maternal serology prior to termination showed both specific immunoglobulin M (IgM) and immunoglobulin G (IgG), whereas retrospective analysis of an earlier sample (12-14 weeks' gestation) showed only IgM reactivity consistent with infection occurring in the first trimester. The finding of a number of tissue cysts but few or no tachyzoites within the placenta and fetal adrenal and heart is characteristic of a chronic infection. However, in contrast, there were still areas of the fetal brain with large numbers of actively dividing, tissue-destructive tachyzoites. These observations show that continued parasite proliferation and tissue destruction can occur within the fetal brain even when there is a marked maternal immune response including maternal IgG. This finding strongly suggests that there may be benefits from treating cases of recently acquired congenital infection to destroy any remaining proliferating parasites located in immunologically protected sites such as the fetal brain.

Maternal choline modifies fetal liver copper, gene expression, DNA methylation, and neonatal growth in the tx-j mouse model of Wilson disease.

PubMed

Medici, Valentina; Shibata, Noreene M; Kharbanda, Kusum K; Islam, Mohammad S; Keen, Carl L; Kim, Kyoungmi; Tillman, Brittany; French, Samuel W; Halsted, Charles H; LaSalle, Janine M

2014-02-01

Maternal diet can affect fetal gene expression through epigenetic mechanisms. Wilson disease (WD), which is caused by autosomal recessive mutations in ATP7B encoding a biliary copper transporter, is characterized by excessive hepatic copper accumulation, but variability in disease severity. We tested the hypothesis that gestational supply of dietary methyl groups modifies fetal DNA methylation and expression of genes involved in methionine and lipid metabolism that are impaired prior to hepatic steatosis in the toxic milk (tx-j) mouse model of WD. Female C3H control and tx-j mice were fed control (choline 8 mmol/Kg of diet) or choline-supplemented (choline 36 mmol/Kg of diet) diets for 2 weeks throughout mating and pregnancy to gestation day 17. A second group of C3H females, half of which were used to cross foster tx-j pups, received the same diet treatments that extended during lactation to 21 d postpartum. Compared with C3H, fetal tx-j livers had significantly lower copper concentrations and significantly lower transcript levels of Cyclin D1 and genes related to methionine and lipid metabolism. Maternal choline supplementation prevented the transcriptional deficits in fetal tx-j liver for multiple genes related to cell growth and metabolism. Global DNA methylation was increased by 17% in tx-j fetal livers after maternal choline treatment (P<0.05). Maternal dietary choline rescued the lower body weight of 21 d tx-j mice. Our results suggest that WD pathogenesis is modified by maternal in utero factors, including dietary choline.

Maternal choline modifies fetal liver copper, gene expression, DNA methylation, and neonatal growth in the tx-j mouse model of Wilson disease

PubMed Central

Medici, Valentina; Shibata, Noreene M; Kharbanda, Kusum K; Islam, Mohammad S; Keen, Carl L; Kim, Kyoungmi; Tillman, Brittany; French, Samuel W; Halsted, Charles H; LaSalle, Janine M

2014-01-01

Maternal diet can affect fetal gene expression through epigenetic mechanisms. Wilson disease (WD), which is caused by autosomal recessive mutations in ATP7B encoding a biliary copper transporter, is characterized by excessive hepatic copper accumulation, but variability in disease severity. We tested the hypothesis that gestational supply of dietary methyl groups modifies fetal DNA methylation and expression of genes involved in methionine and lipid metabolism that are impaired prior to hepatic steatosis in the toxic milk (tx-j) mouse model of WD. Female C3H control and tx-j mice were fed control (choline 8 mmol/Kg of diet) or choline-supplemented (choline 36 mmol/Kg of diet) diets for 2 weeks throughout mating and pregnancy to gestation day 17. A second group of C3H females, half of which were used to cross foster tx-j pups, received the same diet treatments that extended during lactation to 21 d postpartum. Compared with C3H, fetal tx-j livers had significantly lower copper concentrations and significantly lower transcript levels of Cyclin D1 and genes related to methionine and lipid metabolism. Maternal choline supplementation prevented the transcriptional deficits in fetal tx-j liver for multiple genes related to cell growth and metabolism. Global DNA methylation was increased by 17% in tx-j fetal livers after maternal choline treatment (P < 0.05). Maternal dietary choline rescued the lower body weight of 21 d tx-j mice. Our results suggest that WD pathogenesis is modified by maternal in utero factors, including dietary choline. PMID:24220304

Relationship between glutamate, GOT and GPT levels in maternal and fetal blood: a potential mechanism for fetal neuroprotection.

PubMed

Zlotnik, Alexander; Tsesis, Svetlana; Gruenbaum, Benjamin Fredrick; Ohayon, Sharon; Gruenbaum, Shaun Evan; Boyko, Matthew; Sheiner, Eyal; Brotfain, Evgeny; Shapira, Yoram; Teichberg, Vivian Itzhak

2012-09-01

Excess glutamate in the brain is thought to be implicated in the pathophysiology of fetal anoxic brain injury, yet little is known about the mechanisms by which glutamate is regulated in the fetal brain. This study examines whether there are differences between maternal and fetal glutamate concentrations, and whether a correlation between them exists. 10 ml of venous blood was extracted from 87 full-term (>37 weeks gestation) pregnant women in active labor. Immediately after delivery of the neonate, 10 ml of blood from the umbilical artery and vein was extracted. Samples were analyzed for levels of glutamate, glutamate-oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT). Fetal blood glutamate concentrations in both the umbilical artery and vein were found to be significantly higher than maternal blood (p<0.001). Similarly, fetal serum GOT levels in the umbilical artery and vein were found to be significantly higher than maternal GOT levels (p<0.001). The difference in GPT levels between maternal and fetal serum was not statistically significant. There was no difference in fetal glutamate, GOT or GPT between the umbilical artery and vein. There was an association observed between glutamate levels in maternal blood and glutamate levels in both venous (R=0.32, p<0.01) and arterial (R=0.33, p<0.05) fetal blood. This study demonstrated that higher baseline concentrations of blood glutamate are present in fetal blood compared with maternal blood, and this was associated with elevated GOT, but not GPT levels. An association was observed between maternal and fetal blood glutamate levels. Copyright © 2012 Elsevier Ltd. All rights reserved.

Tocolysis for in utero Surgery: Atosiban Performs Distinctly Better than Magnesium Sulfate.

PubMed

Ochsenbein-Kölble, Nicole; Krähenmann, Franziska; Hüsler, Margret; Meuli, Martin; Moehrlen, Ueli; Mazzone, Lucca; Biro, Peter; Zimmermann, Roland

2017-08-17

To compare tocolysis with magnesium sulfate versus atosiban regarding the occurrence of short-term preterm labor and maternal side effects during and after open fetal myelomeningocele (MMC) repair. A prospective nonrandomized cohort study was performed including 30 fetal MMC cases. The first 15 cases (group 1) received magnesium sulfate according to the MOMS protocol. In the following 15 cases (group 2), magnesium sulfate was substituted by atosiban. Chorioamniotic membrane separation (CMS), premature prelabor rupture of the fetal membranes (PPROM), preterm delivery <3 weeks after fetal MMC repair, and maternal complications due to the tocolytic medication were the major endpoints. In both groups, one CMS but no PPROM was diagnosed <3 weeks after fetal MMC repair. One patient of group 2 delivered <3 weeks after fetal MMC repair because of an intraoperative placental abruption at 25 weeks. All women of group 1 showed an electrolyte imbalance during magnesium sulfate administration. One woman of group 1 developed several episodes of a third-degree atrioventricular block within the first 3 days after fetal surgery. Lethargy was found in all women during magnesium sulfate therapy. No maternal side effects were found under atosiban. The use of atosiban resulted in an almost identical short-term uterine outcome without any serious maternal complications as seen when magnesium sulfate was given. Thus, the authors suggest using atosiban instead of magnesium sulfate in the context of open fetal surgery. © 2017 S. Karger AG, Basel.

Evaluating the effects of maternal alcohol consumption on murine fetal brain vasculature using optical coherence tomography.

PubMed

Raghunathan, Raksha; Wu, Chen; Singh, Manmohan; Liu, Chih-Hao; Miranda, Rajesh C; Larin, Kirill V

2018-05-01

Prenatal alcohol exposure (PAE) can result in a range of anomalies including brain and behavioral dysfunctions, collectively termed fetal alcohol spectrum disorder. PAE during the 1st and 2nd trimester is common, and research in animal models has documented significant neural developmental deficits associated with PAE during this period. However, little is known about the immediate effects of PAE on fetal brain vasculature. In this study, we used in utero speckle variance optical coherence tomography, a high spatial- and temporal-resolution imaging modality, to evaluate dynamic changes in microvasculature of the 2nd trimester equivalent murine fetal brain, minutes after binge-like maternal alcohol exposure. Acute binge-like PAE resulted in a rapid (<1 hour) and significant decrease (P < .001) in vessel diameter as compared to the sham group. The data show that a single binge-like maternal alcohol exposure resulted in swift vasoconstriction in fetal brain vessels during the critical period of neurogenesis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mercury concentration in maternal serum, cord blood, and placenta in patients with amalgam dental fillings: effects on fetal biometric measurements.

PubMed

Bedir Findik, Rahime; Celik, Huseyin Tugrul; Ersoy, Ali Ozgur; Tasci, Yasemin; Moraloglu, Ozlem; Karakaya, Jale

2016-11-01

We aimed to determine the extent to which mercury is transmitted from the mother to fetus via the umbilical cord in patients with amalgam dental fillings, and its effect on fetal biometric measurements. Twenty-eight patients as the study group with amalgam fillings, and 32 of them as the control group were included in this prospective case-control study. The mercury levels were measured in the maternal and cord venous sera, and the placental samples. Two groups were compared in terms of these and the fetal/neonatal biometric measurements. In the study group, the maternal and umbilical cord mercury levels were found to be significantly higher than those from the control group (p = 0.006 and p = 0.010, respectively). These high levels did not affect the fetal biometric measurements. The presence of high serum mercury levels in pregnant women with amalgam fillings is important, and warrants further long-term studies in order to investigate the fetal neurological effects as well.

Pregnant Mothers’ Perceptions of how Intimate Partner Violence affects Their Unborn Children

PubMed Central

Alhusen, Jeanne L.; Rahman, Damali

2014-01-01

Objective To explore the perceptions of pregnant women on the experience of intimate partner violence (IPV) as it affects maternal and fetal health. Design Secondary qualitative content analysis. Setting Individual interviews conducted within three urban obstetric and gynecologic clinics Participants Our sample included a subset of eight pregnant women experiencing IPV during the current pregnancy. Participants were selected from a larger parent study that included qualitative data from 13 women. Methods We analyzed in-depth individual interview transcripts in which participants discussed how they perceived IPV to affect their health as well as the health of their unborn children. Constant comparative techniques and conventional content analysis methodology were used in analysis. Results Three themes emerged to illustrate mothers’ perceptions of how IPV influenced maternal and fetal outcomes: protection, fetal awareness, and fetal well-being. Conclusions This analysis provides important insights into concerns that pregnant women experiencing IPV shared about maternal attachment and fetal well-being. Health care providers can use these findings to better assess the physical and psychological concerns of pregnant women experiencing IPV. Further research is needed to better understand how IPV contributes to adverse neonatal outcomes, particularly from a biological perspective. PMID:25651808

Pregnant mothers' perceptions of how intimate partner violence affects their unborn children.

PubMed

Alhusen, Jeanne L; Wilson, Damali

2015-01-01

To explore the perceptions of pregnant women on the experience of intimate partner violence (IPV) as it affects maternal and fetal health. Secondary qualitative content analysis. Individual interviews conducted within three urban obstetric and gynecologic clinics. Our sample included a subset of eight pregnant women experiencing IPV during the current pregnancy. Participants were selected from a larger parent study that included qualitative data from 13 women. We analyzed in-depth individual interview transcripts in which participants discussed how they perceived IPV to affect their health as well as the health of their unborn children. Constant comparative techniques and conventional content analysis methodology were used in analysis. Three themes emerged to illustrate mothers' perceptions of how IPV influenced maternal and fetal outcomes: protection, fetal awareness, and fetal well-being. This analysis provides important insights into concerns that pregnant women experiencing IPV shared about maternal attachment and fetal well-being. Health care providers can use these findings to better assess the physical and psychological concerns of pregnant women experiencing IPV. Further research is needed to better understand how IPV contributes to adverse neonatal outcomes, particularly from a biological perspective. © 2015 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

Placental Transport of Zidovudine in the Rhesus Monkey

PubMed Central

King, Thomas S.; Henderson, George I.; Schenker, Steven; Schenken, Robert S.

1993-01-01

Objective: This study was undertaken to characterize the pharmacokinetics of zidovudine (ZDV) and ZDV-glucuronide (ZDVG) in the material and :fetal circulations of the rhesus monkey. Methods: Cannulas were placed in the maternal external jugular and the fetal internal jugular and carotid artery in 8 pregnant monkeys at .120–130 days gestation. ZDV (3.5 mg/kg) was administered to 5 monkeys and ZDVG (3.5 mg/kg) to 3 monkeys as single intravenous bolus infusions through the maternal catheter. Maternal and fetal blood , samples were collected every 20 min for the first 2 h and then every hour for the next 4 h. Maternal and fetal concentrations of ZDV and ZDVG were determined using high, performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Results: In monkeys who received ZDV, the terminal half-life (T1/2) for ZDV was 37±15 and 33 ± 13 min in the maternal and fetal compartments, respectively. The apparent T1/2 for maternal ZDVG was 124 ± 44 and 142 ± 50 min in the maternal and fetal compartments, respectively. Peak levels of ZDV and ZDVG in the fetal compartment were reached 40 min after injection. The mean fetal/maternal concentration ratios for ZDV and ZDVG ranged from 0.20 ± 0.20 at 20 min to a maximum of 0.74 ± 1.0 at 120 min and from 0.28 ± 0.08 at 20 min to 1.4 ± 1.3 at 180 min, respectively. In monkeys who received ZDVG, the T1/2 for ZDWG in the maternal and fetal compartments was 47 ± 26 and 119 ± 164 min, respectively. ZDVG reached its peak in the fetal compartment at 60 min post-injection. The fetal/maternal rafio ranged from 0.08 ± 0.11 at 20 min to 4.2 ± 4.2 at 180 min post-injection. Conclusions: These data demonstrate that 1) ZDV and ZDVG rapidly cross the placenta to the fetal compartment, 2) ZDV crosses more rapidly than ZDVG, and 3) some metabolism of ZDV to ZDVG occurs in the fetal compartment. PMID:18475334

[Correlation between the inspired fraction of oxygen, maternal partial oxygen pressure, and fetal partial oxygen pressure during cesarean section of normal pregnancies].

PubMed

Castro, Carlos Henrique Viana de; Cruvinel, Marcos Guilherme Cunha; Carneiro, Fabiano Soares; Silva, Yerkes Pereira; Cabral, Antônio Carlos Vieira; Bessa, Roberto Cardoso

2009-01-01

Despite changes in pulmonary function, maternal oxygenation is maintained during obstetric regional blocks. But in those situations, the administration of supplementary oxygen to parturients is a common practice. Good fetal oxygenation is the main justification; however, this has not been proven. The objective of this randomized, prospective study was to test the hypothesis of whether maternal hyperoxia is correlated with an increase in fetal gasometric parameters in elective cesarean sections. Arterial blood gases of 20 parturients undergoing spinal block with different inspired fractions of oxygen were evaluated and correlated with fetal arterial blood gases. An increase in maternal inspired fraction of oxygen did not show any correlation with an increase of fetal partial oxygen pressure. Induction of maternal hyperoxia by the administration of supplementary oxygen did not increase fetal partial oxygen pressure. Fetal gasometric parameters did not change even when maternal parameters changed, induced by hyperoxia, during cesarean section under spinal block.

VIRAL INFECTIONS DURING PREGNANCY

PubMed Central

Silasi, Michelle; Cardenas, Ingrid; Racicot, Karen; Kwon, Ja-Young; Aldo, Paula; Mor, Gil

2015-01-01

Viral infections during pregnancy have long been considered benign conditions with a few notable exceptions, such as herpes virus. The recent Ebola outbreak and other viral epidemics and pandemics show how pregnant women suffer worse outcomes (such as preterm labor and adverse fetal outcomes) than the general population and non-pregnant women. New knowledge about the ways the maternal-fetal interface and placenta interact with the maternal immune system may explain these findings. Once thought to be “immunosuppressed”, the pregnant woman actually undergoes an immunological transformation, where the immune system is necessary to promote and support the pregnancy and growing fetus. When this protection is breached, as in a viral infection, this security is weakened and infection with other microorganisms can then propagate and lead to outcomes, such as preterm labor. In this manuscript, we review the major viral infections relevant to pregnancy, and offer potential mechanisms for the associated adverse pregnancy outcomes. PMID:25582523

[Sequential preparation of microvlllous and basal membranes from human placenta].

PubMed

Long, Ning; Xing, Ai-yun; Yang, Xiao-hua; Zhang, Rong; Wu, Lin

2010-03-01

To improve the technology of isolating paired fractions of the maternal-facing membranes (MVM) and fetal-facing plasma membranes (BM) from a term placenta. The component of buffer was improved based on Illsley method. The time of Mg2+ -aggregated basal membranes was extended. MVM were obtained from the supernatant of low speed centrifugation while BM were further purified on a sucrose step gradient. Yield for MVM and BM prepared by the method were (0.55 +/- 10.10) mg/g and (0.54 +/- 0.02) mg/g wet weight of placenta. They were enriched 16.87-fold and 11.19-fold as determined by the membrane marker enzymes, alkaline phosphatase (MVM) and adenylate cyclase (BM). The modified Illsley method can easily produce both MVM and BM of satisfied quantity from human placenta. It could be applied as a cell molecular model of maternal-fetal exchange interface.

Effects of 2G on Gene Expression of Stress-Related Hormones in Rat Placenta

NASA Technical Reports Server (NTRS)

Benson, S.; Talyansky, Y.; Moyer, E. L.; Lowe, M.; Baer, L. A.; Ronca, A. E.

2017-01-01

Understanding the effects of spaceflight on mammalian reproductive and developmental physiology is important to future human space exploration and permanent settlement beyond Earth orbit. Fetal developmental programming, including modulation of the HPA axis, is thought to originate at the placental-uterine interface, where both transfer of maternal hormones to the fetus and synthesis of endogenous hormones occurs. In healthy rats, fetal corticosterone levels are kept significantly lower by 11BetaHSD-2, which inactivates corticosterone by conversion into cortisone. Placental tissues express endogenous HPA axis-associated hormones including corticotropin-releasing hormone (CRH), pre-opiomelanocortin (POMC), and vasopressin, which may contribute to fetal programming alongside maternal hormones. DNA methylase 3A, 11BetaHSD-2, and 11BetaHSD-1, which are involved in the regulation of maternal cortisol transfer and modulation of the HPA axis, are also expressed in placental tissues along with glucocorticoid receptor and may be affected by differential gravity exposure during pregnancy. Fetuses may respond differently to maternal glucocorticoid exposure during gestation through sexually dimorphic expression of corticosterone-modulating hormones. To elucidate effects of altered gravity on placental gene expression, here we present a ground-based analogue study involving continuous centrifugation to produce 2g hypergravity. We hypothesized that exposure to 2g would induce a decrease in 11BetaHSD-2 expression through the downregulation of DNA methylase 3a and GC receptor, along with concurrent upregulation in endogenous CRH, POMC, and vasopressin expression. Timed pregnant female rats were exposed to 2G from Gestational day 6 to Gestational day 20, and comparisons made with Stationary Control (SC) and Vivarium Control (VC) dams at 1G. Dams were euthanized and placentas harvested on G20. We homogenized placental tissues, extracted and purified RNA, synthesized cDNA, and quantified the expression levels of the genes of interest relative to the GAPDH housekeeping gene, using RT-qPCR and gene-specific cDNA probes. Elucidation of glucocorticoid transfer and synthesis in the placenta can provide new insights into the unique dynamics of mammalian development in microgravity and guide future multi-generational studies in space.

Maternal and fetal Acid-base chemistry: a major determinant of perinatal outcome.

PubMed

Omo-Aghoja, L

2014-01-01

Very small changes in pH may significantly affect the function of various fetal organ systems, such as the central nervous system, and the cardiovascular system with associated fetal distress and poor Apgar score. Review of existing data on maternal-fetal acid-base balance in pregnancy highlight the factors that are associated with derangements of the acid-base status and the impact of the derangements on fetal outcome. Extensive search of electronic databases and manual search of journals for relevant literature on maternal and fetal acid chemistry, clinical studies and case studies were undertaken. There is a substantial reduction in the partial pressure of carbon dioxide (pCO2) in pregnancy. Adequate buffering prevents significant changes in maternal arterial pH. Normal fetal metabolism results in the production of acids which are buffered to maintain extracellular pH within a critical range. Fetal hypoxia can occur when maternal oxygenation is compromised, maternal perfusion of the placenta is reduced, or delivery of oxygenated blood from the placenta to the fetus is impeded. When adequate fetal oxygenation does not occur, metabolisms proceed along with an anaerobic pathway with production of organic acids, such as lactic acid. Accumulation of lactic acid can deplete the buffer system and result in metabolic acidosis with associated low fetal pH, fetal distress and poor Apgar score. There is a significant reduction in pCO2 in pregnancy. This change, however, does not result in a corresponding significant reduction in maternal arterial pH, because of adequate buffering. Very small changes in pH may cause significant derangement in fetal function and outcome.

Antenatal fetal heart rate and "maternal intuition" as predictors of fetal sex.

PubMed

Genuis, S; Genuis, S K; Chang, W C

1996-06-01

To determine if the antenatal fetal heart rate is a reliable predictor of fetal sex, if there is any correlation between "maternal intuition" and fetal gender, and if maternal intuition favors one sex over the other. Two hundred twelve consecutive maternity patients with singleton gestations underwent a total of 2,261 antepartum visits. Fetal heart rate assessment was carried out between 14 and 41 weeks of gestation. At 32 weeks, participants were asked if they had a strong intuitive feeling regarding the fetal gender. Following birth, data on the infant were recorded, and the information was analyzed. There was no significant difference in the baseline fetal heart rate between male and female fetuses at any recorded gestational age. One hundred ten patients (51.9%) in the sample indicated a strong belief about the sex of their fetuses, with the majority (63.6%) predicting a male. The accuracy of maternal intuition, however, was not significantly different from that of random guessing. In the current era of declining family size, an increased focus on absolute reproductive choice and proliferating reproductive technological services, prenatal sex determination and sex selection will continue to provoke increasing attention. Fetal heart rate determination and maternal intuition, however, are not valid predictors of fetal gender.

Using survival analysis to determine association between maternal pelvis height and antenatal fetal head descent in Ugandan mothers.

PubMed

Munabi, Ian Guyton; Luboga, Samuel Abilemech; Mirembe, Florence

2015-01-01

Fetal head descent is used to demonstrate the maternal pelvis capacity to accommodate the fetal head. This is especially important in low resource settings that have high rates of childbirth related maternal deaths and morbidity. This study looked at maternal height and an additional measure, maternal pelvis height, from automotive engineering. The objective of the study was to determine the associations between maternal: height and pelvis height with the rate of fetal head descent in expectant Ugandan mothers. This was a cross sectional study on 1265 singleton mothers attending antenatal clinics at five hospitals in various parts of Uganda. In addition to the routine antenatal examination, each mother had their pelvis height recorded following informed consent. Survival analysis was done using STATA 12. It was found that 27% of mothers had fetal head descent with an incident rate of 0.028 per week after the 25th week of pregnancy. Significant associations were observed between the rate of fetal head descent with: maternal height (Adj Haz ratio 0.93 P < 0.01) and maternal pelvis height (Adj Haz ratio 1.15 P < 0.01). The significant associations observed between maternal: height and pelvis height with rate of fetal head descent, demonstrate a need for further study of maternal pelvis height as an additional decision support tool for screening mothers in low resource settings.

Using survival analysis to determine association between maternal pelvis height and antenatal fetal head descent in Ugandan mothers

PubMed Central

Munabi, Ian Guyton; Luboga, Samuel Abilemech; Mirembe, Florence

2015-01-01

Introduction Fetal head descent is used to demonstrate the maternal pelvis capacity to accommodate the fetal head. This is especially important in low resource settings that have high rates of childbirth related maternal deaths and morbidity. This study looked at maternal height and an additional measure, maternal pelvis height, from automotive engineering. The objective of the study was to determine the associations between maternal: height and pelvis height with the rate of fetal head descent in expectant Ugandan mothers. Methods This was a cross sectional study on 1265 singleton mothers attending antenatal clinics at five hospitals in various parts of Uganda. In addition to the routine antenatal examination, each mother had their pelvis height recorded following informed consent. Survival analysis was done using STATA 12. Results It was found that 27% of mothers had fetal head descent with an incident rate of 0.028 per week after the 25th week of pregnancy. Significant associations were observed between the rate of fetal head descent with: maternal height (Adj Haz ratio 0.93 P < 0.01) and maternal pelvis height (Adj Haz ratio 1.15 P < 0.01). Conclusion The significant associations observed between maternal: height and pelvis height with rate of fetal head descent, demonstrate a need for further study of maternal pelvis height as an additional decision support tool for screening mothers in low resource settings. PMID:26918071

Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1.

PubMed

Qiao, Liping; Wattez, Jean-Sebastien; Lee, Samuel; Guo, Zhuyu; Schaack, Jerome; Hay, William W; Zita, Matteo Moretto; Parast, Mana; Shao, Jianhua

2016-11-01

The main objective of this study was to investigate whether maternal adiponectin regulates fetal growth through the endocrine system in the fetal compartment. Adiponectin knockout (Adipoq (-/-) ) mice and in vivo adenovirus-mediated reconstitution were used to study the regulatory effect of maternal adiponectin on fetal growth. Primary human trophoblast cells were treated with adiponectin and a specific peroxisome proliferator-activated receptor α (PPARα) agonist or antagonist to study the underlying mechanism through which adiponectin regulates fetal growth. The body weight of fetuses from Adipoq (-/-) dams was significantly greater than that of wild-type dams at both embryonic day (E)14.5 and E18.5. Adenoviral vector-mediated maternal adiponectin reconstitution attenuated the increased fetal body weight induced by maternal adiponectin deficiency. Significantly increased blood glucose, triacylglycerol and NEFA levels were observed in Adipoq (-/-) dams, suggesting that nutrient supply contributes to maternal adiponectin-regulated fetal growth. Although fetal blood IGF-1 concentrations were comparable in fetuses from Adipoq (-/-) and wild-type dams, remarkably low levels of IGF-binding protein 1 (IGFBP-1) were observed in the serum of fetuses from Adipoq (-/-) dams. IGFBP-1 was identified in the trophoblast cells of human and mouse placentas. Maternal fasting robustly increased IGFBP-1 levels in mouse placentas, while reducing fetal weight. Significantly low IGFBP-1 levels were found in placentas of Adipoq (-/-) dams. Adiponectin treatment increased IGFBP-1 levels in primary cultured human trophoblast cells, while the PPARα antagonist, MK886, abolished this stimulatory effect. These results indicate that, in addition to nutrient supply, maternal adiponectin inhibits fetal growth by increasing IGFBP-1 expression in trophoblast cells.

Neurotrophic Factors and Maternal Nutrition During Pregnancy.

PubMed

Dhobale, M

2017-01-01

Maternal nutrition is one of the major determinants of pregnancy outcome. It has been suggested that reduced intakes or lack of specific nutrients during pregnancy influences the length of gestation, proper placental and fetal growth during pregnancy. Maternal nutrition, particularly micronutrients such as folate and vitamin B 12 , and long-chain polyunsaturated fatty acids (LCPUFA) are the major determinants of the one carbon cycle and are suggested to be at the heart of intrauterine programming of diseases in adult life. LCPUFA play a key role in the normal feto-placental development, as well as in the development and functional maturation of the brain and central nervous system and also regulate the levels of neurotrophic factors. These neurotrophic factors are known to regulate the development of the placenta at the materno-fetal interface and act in a paracrine and endocrine manner. Neurotrophic factors like brain-derived neurotrophic factor and nerve growth factor are proteins involved in angiogenesis and potentiate the placental development. This chapter mainly focuses on micronutrients since they play a main physiological role during pregnancy. © 2017 Elsevier Inc. All rights reserved.

Maternal-Fetal rejection reactions are unconstrained in preeclamptic women.

PubMed

Nguyen, Tina A; Kahn, Daniel A; Loewendorf, Andrea I

2017-01-01

The risk factors for preeclampsia, extremes of maternal age, changing paternity, concomitant maternal autoimmunity, and/or birth intervals greater than 5 years, suggest an underlying immunopathology. We used peripheral blood and lymphocytes from the UteroPlacental Interface (UPI) of 3rd trimester healthy pregnant women in multicolor flow cytometry-and in vitro suppression assays. The major end-point was the characterization of activation markers, and potential effector functions of different CD4-and CD8 subsets as well as T regulatory cells (Treg). We observed a significant shift of peripheral CD4 -and CD8- T cells from naïve to memory phenotype in preeclamptic women compared to healthy pregnant women consistent with long-standing immune activation. While the proportions of the highly suppressive Cytokine and Activated Treg were increased in preeclampsia, Treg tolerance toward fetal antigens was dysfunctional. Thus, our observations indicate a long-standing inflammatory derangement driving immune activation in preeclampsia; in how far the Treg dysfunction is caused by/causes this immune activation in preeclampsia will be the object of future studies.

Maternal and neonatal copeptin levels at cesarean section and vaginal delivery.

PubMed

Foda, Ashraf A; Abdel Aal, Ibrahim A

2012-12-01

The objective of the study was to measure the copeptin levels in maternal serum and umbilical cord serum at cesarean section and vaginal delivery in normotensive pregnancy and pre-eclamptic women. This was a prospective study at Mansoura University Hospital, Egypt. Ninety cases were included. They were divided into six groups: (1) normal pregnancy near term, as a control group, (2) primiparas who had vaginal delivery, (3) primiparas who had vaginal delivery and mild preeclampsia, (4) elective repeat cesarean section, (5) intrapartum cesarean section for indications other than fetal distress, and (6) intrapartum cesarean section for fetal distress. Serum copeptin concentrations were quantified with an enzyme-linked immunosorbent assay (ELISA). Mean, standard deviation, and paired t-test were used to test for significant change in quantitative data. The vaginal delivery groups had higher levels of maternal serum copeptin than the elective cesarean section group (P<0.01). Higher maternal serum copeptin levels were found in cases with pre-eclampsia as compared with the normotensive cases. The maternal copeptin levels during intrapartum cesarean section were higher than that during elective repeat cesarean section. There was a significant correlation between maternal copeptin levels and the duration of the first stage. In the presence of fetal distress, umbilical cord serum copeptin levels were significantly higher than other groups. Vaginal delivery can be very painful and stressful, and is accompanied by a marked increase of maternal serum copeptin. Increased maternal levels of serum copeptin were found in cases with pre-eclampsia as compared with the normotensive cases, and it may be helpful in assessing the disease. Intrauterine fetal distress is a strong stimulus to the release of copeptin into the fetal circulation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Maternal distress associates with placental genes regulating fetal glucocorticoid exposure and IGF2: Role of obesity and sex.

PubMed

Mina, Theresia H; Räikkönen, Katri; Riley, Simon C; Norman, Jane E; Reynolds, Rebecca M

2015-09-01

Maternal emotional distress symptoms, including life satisfaction, anxiety and depressed mood, are worse in Severely Obese (SO) than lean pregnancy and may alter placental genes regulating fetal glucocorticoid exposure and placental growth. We hypothesised that the associations between increased maternal distress symptoms and changes in placental gene expression including IGF2 and genes regulating fetal glucocorticoid exposure are more pronounced in SO pregnancy. We also considered whether there were sex-specific effects. Placental mRNA levels of 11β-HSDs, NR3C1-α, NR3C2, ABC transporters, mTOR and the IGF2 family were measured in term placental samples from 43 lean (BMI≤25kg/m(2)) and 50 SO (BMI≥40kg/m(2)) women, in whom distress symptoms were prospectively evaluated during pregnancy. The mRNA levels of genes with a similar role in regulating fetal glucocorticoid exposure were strongly inter-correlated. Increased maternal distress symptoms associated with increased NR3C2 and IGF2 isoform 1(IGF2-1) in both lean and SO group (p≤0.05). Increased distress was associated with higher ABCB1 and ABCG2 mRNA levels in SO but lower ABCB1 and higher 11β-HSD1 mRNA levels in lean (p≤0.05) suggesting a protective adaptive response in SO placentas. Increased maternal distress associated with reduced mRNA levels of ABCB1, ABCG2, 11β-HSD2, NR3C1-α and IGF2-1 in placentas of female but not male offspring. The observed sex differences in placental responses suggest greater vulnerability of female fetuses to maternal distress with potentially greater fetal glucocorticoid exposure and excess IGF2. Further studies are needed to replicate these findings and to test whether this translates to potentially greater negative outcomes of maternal distress in female offspring in early childhood. Copyright © 2015 Elsevier Ltd. All rights reserved.

Factors affecting levels of circulating cell-free fetal DNA in maternal plasma and their implications for noninvasive prenatal testing.

PubMed

Kinnings, Sarah L; Geis, Jennifer A; Almasri, Eyad; Wang, Huiquan; Guan, Xiaojun; McCullough, Ron M; Bombard, Allan T; Saldivar, Juan-Sebastian; Oeth, Paul; Deciu, Cosmin

2015-08-01

Sufficient fetal DNA in a maternal plasma sample is required for accurate aneuploidy detection via noninvasive prenatal testing, thus highlighting a need to understand the factors affecting fetal fraction. The MaterniT21™ PLUS test uses massively parallel sequencing to analyze cell-free fetal DNA in maternal plasma and detect chromosomal abnormalities. We assess the impact of a variety of factors, both maternal and fetal, on the fetal fraction across a large number of samples processed by Sequenom Laboratories. The rate of increase in fetal fraction with increasing gestational age varies across the duration of the testing period and is also influenced by fetal aneuploidy status. Maternal weight trends inversely with fetal fraction, and we find no added benefit from analyzing body mass index or blood volume instead of weight. Strong correlations exist between fetal fractions from aliquots taken from the same patient at the same blood draw and also at different blood draws. While a number of factors trend with fetal fraction across the cohort as a whole, they are not the sole determinants of fetal fraction. In this study, the variability for any one patient does not appear large enough to justify postponing testing to a later gestational age. © 2015 John Wiley & Sons, Ltd.

Gestational and Fetal Outcomes in B19 Maternal Infection: a Problem of Diagnosis▿

PubMed Central

Bonvicini, Francesca; Puccetti, Chiara; Salfi, Nunzio C. M.; Guerra, Brunella; Gallinella, Giorgio; Rizzo, Nicola; Zerbini, Marialuisa

2011-01-01

Parvovirus B19 infection during pregnancy is a potential hazard to the fetus because of the virus' ability to infect fetal erythroid precursor cells and fetal tissues. Fetal complications range from transitory fetal anemia and nonimmune fetal hydrops to miscarriage and intrauterine fetal death. In the present study, 72 pregnancies complicated by parvovirus B19 infection were followed up: fetal and neonatal specimens were investigated by serological and/or virological assays to detect fetal/congenital infection, and fetuses and neonates were clinically evaluated to monitor pregnancy outcomes following maternal infection. Analysis of serological and virological maternal B19 markers of infection demonstrated that neither B19 IgM nor B19 DNA detected all maternal infections. IgM serology correctly diagnosed 94.1% of the B19 infections, while DNA testing correctly diagnosed 96.3%. The maximum sensitivity was achieved with the combined detection of both parameters. B19 vertical transmission was observed in 39% of the pregnancies, with an overall 10.2% rate of fetal deaths. The highest rates of congenital infections and B19-related fatal outcomes were observed when maternal infections occurred by the gestational week 20. B19 fetal hydrops occurred in 11.9% of the fetuses, and 28.6% resolved the hydrops with a normal neurodevelopment outcome at 1- to 5-year follow-up. In conclusion, maternal screening based on the concurrent analysis of B19 IgM and DNA should be encouraged to reliably diagnose maternal B19 infection and correctly manage pregnancies at risk. PMID:21849687

Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth.

PubMed

Aye, Irving L M H; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

2015-10-13

Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity.

Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

PubMed Central

Aye, Irving L. M. H.; Rosario, Fredrick J.; Powell, Theresa L.; Jansson, Thomas

2015-01-01

Mothers with obesity or gestational diabetes mellitus have low circulating levels of adiponectin (ADN) and frequently deliver large babies with increased fat mass, who are susceptible to perinatal complications and to development of metabolic syndrome later in life. It is currently unknown if the inverse correlation between maternal ADN and fetal growth reflects a cause-and-effect relationship. We tested the hypothesis that ADN supplementation in obese pregnant dams improves maternal insulin sensitivity, restores normal placental insulin/mechanistic target of rapamycin complex 1 (mTORC1) signaling and nutrient transport, and prevents fetal overgrowth. Compared with dams on a control diet, female C57BL/6J mice fed an obesogenic diet before mating and throughout gestation had increased fasting serum leptin, insulin, and C-peptide, and reduced high-molecular-weight ADN at embryonic day (E) 18.5. Placental insulin and mTORC1 signaling was activated, peroxisome proliferator-activated receptor-α (PPARα) phosphorylation was reduced, placental transport of glucose and amino acids in vivo was increased, and fetal weights were 29% higher in obese dams. Maternal ADN infusion in obese dams from E14.5 to E18.5 normalized maternal insulin sensitivity, placental insulin/mTORC1 and PPARα signaling, nutrient transport, and fetal growth without affecting maternal fat mass. Using a mouse model with striking similarities to obese pregnant women, we demonstrate that ADN functions as an endocrine link between maternal adipose tissue and fetal growth by regulating placental function. Importantly, maternal ADN supplementation reversed the adverse effects of maternal obesity on placental function and fetal growth. Improving maternal ADN levels may serve as an effective intervention strategy to prevent fetal overgrowth caused by maternal obesity. PMID:26417088

Repeated Gestational Exposure of Mice to Chlorpyrifos Oxon Is Associated with Paraoxonase 1 (PON1) Modulated Effects in Maternal and Fetal Tissues

PubMed Central

Co, Aila L.; Hay, Ariel M.; MacDonald, James W.; Bammler, Theo K.; Farin, Federico M.; Costa, Lucio G.; Furlong, Clement E.

2014-01-01

Chlorpyrifos oxon (CPO), the toxic metabolite of the organophosphorus (OP) insecticide chlorpyrifos, causes developmental neurotoxicity in humans and rodents. CPO is hydrolyzed by paraoxonase-1 (PON1), with protection determined by PON1 levels and the human Q192R polymorphism. To examine how the Q192R polymorphism influences fetal toxicity associated with gestational CPO exposure, we measured enzyme inhibition and fetal-brain gene expression in wild-type (PON1+/+), PON1-knockout (PON1−/−), and tgHuPON1R192 and tgHuPON1Q192 transgenic mice. Pregnant mice exposed dermally to 0, 0.50, 0.75, or 0.85 mg/kg/d CPO from gestational day (GD) 6 through 17 were sacrificed on GD18. Biomarkers of CPO exposure inhibited in maternal tissues included brain acetylcholinesterase (AChE), red blood cell acylpeptide hydrolase (APH), and plasma butyrylcholinesterase (BChE) and carboxylesterase (CES). Fetal plasma BChE was inhibited in PON1−/− and tgHuPON1Q192, but not PON1+/+ or tgHuPON1R192 mice. Fetal brain AChE and plasma CES were inhibited in PON1−/− mice, but not in other genotypes. Weighted gene co-expression network analysis identified five gene modules based on clustering of the correlations among their fetal-brain expression values, allowing for correlation of module membership with the phenotypic data on enzyme inhibition. One module that correlated highly with maternal brain AChE activity had a large representation of homeobox genes. Gene set enrichment analysis revealed multiple gene sets affected by gestational CPO exposure in tgHuPON1Q192 but not tgHuPON1R192 mice, including gene sets involved in protein export, lipid metabolism, and neurotransmission. These data indicate that maternal PON1 status modulates the effects of repeated gestational CPO exposure on fetal-brain gene expression and on inhibition of both maternal and fetal biomarker enzymes. PMID:25070982

Maternal and Fetal Acid-Base Chemistry: A Major Determinant of Perinatal Outcome

PubMed Central

Omo-Aghoja, L

2014-01-01

Very small changes in pH may significantly affect the function of various fetal organ systems, such as the central nervous system, and the cardiovascular system with associated fetal distress and poor Apgar score. Review of existing data on maternal-fetal acid-base balance in pregnancy highlight the factors that are associated with derangements of the acid-base status and the impact of the derangements on fetal outcome. Extensive search of electronic databases and manual search of journals for relevant literature on maternal and fetal acid chemistry, clinical studies and case studies were undertaken. There is a substantial reduction in the partial pressure of carbon dioxide (pCO2) in pregnancy. Adequate buffering prevents significant changes in maternal arterial pH. Normal fetal metabolism results in the production of acids which are buffered to maintain extracellular pH within a critical range. Fetal hypoxia can occur when maternal oxygenation is compromised, maternal perfusion of the placenta is reduced, or delivery of oxygenated blood from the placenta to the fetus is impeded. When adequate fetal oxygenation does not occur, metabolisms proceed along with an anaerobic pathway with production of organic acids, such as lactic acid. Accumulation of lactic acid can deplete the buffer system and result in metabolic acidosis with associated low fetal pH, fetal distress and poor Apgar score. There is a significant reduction in pCO2 in pregnancy. This change, however, does not result in a corresponding significant reduction in maternal arterial pH, because of adequate buffering. Very small changes in pH may cause significant derangement in fetal function and outcome. PMID:24669324

Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kou, Hao; Liu, Yansong; Liang, Gai

Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180more » mg/kg · d) from gestational days (GD) 11 to 20, or 180 mg/kg · d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose–effect study and on GD11, 14 and 17 in the time–course study were analyzed by {sup 1}H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. - Highlights: • Prenatal caffeine exposure elevated maternal blood glucocorticoid levels. • Prenatal caffeine exposure altered maternal blood metabonomes. • Maternal metabonome alterations were associated with glucocorticoid elevation. • Maternal metabonomes were altered at early stage after caffeine exposure. • Maternal glucocorticoid and associated metabolites may be involved in fetal programming.« less

Fetal shielding combined with state of the art CT dose reduction strategies during maternal chest CT.

PubMed

Chatterson, Leslie C; Leswick, David A; Fladeland, Derek A; Hunt, Megan M; Webster, Stephen; Lim, Hyun

2014-07-01

Custom bismuth-antimony shields were previously shown to reduce fetal dose by 53% on an 8DR (detector row) CT scanner without dynamic adaptive section collimation (DASC), automatic tube current modulation (ATCM) or adaptive statistical iterative reconstruction (ASiR). The purpose of this study is to compare the effective maternal and average fetal organ dose reduction both with and without bismuth-antimony shields on a 64DR CT scanner using DASC, ATCM and ASiR during maternal CTPA. A phantom with gravid prosthesis and a bismuth-antimony shield were used. Thermoluminescent dosimeters (TLDs) measured fetal radiation dose. The average fetal organ dose and effective maternal dose were determined using 100 kVp, scanning from the lung apices to the diaphragm utilizing DASC, ATCM and ASiR on a 64DR CT scanner with and without shielding in the first and third trimester. Isolated assessment of DASC was done via comparing a new 8DR scan without DASC to a similar scan on the 64DR with DASC. Average third trimester unshielded fetal dose was reduced from 0.22 mGy ± 0.02 on the 8DR to 0.13 mGy ± 0.03 with the conservative 64DR protocol that included 30% ASiR, DASC and ATCM (42% reduction, P<0.01). Use of a shield further reduced average third trimester fetal dose to 0.04 mGy ± 0.01 (69% reduction, P<0.01). The average fetal organ dose reduction attributable to DASC alone was modest (6% reduction from 0.17 mGy ± 0.02 to 0.16 mGy ± 0.02, P=0.014). First trimester fetal organ dose on the 8DR protocol was 0.07 mGy ± 0.03. This was reduced to 0.05 mGy ± 0.03 on the 64DR protocol without shielding (30% reduction, P=0.009). Shields further reduced this dose to below accurately detectable levels. Effective maternal dose was reduced from 4.0 mSv on the 8DR to 2.5 mSv on the 64DR scanner using the conservative protocol (38% dose reduction). ASiR, ATCM and DASC combined significantly reduce effective maternal and fetal organ dose during CTPA. Shields continue to be an effective means of fetal dose reduction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Enzyme markers of maternal malnutrition in fetal rat brain.

PubMed

Shambaugh, G E; Mankad, B; Derecho, M L; Koehler, R R

1987-01-01

The impact of maternal starvation in late gestation on development of some enzymatic mechanisms concerned with neurotransmission and polyamine synthesis was studied in fetal rat brain. Between 17 and 20 d, acetylcholinesterase and choline acetyltransferase activity increased in fetal brains of fed dams, whereas maternal starvation from day 17 to day 20 resulted in heightened acetylcholinesterase but not choline acetyltransferase activity. Ornithine decarboxylase activity on a per-gram wet-weight basis fell between 17 and 20 d in fetal brain from fed dams. Increasing the duration of maternal starvation resulted in a progressive increase in fetal brain ornithine decarboxylase. Arginine and putrescine levels in the brain were lower in fetuses of starved mothers while spermidine and spermine concentrations were unchanged. Since the Km of ornithine decarboxylase for ornithine was found to vary directly with levels of putrescine in fetal brain, lower concentrations of putrescine and greater ornithine decarboxylase activity in fetal brains from starved mothers suggested that levels of this enzyme may be controlled in part by putrescine. Changes in the maternal nutritional state had no effect on the activity of glutamate decarboxylase in fetal brain, and tissue levels of the product, gamma-aminobutyric acid, were unchanged. Thus changes in ornithine decarboxylase and acetylcholinesterase activity in fetal brain may uniquely reflect biochemical alterations consequent to maternal starvation.

Maternal undernutrition in late gestation increases IGF2 signalling molecules and collagen deposition in the right ventricle of the fetal sheep heart.

PubMed

Darby, Jack R T; McMillen, I Caroline; Morrison, Janna L

2018-06-01

This study investigates the impact of decreased fetal plasma glucose concentrations on the developing heart in late gestation, by subjecting pregnant ewes to a 50% global nutrient restriction. Late gestation undernutrition (LGUN) decreased fetal plasma glucose concentrations whilst maintaining a normoxemic blood gas status. LGUN increased the mRNA expression of IGF2 and IGF2R. Fetal plasma glucose concentrations, but not fetal blood pressure, were significantly correlated with IGF2 expression and the activation of CAMKII in the fetal right ventricle. LGUN increased interstitial collagen deposition and altered the protein abundance of phospho-PLB and phospho-troponin I, regulators of cardiac contractility and relaxation. This study shows that a decrease in fetal plasma glucose concentrations may play a role in the development of detrimental changes in the right ventricle in early life, highlighting CAMKII as a potential target for the development of intervention strategies. Exposure of the fetus to a range of environmental stressors, including maternal undernutrition, is associated with an increased risk of death from cardiovascular disease in adult life. This study aimed to determine the effect of maternal nutrient restriction in late gestation on the molecular mechanisms that regulate cardiac growth and development of the fetal heart. Maternal undernutrition resulted in a decrease in fetal glucose concentrations across late gestation, whilst fetal arterial PO2 remained unchanged between the control and late gestation undernutrition (LGUN) groups. There was evidence of an up-regulation of IGF2/IGF2R signalling through the CAMKII pathway in the fetal right ventricle in the LGUN group, suggesting an increase in hypertrophic signalling. LGUN also resulted in an increased mRNA expression of COL1A, TIMP1 and TIMP3 in the right ventricle of the fetal heart. In addition, there was an inverse relationship between fetal glucose concentrations and COL1A expression. The presence of interstitial fibrosis in the heart of the LGUN group was confirmed through the quantification of picrosirius red-stained sections of the right ventricle. We have therefore shown that maternal undernutrition in late gestation may drive the onset of myocardial remodelling in the fetal right ventricle and thus has negative implications for right ventricle function and cardiac health in later life. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Clinical outcomes and predictors of fetal and maternal consequences of pregnancy in lupus nephritis patients.

PubMed

Lv, Jiaxuan; Wang, Wei; Li, Yuehong

2015-08-01

To define the outcomes and risk predictors of fetal and maternal consequences of pregnancy in lupus nephritis (LN) patients. Maternal and fetal outcomes of pregnancy in 52 systemic lupus erythematosus (SLE) patients were observed. Patients were allocated into two groups according to the presence or absence of LN. LN patients were subject to a higher risk of fetal complications, including fetal loss (7/24, 29.2 %, P = 0.001), lower birth weight (2548.2 ± 540.8 vs. 2949.1 ± 592.6 g, P = 0.028) and a higher frequency of small for gestational age births (33.3 vs. 10.7 %, P = 0.002). Higher rates of lupus flares (83.3 vs. 21.4 %, P = 0.001) and increased LAI-P scores (0.65 ± 0.36 vs. 0.21 ± 0.27, P = 0.001) during pregnancy were observed in LN patients. Multivariate analysis showed that increased SLE activity (P = 0.02, OR 4.2, 95 % CI 1.2-14.5), renal damage (P = 0.001, OR 8.4, 95 % CI 2.2-31.8), hypocomplementemia (P = 0.05, OR 3.23, 95 % CI 1.0-10.7), hypoalbuminemia (P = 0.011, OR 5.62, 95 % CI 1.4-23.0) and hypertension (P = 0.021, OR 6.0, 95 % CI 1.5-24.2) during pregnancy were predictors of adverse fetal outcomes. Pregnancy in LN patients should be monitored before and during pregnancy because of poor fetal and maternal outcomes. Increased LAI-P scores, renal damage, hypocomplementemia, hypoalbuminemia and hypertension are predictors of adverse fetal outcomes for SLE patients.

[Time perception, maternal tasks, and maternal role behavior among pregnant Japanese women].

PubMed

Yamamoto, A

1996-01-01

The relationship of time perception, maternal tasks, and maternal role behavior was examined in 140 pregnant Japanese women with a short-term longitudinal design. A model developed by Rubin provided the conceptual framework for this research. The Time Perception Scale. Time Production Method, and the Prefatory Maternal Response measured the study variables. Study results revealed significant differences in duration of time, time production, maternal-fetal attachment, and maternal role behavior before and after quickening(fetal movement)occurred. Medium to strong positive relationships among time orientation, maternal-fetal attachment, gratification, and maternal role behavior were found before and after movement. After quickening, a weak relationship between time orientation and duration was found. After controlling maternal-fetal attachment and gratification in pregnancy and maternal role, orientation in time perception accounted for significant amounts of variance in maternal role behavior before and after fetal movement. Results show that the process of becoming a mother, which started before quickening, increased in magnitude after fetal movement. The function of fetal movement is important in developing motherhood. In the process of becoming a mother, cognitive, emotional, and behavioral aspects in becoming a mother are inseparable from each other. Future orientation of time perception contributes to development of maternal role behavior. Having a future orientation during pregnancy may indicate hope or positive expectation. Based on these findings, several recommendations were proposed: (a)to study further the general process of becoming a mother and the role of time perception in developing motherhood, (b)to disseminate information to the general public about the process in development of motherhood, (c)to construct theory to explain the process of becoming a mother, and(d)to conduct future research to clarify the construct of time perception and attachment.

Quantifying the Interactions between Maternal and Fetal Heart Rates by Transfer Entropy.

PubMed

Marzbanrad, Faezeh; Kimura, Yoshitaka; Palaniswami, Marimuthu; Khandoker, Ahsan H

2015-01-01

Evidence of the short term relationship between maternal and fetal heart rates has been found in previous studies. However there is still limited knowledge about underlying mechanisms and patterns of the coupling throughout gestation. In this study, Transfer Entropy (TE) was used to quantify directed interactions between maternal and fetal heart rates at various time delays and gestational ages. Experimental results using maternal and fetal electrocardiograms showed significant coupling for 63 out of 65 fetuses, by statistically validating against surrogate pairs. Analysis of TE showed a decrease in transfer of information from fetus to the mother with gestational age, alongside the maturation of the fetus. On the other hand, maternal to fetal TE was significantly greater in mid (26-31 weeks) and late (32-41 weeks) gestation compared to early (16-25 weeks) gestation (Mann Whitney Wilcoxon (MWW) p<0.05). TE further increased from mid to late, for the fetuses with RMSSD of fetal heart rate being larger than 4 msec in the late gestation. This difference was not observed for the fetuses with smaller RMSSD, which could be associated with the quiet sleep state. Delay in the information transfer from mother to fetus significantly decreased (p = 0.03) from mid to late gestation, implying a decrease in fetal response time. These changes occur concomitant with the maturation of the fetal sensory and autonomic nervous systems with advancing gestational age. The effect of maternal respiratory rate derived from maternal ECG was also investigated and no significant relationship was found between breathing rate and TE at any lag. In conclusion, the application of TE with delays revealed detailed information on the fetal-maternal heart rate coupling strength and latency throughout gestation, which could provide novel clinical markers of fetal development and well-being.

Quantifying the Interactions between Maternal and Fetal Heart Rates by Transfer Entropy

PubMed Central

Marzbanrad, Faezeh; Kimura, Yoshitaka; Palaniswami, Marimuthu; Khandoker, Ahsan H.

2015-01-01

Evidence of the short term relationship between maternal and fetal heart rates has been found in previous studies. However there is still limited knowledge about underlying mechanisms and patterns of the coupling throughout gestation. In this study, Transfer Entropy (TE) was used to quantify directed interactions between maternal and fetal heart rates at various time delays and gestational ages. Experimental results using maternal and fetal electrocardiograms showed significant coupling for 63 out of 65 fetuses, by statistically validating against surrogate pairs. Analysis of TE showed a decrease in transfer of information from fetus to the mother with gestational age, alongside the maturation of the fetus. On the other hand, maternal to fetal TE was significantly greater in mid (26–31 weeks) and late (32–41 weeks) gestation compared to early (16–25 weeks) gestation (Mann Whitney Wilcoxon (MWW) p<0.05). TE further increased from mid to late, for the fetuses with RMSSD of fetal heart rate being larger than 4 msec in the late gestation. This difference was not observed for the fetuses with smaller RMSSD, which could be associated with the quiet sleep state. Delay in the information transfer from mother to fetus significantly decreased (p = 0.03) from mid to late gestation, implying a decrease in fetal response time. These changes occur concomitant with the maturation of the fetal sensory and autonomic nervous systems with advancing gestational age. The effect of maternal respiratory rate derived from maternal ECG was also investigated and no significant relationship was found between breathing rate and TE at any lag. In conclusion, the application of TE with delays revealed detailed information on the fetal-maternal heart rate coupling strength and latency throughout gestation, which could provide novel clinical markers of fetal development and well-being. PMID:26701122

Impact of chronic maternal stress during early gestation on maternal-fetal stress transfer and fetal stress sensitivity in sheep.

PubMed

Dreiling, Michelle; Schiffner, Rene; Bischoff, Sabine; Rupprecht, Sven; Kroegel, Nasim; Schubert, Harald; Witte, Otto W; Schwab, Matthias; Rakers, Florian

2018-01-01

Acute stress-induced reduction of uterine blood flow (UBF) is an indirect mechanism of maternal-fetal stress transfer during late gestation. Effects of chronic psychosocial maternal stress (CMS) during early gestation, as may be experienced by many working women, on this stress signaling mechanism are unclear. We hypothesized that CMS in sheep during early gestation augments later acute stress-induced decreases of UBF, and aggravates the fetal hormonal, cardiovascular, and metabolic stress responses during later development. Six pregnant ewes underwent repeated isolation stress (CMS) between 30 and 100 days of gestation (dGA, term: 150 dGA) and seven pregnant ewes served as controls. At 110 dGA, ewes were chronically instrumented and underwent acute isolation stress. The acute stress decreased UBF by 19% in both the CMS and control groups (p < .05), but this was prolonged in CMS versus control ewes (74 vs. 30 min, p < .05). CMS increased fetal circulating baseline and stress-induced cortisol and norepinephrine concentrations indicating a hyperactive hypothalamus-pituitary-adrenal (HPA)-axis and sympathetic-adrenal-medullary system. Increased fetal norepinephrine is endogenous as maternal catecholamines do not cross the placenta. Cortisol in the control but not in the CMS fetuses was correlated with maternal cortisol blood concentrations; these findings indicate: (1) no increased maternal-fetal cortisol transfer with CMS, (2) cortisol production in CMS fetuses when the HPA-axis is normally inactive, due to early maturation of the fetal HPA-axis. CMS fetuses were better oxygenated, without shift towards acidosis compared to the controls, potentially reflecting adaptation to repeated stress. Hence, CMS enhances maternal-fetal stress transfer by prolonged reduction in UBF and increased fetal HPA responsiveness.

Maternal Engineered Nanomaterial Exposure and Fetal Microvascular Function: Does the Barker Hypothesis Apply?

PubMed Central

STAPLETON, Phoebe A.; MINARCHICK, Ms. Valerie C.; YI, Jinghai; ENGELS, Mr. Kevin; McBRIDE, Mr. Carroll R.; NURKIEWICZ, Timothy R.

2013-01-01

Objective The continued development and use of engineered nanomaterials (ENM) has given rise to concerns over the potential for human health effects. While the understanding of cardiovascular ENM toxicity is improving, one of the most complex and acutely demanding “special” circulations is the enhanced maternal system to support fetal development. The “Barker Hypothesis” proposes that fetal development within a hostile gestational environment may predispose/program future sensitivity. Therefore, the objective of this study was two-fold: 1) to determine if maternal ENM exposure alters uterine and/or fetal microvascular function and 2) test the Barker Hypothesis at the microvascular level. Study Design Pregnant (gestation day 10) Sprague-Dawley rats were exposed to nano-titanium dioxide aerosols (11.3±0.039 (mg/m3)*hour, 5 hours/day, 8.2±0.85 days) to evaluate the maternal and fetal microvascular consequences of maternal exposure. Microvascular tissue isolation (gestation day 20) and arteriolar reactivity studies (<150μm passive diameter) of the uterine premyometrial and fetal tail arteries were conducted. Results ENM exposures led to significant maternal and fetal microvascular dysfunction which presented as robustly compromised endothelium-dependent and -independent reactivity to pharmacologic and mechanical stimuli. Isolated maternal uterine arteriolar reactivity was consistent with a metabolically impaired profile and hostile gestational environment, impacting fetal weight. The fetal microvessels isolated from exposed dams demonstrate significant impairments to signals of vasodilation specific to mechanistic signaling and shear stress. Conclusion To our knowledge, this is the first report providing evidence that maternal ENM inhalation is capable of influencing fetal health, thereby supporting that the Barker Hypothesis is applicable at the microvascular level. PMID:23643573

Knockout maternal adiponectin increases fetal growth in mice: potential role for trophoblast IGFBP-1

PubMed Central

Qiao, Liping; Wattez, Jean-Sebastien; Lee, Samuel; Guo, Zhuyu; Schaack, Jerome; Hay, William W.; Moretto Zita, Matteo; Parast, Mana; Shao, Jianhua

2016-01-01

Aims/hypothesis The main objective of this study was to investigate whether maternal adiponectin regulates fetal growth through the endocrine system in the fetal compartment. Methods Adiponectin knockout (Adipoq−/−) mice and in vivo adenovirus-mediated reconstitution were used to study the regulatory effect of maternal adiponectin on fetal growth. Primary human trophoblast cells were treated with adiponectin and a specific peroxisome proliferator-activated receptor α (PPARα) agonist or antagonist to study the underlying mechanism through which adiponectin regulates fetal growth. Results The body weight of fetuses from Adipoq−/− dams was significantly greater than that of wild-type dams at both embryonic day (E)14.5 and E18.5. Adenoviral vector-mediated maternal adiponectin reconstitution attenuated the increased fetal body weight induced by maternal adiponectin deficiency. Significantly increased blood glucose, triacylglycerol and NEFA levels were observed in Adipoq−/− dams, suggesting that nutrient supply contributes to maternal adiponectin-regulated fetal growth. Although fetal blood IGF-1 concentrations were comparable in fetuses from Adipoq−/− and wild-type dams, remarkably low levels of IGF-binding protein 1 (IGFBP-1) were observed in the serum of fetuses from Adipoq−/− dams. IGFBP-1 was identified in the trophoblast cells of human and mouse placentas. Maternal fasting robustly increased IGFBP-1 levels in mouse placentas, while reducing fetal weight. Significantly low IGFBP-1 levels were found in placentas of Adipoq−/− dams. Adiponectin treatment increased IGFBP-1 levels in primary cultured human trophoblast cells, while the PPARα antagonist, MK886, abolished this stimulatory effect. Conclusions/interpretation These results indicate that, in addition to nutrient supply, maternal adiponectin inhibits fetal growth by increasing IGFBP-1 expression in trophoblast cells. PMID:27495989

Fructose synthesis and transport at the uterine-placental interface of pigs: cell-specific localization of SLC2A5, SLC2A8, and components of the polyol pathway

USDA-ARS?s Scientific Manuscript database

The fetal fluids and uterine flushings of pigs contain higher concentrations of fructose than glucose, but fructose is not detected in maternal blood. Fructose can be synthesized from glucose via enzymes of the polyol pathway, aldose reductase (AKR1B1) and sorbitol dehydrogenase (SORD), transported ...

Reactive oxygen species are involved in lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation in mice.

PubMed

Xu, De-Xiang; Chen, Yuan-Hua; Zhao, Lei; Wang, Hua; Wei, Wei

2006-12-01

Maternal infection is a cause of adverse developmental outcomes including embryonic resorption, intrauterine fetal death, and preterm labor. Lipopolysaccharide-induced developmental toxicity at early gestational stages has been well characterized. The purpose of the present study was to investigate the effects of maternal lipopolysaccharide exposure at late gestational stages on intrauterine fetal growth and skeletal development and to assess the potential role of reactive oxygen species in lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation. The timed pregnant CD-1 mice were intraperitoneally injected with lipopolysaccharide (25 to 75 microg/kg per day) on gestational day 15 to 17. To investigate the role of reactive oxygen species on lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation, the pregnant mice were injected with alpha-phenyl-N-t-butylnitrone (100 mg/kg, intraperitoneally) at 30 minutes before lipopolysaccharide (75 microg/kg per day, intraperitoneally), followed by an additional dose of alpha-phenyl-N-t-butylnitrone (50 mg/kg, intraperitoneally) at 3 hours after lipopolysaccharide. The number of live fetuses, dead fetuses, and resorption sites was counted on gestational day 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Maternal lipopolysaccharide exposure significantly increased fetal mortality, reduced fetal weight and crown-rump and tail lengths of live fetuses, and retarded skeletal ossification in caudal vertebrae, anterior and posterior phalanges, and supraoccipital bone in a dose-dependent manner. Alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, almost completely blocked lipopolysaccharide-induced fetal death (63.2% in lipopolysaccharide group versus 6.5% in alpha-phenyl-N-t-butylnitrone + lipopolysaccharide group, P < .01). In addition, alpha-phenyl-N-t-butylnitrone significantly reversed lipopolysaccharide-induced intrauterine growth restriction and skeletal development retardation. However, aminoguanidine, a selective inhibitor of inducible nitric oxide synthase, had little effect. Furthermore, lipopolysaccharide-induced intrauterine fetal death, intrauterine fetal growth restriction, and skeletal development retardation were associated with lipid peroxidation and glutathione depletion in maternal liver, placenta, and fetal liver. Alpha-phenyl-N-t-butylnitrone significantly attenuated lipopolysaccharide-induced lipid peroxidation and glutathione depletion in maternal liver, placenta, and fetal liver. Maternal lipopolysaccharide exposure at late gestational stages results in intrauterine fetal growth restriction and skeletal development retardation in mice. Reactive oxygen species might be, at least in part, involved in lipopolysaccharide-induced intrauterine fetal growth restriction and skeletal development retardation.

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.

PubMed

Bukowski, Radek; Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M; Andrews, William; Saade, George R; Ilekis, John V; Reddy, Uma M; Baldwin, Donald A

2017-01-01

Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment ( n  = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL ( n  = 8), PNL ( n  = 10), TL ( n  = 7) and TNL ( n  = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene's 5' promoter or 3'-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5'and 3' UTR regions. The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection.

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface

PubMed Central

Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R.; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M.; Andrews, William; Saade, George R.; Ilekis, John V.; Reddy, Uma M.; Baldwin, Donald A.

2017-01-01

Background Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Methods Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene’s 5′ promoter or 3′-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. Results The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5′and 3′ UTR regions. Conclusions The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection. PMID:28879060

Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy.

PubMed

Cooke, Gerard M

2014-01-01

The first trimester of human fetal life, a period of extremely rapid development of physiological systems, represents the most rapid growth phase in human life. Interference in the establishment of organ systems may result in abnormal development that may be manifest immediately or programmed for later abnormal function. Exposure to environmental chemicals may be affecting development at these early stages, and yet there is limited knowledge of the quantities and identities of the chemicals to which the fetus is exposed during early pregnancy. Clearly, opportunities for assessing fetal chemical exposure directly are extremely limited. Hence, this review describes indirect means of assessing fetal exposure in early pregnancy to chemicals that are considered disrupters of development. Consideration is given to such matrices as maternal hair, fingernails, urine, saliva, sweat, breast milk, amniotic fluid and blood, and fetal matrices such as cord blood, cord tissue, meconium, placenta, and fetal liver. More than 150 articles that presented data from chemical analysis of human maternal and fetal tissues and fluids were reviewed. Priority was given to articles where chemical analysis was conducted in more than one matrix. Where correlations between maternal and fetal matrices were determined, these articles were included and are highlighted, as these may provide the basis for future investigations of early fetal exposure. The determination of fetal chemical exposure, at the time of rapid human growth and development, will greatly assist regulatory agencies in risk assessments and establishment of advisories for risk management concerning environmental chemicals.

Fetal motor activity and maternal cortisol

PubMed Central

DiPietro, Janet A.; Kivlighan, Katie T.; Costigan, Kathleen A.; Laudenslager, Mark L.

2009-01-01

The contemporaneous association between maternal salivary cortisol and fetal motor activity was examined at 32 and 36 weeks gestation. Higher maternal cortisol was positively associated with the amplitude of fetal motor activity at 32 weeks, r(48) = .39, p < .01, and 36 weeks, r(77)=.27, p < .05, and the amount of time fetuses spent moving at 32 weeks during the 50 minute observation period, r(48) = 33, p < .05. Observation of periods of unusually intense fetal motor activity were more common in fetuses of women with higher cortisol, Mann-Whitney U = 58.5. There were no sex differences in fetal motor activity, but the associations between maternal cortisol and fetal motor amplitude and overall movement were significantly stronger for male than female fetuses. PMID:19630038

Fingolimod against endotoxin-induced fetal brain injury in a rat model.

PubMed

Yavuz, And; Sezik, Mekin; Ozmen, Ozlem; Asci, Halil

2017-11-01

Fingolimod is a sphingosine-1-phosphate receptor modulator used for multiple sclerosis treatment and acts on cellular processes such as apoptosis, endothelial permeability, and inflammation. We hypothesized that fingolimod has a positive effect on alleviating preterm fetal brain injury. Sixteen pregnant rats were divided into four groups of four rats each. On gestational day 17, i.p. endotoxin was injected to induce fetal brain injury, followed by i.p. fingolimod (4 mg/kg maternal weight). Hysterotomy for preterm delivery was performed 6 h after fingolimod. The study groups included (i) vehicle controls (i.p. normal saline only); (ii) positive controls (endotoxin plus saline); (iii) saline plus fingolimod; and (iv) endotoxin plus fingolimod treatment. Brain tissues of the pups were dissected for evaluation of interleukin (IL)-6, caspase-3, and S100β on immunohistochemistry. Maternal fingolimod treatment attenuated endotoxin-related fetal brain injury and led to lower immunoreactions for IL-6, caspase-3, and S100β compared with endotoxin controls (P < 0.0001 for all comparisons). Antenatal maternal fingolimod therapy had fetal neuroprotective effects by alleviating preterm birth-related fetal brain injury with inhibitory effects on inflammation and apoptosis. © 2017 Japan Society of Obstetrics and Gynecology.

Implementation of uniform information on fetal movement in a Norwegian population reduced delayed reporting of decreased fetal movement and stillbirths in primiparous women - a clinical quality improvement

PubMed Central

2010-01-01

Background Delayed maternal reporting of decreased fetal movement (DFM) is associated with adverse pregnancy outcomes. Inconsistent information on fetal activity to women during the antenatal period may result in delayed reporting of DFM. We aimed to evaluate an intervention of implementation of uniform information on fetal activity to women during the antenatal period. Methods In a prospective before-and-after study, singleton women presenting DFM in the third trimester across 14 hospitals in Norway were registered. Outcome measures were maternal behavior regarding reporting of DFM, concerns and stillbirth. In addition, cross-sectional studies of all women giving birth were undertaken to assess maternal concerns about fetal activity, and population-based data were obtained from the Medical Birth Registry Norway. Results Pre- and post-intervention cohorts included 19 407 and 46 143 births with 1 215 and 3 038 women with DFM respectively. Among primiparous women with DFM, a reduction in delayed reporting of DFM (≥48 hrs) OR 0.61 (95% CI 0.47-0.81) and stillbirths OR 0.36 (95% CI 0.19-0.69) was shown in the post-intervention period. No difference was shown in rates of consultations for DFM or maternal concerns. Stillbirth rates and maternal behavior among women who were of non-Western origin, smokers, overweight or >34 years old were unchanged. Conclusions Uniform information on fetal activity provided to pregnant women was associated with a reduction in the number of primiparous women who delayed reporting of DFM and a reduction of the stillbirth rates for primiparous women reporting DFM. The information did not appear to increase maternal concerns or rate of consultation. Due to different imperfections in different clinical settings, further studies in other populations replicating these findings are required. PMID:20044943

Multi-channel non-invasive fetal electrocardiography detection using wavelet decomposition

NASA Astrophysics Data System (ADS)

Almeida, Javier; Ruano, Josué; Corredor, Germán.; Romo-Bucheli, David; Navarro-Vargas, José Ricardo; Romero, Eduardo

2017-11-01

Non-invasive fetal electrocardiography (fECG) has attracted the medical community because of the importance of fetal monitoring. However, its implementation in clinical practice is challenging: the fetal signal has a low Signal- to-Noise-Ratio and several signal sources are present in the maternal abdominal electrocardiography (AECG). This paper presents a novel method to detect the fetal signal from a multi-channel maternal AECG. The method begins by applying filters and signal detrending the AECG signals. Afterwards, the maternal QRS complexes are identified and subtracted. The residual signals are used to detect the fetal QRS complex. Intervals of these signals are analyzed by using a wavelet decomposition. The resulting representation feds a previously trained Random Forest (RF) classifier that identifies signal intervals associated to fetal QRS complex. The method was evaluated on a public available dataset: the Physionet2013 challenge. A set of 50 maternal AECG records were used to train the RF classifier. The evaluation was carried out in signals intervals extracted from additional 25 maternal AECG. The proposed method yielded an 83:77% accuracy in the fetal QRS complex classification task.

Maternal salivary testosterone in pregnancy and fetal neuromaturation.

PubMed

Voegtline, Kristin M; Costigan, Kathleen A; DiPietro, Janet A

2017-11-01

Testosterone exposure during pregnancy has been hypothesized as a mechanism for sex differences in brain and behavioral development observed in the postnatal period. The current study documents the natural history of maternal salivary testosterone from 18 weeks gestation of pregnancy to 6 months postpartum, and investigates associations with fetal heart rate, motor activity, and their integration. Findings indicate maternal salivary testosterone increases with advancing gestation though no differences by fetal sex were detected. High intra-individual stability in prenatal testosterone levels extend into the postnatal period, particularly for pregnancies with male fetuses. With respect to fetal development, by 36 weeks gestation higher maternal prenatal salivary testosterone was significantly associated with faster fetal heart rate and less optimal somatic-cardiac integration. Measurement of testosterone in saliva is a useful tool for repeated-measures studies of hormonal concomitants of pregnancy. Moreover, higher maternal testosterone levels are associated with modest interference to fetal neurobehavioral development. © 2017 Wiley Periodicals, Inc.

/sup 32/P-postlabeling assay in mice of transplacental DNA damage induced by the environmental carcinogens safrole, 4-aminobiphenyl, and benzo(a)pyrene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, L.J.; Disher, R.M.; Reddy, M.V.

1986-06-01

Transplacental exposure of fetuses to carcinogens is known to induce tumors in the offspring, often with a high incidence and short latency. While covalent adduction of DNA appears to be essential for tumor initiation, little is known about the binding of carcinogens to the DNA of fetal tissues. A sensitive /sup 32/P-postlabeling method enabled us to study the binding of the environmental carcinogens safrole (600 mumol/kg p.o.), 4-aminobiphenyl (800 mumol/kg), and benzo(a)pyrene (200 mumol/kg) to the DNA of various maternal and fetal tissues after administration of test carcinogens to pregnant ICR mice on day 18 of gestation. The results showmore » that these carcinogens bound to the DNA of maternal and fetal liver, lung, kidney, heart, brain, intestine, skin, maternal uterus, and placenta, with organ-specific quantitative and qualitative differences. It was possible for the first time to analyze DNA adduct patterns in minute amounts of tissue, for example those available from fetal heart. The covalent binding index 24 h after safrole treatment was estimated for the different organs and ranged from 0.1 to 247 and 0.1 to 5.8 for maternal and fetal DNA, respectively. Covalent binding index values of 0.2 to 13 and 0.1 to 0.3 for maternal and fetal DNA, respectively, were found for 4-aminobiphenyl. Benzo(a)pyrene treatment yielded covalent binding index values of 0.6 to 6.5 and 0.3 to 0.7 for maternal and fetal DNA, respectively. In both maternal and fetal tissues, safrole exhibited preferential binding to liver DNA. 4-Aminobiphenyl bound preferentially to DNA of maternal liver and kidney but showed no preference among fetal tissues. Benzo(a)pyrene exhibited weak tissue preference in both maternal and fetal organs.« less

Effect of maternal alcohol and nicotine intake, individually and in combination, on fetal growth in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leichter, J.

1991-03-15

The effect of maternal ethanol and nicotine administration, separately and in combination, on fetal growth of rats was studied. Nicotine was administered by gavage for the entire gestational period. Alcohol was given in drinking water for 4 weeks prior to mating and 30% throughout gestation. Appropriate pair-fed and ad libitum control animals were included to separate the effect of ethanol and nicotine on the outcome of pregnancy from those produced by the confounding variables of malnutrition. Body weights of fetuses exposed to alcohol alone or in combination with nicotine were significantly lower than those of the pair-fed and ad libitummore » controls. However, the difference in fetal body weight between the alcohol plus nicotine and the alcohol alone group was not significant. Similarly, in the rats administered nicotine only, fetal weight was not significantly different compared to control animals. The results of this study indicate that maternal alcohol intake impairs fetal growth and nicotine does not, regardless whether it is administered separately or in combination with alcohol for the entire gestational period.« less

Prenatal Alcohol Exposure Alters Fetal Iron Distribution and Elevates Hepatic Hepcidin in a Rat Model of Fetal Alcohol Spectrum Disorders123

PubMed Central

Huebner, Shane M; Blohowiak, Sharon E; Kling, Pamela J; Smith, Susan M

2016-01-01

Background: Prenatal alcohol exposure (PAE) causes neurodevelopmental disabilities, and gestational iron deficiency (ID) selectively worsens learning and neuroanatomical and growth impairments in PAE. It is unknown why ID worsens outcomes in alcohol-exposed offspring. Objective: We hypothesized that PAE alters maternal-fetal iron distribution or its regulation. Methods: Nulliparous, 10-wk-old, Long-Evans rats were mated and then fed iron-sufficient (100 mg Fe/kg) or iron-deficient (≤4 mg Fe/kg) diets. On gestational days 13.5–19.5, dams received either 5.0 g ethanol/kg body weight (PAE) or isocaloric maltodextrin by oral gavage. On gestational day 20.5, maternal and fetal clinical blood counts, tissue mineral and iron transport protein concentrations, and hepatic hepcidin mRNA expression were determined. Results: In fetal brain and liver (P < 0.001) and in maternal liver (P < 0.005), ID decreased iron (total and nonheme) and ferritin content by nearly 200%. PAE reduced fetal bodyweight (P < 0.001) and interacted with ID (P < 0.001) to reduce it by an additional 20%. Independent of maternal iron status, PAE increased fetal liver iron (30–60%, P < 0.001) and decreased brain iron content (total and nonheme, 15–20%, P ≤ 0.050). ID-PAE brains had lower ferritin, transferrin, and transferrin receptor content (P ≤ 0.002) than ID-maltodextrin brains. PAE reduced fetal hematocrit, hemoglobin, and red blood cell numbers (P < 0.003) independently of iron status. Unexpectedly, and also independent of iron status, PAE increased maternal and fetal hepatic hepcidin mRNA expression >300% (P < 0.001). Conclusions: PAE altered fetal iron distribution independent of maternal iron status in rats. The elevated iron content of fetal liver suggests that PAE may have limited iron availability for fetal erythropoiesis and brain development. Altered fetal iron distribution may partly explain why maternal ID substantially worsens growth and behavioral outcomes in PAE. PMID:27146918

77 FR 44695 - Revised Meeting Notice: Leadership Meeting on Maternal, Fetal, and Infant Opioid Exposure and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-30

... OFFICE OF NATIONAL DRUG CONTROL POLICY Revised Meeting Notice: Leadership Meeting on Maternal, Fetal, and Infant Opioid Exposure and Neonatal Abstinence Syndrome AGENCY: Office of National Drug Control Policy. ACTION: Revised notice. SUMMARY: An ONDCP Leadership Meeting on Maternal, Fetal and Infant...

76 FR 38109 - National Advisory Council on Maternal, Infant and Fetal Nutrition: Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... DEPARTMENT OF AGRICULTURE Food and Nutrition Service National Advisory Council on Maternal, Infant and Fetal Nutrition: Notice of Meeting AGENCY: Food and Nutrition Service, USDA. ACTION: Notice of... notice announces a meeting of the National Advisory Council on Maternal, Infant and Fetal Nutrition...

78 FR 36163 - National Advisory Council on Maternal, Infant and Fetal Nutrition; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... DEPARTMENT OF AGRICULTURE Food and Nutrition Service National Advisory Council on Maternal, Infant and Fetal Nutrition; Notice of Meeting AGENCY: Food and Nutrition Service, USDA. ACTION: Notice of... meeting of the National Advisory Council on Maternal, Infant and Fetal Nutrition. DATES: Date and Time...

Glucocorticoid-induced changes in glucocorticoid receptor mRNA and protein expression in the human placenta as a potential factor for altering fetal growth and development.

PubMed

Bivol, Svetlana; Owen, Suzzanne J; Rose'Meyer, Roselyn B

2016-02-05

Glucocorticoids (GCs) control essential metabolic processes in virtually every cell in the body and play a vital role in the development of fetal tissues and organ systems. The biological actions of GCs are mediated via glucocorticoid receptors (GRs), the cytoplasmic transcription factors that regulate the transcription of genes involved in placental and fetal growth and development. Several experimental studies have demonstrated that fetal exposure to high maternal GC levels early in gestation is associated with adverse fetal outcomes, including low birthweight, intrauterine growth restriction and anatomical and structural abnormalities that may increase the risk of cardiovascular, metabolic and neuroendocrine disorders in adulthood. The response of the fetus to GCs is dependent on gender, with female fetuses becoming hypersensitive to changes in GC levels whereas male fetuses develop GC resistance in the environment of high maternal GCs. In this paper we review GR function and the physiological and pathological effects of GCs on fetal development. We propose that GC-induced changes in the placental structure and function, including alterations in the expression of GR mRNA and protein levels, may play role in inhibiting in utero fetal growth.

Linear Phase Sharp Transition BPF to Detect Noninvasive Maternal and Fetal Heart Rate.

PubMed

Marchon, Niyan; Naik, Gourish; Pai, K R

2018-01-01

Fetal heart rate (FHR) detection can be monitored using either direct fetal scalp electrode recording (invasive) or by indirect noninvasive technique. Weeks before delivery, the invasive method poses a risk factor to the fetus, while the latter provides accurate fetal ECG (FECG) information which can help diagnose fetal's well-being. Our technique employs variable order linear phase sharp transition (LPST) FIR band-pass filter which shows improved stopband attenuation at higher filter orders. The fetal frequency fiduciary edges form the band edges of the filter characterized by varying amounts of overlap of maternal ECG (MECG) spectrum. The one with the minimum maternal spectrum overlap was found to be optimum with no power line interference and maximum fetal heart beats being detected. The improved filtering is reflected in the enhancement of the performance of the fetal QRS detector (FQRS). The improvement has also occurred in fetal heart rate obtained using our algorithm which is in close agreement with the true reference (i.e., invasive fetal scalp ECG). The performance parameters of the FQRS detector such as sensitivity (Se), positive predictive value (PPV), and accuracy (F 1 ) were found to improve even for lower filter order. The same technique was extended to evaluate maternal QRS detector (MQRS) and found to yield satisfactory maternal heart rate (MHR) results.

Trans-abdominal monitoring of fetal arterial blood oxygenation using pulse oximetry

NASA Astrophysics Data System (ADS)

Zourabian, Anna; Siegel, Andrew M.; Chance, Britton; Ramanujam, Nirmala; Rode, Martha; Boas, David A.

2000-10-01

Pulse oximetry (oxygen saturation monitoring) has markedly improved medical care in many fields, including anesthesiology, intensive care, and newborn intensive care. In obstetrics, fetal heart rate monitoring remains the standard for intrapartum assessment of fetal well being. Fetal oxygen saturation monitoring is a new technique currently under development. It is potentially superior to electronic fetal heart rate monitoring (cardiotocography) because it allows direct assessment of both the fetal oxygen status and fetal tissue perfusion. Here we present the analysis for determining the most optimal wavelength selection for pulse oximetry. The wavelengths we chose as the most optimal are the first in the range of 670 - 720 nm and the second in the range of 825 - 925 nm. Further, we discuss the possible systematic errors during our measurements and their contribution to the obtained saturation results. We present feasibility studies for fetal pulse oximetry, monitored noninvasively through the maternal abdomen. Our preliminary experiments show that the fetal pulse can be discriminated from the maternal pulse and thus, in principle, the fetal arterial oxygen saturation can be obtained. We present the methodology for obtaining these data, and discuss the dependence of our measurements on the fetal position with respect to the optode assembly.

Profiling Lgals9 splice variant expression at the fetal-maternal interface: implications in normal and pathological human pregnancy.

PubMed

Heusschen, Roy; Freitag, Nancy; Tirado-González, Irene; Barrientos, Gabriela; Moschansky, Petra; Muñoz-Fernández, Raquel; Leno-Durán, Ester; Klapp, Burghard F; Thijssen, Victor L J L; Blois, Sandra M

2013-01-01

Disruption of fetal-maternal tolerance mechanisms can contribute to pregnancy complications, including spontaneous abortion. Galectin-9 (LGALS9), a tandem repeat lectin associated with immune modulation, is expressed in the endometrium during the mid and late secretory phases and in decidua during human early pregnancy. However, the role of LGALS9 during pregnancy remains poorly understood. We used real-time PCR and immunohistochemical staining to analyze the expression of Lgals9/LGALS9 during mouse gestation as well as in human tissues obtained from normal pregnancy and spontaneous abortions. In mice, three Lgals9 splice variants were detected, the expression of which was differentially regulated during gestation. Furthermore, decidual Lgals9 expression was deregulated in a mouse model of spontaneous abortion, whereas placental levels did not change. We further found that the LGALS9 D5 isoform suppresses interferon gamma production by decidual natural killer cells. In human patients, six Lgals9 splice variants were detected, and a decrease in Lgals9 D5/10 was associated with spontaneous abortion. Altogether, these results show a differential regulation of Lgals9 isoform expression during normal and pathological pregnancies and designate Lgals9 as a potential marker for adverse pregnancy outcomes.

Characteristics and management of mirror syndrome: a systematic review (1956-2016).

PubMed

Allarakia, Sabah; Khayat, Hassan A; Karami, Moyassar M; Aldakhil, Abdulaziz M; Kashi, Ahmed M; Algain, Abdulrahman H; Khan, Mohammad A; Alghifees, Loai S; Alsulami, Raed E

2017-12-20

To describe the clinical features of mirror syndrome and to correlate the effects of different treatments with the fetal outcomes. Online search up to May 2016 was conducted in the PubMed, Embase (Ovid platform) and clinicalTrials.gov without restrictions of language, date or journal. Only papers providing both fetal and maternal presentations and outcomes were included. The study included 74 papers (n=111), with an additional two patients diagnosed at our center (n=113). The mean gestational age at diagnosis was 27 weeks±30 days (16-39 weeks). Whether early or late gestational age at diagnosis, and whether mother and fetus show symptoms simultaneously or on different dates, has insignificant impact on fetal outcome (P=0.06 and P=0.46, respectively). Edema (84%) followed by hypertension (60.1%) were the leading maternal findings. Fetal hydrops (94.7%) and placental edema (62.8%) were the commonest sonographic features. Procedures correcting fetal hydrops/anemia in utero as well as labor induction were the only treatment options correlated with improved fetal survival (χ2 analysis, P=0.01 and Fisher's exact test, P=0.02; respectively). The overall rate of fetal/neonatal mortality was 67.26%. The gestational age at diagnosis and sequence of presentation have insignificant impact on fetal outcome. Improved fetal survival was associated with procedural interventions that correct fetal hydrops as well as labor induction.

Aerobic Exercise during Pregnancy and Presence of Fetal-Maternal Heart Rate Synchronization

PubMed Central

Van Leeuwen, Peter; Gustafson, Kathleen M.; Cysarz, Dirk; Geue, Daniel; May, Linda E.; Grönemeyer, Dietrich

2014-01-01

It has been shown that short-term direct interaction between maternal and fetal heart rates may take place and that this interaction is affected by the rate of maternal respiration. The aim of this study was to determine the effect of maternal aerobic exercise during pregnancy on the occurrence of fetal-maternal heart rate synchronization. Methods In 40 pregnant women at the 36th week of gestation, 21 of whom exercised regularly, we acquired 18 min. RR interval time series obtained simultaneously in the mothers and their fetuses from magnetocardiographic recordings. The time series of the two groups were examined with respect to their heart rate variability, the maternal respiratory rate and the presence of synchronization epochs as determined on the basis of synchrograms. Surrogate data were used to assess whether the occurrence of synchronization was due to chance. Results In the original data, we found synchronization occurred less often in pregnancies in which the mothers had exercised regularly. These subjects also displayed higher combined fetal-maternal heart rate variability and lower maternal respiratory rates. Analysis of the surrogate data showed shorter epochs of synchronization and a lack of the phase coordination found between maternal and fetal beat timing in the original data. Conclusion The results suggest that fetal-maternal heart rate coupling is present but generally weak. Maternal exercise has a damping effect on its occurrence, most likely due to an increase in beat-to-beat differences, higher vagal tone and slower breathing rates. PMID:25162592

Aerobic exercise during pregnancy and presence of fetal-maternal heart rate synchronization.

PubMed

Van Leeuwen, Peter; Gustafson, Kathleen M; Cysarz, Dirk; Geue, Daniel; May, Linda E; Grönemeyer, Dietrich

2014-01-01

It has been shown that short-term direct interaction between maternal and fetal heart rates may take place and that this interaction is affected by the rate of maternal respiration. The aim of this study was to determine the effect of maternal aerobic exercise during pregnancy on the occurrence of fetal-maternal heart rate synchronization. In 40 pregnant women at the 36th week of gestation, 21 of whom exercised regularly, we acquired 18 min. RR interval time series obtained simultaneously in the mothers and their fetuses from magnetocardiographic recordings. The time series of the two groups were examined with respect to their heart rate variability, the maternal respiratory rate and the presence of synchronization epochs as determined on the basis of synchrograms. Surrogate data were used to assess whether the occurrence of synchronization was due to chance. In the original data, we found synchronization occurred less often in pregnancies in which the mothers had exercised regularly. These subjects also displayed higher combined fetal-maternal heart rate variability and lower maternal respiratory rates. Analysis of the surrogate data showed shorter epochs of synchronization and a lack of the phase coordination found between maternal and fetal beat timing in the original data. The results suggest that fetal-maternal heart rate coupling is present but generally weak. Maternal exercise has a damping effect on its occurrence, most likely due to an increase in beat-to-beat differences, higher vagal tone and slower breathing rates.

The role of placental MHC class I expression in immune-assisted separation of the fetal membranes in cattle.

PubMed

Benedictus, Lindert; Koets, Ad P; Rutten, Victor P M G

2015-11-01

The bovine fetus, like that of other species, is a semi-allograft and the regulation of materno-fetal alloimmunity is critical to prevent its immunological rejection. In cattle, a materno-fetal alloimmune response may be beneficial at parturition. It is hypothesized that upregulation of major histocompatibility complex (MHC) class I on the fetal membranes toward the end of gestation induces a maternal alloimmune response that activates innate immune effector mechanisms, aiding in the loss of the adherence between the fetal membranes and the uterus. Loss of fetal-maternal adherence is pivotal for the timely expulsion of the fetal membranes and the absence (or reduction) of the maternal immune response may lead to retained fetal membranes, a common reproductive disorder of cattle. Currently, there is no effective treatment for retained fetal membranes and a better understanding of materno-fetal alloimmune-assisted separation of the fetal membranes may lead to novel targets for the treatment of retained fetal membranes. In this review, the regulation of materno-fetal alloimmunity during pregnancy in cattle, with a focus on placental MHC class I expression, and the importance of maternal alloimmunity for the timely separation of the fetal membranes, are discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Fetal exposure to maternal stress and risk for schizophrenia spectrum disorders among offspring: Differential influences of fetal sex.

PubMed

Fineberg, Anna M; Ellman, Lauren M; Schaefer, Catherine A; Maxwell, Seth D; Shen, Ling; H Chaudhury, Nashid; Cook, Aundrea L; Bresnahan, Michaeline A; Susser, Ezra S; Brown, Alan S

2016-02-28

Exposure to adverse life events during pregnancy has been linked to increased risk of schizophrenia spectrum disorders (SSD) in offspring. Nevertheless, much of the previous work inferred maternal stress from severe life events rather than directly assessing maternal reports of stress. The present study aimed to examine maternal reports of stress during pregnancy and risk for offspring SSD. Participants were 95 SSD cases and 206 controls who were offspring from a large birth cohort study that followed pregnant women from 1959 to 1966. During pregnancy interviews, women were asked if anything worrisome had occurred recently. Interviews were qualitatively coded for stress-related themes, including reports of daily life stress, by two independent raters. None of the maternal psychosocial stress themes were significantly associated with increased odds of offspring SSD in analyses of the full sample. However, results indicated a significant daily life stress by infant sex interaction. Maternal daily life stress during pregnancy was associated with significantly increased odds of SSD among male offspring. Findings suggest sex-specific fetal sensitivity to maternal reported daily life stress during pregnancy on risk for SSD, with males appearing to be more vulnerable to the influences of maternal stress during pregnancy. Published by Elsevier Ireland Ltd.

A possible new approach in the prediction of late gestational hypertension: The role of the fetal aortic intima-media thickness.

PubMed

Visentin, Silvia; Londero, Ambrogio P; Camerin, Martina; Grisan, Enrico; Cosmi, Erich

2017-01-01

The aim was to determine the predictive role of combined screening for late-onset gestational hypertension by fetal ultrasound measurements, third trimester uterine arteries (UtAs) Doppler imaging, and maternal history. This prospective study on singleton pregnancies was conducted at the tertiary center of Maternal and Fetal Medicine of the University of Padua during the period between January 2012 and December 2014. Ultrasound examination (fetal biometry, fetal wellbeing, maternal Doppler study, fetal abdominal aorta intima-media thickness [aIMT], and fetal kidney volumes), clinical data (mother age, prepregnancy body mass index [BMI], and parity), and pregnancy outcomes were collected. The P value <0.05 was defined significant considering a 2-sided alternative hypothesis. The distribution normality of variables were assessed using Kolmogorov-Smirnoff test. Data were presented by mean (±standard deviation), median and interquartile range, or percentage and absolute values. We considered data from 1381 ultrasound examinations at 29 to 32 weeks' gestation, and in 73 cases late gestational hypertension developed after 34 weeks' gestation. The final multivariate model found that fetal aIMT as well as fetal umbilical artery pulsatility index (PI), maternal age, maternal prepregnacy BMI, parity, and mean PI of maternal UtAs, assessed at ultrasound examination of 29 to 32 weeks' gestation, were significant and independent predictors for the development of gestational hypertension after 34 weeks' gestation. The area under the curve of the model was 81.07% (95% confidence interval, 75.83%-86.32%). A nomogram was developed starting from multivariate logistic regression coefficients. Late-gestational hypertension could be independently predicted by fetal aIMT assessment at 29 to 32 weeks' gestation, ultrasound Doppler waveforms, and maternal clinical parameters.

Fetal-sex dependent genomic responses in the circulating lymphocytes of arsenic-exposed pregnant women in New Hampshire.

PubMed

Bommarito, Paige A; Martin, Elizabeth; Smeester, Lisa; Palys, Thomas; Baker, Emily R; Karagas, Margaret R; Fry, Rebecca C

2017-10-01

Exposure to inorganic arsenic (iAs) during pregnancy is associated with adverse health outcomes present both at birth and later in life. A biological mechanism may include epigenetic and genomic alterations in fetal genes involved in immune functioning. To investigate the role of the maternal immune response to in utero iAs exposure, we conducted an analysis of the expression of immune-related genes in pregnant women from the New Hampshire Birth Cohort Study. A set of 31 genes was identified with altered expression in association with levels of urinary total arsenic, urinary iAs, urinary monomethylated arsenic and urinary dimethylated arsenic. Notably, maternal gene expression signatures differed when stratified on fetal sex, with a more robust inflammatory response observed in male pregnancies. Moreover, the differentially expressed genes were also related to birth outcomes. These findings highlight the sex-dependent nature of the maternal iAs-induced inflammatory response in relationship to fetal outcomes. Copyright © 2017. Published by Elsevier Inc.

Higher fetal insulin resistance in Chinese pregnant women with gestational diabetes mellitus and correlation with maternal insulin resistance.

PubMed

Wang, Qiuwei; Huang, Ruiping; Yu, Bin; Cao, Fang; Wang, Huiyan; Zhang, Ming; Wang, Xinhong; Zhang, Bin; Zhou, Hong; Zhu, Ziqiang

2013-01-01

The aim of this study was to determine the effect of gestational diabetes mellitus (GDM) on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM. Maternal fasting blood and venous cord blood samples (reflecting fetal condition) were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention) and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) and the proinsulin-to-insulin ratios (an indicator of fetal β-cell function) were calculated in maternal and cord blood respectively. Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but not proinsulin-to-insulin ratios were significantly higher in the GDM group than in the control group (maternal insulin, 24.8 vs. 15.4 µU/mL, P = 0.004, proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041, respectively; fetal: insulin, 15.1 vs. 7.9 µU/mL, P<0.001, proinsulin, 25.8 vs. 15.1 pmol/L, P = 0.015, and HOMA-IR, 2.8 vs. 1.4, P = 0.017, respectively). Fetal HOMA-IR but not proinsulin-to-insulin ratios was significantly correlated to maternal HOMA-IR (r = 0.307, P = 0.019), in the pregnant women with GDM. Fetal insulin resistance was higher in Chinese pregnant women with GDM than control subjects, and correlated with maternal insulin resistance.

Daily ethanol exposure during late ovine pregnancy: physiological effects in the mother and fetus in the apparent absence of overt fetal cerebral dysmorphology.

PubMed

Kenna, Kelly; De Matteo, Robert; Hanita, Takushi; Rees, Sandra; Sozo, Foula; Stokes, Victoria; Walker, David; Bocking, Alan; Brien, James; Harding, Richard

2011-10-01

High levels of ethanol (EtOH) consumption during pregnancy adversely affect fetal development; however, the effects of lower levels of exposure are less clear. Our objectives were to assess the effects of daily EtOH exposure (3.8 USA standard drinks) on fetal-maternal physiological variables and the fetal brain, particularly white matter. Pregnant ewes received daily intravenous infusions of EtOH (0.75 g/kg maternal body wt over 1 h, 8 fetuses) or saline (8 fetuses) from 95 to 133 days of gestational age (DGA; term ∼145 DGA). Maternal and fetal arterial blood was sampled at 131-133 DGA. At necropsy (134 DGA) fetal brains were collected for analysis. Maternal and fetal plasma EtOH concentrations reached similar maximal concentration (∼0.11 g/dl) and declined at the same rate. EtOH infusions produced mild reductions in fetal arterial oxygenation but there were no changes in maternal oxygenation, maternal and fetal Pa(CO(2)), or in fetal mean arterial pressure or heart rate. Following EtOH infusions, plasma lactate levels were elevated in ewes and fetuses, but arterial pH fell only in ewes. Fetal body and brain weights were similar between groups. In three of eight EtOH-exposed fetuses there were small subarachnoid hemorrhages in the cerebrum and cerebellum associated with focal cortical neuronal death and gliosis. Overall, there was no evidence of cystic lesions, inflammation, increased apoptosis, or white matter injury. We conclude that daily EtOH exposure during the third trimester-equivalent of ovine pregnancy has modest physiological effects on the fetus and no gross effects on fetal white matter development.

Occupational exposure to chemicals and fetal growth: the Generation R Study

PubMed Central

Snijder, Claudia A.; Roeleveld, Nel; te Velde, Egbert; Steegers, Eric A.P.; Raat, Hein; Hofman, Albert; Jaddoe, Vincent W.V.; Burdorf, Alex

2012-01-01

BACKGROUND Developmental diseases, such as birth defects, growth restriction and preterm delivery, account for >25% of infant mortality and morbidity. Several studies have shown that exposure to chemicals during pregnancy is associated with adverse birth outcomes. The aim of this study was to identify whether occupational exposure to various chemicals might adversely influence intrauterine growth patterns and placental weight. METHODS Associations between maternal occupational exposure to various chemicals and fetal growth were studied in 4680 pregnant women participating in a population-based prospective cohort study from early pregnancy onwards in the Netherlands (2002–2006), the Generation R Study. Mothers who filled out a questionnaire during mid-pregnancy (response: 77% of enrolment) were included if they conducted paid employment during pregnancy and had a spontaneously conceived singleton live born pregnancy (n = 4680). A job exposure matrix was used, linking job titles to expert judgement on exposure to chemicals in the workplace. Fetal growth characteristics were repeatedly measured by ultrasound and were used in combination with measurements at birth. Placental weight was obtained from medical records and hospital registries. Linear regression models for repeated measurements were used to study the associations between maternal occupational exposure to chemicals and intrauterine growth. RESULTS We observed that maternal occupational exposure to polycyclic aromatic hydrocarbons, phthalates, alkylphenolic compounds and pesticides adversely influenced several domains of fetal growth (fetal weight, fetal head circumference and fetal length). We found a significant association between pesticide and phthalate exposure with a decreased placental weight. CONCLUSIONS Our results suggest that maternal occupational exposure to several chemicals is associated with impaired fetal growth during pregnancy and a decreased placental weight. Further studies are needed to confirm these findings and to assess post-natal consequences. PMID:22215632

The characteristics of placental transfer and tissue concentrations of nickel in late gestational rats and fetuses.

PubMed

Hou, Y-P; Gu, J-Y; Shao, Y-F; Song, Y-F; Jing, Y-H; Wu, W-S; Pu, S

2011-03-01

The dynamics of nickel (Ni) uptake, transfer, retention and clearance in fetuses and late gestational rats were investigated by assessing its distributions in placenta, maternal and fetal organs and tissues during the 24 h period after a single dose of (63)Ni intraperitoneal injection on gestational day 20. Peak (63)Ni radioactivity was detected at 0.5 h in maternal blood, at 3 h in placenta, fetal membranes, fetal blood, fetal heart, maternal kidney, lung, stomach, liver and brain, at 9 h in fetal kidney, stomach, liver and brain, and lastly at 24 h in fetal lung and amniotic fluid. The maximal (63)Ni radioactivity among all samples was detected consistently in the fetal membranes and placenta. The (63)Ni radioactivity in fetal blood was higher than that in maternal blood from 3 to 24 h. The fetal liver, heart, stomach and brain exhibited higher (63)Ni radioactivity than the corresponding maternal organs from 6 to 24 h. However, maternal kidney consistently exhibited significantly higher (63)Ni radioactivity than the fetal kidney. The (63)Ni in fetal lung and amniotic fluid increased throughout the period of experimental observation. These observations corroborated previous finding that nickel is actively transferred across the blood-placenta-barrier into fetus, but hardly from fetus to mother. Moreover, these results suggest that the placenta has a high affinity for nickel and its barrier does not protect the fetus from nickel exposure. The fact that nickel concentrations are higher in most fetal organs and tissues than in corresponding maternal organs and tissues in late gestation indicates that, unlike the dam, fetuses lack effective means for getting rid of excessive nickel due to its confined environment and relatively weak kidney functions. The situation is exacerbated by mother-to-fetus unidirectional transfer. Consequently, the fetuses are particularly vulnerable to the damaging effects of nickel. Copyright © 2010 Elsevier Ltd. All rights reserved.

Progesterone Decreases in vitro Indoleamine 2, 3-dioxygenase Expression in Dendritic and CD4+ Cells from Maternal-Fetal Interface of Rats.

PubMed

Bianchi, Pedro Kastein Faria da Cunha; Leandro, Rafael Magdanelo; Poscai, Aline Nayara; Yoshinaga, Tulio; Gonçalez, Patrícia Orlandini; Kfoury Junior, José Roberto

2017-07-01

Several mechanisms contribute to the tolerogenic state observed during pregnancy, such as the activity of the enzyme indoleamine 2, 3-dioxygenase (IDO). This initializes the catabolism of tryptophan, inducing T cells to apoptosis due to its deprivation and by the action of its catabolites in the placental microenvironment. Progesterone plays an important part on immunological tolerance mechanisms during pregnancy; however, there is no evidence it is related to IDO activity. Thus, this study aimed to investigate progesterone influence on the maternal-fetal interface of pregnant Wistar rats, by identifying IDO positive cells by immunophenotyping and flow cytometry under exogenous progesterone supplementation. Placenta and embryo cells were cultured and separated into groups that received interferon γ or progesterone, supplemented or not with mifepristone. After 2 and 24 h, these were labeled with an anti-IDO and a series of antibodies specific to leucocytes and progesterone receptor and processed through flow cytometry analysis. Progesterone induced a significant decrease in the expression of IDO in dendritic cells and CD4 + lymphocytes. The blocking of progesterone receptor on these cells by mifepristone restored IDO expression levels and may constitute evidence of the participation of this hormone through a direct route in these cells.

75 FR 38771 - National Advisory Council on Maternal, Infant and Fetal Nutrition: Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-06

... DEPARTMENT OF AGRICULTURE Food and Nutrition Service National Advisory Council on Maternal, Infant and Fetal Nutrition: Notice of Meeting AGENCY: Food and Nutrition Service, USDA. ACTION: Notice of... National Advisory Council on Maternal, Infant and Fetal Nutrition. Date and Time: July 27-29, 2010, 9 a.m...

Maternal anthropometrics are associated with fetal size in different periods of pregnancy and at birth. The Generation R Study.

PubMed

Ay, L; Kruithof, C J; Bakker, R; Steegers, E A P; Witteman, J C M; Moll, H A; Hofman, A; Mackenbach, J P; Hokken-Koelega, A C S; Jaddoe, V W V

2009-06-01

We aimed to examine the associations of maternal anthropometrics with fetal weight measured in different periods of pregnancy and with birth outcomes. Population-based birth cohort study. Data of pregnant women and their children in Rotterdam, the Netherlands. In 8541 mothers, height, prepregnancy body mass index (BMI) and gestational weight gain were available. Fetal growth was measured by ultrasound in mid- and late pregnancy. Regression analyses were used to assess the impact of maternal anthropometrics on fetal weight and birth outcomes. Fetal weight and birth outcomes: weight (grams) and the risks of small (<5th percentile) and large (>95th percentile) size for gestational age at birth. Maternal BMI in pregnancy was positively associated with estimated fetal weight during pregnancy. The effect estimates increased with advancing gestational age. All maternal anthropometrics were positively associated with fetal size (P-values for trend <0.01). Mothers with both their prepregnancy BMI and gestational weight gain quartile in the lowest and highest quartiles showed the highest risks of having a small and large size for gestational age child at birth, respectively. The effect of prepregnancy BMI was strongly modified by gestational weight gain. Fetal growth is positively affected by maternal BMI during pregnancy. Maternal height, prepregnancy BMI and gestational weight gain are all associated with increased risks of small and large size for gestational age at birth in the offspring, with an increased effect when combined.

Microglia, the missing link in maternal immune activation and fetal neurodevelopment; and a possible link in preeclampsia and disturbed neurodevelopment?

PubMed

Prins, Jelmer R; Eskandar, Sharon; Eggen, Bart J L; Scherjon, Sicco A

2018-04-01

Disturbances in fetal neurodevelopment have extensively been related to neurodevelopmental disorders in early and later life. Fetal neurodevelopment is dependent on adequate functioning of the fetal immune system. During pregnancy, the maternal immune system is challenged to both tolerate the semi-allogenic fetus and to protect the mother and fetus from microbes. The fetal immune system is influenced by maternal immune disturbances; therefore, perturbations in maternal immunity likely do not only alter pregnancy outcome but also alter fetal neurodevelopment. A possible common pathway could be modulating the functioning of tissue macrophages in the placenta and brain. Maternal immune tolerance towards the fetus involves several complex adaptations. In this active maternal immune state, the fetus develops its own immunity. As cytokines and other players of the immune system -which can pass the placenta- are involved in neurodevelopment, disruptions in immune balance influence fetal neurodevelopment. Several studies reported an association between maternal immune activation, complications of pregnancy as preeclampsia, and altered neonatal neurodevelopment. A possible pathway involves dysfunctioning of microglia cells, the immune cells of the brain. Functionality of microglia cells during normal pregnancy is, however, poorly understood. The recent outbreak of ZIKA virus (ZKV), but also the literature on virus infections in general and its consequences on microglial cell function and fetal neurodevelopment show the devastating effects a virus infection during pregnancy can have. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Adoptive transfer of paternal antigen-hyporesponsive T cells facilitates a Th2 bias in peripheral lymphocytes and at materno-fetal interface in murine abortion-prone matings.

PubMed

Jin, Li-Ping; Zhou, Yue-Hua; Zhu, Xiao-Yong; Wang, Ming-Yan; Li, Da-Jin

2006-10-01

To investigate the Th1/Th2 cytokine changes in abortion-prone recipient mice adoptively transferred by the paternal antigen-hyporesponsive T cells. The paternal antigen-hyporesponsive T cells were generated by the anti-B7 monoclonal antibody (mAb) treatment and adoptively transferred into pregnant CBA/J mice of abortion-prone matings on day 4 of gestation. The intracellular expressions of Th1 cell-derived cytokine, tumor necrosis factor-alpha, gamma-interferon and interleukin-2 (IL-2) and Th2 cell-derived cytokine, IL-4 and IL-10 in the maternal spleen were analyzed by flow cytometry, and secretions of the Th1 and Th2 cytokines in supernatant of the feto-placental unit culture were analyzed by an enzyme-linked immunosorbent assay. Our findings showed the increased secretion of Th1 cytokines and the decreased secretion of Th2 cytokines in abortion-prone matings. Treatment with anti-B7 mAbs on day 4 of gestation enhanced Th2 and reduced Th1 cytokine production in abortion-prone matings. Similarly, adoptive transfer of paternal antigen-hyporesponsive T cells induced maternal tolerance to the fetus and displayed a Th2 bias both in the peripheral lymphocytes and at the materno-fetal interface of the abortion-prone matings. These findings indicate that the Th2 cytokine bias and an increase in fetal viability induced by the anti-B7 mAb treatment can be transferred to other pregnant mice of the abortion-prone matings.

The effects of Qi exercise on maternal/fetal interaction and maternal well-being during pregnancy.

PubMed

Ji, Eun Sun; Han, Hae-Ra

2010-01-01

To investigate the effects of Qi exercise on maternal outcomes during pregnancy. A prospective, two-group, quasi-experimental, pretest/post test design was used. A convenience sample was recruited from one women's wellness center and one women's health clinic in Seoul, Korea. Participants were healthy pregnant women at more than 18 weeks gestation. A total of 70 women were included in the final analysis. Qi exercise was carried out for 90 minutes, twice a week for 12 weeks. Study outcomes were measured by the Intrapersonal Communication Questionnaire (Talking to Your Baby), Zung's Self-rating Depression Scale (ZSDS), the State Trait Anxiety Inventory (STAI), and the Pregnancy Mild Discomfort Index. Analysis of covariance was used to compare outcomes between groups, after adjusting for baseline scores. The Qi exercise group had higher post test maternal/fetal interaction and lower maternal depressive symptoms and physical discomfort scores than the control group. There was no difference in anxiety. The findings suggest that the holistic approach of Qi exercise may positively influence maternal/fetal interaction and mother's health. Whether these beneficial effects can be sustained throughout pregnancy requites additional research.

Second generation noninvasive fetal genome analysis reveals de novo mutations, single-base parental inheritance, and preferred DNA ends

PubMed Central

Chan, K. C. Allen; Jiang, Peiyong; Sun, Kun; Cheng, Yvonne K. Y.; Tong, Yu K.; Cheng, Suk Hang; Wong, Ada I. C.; Hudecova, Irena; Leung, Tak Y.; Chiu, Rossa W. K.; Lo, Yuk Ming Dennis

2016-01-01

Plasma DNA obtained from a pregnant woman was sequenced to a depth of 270× haploid genome coverage. Comparing the maternal plasma DNA sequencing data with the parental genomic DNA data and using a series of bioinformatics filters, fetal de novo mutations were detected at a sensitivity of 85% and a positive predictive value of 74%. These results represent a 169-fold improvement in the positive predictive value over previous attempts. Improvements in the interpretation of the sequence information of every base position in the genome allowed us to interrogate the maternal inheritance of the fetus for 618,271 of 656,676 (94.2%) heterozygous SNPs within the maternal genome. The fetal genotype at each of these sites was deduced individually, unlike previously, where the inheritance was determined for a collection of sites within a haplotype. These results represent a 90-fold enhancement in the resolution in determining the fetus’s maternal inheritance. Selected genomic locations were more likely to be found at the ends of plasma DNA molecules. We found that a subset of such preferred ends exhibited selectivity for fetal- or maternal-derived DNA in maternal plasma. The ratio of the number of maternal plasma DNA molecules with fetal preferred ends to those with maternal preferred ends showed a correlation with the fetal DNA fraction. Finally, this second generation approach for noninvasive fetal whole-genome analysis was validated in a pregnancy diagnosed with cardiofaciocutaneous syndrome with maternal plasma DNA sequenced to 195× coverage. The causative de novo BRAF mutation was successfully detected through the maternal plasma DNA analysis. PMID:27799561

Effects of prenatal maternal stress on serotonin and fetal development.

PubMed

St-Pierre, Joey; Laurent, Laetitia; King, Suzanne; Vaillancourt, Cathy

2016-12-01

Fetuses are exposed to many environmental perturbations that can influence their development. These factors can be easily identifiable such as drugs, chronic diseases or prenatal maternal stress. Recently, it has been demonstrated that the serotonin synthetized by the placenta was crucial for fetal brain development. Moreover, many studies show the involvement of serotonin system alteration in psychiatric disease during childhood and adulthood. This review summarizes existing studies showing that prenatal maternal stress, which induces alteration of serotonin systems (placenta and fetal brain) during a critical window of early development, could lead to alteration of fetal development and increase risks of psychiatric diseases later in life. This phenomenon, termed fetal programming, could be moderated by the sex of the fetus. This review highlights the need to better understand the modification of the maternal, placental and fetal serotonin systems induced by prenatal maternal stress in order to find early biomarkers of psychiatric disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-invasive prenatal detection of achondroplasia using circulating fetal DNA in maternal plasma.

PubMed

Lim, Ji Hyae; Kim, Mee Jin; Kim, Shin Young; Kim, Hye Ok; Song, Mee Jin; Kim, Min Hyoung; Park, So Yeon; Yang, Jae Hyug; Ryu, Hyun Mee

2011-02-01

To perform a reliable non-invasive detection of the fetal achondroplasia using maternal plasma. We developed a quantitative fluorescent-polymerase chain reaction (QF-PCR) method suitable for detection of the FGFR3 mutation (G1138A) causing achondroplasia. This method was applied in a non-invasive detection of the fetal achondroplasia using circulating fetal-DNA (cf-DNA) in maternal plasma. Maternal plasmas were obtained at 27 weeks of gestational age from women carrying an achondroplasia fetus or a normal fetus. Two percent or less achondroplasia DNA was reliably detected by QF-PCR. In a woman carrying a normal fetus, analysis of cf-DNA showed only one peak of the wild-type G allele. In a woman expected an achondroplasia fetus, analysis of cf-DNA showed the two peaks of wild-type G allele and mutant-type A allele and accurately detected the fetal achondroplasia. The non-invasive method using maternal plasma and QF-PCR may be useful for diagnosis of the fetal achondroplasia.

Chronic ethanol exposure and folic acid supplementation: fetal growth and folate status in the maternal and fetal guinea pig.

PubMed

Hewitt, Amy J; Knuff, Amber L; Jefkins, Matthew J; Collier, Christine P; Reynolds, James N; Brien, James F

2011-05-01

Chronic ethanol exposure (CEE) can produce developmental abnormalities in the CNS of the embryo and developing fetus. Folic acid (FA) is an important nutrient during pregnancy and low folate status exacerbates ethanol-induced teratogenicity. This study tested the hypotheses that (1) CEE depletes folate stores in the mother and fetus; and (2) maternal FA supplementation maintains folate stores. CEE decreased fetal body, brain, hippocampus weights, and brain to body weight ratio but not hippocampus to body weight ratio. These effects of CEE were not mitigated by maternal FA administration. The FA regimen prevented the CEE-induced decrease of term fetal liver folate. However, it did not affect maternal liver folate or fetal RBC folate at term, and did not mitigate the nutritional deficit-induced decrease of term fetal hippocampus folate. This study suggests that maternal FA supplementation may have differential effects on folate status in the mother and the fetus. Copyright © 2011 Elsevier Inc. All rights reserved.

Fetal radiation dose estimates for I-131 sodium iodide in cases where conception occurs after administration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sparks, R.B.; Stabin, M.G.

1999-01-01

After administration of I-131 to the female patient, the possibility of radiation exposure of the embryo/fetus exists if the patient becomes pregnant while radioiodine remains in the body. Fetal radiation dose estimates for such cases were calculated. Doses were calculated for various maternal thyroid uptakes and time intervals between administration and conception, including euthyroid and hyperthyroid cases. The maximum fetal dose calculating was about 9.8E-03 mGy/MBq, which occurred with 100% maternal thyroid uptake and a 1 week interval between administration and conception. Placental crossover of the small amount of radioiodine remaining 90 days after conception was also considered. Such crossovermore » could result in an additional fetal dose of 9.8E-05 mGy/MBq and a maximum fetal thyroid self dose of 3.5E-04 mGy/MBq.« less

Complications of shoulder dystocia.

PubMed

Dajani, Nafisa K; Magann, Everett F

2014-06-01

Complications of shoulder dystocia are divided into fetal and maternal. Fetal brachial plexus injury (BPI) is the most common fetal complication occurring in 4-40% of cases. BPI has also been reported in abdominal deliveries and in deliveries not complicated by shoulder dystocia. Fractures of the fetal humerus and clavicle occur in about 10.6% of cases of shoulder dystocia and usually heal with no sequel. Hypoxic ischemic brain injury is reported in 0.5-23% of cases of shoulder dystocia. The risk correlates with the duration of head-to-body delivery and is especially increased when the duration is >5 min. Fetal death is rare and is reported in 0.4% of cases. Maternal complications of shoulder dystocia include post-partum hemorrhage, vaginal lacerations, anal tears, and uterine rupture. The psychological stress impact of shoulder dystocia is under-recognized and deserves counseling prior to home discharge. Copyright © 2014 Elsevier Inc. All rights reserved.

Transfer entropy analysis of maternal and fetal heart rate coupling.

PubMed

Marzbanrad, Faezeh; Kimura, Yoshitaka; Endo, Miyuki; Palaniswami, Marimuthu; Khandoker, Ahsan H

2015-01-01

Although evidence of the short term relationship between maternal and fetal heart rates has been found in previous model-based studies, knowledge about the mechanism and patterns of the coupling during gestation is still limited. In this study, a model-free method based on Transfer Entropy (TE) was applied to quantify the maternal-fetal heart rate couplings in both directions. Furthermore, analysis of the lag at which TE was maximum and its changes throughout gestation, provided more information about the mechanism of coupling and its latency. Experimental results based on fetal electrocardiograms (fECGs) and maternal ECG showed the evidence of coupling for 62 out of 65 healthy mothers and fetuses in each direction, by statistically validating against the surrogate pairs. The fetuses were divided into three gestational age groups: early (16-25 weeks), mid (26-31 weeks) and late (32-41 weeks) gestation. The maximum TE from maternal to fetal heart rate significantly increased from early to mid gestation, while the coupling delay on both directions decreased significantly from mid to late gestation. These changes occur concomitant with the maturation of the fetal sensory and autonomic nervous systems with advancing gestational age. In conclusion, the application of TE with delays revealed detailed information about the changes in fetal-maternal heart rate coupling strength and latency throughout gestation, which could provide novel clinical markers of fetal development and well-being.

Absence of the HLA-G*0113N allele in Amerindian populations from the Brazilian Amazon region.

PubMed

Mendes-Junior, Celso T; Castelli, Erick C; Moreau, Philippe; Simões, Aguinaldo L; Donadi, Eduardo A

2010-04-01

The HLA-G gene is predominantly expressed at the maternal-fetal interface and has been associated with maternal-fetal tolerance. The HLA-G*0113N is a null allele defined by the insertion of a premature stop codon at exon 2, observed in a single Ghanaian individual. Likewise the G*0105N allele, the occurrence of the HLA-G*0113N in a population from an area with high pathogen load suggests that the reduced HLA-G expression in G*0113N heterozygous placentas could improve the intrauterine defense against infections. The presence of the G*0113N allele here was investigated in 150 Amerindians from five isolated tribes that inhabit the Central Amazon and in 295 admixed individuals from the State of São Paulo, Southeastern Brazil, previously genotyped for HLA-G. No copy of the G*0113N null allele was found in both population samples by exon 2 sequence-based analysis, reinforcing its restricted occurrence in Africa.

Maternal pelvic dimensions and neonatal size: Implications for growth plasticity in early life as adaptation.

PubMed

Wells, Jonathan C K; Figueiroa, José N; Alves, Joao G

2017-01-01

Patterns of fetal growth predict non-communicable disease risk in adult life, but fetal growth variability appears to have a relatively weak association with maternal nutritional dynamics during pregnancy. This challenges the interpretation of fetal growth variability as 'adaptation'. We hypothesized that associations of maternal size and nutritional status with neonatal size are mediated by the dimensions of the maternal pelvis. We analysed data on maternal height, body mass index (BMI) and pelvic dimensions (conjugate, inter-spinous and inter-cristal diameters) and neonatal gestational age, weight, length, thorax girth and head girth ( n = 224). Multiple regression analysis was used to identify independent maternal predictors of neonatal size, and the mediating role of neonatal head girth in these associations. Pelvic dimensions displaced maternal BMI as a predictor of birth weight, explaining 11.6% of the variance. Maternal conjugate and inter-spinous diameters predicted neonatal length, thorax girth and head girth, whereas inter-cristal diameter only predicted neonatal length. Associations of pelvic dimensions with birth length, but not birth weight, were mediated by neonatal head girth. Pelvic dimensions predicted neonatal size better than maternal BMI, and these associations were mostly independent of maternal height. Sensitivity of fetal growth to pelvic dimensions reduces the risk of cephalo-pelvic disproportion, potentially a strong selective pressure during secular trends in height. Selection on fetal adaptation to relatively inflexible components of maternal phenotype, rather than directly to external ecological conditions, may help explain high levels of growth plasticity during late fetal life and early infancy.

Nutrition During Pregnancy and the Effect of Carbohydrates on the Offspring's Metabolic Profile: In Search of the "Perfect Maternal Diet".

PubMed

Tzanetakou, Irene P; Mikhailidis, Dimitri P; Perrea, Despina N

2011-01-01

Fetal growth and development is primarily dependent upon the nutritional, hormonal and metabolic environment provided by the mother. A wartime famine study in Holland first showed that a low food intake reduces the glucose offered to the fetus and thus produces smaller size infants at birth. Maternal glucose regulation is however affected by numerous factors including physiological changes of pregnancy (e.g. insulin resistance [IR]), pathological conditions (e.g. gestational diabetes mellitus) and maternal nutrition. Maternal glucose is substantially influenced by the type of carbohydrates in the diet through its direct effect on glycemia. The rate at which each carbohydrate raises blood glucose levels after ingestion, can be measured via the dietary glycemic index (GI). Carbohydrate type and the GI of the diet enhance or inhibit abnormal hyperglycemia during pregnancy caused by either pathological conditions or the inability of the mother to cope with the physiological IR of pregnancy. In turn, maternal gestational hyperglycemia may be involved in the pathogenesis of IR, impaired glucose tolerance, type 2 diabetes mellitus, the Metabolic Syndrome and subsequent cardiovascular diseases in adult offspring. A low GI maternal diet has been associated with measurable benefits to the offspring. These include a positive effect on altering maternal blood glucose production, insulinemia and reduced adiposity as well as fetal and placental insulin and glucose regulation, fetal growth, birth weight and offspring adiposity. We review the possible links between dietary carbohydrate in health during pregnancy and the effect of maternal carbohydrate ingestion on programming the offspring's metabolic profile.

Hyperparathyroidism in pregnancy: options for localization and surgical therapy.

PubMed

McMullen, Todd P W; Learoyd, Diana L; Williams, David C; Sywak, Mark S; Sidhu, Stan B; Delbridge, Leigh W

2010-08-01

Hyperparathyroidism in pregnancy is a threat to the health of both mother and fetus. The mothers suffer commonly from nephrolithiasis, hyperemesis, or even hypercalcemic crisis. Untreated disease will commonly complicate fetal development and fetal death is a significant risk. Treatment options, including medical and surgical therapy, are debated in the literature. This is a case series comprising seven patients with primary hyperparathyroidism in pregnancy. Data collected included symptoms at diagnosis, biochemical abnormalities, pathologic findings, treatment regimes, and subsequent maternal and fetal outcomes. Seven women, aged 20 to 39 years, presented with hyperparathyroidism during pregnancy. The earliest presented at 8 weeks and the latest at 38 weeks. Four of seven patients experienced renal calculi. Calcium levels were 2.7-3.5 mmol/l. All were found to have solitary parathyroid adenomas, of which two were in ectopic locations. Fetal complications included three preterm deliveries and one fetal death with no cases of neonatal tetany. Maternal and fetal complications could not be predicted based on duration or severity of hypercalcemia. Three patients were treated during pregnancy with surgery, and two of these had ectopic glands that required reoperations with a novel approach using Tc-99m sestamibi scanning during pregnancy to assist in localizing the abnormal gland. Four cases were treated postpartum with a combination of open and minimally invasive approaches after localization. No operative complications or fetal loss related to surgery were observed in this cohort. Primary hyperparathyroidism in pregnancy represents a significant risk for maternal and fetal complications that cannot be predicted by duration of symptoms or serum calcium levels. Surgical treatment should be considered early, and a minimally invasive approach with ultrasound is best suited to mitigating risk to mother and fetus. Equally important, Tc-99m sestamibi imaging may be used safely for localization of the parathyroids after negative cervical explorations.

Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth: A Mendelian Randomization Analysis.

PubMed

Zhang, Ge; Bacelis, Jonas; Lengyel, Candice; Teramo, Kari; Hallman, Mikko; Helgeland, Øyvind; Johansson, Stefan; Myhre, Ronny; Sengpiel, Verena; Njølstad, Pål Rasmus; Jacobsson, Bo; Muglia, Louis

2015-08-01

Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach. We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 × 10-9), birth weight (p = 2.19 × 10-15), and gestational age (p = 1.51 × 10-7). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal height resulting in ~0.4 more gestational d. Limitations of this study include potential influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampling of study subjects. Our results demonstrate that the observed association between maternal height and fetal growth measures (i.e., birth length and birth weight) is mainly defined by fetal genetics. In contrast, the association between maternal height and gestational age is more likely to be causal. In addition, our approach that utilizes the genetic score derived from the nontransmitted maternal haplotype as a genetic instrument is a novel extension to the Mendelian randomization methodology in casual inference between parental phenotype (or exposure) and outcomes in offspring.

Assessing the Causal Relationship of Maternal Height on Birth Size and Gestational Age at Birth: A Mendelian Randomization Analysis

PubMed Central

Zhang, Ge; Bacelis, Jonas; Lengyel, Candice; Teramo, Kari; Hallman, Mikko; Helgeland, Øyvind; Johansson, Stefan; Myhre, Ronny; Sengpiel, Verena; Njølstad, Pål Rasmus; Jacobsson, Bo; Muglia, Louis

2015-01-01

Background Observational epidemiological studies indicate that maternal height is associated with gestational age at birth and fetal growth measures (i.e., shorter mothers deliver infants at earlier gestational ages with lower birth weight and birth length). Different mechanisms have been postulated to explain these associations. This study aimed to investigate the casual relationships behind the strong association of maternal height with fetal growth measures (i.e., birth length and birth weight) and gestational age by a Mendelian randomization approach. Methods and Findings We conducted a Mendelian randomization analysis using phenotype and genome-wide single nucleotide polymorphism (SNP) data of 3,485 mother/infant pairs from birth cohorts collected from three Nordic countries (Finland, Denmark, and Norway). We constructed a genetic score based on 697 SNPs known to be associated with adult height to index maternal height. To avoid confounding due to genetic sharing between mother and infant, we inferred parental transmission of the height-associated SNPs and utilized the haplotype genetic score derived from nontransmitted alleles as a valid genetic instrument for maternal height. In observational analysis, maternal height was significantly associated with birth length (p = 6.31 × 10−9), birth weight (p = 2.19 × 10−15), and gestational age (p = 1.51 × 10−7). Our parental-specific haplotype score association analysis revealed that birth length and birth weight were significantly associated with the maternal transmitted haplotype score as well as the paternal transmitted haplotype score. Their association with the maternal nontransmitted haplotype score was far less significant, indicating a major fetal genetic influence on these fetal growth measures. In contrast, gestational age was significantly associated with the nontransmitted haplotype score (p = 0.0424) and demonstrated a significant (p = 0.0234) causal effect of every 1 cm increase in maternal height resulting in ~0.4 more gestational d. Limitations of this study include potential influences in causal inference by biological pleiotropy, assortative mating, and the nonrandom sampling of study subjects. Conclusions Our results demonstrate that the observed association between maternal height and fetal growth measures (i.e., birth length and birth weight) is mainly defined by fetal genetics. In contrast, the association between maternal height and gestational age is more likely to be causal. In addition, our approach that utilizes the genetic score derived from the nontransmitted maternal haplotype as a genetic instrument is a novel extension to the Mendelian randomization methodology in casual inference between parental phenotype (or exposure) and outcomes in offspring. PMID:26284790

Fetal Neurobehavioral Development and the Role of Maternal Nutrient Intake and Psychological Health

ERIC Educational Resources Information Center

Spann, Marisa; Smerling, Jennifer; Gustafsson, Hanna C.; Foss, Sophie; Monk, Catherine

2014-01-01

Measuring and understanding fetal neurodevelopment provides insight regarding the developing brain. Maternal nutrient intake and psychological stress during pregnancy each impact fetal neurodevelopment and influence childhood outcomes and are thus important factors to consider when studying fetal neurobehavioral development. The authors provide an…

Rapid resolution of fetal goiter associated with maternal Grave's disease: a case report.

PubMed

Friedland, D R; Rothschild, M A

2000-08-11

The incidence of abnormal fetal thyroid function with maternal Grave's disease is about 2-12%. The development of larger fetal goiters can complicate labor and precipitate life-threatening airway obstruction at delivery. A case is presented of a large stable goiter confirmed by sonography, which unexpectedly resolved by the time of parturition. A 3 x 6 cm fetal goiter was detected at 34 weeks gestation in a mother treated with propylthiouracil for Grave's disease. A repeat sonogram at 36 weeks showed no change in goiter size. Umbilical blood sampling showed the fetus to be markedly hyperthyroid. Planned Cesarean section took place 11 days after the final sonogram. A multi-disciplinary operative team was present including the Otolaryngology service with equipment for emergency intubation, bronchoscopy and tracheotomy. Upon delivery, the infant had no evidence of goiter and no airway compromise. Fetal goiter is a rare entity, and recent advances in the field of maternal-fetal medicine have enabled intra-uterine diagnosis and treatment of such conditions. A review of published case reports demonstrates two trends in treated fetuses: preterm progressive resolution of the goiter, or delivery with gross evidence of goiter. This reported case is unique, as a persistent goiter resolved completely in less than 2 weeks. Otolaryngologic response to and management of potential congenital airway compromise is discussed.

Higher Fetal Insulin Resistance in Chinese Pregnant Women with Gestational Diabetes Mellitus and Correlation with Maternal Insulin Resistance

PubMed Central

Wang, Qiuwei; Huang, Ruiping; Yu, Bin; Cao, Fang; Wang, Huiyan; Zhang, Ming; Wang, Xinhong; Zhang, Bin; Zhou, Hong; Zhu, Ziqiang

2013-01-01

Objective The aim of this study was to determine the effect of gestational diabetes mellitus (GDM) on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM. Measurements Maternal fasting blood and venous cord blood samples (reflecting fetal condition) were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention) and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) and the proinsulin-to-insulin ratios (an indicator of fetal β-cell function) were calculated in maternal and cord blood respectively. Results Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but not proinsulin-to-insulin ratios were significantly higher in the GDM group than in the control group (maternal insulin, 24.8 vs. 15.4 µU/mL, P = 0.004, proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041, respectively; fetal: insulin, 15.1 vs. 7.9 µU/mL, P<0.001, proinsulin, 25.8 vs. 15.1 pmol/L, P = 0.015, and HOMA-IR, 2.8 vs. 1.4, P = 0.017, respectively). Fetal HOMA-IR but not proinsulin-to-insulin ratios was significantly correlated to maternal HOMA-IR (r = 0.307, P = 0.019), in the pregnant women with GDM. Conclusions Fetal insulin resistance was higher in Chinese pregnant women with GDM than control subjects, and correlated with maternal insulin resistance. PMID:23560057

RF Safety Analysis of a Novel Ultra-wideband Fetal Monitoring System.

PubMed

Bushberg, Jerrold T; Tupin, J Paul

2017-05-01

The LifeWave Ultra-Wideband RF sensor (LWUWBS) is a monitoring solution for a variety of physiologic assessment applications, including maternal fetal monitoring in both the antepartum and intrapartum periods. The system uses extremely low power radio frequency (RF) ultra-wide band (UWB) signals to provide continuous fetal heart rate and contractions monitoring during labor and delivery. Even with the incorporation of three very conservative assumptions, (1) concentration of the RF energy in 1 cm, (2) minimal (2.5 cm) maternal tissue attenuation of fetal exposure, and (3) absence of normal thermoregulatory compensation, the maternal whole body spatial-averaged specific absorption rate (WBSAR) would be 34,000 times below the FCC public exposure limit of 0.08 W kg and, at 8 wk or more gestation, the peak spatial-averaged specific absorption rate (PSSAR) in the fetus would be more than 160 times below the localized exposure limit of 1.6 mW g. Even when using very conservative assumptions, an analysis of the LWUWBS's impact on tissue heating is a factor of 7 lower than what is allowed for fetal ultrasound and at least a factor of 650 compared to fetal MRI. The actual transmitted power levels of the LWUWBS are well below all Federal safety standards, and the potential for tissue heating is substantially lower than associated with current ultrasonic fetal monitors and MRI.

Oral supplements of inulin during gestation offsets rotenone-induced oxidative impairments and neurotoxicity in maternal and prenatal rat brain.

PubMed

Krishna, Gokul; Muralidhara

2018-05-25

Environmental insults including pesticide exposure and their entry into the immature brain are of increased concern due to their developmental neurotoxicity. Several lines of evidence suggest that maternal gut microbiota influences in utero fetal development via modulation of host's microbial composition with prebiotics. Hence we examined the hypothesis if inulin (IN) supplements during pregnancy in rats possess the potential to alleviate brain oxidative response and mitochondrial deficits employing a developmental model of rotenone (ROT) neurotoxicity. Initially, pregnant Sprague-Dawley rats were gavaged during gestational days (GDs) 6-19 with 0 (control), 10 (low), 30 (mid) or 50 (high) mg/kg bw/day of ROT to recapitulate developmental effects on general fetotoxicity (assessed by the number of fetuses, fetal body and placental weights), markers of oxidative stress and cholinergic activities in maternal brain regions and whole fetal-brain. Secondly, dams orally supplemented with inulin (2×/day, 2 g/kg/bw) on GD 0-21 were administered ROT (50 mg/kg, GD 6-19). IN supplements increased maternal cecal bacterial numbers that significantly corresponded with improved exploratory-related behavior among ROT administered rats. In addition, IN supplements improved fetal and placental weight on GD 19. IN diminished gestational ROT-induced increased reactive oxygen species levels, protein and lipid peroxidation biomarkers, and cholinesterase activity in maternal brain regions (cortex, cerebellum, and striatum) and fetal brain. Moreover, in the maternal cortex, mitochondrial assessment revealed IN protected against ROT-induced reduction in NADH cytochrome c oxidoreductase and ATPase activities. These data suggest a potential role for indigestible oligosaccharides in reducing oxidative stress-mediated developmental origins of neurodegenerative disorders. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A possible new approach in the prediction of late gestational hypertension

PubMed Central

Visentin, Silvia; Londero, Ambrogio P.; Camerin, Martina; Grisan, Enrico; Cosmi, Erich

2017-01-01

Abstract The aim was to determine the predictive role of combined screening for late-onset gestational hypertension by fetal ultrasound measurements, third trimester uterine arteries (UtAs) Doppler imaging, and maternal history. This prospective study on singleton pregnancies was conducted at the tertiary center of Maternal and Fetal Medicine of the University of Padua during the period between January 2012 and December 2014. Ultrasound examination (fetal biometry, fetal wellbeing, maternal Doppler study, fetal abdominal aorta intima-media thickness [aIMT], and fetal kidney volumes), clinical data (mother age, prepregnancy body mass index [BMI], and parity), and pregnancy outcomes were collected. The P value <0.05 was defined significant considering a 2-sided alternative hypothesis. The distribution normality of variables were assessed using Kolmogorov–Smirnoff test. Data were presented by mean (±standard deviation), median and interquartile range, or percentage and absolute values. We considered data from 1381 ultrasound examinations at 29 to 32 weeks’ gestation, and in 73 cases late gestational hypertension developed after 34 weeks’ gestation. The final multivariate model found that fetal aIMT as well as fetal umbilical artery pulsatility index (PI), maternal age, maternal prepregnacy BMI, parity, and mean PI of maternal UtAs, assessed at ultrasound examination of 29 to 32 weeks’ gestation, were significant and independent predictors for the development of gestational hypertension after 34 weeks’ gestation. The area under the curve of the model was 81.07% (95% confidence interval, 75.83%–86.32%). A nomogram was developed starting from multivariate logistic regression coefficients. Late-gestational hypertension could be independently predicted by fetal aIMT assessment at 29 to 32 weeks’ gestation, ultrasound Doppler waveforms, and maternal clinical parameters. PMID:28079791

Non-invasive prenatal diagnosis.

PubMed

Meaney, Cathy; Norbury, Gail

2011-01-01

The discovery of cell-free fetal DNA in the maternal plasma of pregnant women has facilitated the development of non-invasive prenatal diagnosis (NIPD). This has been successfully implemented in diagnostic laboratories for Rhesus typing and fetal sex determination for X-linked disorders and congenital adrenal hyperplasia (CAH) from 7 weeks gestation. Using real-time PCR, fluorescently labelled target gene specific probes can identify and quantify low copy number fetal-specific sequences in a high background of maternal DNA in the cell-free DNA extracted from maternal plasma.NIPD to detect specific fetal mutations in single gene disorders, currently by standard PCR techniques, can only be undertaken for paternally derived or de novo mutations because of the background maternal DNA. For routine use, this testing is limited by the large amounts of cell-free maternal DNA in the sample, the lack of universal fetal markers, and appropriate reference materials.

Diet around conception and during pregnancy--effects on fetal and neonatal outcomes.

PubMed

Kind, Karen L; Moore, Vivienne M; Davies, Michael J

2006-05-01

Substrate supply to the fetus is a major regulator of prenatal growth. Maternal nutrition influences the availability of nutrients for transfer to the fetus. Animal experiments demonstrate that restriction of maternal protein or energy intake can retard fetal growth. Effects of maternal nutrition vary with the type and timing of the restriction and the species studied. Maternal undernutrition before conception and/or in early pregnancy can alter fetal physiology in late gestation, and influence postnatal function, often without measurable effects on birth size. In contrast, to date, observational and intervention studies in humans provide limited support for a major role of maternal nutrition in determining birth size, except where women are quite malnourished. However, recent studies report associations between newborn size and the balance of macronutrients in women's diets in Western settings. Associations between maternal dietary composition and adult blood pressure of the offspring are also reported in human populations. Most studies in women have focused on dietary content or supplementation during mid-late pregnancy. Further investigation of how maternal dietary composition, before conception and throughout pregnancy, affects fetal physiology and health of the baby will increase the understanding of how maternal diet and nutritional status influence fetal, neonatal and longer-term outcomes.

Can the season of birth risk factor for schizophrenia be prevented by bright light treatment for the second trimester mother around the winter solstice?

PubMed

Schwartz, Paul J

2014-12-01

The season of birth risk factor for schizophrenia exerts a pervasive effect on the global population, particularly at northerly latitudes. The winter infection hypothesis and the low vitamin D hypothesis are both compelling but lack conclusive clinical data. The present work develops a maternal-fetal chronobiological hypothesis for this season of birth risk factor and its prevention by maternal bright light treatment. Around the winter solstice, due to decreased sunlight, the chronobiological apparatus of the at-risk second trimester mother is characterized by a reduced amplitude circadian pacemaker, and a reduced maximum of her nocturnal plasma melatonin concentrations (MTmax) and an increased minimum of her nocturnal core body temperatures (Tmin)--both of which exert adverse effects on the fetal hippocampus and dorsal striatum. The consequences for the fetus include reduced volume and increased excitability of the hippocampus, ventral striatal dysfunction, increased presynaptic nigrostriatal dopamine transmission, and increased propensity for pathological nigrostriatal neuronal phasic firing. Thus, the maternal-fetal chronobiological hypothesis fully accounts for the fetal precursors of the major pathognomonic abnormalities in adults with schizophrenia. Bright light treatment for the second trimester mother around the winter solstice, by increasing maternal circadian amplitude, could possibly prevent the fetal hippocampal and striatal abnormalities and eliminate the season of birth risk factor for schizophrenia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prenatal Antecedents of Newborn Neurological Maturation

PubMed Central

DiPietro, Janet A.; Kivlighan, Katie T.; Costigan, Kathleen A.; Rubin, Suzanne E.; Shiffler, Dorothy E.; Henderson, Janice L.; Pillion, Joseph P.

2009-01-01

Fetal neurobehavioral development was modeled longitudinally using data collected at weekly intervals from 24- to -38 weeks gestation in a sample of 112 healthy pregnancies. Predictive associations between 3 measures of fetal neurobehavioral functioning and their developmental trajectories to neurological maturation in the 1st weeks after birth were examined. Prenatal measures included fetal heart rate variability, fetal movement, and coupling between fetal motor activity and heart rate patterning; neonatal outcomes include a standard neurologic examination (n = 97) and brainstem auditory evoked potential (BAEP; n = 47). Optimality in newborn motor activity and reflexes was predicted by fetal motor activity; fetal heart rate variability and somatic-cardiac coupling predicted BAEP parameters. Maternal pregnancy-specific psychological stress was associated with accelerated neurologic maturation. PMID:20331657

Impacts of maternal dietary protein intake on fetal survival, growth, and development.

PubMed

Herring, Cassandra M; Bazer, Fuller W; Johnson, Gregory A; Wu, Guoyao

2018-03-01

Maternal nutrition during gestation, especially dietary protein intake, is a key determinant in embryonic survival, growth, and development. Low maternal dietary protein intake can cause embryonic losses, intra-uterine growth restriction, and reduced postnatal growth due to a deficiency in specific amino acids that are important for cell metabolism and function. Of note, high maternal dietary protein intake can also result in intra-uterine growth restriction and embryonic death, due to amino acid excesses, as well as the toxicity of ammonia, homocysteine, and H 2 S that are generated from amino acid catabolism. Maternal protein nutrition has a pronounced impact on fetal programming and alters the expression of genes in the fetal genome. As a precursor to the synthesis of molecules (e.g. nitric oxide, polyamines, and creatine) with cell signaling and metabolic functions, L-arginine (Arg) is essential during pregnancy for growth and development of the conceptus. With inadequate maternal dietary protein intake, Arg and other important amino acids are deficient in mother and fetus. Dietary supplementation of Arg during gestation has been effective in improving embryonic survival and development of the conceptus in many species, including humans, pigs, sheep, mice, and rats. Both the balance among amino acids and their quantity are critical for healthy pregnancies and offspring. Impact statement This review aims at: highlighting adverse effects of elevated levels of ammonia in mother or fetus on embryonic/fetal survival, growth, and development; helping nutritionists and practitioners to understand the mechanisms whereby elevated levels of ammonia in mother or fetus results in embryonic/fetal death, growth restriction, and developmental abnormalities; and bringing, into the attention of nutritionists and practitioners, the problems of excess or inadequate dietary intake of protein or amino acids on pregnancy outcomes in animals and humans. The article provides new, effective means to improve embryonic/fetal survival and growth in mammals.

Effect of simple, targeted diet in pregnant women with metabolic risk factors on maternal and fetal outcomes (ESTEEM): study protocol for a pragmatic multicentre randomised trial

PubMed Central

Al Wattar, Bassel H; Dodds, Julie; Placzek, Anna; Spyreli, Eleni; Moore, Amanda; Hooper, Richard; Beresford, Lee; Roseboom, Tessa J; Bes-Rastrollo, Maira; Hitman, Graham; Khan, Khalid S; Thangaratinam, Shakila

2016-01-01

Introduction Women with metabolic risk factors are at higher risk of adverse pregnancy outcomes. Mediterranean-based dietary interventions have the potential to minimise these risks. We aim to evaluate the effectiveness of a simple, targeted intervention modelled on Mediterranean diet in preventing maternal and fetal complications in pregnant women with metabolic risk factors. Methods and analysis Pregnant women with a singleton pregnancy <18 weeks gestation, and without pre-existing diabetes, chronic renal disease and autoimmune diseases will be recruited. Women with metabolic risk factors will be randomised to receive a dietary intervention based on a Mediterranean pattern, supplemented with extra virgin olive oil and mixed nuts until delivery. The intervention will be delivered through a series of one to one and group sessions. The primary outcome is a composite maternal outcome of pre-eclampsia or gestational diabetes and a composite fetal outcome of stillbirth, small for gestational age fetus or admission to the neonatal intensive care unit. Secondary outcomes include maternal, fetal, dietary and laboratory outcomes. We aim to randomise 1230 eligible women with metabolic risk factors. We will also compare the outcomes in women with and without these risk factors. The sample size will provide us with 80% power at 5% significance, assuming a 20% loss to follow-up to detect a 30% reduction in maternal and fetal complications. Ethics and dissemination The ESTEEM trial is designed to provide a definitive estimate of the effects of Mediterranean dietary pattern in pregnancy on maternal and fetal outcomes. The pragmatic nature of ESTEEM ensures the applicability of its findings into clinical practice. The findings of the study will be published in peer-reviewed journals and presented at national and international scientific meetings and congresses. Ethical approval was granted by the NHS Research Ethics Committees (14/EE/1048). Trial registration number NCT02218931; Pre-results. PMID:27798035

Weighing the Social and Ethical Considerations of Maternal-Fetal Surgery.

PubMed

Antiel, Ryan M; Flake, Alan W; Collura, Christopher A; Johnson, Mark P; Rintoul, Natalie E; Lantos, John D; Curlin, Farr A; Tilburt, Jon C; Brown, Stephen D; Feudtner, Chris

2017-12-01

The ethics of maternal-fetal surgery involves weighing the importance of potential benefits, risks, and other consequences involving the pregnant woman, fetus, and other family members. We assessed clinicians' ratings of the importance of 9 considerations relevant to maternal-fetal surgery. This study was a discrete choice experiment contained within a 2015 national mail-based survey of 1200 neonatologists, pediatric surgeons, and maternal-fetal medicine physicians, with latent class analysis subsequently used to identify groups of physicians with similar ratings. Of 1176 eligible participants, 660 (56%) completed the discrete choice experiment. The highest-ranked consideration was of neonatal benefits, which was followed by consideration of the risk of maternal complications. By using latent class analysis, we identified 4 attitudinal groups with similar patterns of prioritization: "fetocentric" ( n = 232), risk-sensitive ( n = 197), maternal autonomy ( n = 167), and family impact and social support ( n = 64). Neonatologists were more likely to be in the fetocentric group, whereas surgeons were more likely to be in the risk-sensitive group, and maternal-fetal medicine physicians made up the largest percentage of the family impact and social support group. Physicians vary in how they weigh the importance of social and ethical considerations regarding maternal-fetal surgery. Understanding these differences may help prevent or mitigate disagreements or tensions that may arise in the management of these patients. Copyright © 2017 by the American Academy of Pediatrics.

Second-trimester maternal serum marker screening: maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome.

PubMed

Yaron, Y; Cherry, M; Kramer, R L; O'Brien, J E; Hallak, M; Johnson, M P; Evans, M I

1999-10-01

We evaluated the value of all 3 common biochemical serum markers, maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and unconjugated estriol, and combinations thereof as predictors of pregnancy outcome. A total of 60,040 patients underwent maternal serum screening. All patients had maternal serum alpha-fetoprotein measurements; beta-human chorionic gonadotropin was measured in 45,565 patients, and 24,504 patients had determination of all 3 markers, including unconjugated estriol. The incidences of various pregnancy outcomes were evaluated according to the serum marker levels by using clinically applied cutoff points. In confirmation of previous observations, increased maternal serum alpha-fetoprotein levels (>2.5 multiples of the median) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, intrauterine growth restriction, intrauterine fetal death, oligohydramnios, and abruptio placentae. Increased beta-human chorionic gonadotropin levels (>2.5 multiples of the median [MoM]) were significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, and intrauterine fetal death. Finally, decreased unconjugated estriol levels (<0.5 MoM) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, intrauterine growth restriction, and intrauterine fetal death. As with increased second-trimester maternal serum alpha-fetoprotein levels, increased serum beta-human chorionic gonadotropin and low unconjugated estriol levels are significantly associated with adverse pregnancy outcomes. These are most likely attributed to placental dysfunction. Multiple-marker screening can be used not only for the detection of fetal anomalies and aneu-ploidy but also for detection of high-risk pregnancies.

Review: Adiponectin – The Missing Link between Maternal Adiposity, Placental Transport and Fetal Growth?

PubMed Central

Aye, Irving L. M. H.; Powell, Theresa L.; Jansson, Thomas

2012-01-01

Adiponectin has well-established insulin-sensitizing effects in non-pregnant individuals. Pregnant women who are obese or have gestational diabetes typically have low circulating levels of adiponectin, which is associated with increased fetal growth. Lean women, on the other hand, have high circulating levels of adiponectin. As a result, maternal serum adiponectin is inversely correlated to fetal growth across the full range of birth weights, suggesting that maternal adiponectin may limit fetal growth. In the mother, adiponectin is predicted to promote insulin sensitivity and stimulate glucose uptake in maternal skeletal muscle thereby reducing nutrient availability for placental transfer. Adiponectin prevents insulin-stimulated amino acid uptake in cultured primary human trophoblast cells by modulating insulin receptor substrate phosphorylation. Furthermore, chronic administration of adiponectin to pregnant mice inhibits placental insulin and mammalian target of rapamycin complex 1 (mTORC1) signaling, down-regulates the activity and expression of key placental nutrient transporters and decreases fetal growth. Preliminary findings indicate that adiponectin binds to the adiponectin receptor-2 on the trophoblast cell and activates p38 MAPK and PPAR-α, which inhibits the insulin/IGF-1 signaling pathway. In contrast to maternal adiponectin, recent reports suggest that fetal adiponectin may promote expansion of adipose tissue and stimulate fetal growth. Regulation of placental function by adiponectin constitutes a novel physiological mechanism by which the endocrine functions of maternal adipose tissue influence fetal growth. These findings may help us better understand the factors determining birth weight in normal pregnancies and in pregnancy complications associated with altered maternal adiponectin levels such as obesity and gestational diabetes. PMID:23245987

Prospective validation of first-trimester combined screening for trisomy 21.

PubMed

Kagan, K O; Etchegaray, A; Zhou, Y; Wright, D; Nicolaides, K H

2009-07-01

To examine the performance of the new algorithm in screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). This was a prospective screening study for trisomy 21 in singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation using an algorithm combining maternal age, fetal NT thickness based on the mixture model for the assessment of NT, and maternal serum free beta-hCG and PAPP-A based on a multiple regression model for the assessment of serum biochemistry. The NT measurements were performed by 60 operators who had obtained The Fetal Medicine Foundation certificate of competence in the 11-13-week scan. The study population consisted of 19 614 pregnancies with a normal karyotype or delivery of a phenotypically normal baby (euploid group) and 122 cases of trisomy 21. In the euploid fetuses the NT was above the previously defined 50(th), 95(th) and 99(th) centiles in 10 033 (51.2%), 618 (3.2%) and 123 (0.6%) cases and the respective values for trisomy 21 were 117 (95.9%), 94 (77.0%) and 57 (46.7%). The median fetal NT was within 0.1 mm of the expected in 47 (78.3%) of the 60 sonographers and within 0.2 mm in all. In the euploid fetuses the median free beta-hCG was 1.0 (range, 0.1-29.4) multiples of the median (MoM) and the median PAPP-A was 1.0 (range, 0.2-3.3) MoM. The median MoM values were 1.0 or close to 1.0 MoM for each subgroup of pregnancy characteristics, including gestations of 11, 12 and 13 weeks, maternal weight of < 60 kg, 60-80 kg and > 80 kg, different ethnic origins, cigarette smokers and non-smokers, natural conception and in vitro fertilization. For a false-positive rate of 3%, the detection rate of trisomy 21 in screening by maternal age and fetal NT was 81% (95% CI, 73-89%), by maternal age and maternal serum biochemistry it was 63% (95% CI, 56-72%) and by combined screening based on maternal age, fetal NT and maternal serum biochemistry it was 90% (95% CI, 84-96%). This study has validated the new risk algorithm and demonstrated that in combined screening for trisomy 21 based on maternal age, fetal NT and free beta-hCG and PAPP-A the detection rate is about 90% for a 3% false-positive rate. (c) 2009 ISUOG.

Adverse maternal outcomes associated with fetal macrosomia: what are the risk factors beyond birthweight?

PubMed

Fuchs, Florent; Bouyer, Jean; Rozenberg, Patrick; Senat, Marie-Victoire

2013-04-08

To identify risk factors, beyond fetal weight, associated with adverse maternal outcomes in delivering infants with a birthweight of 4000 g or greater, and to quantify their role in maternal complications. All women (n = 1564) with singleton pregnancies who attempted vaginal delivery and delivered infants weighing at least 4000 g, in two French tertiary care centers from 2005 to 2008, were included in our study. The studied outcome was maternal complications defined as composite item including the occurrence of a third- or fourth-degree perineal laceration, or the occurrence of severe postpartum hemorrhage requiring the use of prostaglandins, uterine artery embolization, internal iliac artery ligation or haemostatic hysterectomy, or the occurrence of blood transfusion. Univariate analysis, multivariable logistic regression and estimation of attributable risk were used. Maternal complications were increased in Asian women (adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 1.1-9.3, Attributable risk (AR): 3%), in prolonged labor (aOR = 1.9 [95% CI; 1.1-3.4], AR = 12%) and in cesarean delivery during labor (aOR = 2.2 [95% CI; 1.3-3.9], AR = 17%). Delivering infants with a birthweight > 4500 g also increased the occurrence of maternal complications (aOR = 2.7 [95% CI; 1.4-5.1]) but with an attributable risk of only 10%. Multiparous women with a previous delivery of a macrosomic infant were at lower risk of maternal complications (aOR = 0.5 [95% CI; 0.2-0.9]). In women delivering infants with a birthweight of 4000 g or greater, some maternal characteristics as well as labor parameters may worsen maternal outcome beyond the influence of increased fetal weight.

Postpartum bonding: the role of perinatal depression, anxiety and maternal-fetal bonding during pregnancy.

PubMed

Dubber, S; Reck, C; Müller, M; Gawlik, S

2015-04-01

Adverse effects of perinatal depression on the mother-child interaction are well documented; however, the influence of maternal-fetal bonding during pregnancy on postpartum bonding has not been clearly identified. The subject of this study was to investigate prospectively the influence of maternal-fetal bonding and perinatal symptoms of anxiety and depression on postpartum mother-infant bonding. Data from 80 women were analyzed for associations of symptoms of depression and anxiety as well as maternal bonding during pregnancy to maternal bonding in the postpartum period using the Edinburgh Postnatal Depression Scale (EPDS), the State-Trait Anxiety Inventory (STAI), the Pregnancy Related Anxiety Questionnaire (PRAQ-R), the Maternal-Fetal Attachment Scale (MFAS) and the Postpartum Bonding Questionnaire (PBQ-16). Maternal education, MFAS, PRAQ-R, EPDS and STAI-T significantly correlated with the PBQ-16. In the final regression model, MFAS and EPDS postpartum remained significant predictors of postpartum bonding and explained 20.8 % of the variance. The results support the hypothesized negative relationship between maternal-fetal bonding and postpartum maternal bonding impairment as well as the role of postpartum depressive symptoms. Early identification of bonding impairment during pregnancy and postpartum depression in mothers plays an important role for the prevention of potential bonding impairment in the early postpartum period.

PCR/LDR/capillary electrophoresis for detection of single-nucleotide differences between fetal and maternal DNA in maternal plasma.

PubMed

Yi, Ping; Chen, Zhuqin; Zhao, Yan; Guo, Jianxin; Fu, Huabin; Zhou, Yuanguo; Yu, Lili; Li, Li

2009-03-01

The discovery of fetal DNA in maternal plasma has opened up an approach for noninvasive diagnosis. We have now assessed the possibility of detecting single-nucleotide differences between fetal and maternal DNA in maternal plasma by polymerase chain reaction (PCR)/ligase detection reaction((LDR)/capillary electrophoresis. PCR/LDR/capillary electrophoresis was applied to detect the genotype of c.454-397T>gene (ESR1) from experimental DNA models of maternal plasma at different sensitivity levels and 13 maternal plasma samples.alphaC in estrogen receptor. (1) Our results demonstrated that the technique could discriminate low abundance single-nucleotide mutation with a mutant/normal allele ratio up to 1:10 000. (2) Examination of ESR1 c.454-397T>C genotypes by using the method of restriction fragment length analysis was performed in 25 pregnant women, of whom 13 pregnant women had homozygous genotypes. The c.454-397T>C genotypes of paternally inherited fetal DNA in maternal plasma of these 13 women were detected by PCR/LDR/capillary electrophoresis, which were accordant with the results of umbilical cord blood. PCR/LDR/capillary electrophoresis has very high sensitivity to distinguish low abundance single nucleotide differences and can discriminate point mutations and single-nucleotide polymorphisms(SNPs) of paternally inherited fetal DNA in maternal plasma.

An Effective Technique for Enhancing an Intrauterine Catheter Fetal Electrocardiogram

NASA Astrophysics Data System (ADS)

Horner, Steven L.; Holls, William M.

2003-12-01

Physician can obtain fetal heart rate, electrophysiological information, and uterine contraction activity for determining fetal status from an intrauterine catheters electrocardiogram with the maternal electrocardiogram canceled. In addition, the intrauterine catheter would allow physicians to acquire fetal status with one non-invasive to the fetus biosensor as compared to invasive to the fetus scalp electrode and intrauterine pressure catheter used currently. A real-time maternal electrocardiogram cancellation technique of the intrauterine catheters electrocardiogram will be discussed along with an analysis for the methods effectiveness with synthesized and clinical data. The positive results from an original detailed subjective and objective analysis of synthesized and clinical data clearly indicate that the maternal electrocardiogram cancellation method was found to be effective. The resulting intrauterine catheters electrocardiogram from effectively canceling the maternal electrocardiogram could be used for determining fetal heart rate, fetal electrocardiogram electrophysiological information, and uterine contraction activity.

[Incidence of fetal macrosomia: maternal and fetal morbidity].

PubMed

Rodríguez-Rojas, R R; Cantú-Esquivel, M G; Benavides-de la Garza, L; Benavides-de Anda, L

1996-06-01

The macrosomia is an obstetric eventuality associated to high maternal-fetal morbidity-mortality. This assay was planned in order to know the incidence of macrosomia in our institution, the relation between vaginal and abdominal deliveries and the fetal-maternal morbidity we reviewed 3590 records and we found 5.6% incidence of macrosomia in the global obstetric population. There was 58% of vaginal deliveries, 68% of the newborn were male. The main complications were in the C. sections, 2 laceration of the hysterectomy, and 2 peroperative atonias. In the vaginal deliveries, the lacerations of III and IV grade were 9 of each grade. The main fetal complications were 5 slight to severe asphyxia and 4 shoulder dystocias. This assay concludes that the macrosomia in our service is similar to the already published ones, a 42% were C. section and the maternal-fetal morbidity was low.

Fetal programming of insulin-like growth factor (IGF)-I and IGF-binding protein-3: evidence for an altered response to undernutrition in late gestation following exposure to periconceptual undernutrition in the sheep.

PubMed

Gallaher, B W; Breier, B H; Keven, C L; Harding, J E; Gluckman, P D

1998-12-01

It has been demonstrated in several animal models that undernutrition in utero has significant long lasting effects on subsequent fetal and postnatal development. To address the hypothesis that the insulin-like growth factors (IGFs) may mediate such effects, our study examined whether a period of periconceptual maternal undernutrition could have a lasting influence on the IGF axis in the fetal sheep. Ewes were either allowed to feed ad libitum or kept undernourished from day 60 prior to mating until day 30 after conception, and then both groups were allowed to feed ad libitum. These groups were further divided at day 105 of gestation, either being fed ad libitum or undernourished until day 115 of gestation. Fetal and maternal blood samples were obtained at both day 105 and 115 of gestation. We describe the development of a specific homologous RIA to measure ovine IGF-binding protein-3 (IGFBP-3) in fetal and maternal sheep plasma. Fetal plasma IGFBP-3 and IGF-I concentrations were significantly (P<0.05) reduced at day 115 of gestation after maternal undernutrition. The fetal plasma IGFBP-2 levels were unchanged. The degree of reduction in fetal plasma IGFBP-3 and IGF-I between day 105 and 115 of gestation as a response to acute maternal undernutrition was significantly greater (P<0.05) in fetuses of mothers receiving low periconceptual nutrition. The response of maternal plasma IGFBP-3 and IGF-I to undernutrition did not depend on the level of periconceptual nutrition. Western blot data indicate that changes in either maternal or fetal plasma IGFBP-3 concentrations were not the result of increased proteolytic activity. These results suggest that exposure to maternal periconceptual undernutrition reprograms IGFBP-3 and IGF-I regulation in the developing sheep fetus, altering its response to undernutrition in late gestation.

Standard curves of placental weight and fetal/placental weight ratio in Japanese population: difference according to the delivery mode, fetal sex, or maternal parity.

PubMed

Ogawa, Masaki; Matsuda, Yoshio; Nakai, Akihito; Hayashi, Masako; Sato, Shoji; Matsubara, Shigeki

2016-11-01

Placental weight (PW) and fetal/placental weight ratio (F/P) have been considered to be useful parameters for understanding the pathophysiology of fetal growth. However, there have been no standard data on PW and F/P in Asian populations. This study was conducted to establish nomograms of PW and F/P in the Japanese population and to clarify characteristics of PW and F/P in this population. Included in the study were 79,590 Japanese cases: 58,871 vaginal and 20,719 cesarean deliveries at obstetrical facilities (2001-2002) and registered to the Japan Society of Obstetrics and Gynecology Database. Multiple pregnancies, stillbirths, and fetal anomalies were excluded. Nomograms of PW and F/P were created by spline methods in groups categorized by fetal sex (male or female) and maternal parity (primipara or multipara). Standard curves of PW and F/P were established, which indicated that PW and F/P were lower in cesarean deliveries than vaginal deliveries, especially during preterm period. PW differed depending on fetal sex and maternal parity. F/P differed according to fetal sex. We for the first time established standard curves of PW and F/P in the Japanese population with statistically sufficient data, which showed that PW and F/P were lower in cesarean deliveries. PW and F/P were also affected by fetal sex. These data might be useful to understand the pathophysiology between the fetus and placenta in utero. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Strategies for optimizing maternal nutrition to promote infant development.

PubMed

Hambidge, K Michael; Krebs, Nancy F

2018-06-22

The growing appreciation of the multi-faceted importance of optimal maternal nutrition to the health and development of the infant and young child is tempered by incompletely resolved strategies for combatting challenges. To review the importance of maternal nutrition and strategies being employed to optimize outcomes. Selected data from recent literature with special focus on rationale for and currently published results of maternal nutrition supplements, including lipid based nutrition supplements. 1) An impelling rationale for improving the maternal and in utero environment of low resource populations has emerged to achieve improved fetal and post-natal growth and development. 2) Based partly on population increases in adult height over one-two generations, much can be achieved by reducing poverty. 3) Maternal, newborn and infant characteristics associated with low resource environments include evidence of undernutrition, manifested by underweight and impaired linear growth. 4) Apart from broad public health and educational initiatives, to date, most specific efforts to improve fetal growth and development have included maternal nutrition interventions during gestation. 5) The relatively limited but real benefits of both iron/folic acid (IFA) and multiple micronutrient (MMN) maternal supplements during gestation have now been reasonably defined. 6) Recent investigations of a maternal lipid-based primarily micronutrient supplement (LNS) have not demonstrated a consistent benefit beyond MMN alone. 7) However, effects of both MMN and LNS appear to be enhanced by commencing early in gestation. Poor maternal nutritional status is one of a very few specific factors in the human that not only contributes to impaired fetal and early post-natal growth but for which maternal interventions have demonstrated improved in utero development, documented primarily by both improvements in low birth weights and by partial corrections of impaired birth length. A clearer definition of the benefits achievable by interventions specifically focused on correcting maternal nutrition deficits should not be limited to improvements in the quality of maternal nutrition supplements, but on the cumulative quantity and timing of interventions (also recognizing the heterogeneity between populations). Finally, in an ideal world these steps are only a prelude to improvements in the total environment in which optimal nutrition and other health determinants can be achieved.

Perioperative considerations for neurosurgical procedures in the gravid patient: Continuing Professional Development.

PubMed

Chowdhury, Tumul; Chowdhury, Meenakshi; Schaller, Bernhard; Cappellani, Ronald B; Daya, Jayesh

2013-11-01

The complexity of neurosurgical procedures and their interactions with maternal and fetal physiologies are key factors in determining the overall maternal and fetal outcome. The literature and guidelines provide only partial information regarding the standard of care in these cases. The purpose of this Continuing Professional Development module is to review the issues related to common neurosurgical conditions and their optimal anesthetic management. The most common neurosurgical conditions found in pregnancy include brain tumours, cerebrovascular diseases, spinal pathologies, and neurotrauma. Though rare, these conditions and related procedures may affect maternal and fetal outcome. Maternal considerations should be given priority in cases of emergent surgeries irrespective of trimester. In the early first trimester, risk of fetal loss and congenital malformation are substantial; hence, proper counselling should be given to the mother with special emphasis on therapeutic abortion. When indicated, anticonvulsants should be started as early as possible and continued throughout pregnancy. Surgical procedures can be performed with relative safety during the second trimester and early third trimester. After 34 weeks, delivery seems to be the first choice, and the role of regional anesthesia in this situation should be carefully planned after proper review of neurosurgical pathology and maternal condition. During acute neurological deterioration, however, Cesarean delivery under general anesthesia should be anticipated. A multidisciplinary approach with good communication amongst all team members certainly plays a crucial role for successful management of such cases.

Maternal Obesity and Occurrence of Fetal Macrosomia: A Systematic Review and Meta-Analysis

PubMed Central

Gaudet, Laura; Ferraro, Zachary M.; Walker, Mark

2014-01-01

Objective. To determine a precise estimate for the contribution of maternal obesity to macrosomia. Data Sources. The search strategy included database searches in 2011 of PubMed, Medline (In-Process & Other Non-Indexed Citations and Ovid Medline, 1950–2011), and EMBASE Classic + EMBASE. Appropriate search terms were used for each database. Reference lists of retrieved articles and review articles were cross-referenced. Methods of Study Selection. All studies that examined the relationship between maternal obesity (BMI ≥30 kg/m2) (pregravid or at 1st prenatal visit) and fetal macrosomia (birth weight ≥4000 g, ≥4500 g, or ≥90th percentile) were considered for inclusion. Tabulation, Integration, and Results. Data regarding the outcomes of interest and study quality were independently extracted by two reviewers. Results from the meta-analysis showed that maternal obesity is associated with fetal overgrowth, defined as birth weight ≥ 4000 g (OR 2.17, 95% CI 1.92, 2.45), birth weight ≥4500 g (OR 2.77,95% CI 2.22, 3.45), and birth weight ≥90% ile for gestational age (OR 2.42, 95% CI 2.16, 2.72). Conclusion. Maternal obesity appears to play a significant role in the development of fetal overgrowth. There is a critical need for effective personal and public health initiatives designed to decrease prepregnancy weight and optimize gestational weight gain. PMID:25544943

Chemokine scavenger D6 is expressed by trophoblasts and aids the survival of mouse embryos transferred into allogeneic recipients.

PubMed

Madigan, Judith; Freeman, Dilys J; Menzies, Fiona; Forrow, Steve; Nelson, Scott M; Young, Anne; Sharkey, Andrew; Moffett, Ashley; Graham, Gerard J; Greer, Ian A; Rot, Antal; Nibbs, Robert J B

2010-03-15

Proinflammatory CC chemokines are thought to drive recruitment of maternal leukocytes into gestational tissues and regulate extravillous trophoblast migration. The atypical chemokine receptor D6 binds many of these chemokines and is highly expressed by the human placenta. D6 is thought to act as a chemokine scavenger because, when ectopically expressed in cell lines in vitro, it efficiently internalizes proinflammatory CC chemokines and targets them for destruction in the absence of detectable chemokine-induced signaling. Moreover, D6 suppresses inflammation in many mouse tissues, and notably, D6-deficient fetuses in D6-deficient female mice show increased susceptibility to inflammation-driven resorption. In this paper, we report strong anti-D6 immunoreactivity, with specific intracellular distribution patterns, in trophoblast-derived cells in human placenta, decidua, and gestational membranes throughout pregnancy and in trophoblast disease states of hydatidiform mole and choriocarcinoma. We show, for the first time, that endogenous D6 in a human choriocarcinoma-derived cell line can mediate progressive chemokine scavenging and that the D6 ligand CCL2 can specifically associate with human syncytiotrophoblasts in term placenta in situ. Moreover, despite strong chemokine production by gestational tissues, levels of D6-binding chemokines in maternal plasma decrease during pregnancy, even in women with pre-eclampsia, a disease associated with increased maternal inflammation. In mice, D6 is not required for syngeneic or semiallogeneic fetal survival in unchallenged mice, but interestingly, it does suppress fetal resorption after embryo transfer into fully allogeneic recipients. These data support the view that trophoblast D6 scavenges maternal chemokines at the fetomaternal interface and that, in some circumstances, this can help to ensure fetal survival.

Microchimeric cells in systemic lupus erythematosus: targets or innocent bystanders?

PubMed

Stevens, A M

2006-01-01

During pregnancy maternal and fetal cells commute back and forth leading to fetal microchimerism in the mother and maternal microchimerism in the child that can persist for years after the birth. Chimeric fetal and maternal cells can be hematopoietic or can differentiate into somatic cells in multiple organs, potentially acting as targets for 'autoimmunity' and so have been implicated in the pathogenesis of autoimmune diseases that resemble graft-versus-host disease after stem cell transplantation. Fetal cells have been found in women with systemic lupus erythematosus, both in the blood and a target organ, the kidney, suggesting that they may be involved in pathogenesis. Future studies will address how the host immune system normally tolerates maternal and fetal cells or how the balance may change during autoimmunity.

Maternal serum free-beta-chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency thickness at 10-13(+6) weeks in relation to co-variables in pregnant Saudi women.

PubMed

Ardawi, Mohammed-Salleh M; Nasrat, Hasan A; Rouzi, Abdulrahim A; Qari, Mohammed H; Al-Qahtani, Mohammed H; Abuzenadah, Adel M

2007-04-01

To establish normative values and distribution parameters of first-trimester screening markers, namely, fetal nuchal translucency (NT), maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), at 10 to 13(+6) weeks of gestation in Saudi women and to evaluate the effect of co-variables including maternal body weight, gravidity, parity, fetal gender, twin pregnancy, smoking and ethnicity on these markers. A cohort of Saudi women (first cohort n = 1616) with singleton pregnancies prospectively participated in the present study, and fetal NT together with maternal serum free beta-hCG and PAPP-A were determined at 10 to 13(+6) weeks of gestation. The distribution of gestational age-independent multiples of the median (MoM) of the parameters was defined and normative values were established, and correction for maternal body weight was made accordingly. The influence of various co-variables was examined using the data collected from the first and the second (n = 1849) cohorts of women and 62 twin pregnancies, and compared with other studies. All markers exhibited log-normally distributed MoMs. Gestational age-independent normative values were established. Maternal body weight was corrected, particularly for maternal free beta-hCG and PAPP-A using standard methods. Fetal NT showed a negative relationship with increasing gravidity (r = -0.296) or parity (r = -0.311), whereas both free beta-hCG and PAPP-A exhibited a significant positive relationship. There was a significant increase in the MoM of free beta-hCG in female fetuses. Smoking decreased MoM values of free beta-hCG (by 14.6%; P < 0.01) and PAPP-A (by 18.8%; P < 0.001). Twin pregnancy showed significant increases in MoM values of free beta-hCG (by 1.87-fold) and PAPP-A (by 2.24-fold), with no significant changes in fetal NT MoM values. Fetal NT MoM values were lower in Africans and Asians but higher in Orientals, as compared to Saudi women (P < 0.05; in each case). MoM values (body weight-corrected) of free beta-hCG were 25.2% higher in Africans and 19.4% higher in Orientals but 6.8% lower in other Arabian and Asian (by 5.8%) women as compared to Saudi women (P < 0.05; in each case). The normative values and distribution parameters for fetal NT, maternal serum free beta-hCG and PAPP-A were established in Saudi singleton pregnancies, the maternal body weight together with smoking, twin pregnancy and ethnicity being important first-trimester screening co-variables. Gravidity, parity and fetal gender are also considered to influence one or more of the first-trimester markers examined. Copyright (c) 2007 John Wiley & Sons, Ltd.

Adverse Maternal Environment Increases Fetal Liver Hydroxymethylation and Alters the Transcriptome

USDA-ARS?s Scientific Manuscript database

Suboptimal maternal nutrition during fetal liver development can alter the offspring’s ability to metabolize excess fats and increases obesity in offspring. We developed a model of adverse maternal environment (AME) which overlays maternal prenatal stress with chronic exposure to a western diet. O...

Severe gestational hypertriglyceridemia: A practical approach for clinicians

PubMed Central

Wong, Bertha; Ooi, Teik C

2015-01-01

Severe gestational hypertriglyceridemia is a potentially life threatening and complex condition to manage, requiring attention to a delicate balance between maternal and fetal needs. During pregnancy, significant alterations to lipid homeostasis occur to ensure transfer of nutrients to the fetus. In women with an underlying genetic predisposition or a secondary exacerbating factor, severe gestational hypertriglyceridemia can arise, leading to devastating complications, including acute pancreatitis. Multidisciplinary care, implementation of a low-fat diet with nutritional support, and institution of a hierarchical therapeutic approach are all crucial to reduce maternal and fetal morbidity. To avoid maternal pancreatitis, close surveillance of triglycerides throughout pregnancy with elective hospitalization for refractory cases is recommended. Careful dietary planning is required to prevent neural and retinal complications from fetal essential fatty acid deficiency. Questions remain about the safety of fibrates and plasmapheresis in pregnancy as well as the optimal timing for induction and delivery of these women. PMID:27512474

Role of catecholamines in maternal-fetal stress transfer in sheep.

PubMed

Rakers, Florian; Bischoff, Sabine; Schiffner, Rene; Haase, Michelle; Rupprecht, Sven; Kiehntopf, Michael; Kühn-Velten, W Nikolaus; Schubert, Harald; Witte, Otto W; Nijland, Mark J; Nathanielsz, Peter W; Schwab, Matthias

2015-11-01

We sought to evaluate whether in addition to cortisol, catecholamines also transfer psychosocial stress indirectly to the fetus by decreasing uterine blood flow (UBF) and increasing fetal anaerobic metabolism and stress hormones. Seven pregnant sheep chronically instrumented with uterine ultrasound flow probes and catheters at 0.77 gestation underwent 2 hours of psychosocial stress by isolation. We used adrenergic blockade with labetalol to examine whether decreased UBF is catecholamine mediated and to determine to what extent stress transfer from mother to fetus is catecholamine dependent. Stress induced transient increases in maternal cortisol and norepinephrine (NE). Maximum fetal plasma cortisol concentrations were 8.1 ± 2.1% of those in the mother suggesting its maternal origin. In parallel to the maternal NE increase, UBF decreased by maximum 22% for 30 minutes (P < .05). Fetal NE remained elevated for >2 hours accompanied by a prolonged blood pressure increase (P < .05). Fetuses developed a delayed and prolonged shift toward anaerobic metabolism in the presence of an unaltered oxygen supply. Adrenergic blockade prevented the stress-induced UBF decrease and, consequently, the fetal NE and blood pressure increase and the shift toward anaerobic metabolism. We conclude that catecholamine-induced decrease of UBF is a mechanism of maternal-fetal stress transfer. It may explain the influence of maternal stress on fetal development and on programming of adverse health outcomes in later life especially during early pregnancy when fetal glucocorticoid receptor expression is limited. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of maternal position on fetal behavioural state and heart rate variability in healthy late gestation pregnancy

PubMed Central

Burgess, Wendy; McIntyre, Jordan P. R.; Gunn, Alistair J.; Lear, Christopher A.; Bennet, Laura; Mitchell, Edwin A.; Thompson, John M. D.

2016-01-01

Key points Fetal behavioural state in healthy late gestation pregnancy is affected by maternal position.Fetal state 1F is more likely to occur in maternal supine or right lateral positions.Fetal state 4F is less likely to occur when the woman lies supine or semi‐recumbent.Fetal state change is more likely when the woman is supine or semi‐recumbent.Fetal heart rate variability is affected by maternal position with variability reduced in supine and semi‐recumbent positions. Abstract Fetal behavioural states (FBS) are measures of fetal wellbeing. In acute hypoxaemia, the human fetus adapts to a lower oxygen consuming state with changes in the cardiotocograph and reduced fetal activity. Recent studies of late gestation stillbirth described the importance of sleep position in the risk of intrauterine death. We designed this study to assess the effects of different maternal positions on FBS in healthy late gestation pregnancies under controlled conditions. Twenty‐nine healthy women had continuous fetal ECG recordings under standardized conditions in four randomly allocated positions, left lateral, right lateral, supine and semi‐recumbent. Two blinded observers, assigned fetal states in 5 min blocks. Measures of fetal heart rate variability were calculated from ECG beat to beat data. Compared to state 2F, state 4F was less likely to occur when women were semi‐recumbent [odds ratio (OR) = 0.11, 95% confidence interval (95% CI) 0.02, 0.55], and supine (OR = 0.27, 95% CI 0.07, 1.10). State 1F was more likely on the right (OR = 2.36, 95% CI 1.11, 5.04) or supine (OR = 4.99, 95% CI 2.41, 10.43) compared to the left. State change was more likely when the mother was semi‐recumbent (OR = 2.17, 95% CI 1.19, 3.95) or supine (OR = 2.67, 95% CI 1.46, 4.85). There was a significant association of maternal position to mean fetal heart rate. The measures of heart rate variability (SDNN and RMSSD) were reduced in both semi‐recumbent and supine positions. In healthy late gestation pregnancy, maternal position affects FBS and heart rate variability. These effects are likely fetal adaptations to positions which may produce a mild hypoxic stress. PMID:27871127

Effect of maternal position on fetal behavioural state and heart rate variability in healthy late gestation pregnancy.

PubMed

Stone, Peter R; Burgess, Wendy; McIntyre, Jordan P R; Gunn, Alistair J; Lear, Christopher A; Bennet, Laura; Mitchell, Edwin A; Thompson, John M D

2017-02-15

Fetal behavioural state in healthy late gestation pregnancy is affected by maternal position. Fetal state 1F is more likely to occur in maternal supine or right lateral positions. Fetal state 4F is less likely to occur when the woman lies supine or semi-recumbent. Fetal state change is more likely when the woman is supine or semi-recumbent. Fetal heart rate variability is affected by maternal position with variability reduced in supine and semi-recumbent positions. Fetal behavioural states (FBS) are measures of fetal wellbeing. In acute hypoxaemia, the human fetus adapts to a lower oxygen consuming state with changes in the cardiotocograph and reduced fetal activity. Recent studies of late gestation stillbirth described the importance of sleep position in the risk of intrauterine death. We designed this study to assess the effects of different maternal positions on FBS in healthy late gestation pregnancies under controlled conditions. Twenty-nine healthy women had continuous fetal ECG recordings under standardized conditions in four randomly allocated positions, left lateral, right lateral, supine and semi-recumbent. Two blinded observers, assigned fetal states in 5 min blocks. Measures of fetal heart rate variability were calculated from ECG beat to beat data. Compared to state 2F, state 4F was less likely to occur when women were semi-recumbent [odds ratio (OR) = 0.11, 95% confidence interval (95% CI) 0.02, 0.55], and supine (OR = 0.27, 95% CI 0.07, 1.10). State 1F was more likely on the right (OR = 2.36, 95% CI 1.11, 5.04) or supine (OR = 4.99, 95% CI 2.41, 10.43) compared to the left. State change was more likely when the mother was semi-recumbent (OR = 2.17, 95% CI 1.19, 3.95) or supine (OR = 2.67, 95% CI 1.46, 4.85). There was a significant association of maternal position to mean fetal heart rate. The measures of heart rate variability (SDNN and RMSSD) were reduced in both semi-recumbent and supine positions. In healthy late gestation pregnancy, maternal position affects FBS and heart rate variability. These effects are likely fetal adaptations to positions which may produce a mild hypoxic stress. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Fetal and maternal dose assessment for diagnostic scans during pregnancy

NASA Astrophysics Data System (ADS)

Rafat Motavalli, Laleh; Miri Hakimabad, Hashem; Hoseinian Azghadi, Elie

2016-05-01

Despite the concerns about prenatal exposure to ionizing radiation, the number of nuclear medicine examinations performed for pregnant women increased in the past decade. This study attempts to better quantify radiation doses due to diagnostic nuclear medicine procedures during pregnancy with the help of our recently developed 3, 6, and 9 month pregnant hybrid phantoms. The reference pregnant models represent the adult female international commission on radiological protection (ICRP) reference phantom as a base template with a fetus in her gravid uterus. Six diagnostic scintigraphy scans using different radiopharmaceuticals were selected as typical diagnostic nuclear medicine procedures. Furthermore, the biokinetic data of radioiodine was updated in this study. A compartment representing iodide in fetal thyroid was addressed explicitly in the biokinetic model. Calculations were performed using the Monte Carlo transport method. Tabulated dose coefficients for both maternal and fetal organs are provided. The comparison was made with the previously published fetal doses calculated for stylized pregnant female phantoms. In general, the fetal dose in previous studies suffers from an underestimation of up to 100% compared to fetal dose at organ level in this study. A maximum of difference in dose was observed for the fetal thyroid compared to the previous studies, in which the traditional models did not contain the fetal thyroid. Cumulated activities of major source organs are primarily responsible for the discrepancies in the organ doses. The differences in fetal dose depend on several other factors including chord length distribution between fetal organs and maternal major source organs, and anatomical differences according to gestation periods. Finally, considering the results of this study, which was based on the realistic pregnant female phantoms, a more informed evaluation of the risks and benefits of the different procedures could be made.

Noninvasive prenatal testing: the future is now.

PubMed

Norwitz, Errol R; Levy, Brynn

2013-01-01

Prenatal detection of chromosome abnormalities has been offered for more than 40 years, first by amniocentesis in the early 1970s and additionally by chorionic villus sampling (CVS) in the early 1980s. Given the well-recognized association between increasing maternal age and trisomy,1-3 the primary utilization of prenatal testing has been by older mothers. This has drastically reduced the incidence of aneuploid children born to older mothers.4 Although younger women have relatively low risks of conceiving a child with aneuploidy, the majority of pregnant women are in their late teens, 20s, and early 30s. As such, most viable aneuploid babies are born to these younger mothers.5 Invasive prenatal diagnosis (CVS and amniocentesis) is not a feasible option for all low-risk mothers, as these procedures carry a small but finite risk and would ultimately cause more miscarriages than they would detect aneuploidy. For this reason, a number of noninvasive tests have been developed-including first-trimester risk assessment at 11 to 14 weeks, maternal serum analyte (quad) screening at 15 to 20 weeks, and sonographic fetal structural survey at 18 to 22 weeks-all of which are designed to give a woman an adjusted (more accurate) estimate of having an aneuploid fetus using as baseline her a priori age-related risk. Ultrasound and maternal serum analysis are considered screening procedures and both require follow up by CVS or amniocentesis in screen-positive cases for a definitive diagnosis of a chromosome abnormality in the fetus. The ability to isolate fetal cells and fetal DNA from maternal blood during pregnancy has opened up exciting opportunities for improved noninvasive prenatal testing (NIPT). Direct analysis of fetal cells from maternal circulation has been challenging given the scarcity of fetal cells in maternal blood (1:10,000-1:1,000,000) and the focus has shifted to the analysis of cell-free fetal DNA, which is found at a concentration almost 25 times higher than that available from nucleated blood cells extracted from a similar volume of whole maternal blood. There have now been numerous reports on the use of cell-free DNA (cfDNA) for NIPT for chromosomal aneuploidies-especially trisomy (an extra copy of a chromosome) or monosomy (a missing chromosome)-and a number of commercial products are already being marketed for this indication. This article reviews the various techniques being used to analyze cell-free DNA in the maternal circulation for the prenatal detection of chromosome abnormalities and the evidence in support of each. A number of areas of ongoing controversy are addressed, including the timing of maternal blood sampling, the need for genetic counseling, and the use of confirmatory invasive testing. Future applications for this technology are also reviewed.

Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy

PubMed Central

Fragiadakis, Gabriela K.; Baca, Quentin J.; Gherardini, Pier Federico; Ganio, Edward A.; Gaudilliere, Dyani K.; Tingle, Martha; Lancero, Hope L.; McNeil, Leslie S.; Spitzer, Matthew H.; Wong, Ronald J.; Shaw, Gary M.; Darmstadt, Gary L.; Sylvester, Karl G.; Winn, Virginia D.; Carvalho, Brendan; Lewis, David B.; Stevenson, David K.; Nolan, Garry P.; Aghaeepour, Nima; Angst, Martin S.; Gaudilliere, Brice L.

2016-01-01

Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus are critical for the maintenance of pregnancy and the delivery of an immuno-competent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes. This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. The approach enabled mapping of known phenotypical and functional characteristics of fetal immunity (including the functional hyper-responsiveness of CD4+ and CD8+ T cells and the global blunting of innate immune responses). It also allowed discovery of new properties that distinguish the fetal and maternal immune systems. For example, examination of paired samples revealed differences in endogenous signaling tone that are unique to a mother and her offspring, including increased ERK1/2, MAPKAPK2, rpS6, and CREB phosphorylation in fetal Tbet+CD4+ T cells, CD8+ T cells, B cells and CD56loCD16+ NK cells and decreased ERK1/2, MAPKAPK2, and STAT1 phosphorylation in fetal intermediate and non-classical monocytes. This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes. PMID:27793998

Analysis of correlations between the placental expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus.

PubMed

Stanirowski, Paweł Jan; Szukiewicz, Dariusz; Pyzlak, Michał; Abdalla, Nabil; Sawicki, Włodzimierz; Cendrowski, Krzysztof

2017-10-16

The aim of the study was to analyze the correlations between the expression of glucose transporters GLUT-1, GLUT-4, and GLUT-9 in human term placenta and selected maternal and fetal parameters in pregnancies complicated by diabetes mellitus (DM). Placental samples were obtained from healthy control (n = 25) and diabetic pregnancies, including diet-controlled gestational diabetes mellitus (GDMG1) (n = 16), insulin-controlled gestational diabetes mellitus (GDMG2) (n = 6), and pregestational DM (PGDM) (n = 6). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected glucose transporter proteins. For the purposes of correlation analysis, the following parameters were selected: type of diabetes, gestational age, maternal prepregnancy body mass index (BMI), gestational weight gain, third trimester glycated hemoglobin concentration, placental weight, fetal birth weight (FBW) as well as ultrasonographic indicators of fetal adiposity, including subscapular (SSFM), abdominal (AFM), and midthigh (MTFM) fat mass measurements. In the PGDM group, the analysis demonstrated positive correlations between the placental expression of GLUT-1, GLUT-4, and GLUT-9 and FBW, AFM, and SSFM measurements (p < .05). Similarly in the GDMG2 patients positive correlations between GLUT-4 expression, FBW and SSFM were observed (p < .05). In the multivariate regression analysis, only the type of diabetes and FBW were significantly associated with GLUTs expression (p < .001). In addition, maternal prepregnancy BMI significantly contributed to GLUT-1 expression (p < .001). The study results revealed that placental expression of GLUT-1, GLUT-4, and GLUT-9 may be involved in the intensification of the fetal growth in pregnancies complicated by GDM/PGDM.

Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy.

PubMed

Fragiadakis, Gabriela K; Baca, Quentin J; Gherardini, Pier Federico; Ganio, Edward A; Gaudilliere, Dyani K; Tingle, Martha; Lancero, Hope L; McNeil, Leslie S; Spitzer, Matthew H; Wong, Ronald J; Shaw, Gary M; Darmstadt, Gary L; Sylvester, Karl G; Winn, Virginia D; Carvalho, Brendan; Lewis, David B; Stevenson, David K; Nolan, Garry P; Aghaeepour, Nima; Angst, Martin S; Gaudilliere, Brice L

2016-12-01

Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus is critical for the maintenance of pregnancy and the delivery of an immunocompetent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes. This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. The approach enabled mapping of known phenotypical and functional characteristics of fetal immunity (including the functional hyperresponsiveness of CD4 + and CD8 + T cells and the global blunting of innate immune responses). It also allowed discovery of new properties that distinguish the fetal and maternal immune systems. For example, examination of paired samples revealed differences in endogenous signaling tone that are unique to a mother and her offspring, including increased ERK1/2, MAPK-activated protein kinase 2, rpS6, and CREB phosphorylation in fetal Tbet + CD4 + T cells, CD8 + T cells, B cells, and CD56 lo CD16 + NK cells and decreased ERK1/2, MAPK-activated protein kinase 2, and STAT1 phosphorylation in fetal intermediate and nonclassical monocytes. This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes. Copyright © 2016 by The American Association of Immunologists, Inc.

Neuromyelitis optica in pregnancy complicated by posterior reversible encephalopathy syndrome, eclampsia and fetal death.

PubMed

Igel, Catherine; Garretto, Diana; Robbins, Matthew S; Swerdlow, Michael; Judge, Nancy; Dayal, Ashlesha

2015-03-01

Neuromyelitis optica (NMO) is a demyelinating syndrome characterized by optic neuritis and acute myelitis with poor recovery and a progressive course. We report a poor outcome complicated by posterior reversible encephalopathy syndrome (PRES) and eclampsia and review available literature and current evidence for anticipation of adverse fetal and maternal effects. After a pregnancy complicated by multiple admissions for painful NMO exacerbations, a primiparous patient with seropositive NMO presented at 31 + 3/7 weeks with eclampsia, HELLP and subsequent fetal death. MRI confirmed PRES. NMO may be associated with eclampsia and leads to adverse maternal and fetal outcomes. Posited mechanisms include antibody-mediated placental damage and a heightened risk of eclampsia-associated PRES. Further characterization of the course of NMO and its relationship with pregnancy outcomes in larger series would be invaluable.

Neuromyelitis Optica in Pregnancy Complicated by Posterior Reversible Encephalopathy Syndrome, Eclampsia and Fetal Death

PubMed Central

Igel, Catherine; Garretto, Diana; Robbins, Matthew S; Swerdlow, Michael; Judge, Nancy; Dayal, Ashlesha

2015-01-01

Neuromyelitis optica (NMO) is a demyelinating syndrome characterized by optic neuritis and acute myelitis with poor recovery and a progressive course. We report a poor outcome complicated by posterior reversible encephalopathy syndrome (PRES) and eclampsia and review available literature and current evidence for anticipation of adverse fetal and maternal effects. After a pregnancy complicated by multiple admissions for painful NMO exacerbations, a primiparous patient with seropositive NMO presented at 31 + 3/7 weeks with eclampsia, HELLP and subsequent fetal death. MRI confirmed PRES. NMO may be associated with eclampsia and leads to adverse maternal and fetal outcomes. Posited mechanisms include antibody-mediated placental damage and a heightened risk of eclampsia-associated PRES. Further characterization of the course of NMO and its relationship with pregnancy outcomes in larger series would be invaluable. PMID:25584107

Improving Perinatal Care in the Rural Regions Worldwide by Wireless Enabled Antepartum Fetal Monitoring: A Demonstration Project

PubMed Central

Tapia-Conyer, Roberto; Lyford, Shelley; Saucedo, Rodrigo; Casale, Michael; Gallardo, Hector; Becerra, Karen; Mack, Jonathan; Mujica, Ricardo; Estrada, Daniel; Sanchez, Antonio; Sabido, Ramon; Meier, Carlos; Smith, Joseph

2015-01-01

Background. Fetal and neonatal morbidity and mortality are significant problems in developing countries; remote maternal-fetal monitoring offers promise in addressing this challenge. The Gary and Mary West Health Institute and the Instituto Carlos Slim de la Salud conducted a demonstration project of wirelessly enabled antepartum maternal-fetal monitoring in the state of Yucatán, Mexico, to assess whether there were any fundamental barriers preventing deployment and use. Methods. Following informed consent, high-risk pregnant women at 27–29 weeks of gestation at the Chemax primary clinic participated in remote maternal-fetal monitoring. Study participants were randomized to receive either prototype wireless monitoring or standard-of-care. Feasibility was evaluated by assessing technical aspects of performance, adherence to monitoring appointments, and response to recommendations. Results. Data were collected from 153 high-risk pregnant indigenous Mayan women receiving either remote monitoring (n = 74) or usual standard-of-care (n = 79). Remote monitoring resulted in markedly increased adherence (94.3% versus 45.1%). Health outcomes were not statistically different in the two groups. Conclusions. Remote maternal-fetal monitoring is feasible in resource-constrained environments and can improve maternal compliance for monitoring sessions. Improvement in maternal-fetal health outcomes requires integration of such technology into sociocultural context and addressing logistical challenges of access to appropriate emergency services. PMID:25691900

21 CFR 884.2600 - Fetal cardiac monitor.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen with...

21 CFR 884.2600 - Fetal cardiac monitor.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen with...

21 CFR 884.2600 - Fetal cardiac monitor.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen with...

21 CFR 884.2600 - Fetal cardiac monitor.

Code of Federal Regulations, 2011 CFR

2011-04-01

... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen with...

21 CFR 884.2600 - Fetal cardiac monitor.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen with...

Dose-dependent lipopolysaccharide-induced fetal brain injury in the guinea pig.

PubMed

Harnett, Erica L; Dickinson, Michelle A; Smith, Graeme N

2007-08-01

This study determined whether a lipopolysaccharide (LPS) dose-dependent increase in fetal brain injury occurs to further characterize the relationship between maternal inflammation and fetal brain injury. Pregnant guinea pigs (n = 59) at 70% gestation were injected intraperitoneally with 1, 5, 25, 50, 100, 200, or 300 microg LPS per kilogram of maternal body weight or an equivalent volume of vehicle. Animals were killed 7 days later. Maternal serum and amniotic fluid samples were assayed for proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 using enzyme-linked immunosorbent assay kits. Fetal brains (n = 72) were stained for evidence of cell death with NeuroTACS stain. Seven days after LPS injections, cytokine concentrations in maternal serum and amniotic fluid were not different (P > .05) from controls. Levels of cell death in all brain regions examined were highest following the maternal administration of 300 mug/kg LPS (P < .05). The dose effect was brain region-dependent (P < .05). A threshold of maternal infection/inflammation exists, beyond which demonstrable fetal brain injury may result.

Does the Use of Diagnostic Technology Reduce Fetal Mortality?

PubMed

Grytten, Jostein; Skau, Irene; Sørensen, Rune; Eskild, Anne

2018-01-19

To examine the effect that the introduction of new diagnostic technology in obstetric care has had on fetal death. The Medical Birth Registry of Norway provided detailed medical information for approximately 1.2 million deliveries from 1967 to 1995. Information about diagnostic technology was collected directly from the maternity units, using a questionnaire. The data were analyzed using a hospital fixed-effects regression with fetal mortality as the outcome measure. The key independent variables were the introduction of ultrasound and electronic fetal monitoring at each maternity ward. Hospital-specific trends and risk factors of the mother were included as control variables. The richness of the data allowed us to perform several robustness tests. The introduction of ultrasound caused a significant drop in fetal mortality rate, while the introduction of electronic fetal monitoring had no effect on the rate. In the population as a whole, ultrasound contributed to a reduction in fetal deaths of nearly 20 percent. For post-term deliveries, the reduction was well over 50 percent. The introduction of ultrasound made a major contribution to the decline in fetal mortality at the end of the last century. © Health Research and Educational Trust.

Influence of maternal body mass index on accuracy and reliability of external fetal monitoring techniques.

PubMed

Cohen, Wayne R; Hayes-Gill, Barrie

2014-06-01

To evaluate the performance of external electronic fetal heart rate and uterine contraction monitoring according to maternal body mass index. Secondary analysis of prospective equivalence study. Three US urban teaching hospitals. Seventy-four parturients with a normal term pregnancy. The parent study assessed performance of two methods of external fetal heart rate monitoring (abdominal fetal electrocardiogram and Doppler ultrasound) and of uterine contraction monitoring (electrohystero-graphy and tocodynamometry) compared with internal monitoring with fetal scalp electrode and intrauterine pressure transducer. Reliability of external techniques was assessed by the success rate and positive percent agreement with internal methods. Bland-Altman analysis determined accuracy. We analyzed data from that study according to maternal body mass index. We assessed the relationship between body mass index and monitor performance with linear regression, using body mass index as the independent variable and measures of reliability and accuracy as dependent variables. There was no significant association between maternal body mass index and any measure of reliability or accuracy for abdominal fetal electrocardiogram. By contrast, the overall positive percent agreement for Doppler ultrasound declined (p = 0.042), and the root mean square error from the Bland-Altman analysis increased in the first stage (p = 0.029) with increasing body mass index. Uterine contraction recordings from electrohysterography and tocodynamometry showed no significant deterioration related to maternal body mass index. Accuracy and reliability of fetal heart rate monitoring using abdominal fetal electrocardiogram was unaffected by maternal obesity, whereas performance of ultrasound degraded directly with maternal size. Both electrohysterography and tocodynamometry were unperturbed by obesity. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Fetal Genotyping in Maternal Blood by Digital PCR: Towards NIPD of Monogenic Disorders Independently of Parental Origin.

PubMed

Perlado, Sara; Bustamante-Aragonés, Ana; Donas, Marta; Lorda-Sánchez, Isabel; Plaza, Javier; Rodríguez de Alba, Marta

2016-01-01

To date, non-invasive prenatal diagnosis (NIPD) of monogenic disorders has been limited to cases with a paternal origin. This work shows a validation study of the Droplet Digital PCR (ddPCR) technology for analysis of both paternally and maternally inherited fetal alleles. For the purpose, single nucleotide polymorphisms (SNPs) were studied with the only intention to mimic monogenic disorders. NIPD SNP genotyping was performed by ddPCR in 55 maternal plasma samples. In 19 out of 55 cases, inheritance of the paternal allele was determined by presence/absence criteria. In the remaining 36, determination of the maternally inherited fetal allele was performed by relative mutation dosage (RMD) analysis. ddPCR exhibited 100% accuracy for detection of paternal alleles. For diagnosis of fetal alleles with maternal origin by RMD analysis, the technology showed an accuracy of 96%. Twenty-nine out of 36 were correctly diagnosed. There was one FP and six maternal plasma samples that could not be diagnosed. In this study, ddPCR has shown to be capable to detect both paternal and maternal fetal alleles in maternal plasma. This represents a step forward towards the introduction of NIPD for all pregnancies independently of the parental origin of the disease.

Development of a PCR/LDR/capillary electrophoresis assay with potential for the detection of a beta-thalassemia fetal mutation in maternal plasma.

PubMed

Yi, Ping; Chen, Zhuqin; Yu, Lili; Zheng, Yingru; Liu, Guodong; Xie, Haichang; Zhou, Yuanguo; Zheng, Xiuhui; Han, Jian; Li, Li

2010-08-01

Analysis of fetal DNA in maternal plasma has recently been introduced for non-invasive prenatal diagnosis. We have now investigated the feasibility of polymerase chain reaction (PCR)/ligase detection reaction (LDR)/capillary electrophoresis for the detection of fetal point mutations, such as the beta-thalassemia mutation, IVS2 654(C --> T), in maternal plasma DNA. The sensitivity of LDR/capillary electrophoresis was examined by quantifying the mutant PCR products in the presence of a vast excess of non-mutant competitor template, a situation that mimics the detection of rare fetal mutations in the presence of excess maternal DNA. PCR/LDR/capillary electrophoresis was applied to detect the mutation, IVS2 654(C --> T), in an experimental model at different sensitivity levels and from 10 maternal plasma samples. Our results demonstrated that this approach to detect a low abundance IVS2 654(C --> T) mutation achieved a sensitivity of approximately 1:10,000. The approach was applied to maternal plasma DNA to detect the paternally inherited fetal IVS2 654(C --> T) mutation, and the results were equivalent to those obtained by PCR/reverse dot blot of amniotic fluid cell DNA. PCR/LDR/capillary electrophoresis has a very high sensitivity that can distinguish low abundance single nucleotide differences and can detect paternally inherited fetal point mutations in maternal plasma.

Maternal age and risk of labor and delivery complications.

PubMed

Cavazos-Rehg, Patricia A; Krauss, Melissa J; Spitznagel, Edward L; Bommarito, Kerry; Madden, Tessa; Olsen, Margaret A; Subramaniam, Harini; Peipert, Jeffrey F; Bierut, Laura Jean

2015-06-01

We utilized an updated nationally representative database to examine associations between maternal age and prevalence of maternal morbidity during complications of labor and delivery. We used hospital inpatient billing data from the 2009 United States Nationwide Inpatient Sample, part of the Healthcare Cost and Utilization Project. To determine whether the likelihood that maternal morbidity during complications of labor and delivery differed among age groups, separate logistic regression models were run for each complication. Age was the main independent variable of interest. In analyses that controlled for demographics and clinical confounders, we found that complications with the highest odds among women, 11-18 years of age, compared to 25-29 year old women, included preterm delivery, chorioamnionitis, endometritis, and mild preeclampsia. Pregnant women who were 15-19 years old had greater odds for severe preeclampsia, eclampsia, postpartum hemorrhage, poor fetal growth, and fetal distress. Pregnant women who were ≥35 years old had greater odds for preterm delivery, hypertension, superimposed preeclampsia, severe preeclampsia, and decreased risk for chorioamnionitis. Older women (≥40 years old) had increased odds for mild preeclampsia, fetal distress, and poor fetal growth. Our findings underscore the need for pregnant women to be aware of the risks associated with extremes of age so that they can watch for signs and symptoms of such complications.

Skin infections in pregnancy.

PubMed

Müllegger, Robert R; Häring, Nina S; Glatz, Martin

2016-01-01

A wide array of infectious diseases can occur in pregnancy. Their acquisition, clinical presentation, and course during gestation may be altered due to an impairment of the maternal cellular immunity. Some infectious diseases can lead to serious consequences for the mother or the offspring, including congenital malformations. This review describes in detail the clinical presentation, course, management, and associated maternal and fetal risks of selected viral (varicella-zoster virus infections, condylomata acuminata), fungal (candida vulvovaginitis), bacterial (Lyme borreliosis), and parasitic (scabies) infections. The treatment options are critically reviewed. First-line therapies include acyclovir and varicella-zoster virus immunoglobulin for varicella-zoster virus infections, surgical modalities for genital warts, topical clotrimazole and oral fluconazole for Candida vulvovaginitis, amoxicillin and cefuroxime for Lyme borreliosis, and permethrin for scabies. A synopsis of maternal and fetal risks of other important infections is also included. Copyright © 2016 Elsevier Inc. All rights reserved.

Heat Exposure and Maternal Health in the Face of Climate Change

PubMed Central

Kuehn, Leeann; McCormick, Sabrina

2017-01-01

Climate change will increasingly affect the health of vulnerable populations, including maternal and fetal health. This systematic review aims to identify recent literature that investigates increasing heat and extreme temperatures on pregnancy outcomes globally. We identify common research findings in order to create a comprehensive understanding of how immediate effects will be sustained in the next generation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide, we systematically reviewed articles from PubMed and Cochrane Reviews. We included articles that identify climate change-related exposures and adverse health effects for pregnant women. There is evidence that temperature extremes adversely impact birth outcomes, including, but not limited to: changes in length of gestation, birth weight, stillbirth, and neonatal stress in unusually hot temperature exposures. The studies included in this review indicate that not only is there a need for further research on the ways that climate change, and heat in particular, may affect maternal health and neonatal outcomes, but that uniform standards for assessing the effects of heat on maternal fetal health also need to be established. PMID:28758917

Heat Exposure and Maternal Health in the Face of Climate Change.

PubMed

Kuehn, Leeann; McCormick, Sabrina

2017-07-29

Climate change will increasingly affect the health of vulnerable populations, including maternal and fetal health. This systematic review aims to identify recent literature that investigates increasing heat and extreme temperatures on pregnancy outcomes globally. We identify common research findings in order to create a comprehensive understanding of how immediate effects will be sustained in the next generation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide, we systematically reviewed articles from PubMed and Cochrane Reviews. We included articles that identify climate change-related exposures and adverse health effects for pregnant women. There is evidence that temperature extremes adversely impact birth outcomes, including, but not limited to: changes in length of gestation, birth weight, stillbirth, and neonatal stress in unusually hot temperature exposures. The studies included in this review indicate that not only is there a need for further research on the ways that climate change, and heat in particular, may affect maternal health and neonatal outcomes, but that uniform standards for assessing the effects of heat on maternal fetal health also need to be established.

Pharmacokinetics of ethanol and its metabolite, acetaldehyde, and fetolethality in the third-trimester pregnant guinea pig for oral administration of acute, multiple-dose ethanol.

PubMed

Clarke, D W; Steenaart, N A; Slack, C J; Brien, J F

1986-08-01

The pharmacokinetics of ethanol and its metabolite, acetaldehyde, were determined in the third-trimester pregnant guinea pig (56-59 days gestation) for oral intubation of four doses of 1 g ethanol/kg maternal body weight, administered at 1-h intervals. Animals (n = 4-7) were sacrificed at each of selected times during the 26-h study. Ethanol and acetaldehyde concentrations were determined by headspace gas-liquid chromatography. The maternal and fetal blood ethanol concentration-time curves were virtually superimposable, which indicated unimpeded bidirectional placental transfer of ethanol in the maternal-fetal unit. The blood and brain ethanol concentrations were similar in each of the maternal and fetal compartments during the study, which indicated rapid equilibrium distribution of ethanol. There was accumulation of ethanol in the amniotic fluid resulting in higher ethanol concentration compared with maternal and fetal blood during the elimination phase, which indicated that the amniotic fluid may serve as a reservoir for ethanol in utero. Acetaldehyde was measurable in all the biological fluids and tissues at concentrations that were at least 1,000-fold less than the respective ethanol concentrations and were variable. There was ethanol-induced fetolethality that was delayed and variable among animals, and was 55% at 23 h. At this time interval, the ethanol concentrations in maternal blood and brain, fetal brain, and amniotic fluid were 35- to 53-fold greater and the acetaldehyde concentrations in maternal blood and fetal brain were four- to five-fold higher in the animals with dead fetuses compared with the guinea pigs with live litters. These data indicated that decreased ethanol elimination from the maternal-fetal unit was related temporally to the fetolethality.

Maternal treatment with a high dose of CpG ODN during gestation alters fetal craniofacial and distal limb development in C57BL/6 mice.

PubMed

Prater, M Renee; Johnson, Victor J; Germolec, Dori R; Luster, Michael I; Holladay, Steven D

2006-01-16

Synthetic oligodeoxynucleotides (ODN) containing CpG motifs, characteristic of bacterial DNA, are currently being evaluated as vaccine adjuvants for inducing protective immunity. Recently, there is increasing pressure to vaccinate pregnant women against maternally transmitted diseases including AIDS and tetanus, as well as against potential bio-weapons such as anthrax. CpG vaccines are effective because they trigger transient increases in T(H)1 cytokine production. Recent literature suggests, however, that a shift toward a T(H)1 cytokine profile during pregnancy may increase the risk of fetal morphologic defects. On this basis, we hypothesized that exposure to CpG motifs during pregnancy could result in T(H)1 inflammation leading to adverse effects on fetal development. To address this hypothesis, pregnant C57BL/6 mice were injected with CpG ODN (0-300 microg/dam) and maternal and fetal outcomes were determined. Injection of dams with the highest dose of CpG ODN resulted in markedly increased fetal resorptions and craniofacial/limb defects, while lower doses had little, if any effects. Histological examination of placentas revealed cellular necrosis with mixed inflammation and calcification in the spongiotrophoblast layer and dysregulation of labyrinthine vascular development. Concomitant elevations in maternal serum cytokine levels were observed including interleukin (IL)-2, IL-10 and IL-12. Treatment with 300 microg of non-CpG ODN did not cause any adverse effects. The 300 microg dose of CpG ODN used in the present study is 30-fold higher than the highest dose that has been administered to humans during clinical trials. These results suggest that the induction of T(H)1 cytokines during pregnancy by CpG motifs may potentially increase the risk of fetal loss and morphologic defects in mice, at least at high doses, and support the need for further investigation of teratogenesis that may result from exposure to vaccine adjuvants designed to produce T(H)1 cytokine profile shifts.

Urogenital teratogenicity of synthetic and natural estrogens in the rat: diethylstilbestrol and estradiol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henry, E.C.

1984-01-01

Diethylstilbestrol (DES), a synthetic estrogen and a carcinogen, is a potent urogenital teratogen in humans and rodents. The natural estrogen, estradiol (E/sub 2/), induces malformations in rats only at a maternal toxic dose. This difference in potency could result from differences in fetal sensitivity, or in the distribution and/or metabolism of the two compounds. The current studies tested the hypothesis that the teratogenicity of DES is mediated by its estrogenic activity (rather than its metabolic activation). The two estrogens were directly compared by injecting them into day 19 fetuses, bypassing any maternal modifying factors. Both DES (0.1, 1 or 10more » ..mu..g/fetus) and E/sub 2/ (10 or 100 ..mu..g/fetus) caused dose-related incidences of urogenital malformations (diagnosed at 6-7 weeks), but DES was 10- to 100-fold more potent. Between 24 h and 9 days after DES or E/sub 2/ exposure, histologic evidence of estrogenic stimulation was observed, including premature myometrial growth and differentiation, and vaginal epithelial thickening. Thus, DES and E/sub 2/ act directly in the fetus, to produce similar teratogenic effects, without maternal mediation. Following both maternal and fetal administration of /sup 14/C-DES or /sup 3/H-E/sub 2/, the /sup 14/C (from DES) was concentrated in fetal tissues, whereas /sup 3/H (from E/sub 2/) was retained in fetal plasma (protein-bound). Fetal genital tract contained the largest proportion of unchanged E/sub 2/ (74%) or DES (86%). It was concluded that (1) the teratogenicity of DES reflects its estrogenic activity in the fetus; (2) the fetus is sensitive to a brief exposure to estrogens, including LY and (3) the synthetic estrogen is more potent that estradiol because of its greater availability to fetal genital tissues: protein binding and rapid metabolism reduce the teratogenicity of the natural estrogen.« less

Management of Hypertensive Crisis for the Obstetrician/Gynecologist.

PubMed

ElFarra, Jamil; Bean, Cynthia; Martin, James N

2016-12-01

Hypertensive disorders of pregnancy are among the leading preventable contributors of maternal and fetal adverse outcomes, including maternal and fetal death. Blood pressure increase has a strong association with unfavorable pregnancy outcomes, including stroke and pulmonary edema. A persistent blood pressure measurement greater than or equal to 160/110 mm Hg lasting for more than 15 minutes, during pregnancy or postpartum, is considered an obstetric emergency and requires rapid appropriate treatment. Following evidence-based guidelines, implementing institutional polices, and understanding the classification and pathophysiology of hypertensive disorders of pregnancy are essential and can significantly improve the rate of preventable complications. Copyright © 2016 Elsevier Inc. All rights reserved.

Oxidative stress and maternal obesity: feto-placental unit interaction.

PubMed

Malti, N; Merzouk, H; Merzouk, S A; Loukidi, B; Karaouzene, N; Malti, A; Narce, M

2014-06-01

To determine oxidative stress markers in maternal obesity during pregnancy and to evaluate feto-placental unit interaction, especially predictors of fetal metabolic alterations. 40 obese pregnant women (prepregnancy BMI > 30 kg/m²) were compared to 50 control pregnant women. Maternal, cord blood and placenta samples were collected at delivery. Biochemical parameters (total cholesterol and triglycerides) and oxidative stress markers (malondialdehyde, carbonyl proteins, superoxide anion expressed as reduced Nitroblue Tetrazolium, nitric oxide expressed as nitrite, reduced glutathione, catalase, superoxide dismutase) were assayed by biochemical methods. Maternal, fetal and placental triglyceride levels were increased in obese group compared to control. Maternal malondialdehyde, carbonyl proteins, nitric oxide and superoxide anion levels were high while reduced glutathione concentrations and superoxide dismutase activity were low in obesity. In the placenta and in newborns of these obese mothers, variations of redox balance were also observed indicating high oxidative stress. Maternal and placental interaction constituted a strong predictor of fetal redox variations in obese pregnancies. Maternal obesity compromised placental metabolism and antioxidant status which strongly impacted fetal redox balance. Oxidative stress may be one of the key downstream mediators that initiate programming of the offspring. Maternal obesity is associated with metabolic alterations and dysregulation of redox balance in the mother-placenta - fetus unit. These perturbations could lead to maternal and fetal complications and should be carefully considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

Selective loss of mouse embryos due to the expression of transgenic major histocompatibility class I molecules early in embryogenesis.

PubMed

Aït-Azzouzene, D; Langkopf, A; Cohen, J; Bleux, C; Gendron, M C; Kanellopoulos-Langevin, C

1998-05-01

Among the numerous hypotheses proposed to explain the absence of fetal rejection by the mother in mammals, it has been suggested that regulation of expression of the polymorphic major histocompatibility complex (MHC) at the fetal-maternal interface plays a major role. In addition to a lack of MHC gene expression in the placenta throughout gestation, the absence of polymorphic MHC molecules on the early embryo, as well as their low level of expression after midgestation, could contribute to this important biologic phenomenon. In order to test this hypothesis, we have produced transgenic mice able to express polymorphic MHC class I molecules early in embryogenesis. We have placed the MHC class la gene H-2Kb under the control of a housekeeping gene promoter, the hydroxy-methyl-glutaryl coenzyme A reductase (HMG) gene minimal promoter. This construct has been tested for functionality after transfection into mouse fibroblast L cells. The analysis of three founder transgenic mice and their progeny suggested that fetoplacental units that could express the H-2Kb heavy chains are unable to survive in utero beyond midgestation. We have shown further that a much higher resorption rate, on days 11 to 13 of embryonic development, is observed among transgenic embryos developing from eggs microinjected at the one-cell stage with the pHMG-Kb construct than in control embryos. This lethality is not due to immune phenomena, since it is observed in histocompatible combinations between mother and fetus. These results are discussed in the context of what is currently known about the regulation of MHC expression at the fetal-maternal interface and in various transgenic mouse models.

Second-trimester amniotic fluid corticotropin-releasing hormone and urocortin in relation to maternal stress and fetal growth in human pregnancy.

PubMed

La Marca-Ghaemmaghami, Pearl; Dainese, Sara M; Stalla, Günter; Haller, Marina; Zimmermann, Roland; Ehlert, Ulrike

2017-05-01

This study explored the association between the acute psychobiological stress response, chronic social overload and amniotic fluid corticotropin-releasing hormone (CRH) and urocortin (UCN) in 34 healthy, second-trimester pregnant women undergoing amniocentesis. The study further examined the predictive value of second-trimester amniotic fluid CRH and UCN for fetal growth and neonatal birth outcome. The amniocentesis served as a naturalistic stressor, during which maternal state anxiety and salivary cortisol was measured repeatedly and an aliquot of amniotic fluid was collected. The pregnant women additionally completed a questionnaire on chronic social overload. Fetal growth parameters were obtained at amniocentesis using fetal ultrasound biometry and at birth from medical records. The statistical analyzes revealed that the acute maternal psychobiological stress response was unassociated with the amniotic fluid peptides, but that maternal chronic overload and amniotic CRH were positively correlated. Moreover, amniotic CRH was negatively associated with fetal size at amniocentesis and positively with growth in size from amniocentesis to birth. Hardly any studies have previously explored whether acute maternal psychological stress influences fetoplacental CRH or UCN levels significantly. Our findings suggest that (i) chronic, but not acute maternal stress may affect fetoplacental CRH secretion and that (ii) CRH is complexly involved in fetal growth processes as previously shown in animals.

Matching of maternal and fetal flow ratios in the sheep placenta.

PubMed

Stock, M K; Reid, D L; Phernetton, T M; Rankin, J H

1989-01-01

Local interaction of maternal and fetal placental blood flows was studied in two groups of unanaesthetized near-term sheep. Five sheep were exposed to a simulated dive to 100 feet of seawater (4.03 atmospheres) for 25 min. Six fetuses received an infusion of noradrenaline (6.8 micrograms/[kg x min]). Radioactive microspheres were administered simultaneously to mother and fetus before (control) and after (test) the experimental manipulation. Maternal and fetal relative activities, defined as % of total placental radioactivity divided by % of total placental weight, were calculated for 1-g pieces of cotyledonary tissue under control and test conditions. Pieces of cotyledons were defined as matched if the direction of change in relative activity from control to test was the same for mother and fetus. In the absence of an interaction between the maternal and fetal placental circulations, the probability of a piece of cotyledon being matched is 0.5. In each series of experiments the proportion of all cotyledon pieces having maternal and fetal relative activities that changed in the same direction was significantly greater than 0.5. Thus, the majority of the placental mass responds to a physical or chemical perturbation of the fetus in such a way that changes in relative perfusion are qualitatively matched in the adjacent maternal and fetal placental circulations.

Combined Screening for Early Detection of Pre-Eclampsia

PubMed Central

Park, Hee Jin; Shim, Sung Shin; Cha, Dong Hyun

2015-01-01

Although the precise pathophysiology of pre-eclampsia remains unknown, this condition continues to be a major cause of maternal and fetal mortality. Early prediction of pre-eclampsia would allow for timely initiation of preventive therapy. A combination of biophysical and biochemical markers are superior to other tests for early prediction of the development of pre-eclampsia. Apart from the use of parameters in first-trimester aneuploidy screening, cell-free fetal DNA quantification is emerging as a promising marker for prediction of pre-eclampsia. This article reviews the current research of the most important strategies for prediction of pre-eclampsia, including the use of maternal risk factors, mean maternal arterial pressure, ultrasound parameters, and biomarkers. PMID:26247944

A Summary of Pathways or Mechanisms Linking Preconception Maternal Nutrition with Birth Outcomes.

PubMed

King, Janet C

2016-07-01

Population, human, animal, tissue, and molecular studies show collectively and consistently that maternal nutrition in the pre- or periconception period influences fetal growth and development, which subsequently affects the individual's long-term health. It is known that nutrition during pregnancy is an important determinant of the offspring's growth and health. However, now there is evidence that the mother's nutritional status at conception also influences pregnancy outcome and long-term health. For example, the mother's nutritional status at conception influences the way energy is partitioned between maternal and fetal needs. Furthermore, placental development during the first weeks of gestation reflects maternal nutrition and establishes mechanisms for balancing maternal and fetal nutritional needs. Also, maternal nutritional signals at fertilization influence epigenetic remodeling of fetal genes. These findings all indicate that maternal parenting begins before conception. The following papers from a symposium on preconception nutrition presented at the 2015 Scientific Sessions and Annual Meeting of the ASN emphasize the importance of maternal nutrition at conception on the growth and long-term health of the child. © 2016 American Society for Nutrition.

Cigarette Smoke Exposure during Pregnancy Alters Fetomaternal Cell Trafficking Leading to Retention of Microchimeric Cells in the Maternal Lung

PubMed Central

Vogelgesang, Anja; Scapin, Cristina; Barone, Caroline; Tam, Elaine

2014-01-01

Cigarette smoke exposure causes chronic oxidative lung damage. During pregnancy, fetal microchimeric cells traffic to the mother. Their numbers are increased at the site of acute injury. We hypothesized that milder chronic diffuse smoke injury would attract fetal cells to maternal lungs. We used a green-fluorescent-protein (GFP) mouse model to study the effects of cigarette smoke exposure on fetomaternal cell trafficking. Wild-type female mice were exposed to cigarette smoke for about 4 weeks and bred with homozygote GFP males. Cigarette smoke exposure continued until lungs were harvested and analyzed. Exposure to cigarette smoke led to macrophage accumulation in the maternal lung and significantly lower fetal weights. Cigarette smoke exposure influenced fetomaternal cell trafficking. It was associated with retention of GFP-positive fetal cells in the maternal lung and a significant reduction of fetal cells in maternal livers at gestational day 18, when fetomaternal cell trafficking peaks in the mouse model. Cells quickly clear postpartum, leaving only a few, difficult to detect, persisting microchimeric cells behind. In our study, we confirmed the postpartum clearance of cells in the maternal lungs, with no significant difference in both groups. We conclude that in the mouse model, cigarette smoke exposure during pregnancy leads to a retention of fetal microchimeric cells in the maternal lung, the site of injury. Further studies will be needed to elucidate the effect of cigarette smoke exposure on the phenotypic characteristics and function of these fetal microchimeric cells, and confirm its course in cigarette smoke exposure in humans. PMID:24832066

Transplacental Passage of Acetaminophen in Term Pregnancy.

PubMed

Nitsche, Joshua F; Patil, Avinash S; Langman, Loralie J; Penn, Hannah J; Derleth, Douglas; Watson, William J; Brost, Brian C

2017-05-01

Objective  The objective of this study was to determine the maternal and fetal pharmacokinetic (PK) profiles of acetaminophen after administration of a therapeutic oral dose. Study Design  After obtaining Institutional Review Board approval and their written informed consent, pregnant women were given a single oral dose (1,000 mg) of acetaminophen upon admission for scheduled cesarean delivery. Maternal venous blood and fetal cord blood were obtained at the time of delivery and acetaminophen levels were measured using gas chromatography-mass spectroscopy. PK parameters were calculated by noncompartmental analysis. Nonparametric correlation of maternal/fetal acetaminophen levels and PK curves were calculated. Results  In this study, 34 subjects were enrolled (median, 32 years; range, 25-39 years). The median maternal weight was 82 kg (range, 62-100 kg). All but two subjects were delivered beyond 39 weeks' gestation. The median newborn birth weight was 3,590 g (interquartile range, 3,403-3,848 g). Noncompartmental analysis described similar PK parameters in the maternal ( T 1/2 , 84 minutes; apparent clearance [Cl/F], 28.8 L/h; apparent volume of distribution [V d /F], 57.5 L) and fetal compartments ( T 1/2 , 82 minutes; Cl/F, 31.2 L/h; V d /F, 61.2 L). Paired maternal/fetal acetaminophen levels were highly correlated ( p  < 0.0001). Conclusion  Fetal acetaminophen PKs in the fetus parallels that in the mother suggesting that placental transfer is flow limited. Maternal acetaminophen levels can be used as a surrogate for fetal exposure. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A novel LabVIEW-based multi-channel non-invasive abdominal maternal-fetal electrocardiogram signal generator.

PubMed

Martinek, Radek; Kelnar, Michal; Koudelka, Petr; Vanus, Jan; Bilik, Petr; Janku, Petr; Nazeran, Homer; Zidek, Jan

2016-02-01

This paper describes the design, construction, and testing of a multi-channel fetal electrocardiogram (fECG) signal generator based on LabVIEW. Special attention is paid to the fetal heart development in relation to the fetus' anatomy, physiology, and pathology. The non-invasive signal generator enables many parameters to be set, including fetal heart rate (FHR), maternal heart rate (MHR), gestational age (GA), fECG interferences (biological and technical artifacts), as well as other fECG signal characteristics. Furthermore, based on the change in the FHR and in the T wave-to-QRS complex ratio (T/QRS), the generator enables manifestations of hypoxic states (hypoxemia, hypoxia, and asphyxia) to be monitored while complying with clinical recommendations for classifications in cardiotocography (CTG) and fECG ST segment analysis (STAN). The generator can also produce synthetic signals with defined properties for 6 input leads (4 abdominal and 2 thoracic). Such signals are well suited to the testing of new and existing methods of fECG processing and are effective in suppressing maternal ECG while non-invasively monitoring abdominal fECG. They may also contribute to the development of a new diagnostic method, which may be referred to as non-invasive trans-abdominal CTG +  STAN. The functional prototype is based on virtual instrumentation using the LabVIEW developmental environment and its associated data acquisition measurement cards (DAQmx). The generator also makes it possible to create synthetic signals and measure actual fetal and maternal ECGs by means of bioelectrodes.

Outcomes of Medically Indicated Preterm Births Differ by Indication.

PubMed

Wang, Michelle J; Kuper, Spencer G; Steele, Robin; Sievert, Rachel A; Tita, Alan T; Harper, Lorie M

2018-07-01

 We aim to examine whether outcomes of preterm birth (PTB) are further modified by the indication for delivery.  We performed a retrospective cohort study of all singletons delivered at 23 to 34 weeks from 2011 to 2014. Women were classified by their primary indication for delivery: maternal (preeclampsia) or fetal/obstetric (growth restriction, nonreassuring fetal status, and vaginal bleeding). The primary neonatal outcome was a composite of neonatal death, cord pH <7 or base excess < - 12, 5-minute Apgar ≤3, C-reactive protein during resuscitation, culture-proven sepsis, intraventricular hemorrhage, and necrotizing enterocolitis. Secondary outcomes included the individual components of the primary outcome. Groups were compared using Student's t -test and chi-squared tests. Logistic regression was used to adjust for confounding variables.  Of 528 women, 395 (74.8%) were delivered for maternal and 133 (25.2%) for fetal/obstetric indications. Compared with those delivered for a maternal indication, those with a fetal/obstetric indication for delivery had an increased risk of the composite neonatal outcome (adjusted odds ratio [AOR]: 1.9, 95% confidence interval [CI]: 1.13-3.21) and acidemia at birth (AOR: 4.2, 95% CI: 1.89-9.55).  Preterm infants delivered for fetal/obstetric indications have worsened outcomes compared with those delivered for maternal indications. Additional research is needed to further tailor counseling specific to the indication for delivery. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Impaired Gal-9 Dysregulates the PBMC-Induced Th1/Th2 Imbalance in Abortion-Prone Matings

PubMed Central

He, Mengzhou; Jiang, Ming; Zhou, Yuan; Li, Fanfan; Yang, Meitao; Fan, Yao; Xie, Yin; Beejadhursing, Rajluxmee; Feng, Ling

2018-01-01

Recurrent miscarriage is defined as the loss of 3 or more consecutive pregnancies; however, the underlying immunologic mechanisms that trigger pregnancy loss remain largely unelucidated. Galectin-9 (Gal-9) may modulate a variety of biologic functions and play an important role in Th1/Th2 immune deviation. To analyze the mechanism of Gal-9 in abortion, we used the classical abortion-prone mouse model (DBA/2-mated CBA/J mice) to detect the expression of Gal-9 at the maternal-fetal interface. We also mimicked the immune environment of pregnancy by culturing trophoblast cells with peripheral blood mononuclear cells (PBMCs) to explore how Gal-9 might be involved in the pathogenesis of abortion. We found that the expression levels of Gal-9 in abortion-prone matings were lower than that for controls. Using a coculture system, we detected a Th1 preponderance in the coculture from abortion-prone matings. Furthermore, Gal-9 blockade augmented the imbalance of Th1/Th2 immunity in abortion-prone matings by promoting the secretion of Th1-derived cytokines in coculture, while there was a Th2 preponderance when we administered recombinant Gal-9. In conclusion, our results suggest that the Gal-9 signal is important for the regulation of PBMC function toward a Th2 bias at the maternal-fetal interface, which is beneficial for the maintenance of a normal pregnancy. PMID:29651447

Comparison of fetal and maternal heart rate measures using electrocardiographic and cardiotocographic methods.

PubMed

Kisilevsky, Barbara S; Brown, C Ann

2016-02-01

To determine the reliability at term of: (1) two methods of measuring fetal heart rate (HR), electrocardiographic (ECG, the 'gold standard') and cardiotocographic (CTG) and (2) two ECG methods of measuring maternal HR variability over relatively brief periods of time (s-min). During 20 min of rest (N=39) and during 2 min of auditory stimulation (mother's recorded voice, n=19), fetal HR data were collected using an ECG (Monica AN24) and a Hewlett-Packard Model 1351A CTG. Simultaneously, maternal HR data (n=37) were collected using the same ECG device (Monica AN24) and a second stand-alone cardiac monitor (Spacelab 514T cardiac monitor with a QRS detector). During 20 min of maternal rest, correlations of individual fetal CTG with ECG measures of HR at each second were moderate to high (r=.57-.97) for 77% of fetuses. Correlations of HR averaged over fetuses and over each of the 20 min were high (r=.93-.97); fetal HR averaged over 20 min varied between devices from 0.0 to 0.8 bpm. During 2 min of maternal voice presentation, correlations of fetal HR over each second were moderate to high (r=.54-.99) for 95% of fetuses and high (all rs=.99) when averaged across fetuses in 30s or 2 min epochs. Average fetal HR between devices over the 2 min voice varied from 0.0 to 0.6 bpm. Correlations and/or % agreement between the two ECG methods of measuring maternal HR were high. Average maternal HR over 10 min showed 81% of pairs with a difference of ≤ 1 bpm; correlations for HR variability measures varied from r=.89 to .97. Good reliability was demonstrated between individual spontaneous and auditory induced fetal CTG and ECG with high correlations when HR data were averaged over fetuses or in 30-120 s epochs. High reliability of maternal HR measures was obtained using two ECG devices. Copyright © 2016 Elsevier Inc. All rights reserved.

Extraction of fetal ECG signal by an improved method using extended Kalman smoother framework from single channel abdominal ECG signal.

PubMed

Panigrahy, D; Sahu, P K

2017-03-01

This paper proposes a five-stage based methodology to extract the fetal electrocardiogram (FECG) from the single channel abdominal ECG using differential evolution (DE) algorithm, extended Kalman smoother (EKS) and adaptive neuro fuzzy inference system (ANFIS) framework. The heart rate of the fetus can easily be detected after estimation of the fetal ECG signal. The abdominal ECG signal contains fetal ECG signal, maternal ECG component, and noise. To estimate the fetal ECG signal from the abdominal ECG signal, removal of the noise and the maternal ECG component presented in it is necessary. The pre-processing stage is used to remove the noise from the abdominal ECG signal. The EKS framework is used to estimate the maternal ECG signal from the abdominal ECG signal. The optimized parameters of the maternal ECG components are required to develop the state and measurement equation of the EKS framework. These optimized maternal ECG parameters are selected by the differential evolution algorithm. The relationship between the maternal ECG signal and the available maternal ECG component in the abdominal ECG signal is nonlinear. To estimate the actual maternal ECG component present in the abdominal ECG signal and also to recognize this nonlinear relationship the ANFIS is used. Inputs to the ANFIS framework are the output of EKS and the pre-processed abdominal ECG signal. The fetal ECG signal is computed by subtracting the output of ANFIS from the pre-processed abdominal ECG signal. Non-invasive fetal ECG database and set A of 2013 physionet/computing in cardiology challenge database (PCDB) are used for validation of the proposed methodology. The proposed methodology shows a sensitivity of 94.21%, accuracy of 90.66%, and positive predictive value of 96.05% from the non-invasive fetal ECG database. The proposed methodology also shows a sensitivity of 91.47%, accuracy of 84.89%, and positive predictive value of 92.18% from the set A of PCDB.

Fetal Microsatellite in the Heme Oxygenase 1 Promoter Is Associated With Severe and Early-Onset Preeclampsia.

PubMed

Kaartokallio, Tea; Utge, Siddheshwar; Klemetti, Miira M; Paananen, Jussi; Pulkki, Kari; Romppanen, Jarkko; Tikkanen, Ilkka; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Lakkisto, Päivi; Laivuori, Hannele

2018-01-01

Preeclampsia is a vascular pregnancy disorder that often involves impaired placental development. HO-1 (heme oxygenase 1, encoded by HMOX1 ) is a stress response enzyme crucial for endothelial and placental function. Long version of the guanine-thymine (GT n ) microsatellite in the HMOX1 promoter decreases HO-1 expression, and the long maternal repeat is associated with late-onset preeclampsia. Our aim was to study whether the length of fetal repeat is associated with mother's preeclampsia, whether the length of fetal and maternal repeats affect HO-1 levels in placenta and maternal serum, and whether HO-1 levels are altered in preeclampsia. We genotyped the repeat in the cord blood of 609 preeclamptic and 745 nonpreeclamptic neonates. HO-1 levels were measured in 36 placental samples, and in the first (222 cases/243 controls) and third (176 cases/53 controls) pregnancy trimester serum samples using enzyme-linked immunosorbent assay. The long fetal GT n repeat was associated with preeclampsia and its severe and early-onset subtypes. Interaction analysis suggested the maternal and fetal effects to be independent. Placental or serum HO-1 levels were not altered in preeclamptics, possibly reflecting heterogeneity of preeclampsia. Carriers of the long fetal and maternal repeats had lower placental and serum HO-1 levels, respectively, providing functional evidence for the association. We conclude that the long fetal GT n repeat may increase mother's risk for especially severe and early-onset preeclampsia. The fetal and maternal risk alleles likely predispose to different disease subtypes. © 2017 American Heart Association, Inc.

Severe fetal and neonatal hyperthyroidism years after surgical treatment of maternal Graves' disease.

PubMed

Dierickx, I; Decallonne, B; Billen, J; Vanhole, C; Lewi, L; De Catte, L; Verhaeghe, J

2014-02-01

Fetal/neonatal hyperthyroidism is a well-known complication of maternal Graves' disease with high concentrations of TSH-receptor antibodies (TRAb). Few data are available on the management of fetal hyperthyroidism in surgically treated Graves' disease. Clinical, ultrasound and biochemical data are reported in a fetus/neonate whose mother underwent a thyroidectomy > 10 years before and whose sibling was thin and hyperthyroid at birth. Maternal TRAb were persistently > 40 U/l; unequivocal signs of fetal hyperthyroidism were identified at 29 weeks gestational age (GA). The fetus was treated through maternal antithyroid drug (ATD) administration; the dose was reduced gradually once fetal tachycardia and valve dysfunction disappeared and normal T4 was confirmed by fetal blood sampling. Maternal euthyroidism was maintained. The neonate showed normal growth for GA and T4 concentration at birth but severe hyperthyroidism relapsed from day 13 until day 58. TSH remained strongly suppressed throughout the pre- and postnatal course. Prenatal ATD in a taper-off regime allowed normal T4 and growth in a hyperthyroid fetus from a thyroidectomised Graves' mother. Fetal TSH cannot be used to adjust the ATD dose. Prenatal ATD appears to postpone the onset but does not affect the severity or duration of the neonatal hyperthyroid flare.

Fetal transesophageal echocardiography: clinical introduction as a monitoring tool during cardiac intervention in a human fetus.

PubMed

Kohl, T; Müller, A; Tchatcheva, K; Achenbach, S; Gembruch, U

2005-12-01

Because of insufficient imaging by maternal transabdominal fetal echocardiography (TAE) in a human fetus with aortic atresia, imperforate atrial septum and progressive cardiac failure, we assessed the feasibility of fetal transesophageal echocardiography (TEE) as a monitoring tool during fetal cardiac intervention at 24 + 6 weeks of gestation. Percutaneous fetoscopic intraesophageal deployment of the ultrasound catheter was achieved and did not result in any maternal or fetal complications. Fetal TEE permitted substantially clearer definition of fetal cardiac anatomy and intracardiac device manipulations than conventional maternal TAE. Despite the employment of various devices, no sufficiently large opening could be achieved within the atrial septum. Although the fetus tolerated the procedure remarkably well and satisfactory fetoplacental flow could be documented at the end of the procedure, the fetus died from progressive cardiac failure 3 days after the intervention. Fetoscopic TEE is feasible in the human fetus and permits substantially clearer definition of fetal cardiac anatomy and intracardiac manipulations than conventional maternal TAE. Based on the observation of spontaneous closure of multiple iatrogenic perforations of the atrial septum, specialized devices are required in order to improve the technical success rate of septoplasty methods and hence the survival odds of these high-risk patients.

Vertical Transmission of Listeria monocytogenes: Probing the Balance between Protection from Pathogens and Fetal Tolerance.

PubMed

Lamond, Nicole M; Freitag, Nancy E

2018-05-25

Protection of the developing fetus from pathogens is one of the many critical roles of the placenta. Listeria monocytogenes is one of a select number of pathogens that can cross the placental barrier and cause significant harm to the fetus, leading to spontaneous abortion, stillbirth, preterm labor, and disseminated neonate infection despite antibiotic treatment. Such severe outcomes serve to highlight the importance of understanding how L. monocytogenes mediates infiltration of the placental barrier. Here, we review what is currently known regarding vertical transmission of L. monocytogenes as a result of cell culture and animal models of infection. In vitro cell culture and organ models have been useful for the identification of L. monocytogenes virulence factors that contribute to placental invasion. Examples include members of the Internalin family of bacterial surface proteins such as Interalin (Inl)A, InlB, and InlP that promote invasion of cells at the maternal-fetal interface. A number of animal models have been used to interrogate L. monocytogenes vertical transmission, including mice, guinea pigs, gerbils, and non-human primates; each of these models has advantages while still not providing a comprehensive understanding of L. monocytogenes invasion of the human placenta and/or fetus. These models do, however, allow for the molecular investigation of the balance between fetal tolerance and immune protection from L. monocytogenes during pregnancy.

Parvovirus B19 infection in pregnancy.

PubMed

de Jong, Eveline P; de Haan, Timo R; Kroes, Aloys C M; Beersma, Matthias F C; Oepkes, Dick; Walther, Frans J

2006-05-01

Parvovirus B19 is a small single-stranded DNA virus and a potent inhibitor of erythropoiesis, due to its cytotoxicity to erythroid progenitor cells. Infection with parvovirus B19 during pregnancy can cause several serious complications in the fetus, such as fetal anemia, neurological anomalies, hydrops fetalis, and fetal death. Early diagnosis and treatment of intrauterine parvovirus B19 infection is essential in preventing these fetal complications. Testing maternal serum for IgM antibodies against parvovirus B19 and DNA detection by PCR can confirm maternal infection. If maternal infection has occurred, ultrasound investigation of the fetus and measurement of the peak systolic flow velocity of the middle cerebral artery are sensitive non-invasive procedures to diagnose fetal anemia and hydrops. Intrauterine transfusion is currently the only effective treatment to alleviate fetal anemia, but if the fetus is (near) term, induction of delivery should be considered. Most maternal infections with parvovirus B19 occur through contact with infected children at home. Individual counseling of susceptible pregnant women will reduce unnecessary fetal deaths.

Hearings Before the Select Committee on Nutrition and Human Needs of the United States Senate, Ninety-Third Congress, First Session. Maternal, Fetal, and Infant Nutrition--1973. Part 1--Consequences of Malnutrition; Part 2--Government Responses. Hearings Held Washington, D.C., June 5, 6, and 7, 1973.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Select Committee on Nutrition and Human Needs.

Part One of these hearings before the Select Committee on Nutrition and Human Needs of the United States Senate includes the testimony of scientists and doctors engaged in research regarding the relationship between maternal, fetal, and infant nutrition and optimum mental and physical development of the child. In testimony it was shown that the…

The tripartite immune conflict in placentals and a hypothesis on fetal-->maternal microchimerism.

PubMed

Apari, Péter; Rózsa, Lajos

2009-01-01

There is a two-way traffic of immune cells through the placenta; and fetal immune cells are often present in the maternal body even long after giving birth. We present an adaptationist theory to interpret fetal-->maternal microchimerism and the diverse set of concomitant medical phenomena. We handle fetal, maternal, and paternal adaptive interests separately and in interaction with one another. Fetuses may benefit from immunological information gathered by migrant cells in the maternal body, and also from improved maternal defence. However, they may be jeopardized by a selfish maternal usage of fetal-->maternal microchimerism - i.e., some mothers get pregnant only to improve their immune system and then to abort. The use of microchimeric cells by the maternal immune system may contribute to the adaptive benefits of female choosiness and polyandry. While fathers may enjoy an indirect benefit from enhanced fetal and maternal health, they also face the risk of wasting sexual efforts due to selfish pregnancies of cheating females. Paternal alleles acting via clones of microchimeric cells in the maternal body could launch an immunological attack against the non-kin sperm in the female genitalia, or against the non-kin fetus in the womb. Furthermore, an intraspecific version of Zahavi's Mafia Hypothesis could explain a potential interaction between the abortion of fetuses and a subsequent rise of an autoimmune disease. We suggest that males may be capable to provoke microchimerism-induced autoimmune-like diseases in the mother in revenge of selfish pregnancies. This hypothetic paternal threat could increase the maternal costs associated to selfish pregnancies. From a medical point of view, we propose new interpretations for autoimmune-like diseases, infertility, miscarriage, and also for the prevailing connections among them. Specifically, we argue that miscarriages may cause autoimmune diseases, a reversed causality as compared to the currently accepted one.

Profiling the activity of environmental chemicals in prenatal developmental toxicity studies using the U.S. EPA’s ToxRefDB

EPA Science Inventory

As the primary source for regulatory developmental toxicity information, prenatal studies characterize maternal effects and fetal endpoints including malformations, resorptions, and fetal weight reduction. Results from 383 rat and 368 rabbit prenatal studies on 387 chemicals, mo...

Fetal movement detection: comparison of the Toitu actograph with ultrasound from 20 weeks gestation.

PubMed

DiPietro, J A; Costigan, K A; Pressman, E K

1999-01-01

This study evaluates the validity of Doppler-detected fetal movement by a commercially available monitor and investigates whether characteristics of maternal body habitus and the intrauterine environment affect its performance. Fetal movement was evaluated in normal pregnancies using both ultrasound visualization and a fetal actocardiograph (Toitu MT320; Tofa Medical Inc., Malvern, PA). Data were collected for 32 min on 34 fetuses stratified by gestational age (20-25 weeks; 28-32 weeks; 35-39 weeks). Fetal and maternal characteristics were recorded. Comparisons between ultrasound-detected trunk and limb movements and actograph records were conducted based both on 10-s time intervals and on detection of individual movements. Time-based comparisons indicated agreement between ultrasound and actograph 94.7% of the time; this association rose to 98% when movements of less than 1 s duration were excluded. Individual movements observed on ultrasound were detected by the actograph 91% of the time, and 97% of the time when brief, isolated movements were excluded. The overall kappa value for agreement was 0.88. The actograph was reliable in detecting periods of quiescence as well as activity. These findings did not vary by gestational age. The number of movements detected by the actograph, but not the single-transducer ultrasound, significantly increased over gestation. Maternal age, parity, weight, height, or body mass index were not consistently associated with actograph validity. Characteristics of the uterine environment, including placenta location, fetal presentation, and amniotic fluid volume also did not affect results. The Toitu actograph accurately detects fetal movement and quiescence from as early as 20 weeks gestation and has utility in both clinical and research settings. Actographs are most useful for providing objective and quantifiable measures of fetal activity level, including number and duration of movements, while visualization through ultrasound is necessary for studies of movement quality, source, or mechanics.

Prenatal Lead Exposure and Fetal Growth: Smaller Infants Have Heightened Susceptibility

PubMed Central

Rodosthenous, Rodosthenis S.; Burris, Heather H.; Svensson, Katherine; Amarasiriwardena, Chitra J.; Cantoral, Alejandra; Schnaas, Lourdes; Mercado-García, Adriana; Coull, Brent A.; Wright, Robert O.; Téllez-Rojo, Martha M.; Baccarelli, Andrea A.

2016-01-01

Background As population lead levels decrease, the toxic effects of lead may be distributed to more sensitive populations, such as infants with poor fetal growth. Objectives To determine the association of prenatal lead exposure and fetal growth; and to evaluate whether infants with poor fetal growth are more susceptible to lead toxicity than those with normal fetal growth. Methods We examined the association of second trimester maternal blood lead levels (BLL) with birthweight-for-gestational age (BWGA) z-score in 944 mother-infant participants of the PROGRESS cohort. We determined the association between maternal BLL and BWGA z-score by using both linear and quantile regression. We estimated odds ratios for small-for-gestational age (SGA) infants between maternal BLL quartiles using logistic regression. Maternal age, body mass index, socioeconomic status, parity, household smoking exposure, hemoglobin levels, and infant sex were included as confounders. Results While linear regression showed a negative association between maternal BLL and BWGA z-score (β=−0.06 z-score units per log2 BLL increase; 95% CI: −0.13, 0.003; P=0.06), quantile regression revealed larger magnitudes of this association in the <30th percentiles of BWGA z-score (β range [−0.08, −0.13] z-score units per log2 BLL increase; all P values <0.05). Mothers in the highest BLL quartile had an odds ratio of 1.62 (95% CI: 0.99–2.65) for having a SGA infant compared to the lowest BLL quartile. Conclusions While both linear and quantile regression showed a negative association between prenatal lead exposure and birthweight, quantile regression revealed that smaller infants may represent a more susceptible subpopulation. PMID:27923585

Prenatal lead exposure and fetal growth: Smaller infants have heightened susceptibility.

PubMed

Rodosthenous, Rodosthenis S; Burris, Heather H; Svensson, Katherine; Amarasiriwardena, Chitra J; Cantoral, Alejandra; Schnaas, Lourdes; Mercado-García, Adriana; Coull, Brent A; Wright, Robert O; Téllez-Rojo, Martha M; Baccarelli, Andrea A

2017-02-01

As population lead levels decrease, the toxic effects of lead may be distributed to more sensitive populations, such as infants with poor fetal growth. To determine the association of prenatal lead exposure and fetal growth; and to evaluate whether infants with poor fetal growth are more susceptible to lead toxicity than those with normal fetal growth. We examined the association of second trimester maternal blood lead levels (BLL) with birthweight-for-gestational age (BWGA) z-score in 944 mother-infant participants of the PROGRESS cohort. We determined the association between maternal BLL and BWGA z-score by using both linear and quantile regression. We estimated odds ratios for small-for-gestational age (SGA) infants between maternal BLL quartiles using logistic regression. Maternal age, body mass index, socioeconomic status, parity, household smoking exposure, hemoglobin levels, and infant sex were included as confounders. While linear regression showed a negative association between maternal BLL and BWGA z-score (β=-0.06 z-score units per log 2 BLL increase; 95% CI: -0.13, 0.003; P=0.06), quantile regression revealed larger magnitudes of this association in the <30th percentiles of BWGA z-score (β range [-0.08, -0.13] z-score units per log 2 BLL increase; all P values<0.05). Mothers in the highest BLL quartile had an odds ratio of 1.62 (95% CI: 0.99-2.65) for having a SGA infant compared to the lowest BLL quartile. While both linear and quantile regression showed a negative association between prenatal lead exposure and birthweight, quantile regression revealed that smaller infants may represent a more susceptible subpopulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Peruvian newborn fetal growth according to its sex, geographical area, and maternal parity and height].

PubMed

Rendón, Manuel Ticona; Apaza, Diana Huanco

2008-09-01

Birth weight is the most important indicator of fetal growth, fetal development, and nutritional estate of newborn, and several factors affect it. To know the fetal growth of Peruvian newborns according to fetal sex, maternal parity and height, and geographical area. Prospective and cross sectional study. Successive newborn data of 29 hospitals of Ministerio de Salud del Peru was obtained during 2005 year, all of them without intrauterine growth delay. Student ttest was used to compare: male and female, primiparous and multiparous, and coast, mountain, and rainforest newborn average weight (meaningful difference: p < 0.05). Maternal height was related to newborn weight, height, cephalic perimeter, and gestational age. From 50,568 selected alive newborns, male had an average weight from 19 to 41 g higher than female, and multiparous newborns had from 22 to 53 g more than primiparous newborns. Maternal height has a direct connection with newborn weight, height, and cephalic perimeter. Coast newborns had an average weight from 133 to 210 g higher than those from mountain, and from 76 to 142 g higher than those from rainforest; average weight of rainforest newborns was from 19 to 83 g higher to those from mountain. Weight differences due to fetal sex, maternal parity and height, and geographic region were meaningful among 36 to 42 weeks of gestation. Fetal sex, maternal parity and height, and geographical region affect newborn weight. It is recommended to use weight and gestational age as correction factors to appropriately classify Peruvian newborns.

Risk of fetal death associated with maternal drug dependence and placental abruption: a population-based study.

PubMed

McDonald, Sarah D; Vermeulen, Marian J; Ray, Joel G

2007-07-01

Substance use in pregnancy is associated with placental abruption, but the risk of fetal death independent of abruption remains undetermined. Our objective was to examine the effect of maternal drug dependence on placental abruption and on fetal death in association with abruption and independent of it. To examine placental abruption and fetal death, we performed a retrospective population-based study of 1 854 463 consecutive deliveries of liveborn and stillborn infants occurring between January 1, 1995 and March 31, 2001, using the Canadian Institute for Health Information Discharge Abstract Database. Maternal drug dependence was associated with a tripling of the risk of placental abruption in singleton pregnancies (adjusted odds ratio [OR] 3.1; 95% confidence intervals [CI] 2.6-3.7), but not in multiple gestations (adjusted OR 0.88; 95% CI 0.12-6.4). Maternal drug dependence was associated with an increased risk of fetal death independent of abruption (adjusted OR 1.6: 95% CI 1.1-2.2) in singleton pregnancies, but not in multiples. Risk of fetal death was increased with placental abruption in both singleton and multiple gestations, even after controlling for drug dependence (adjusted OR 11.4 in singleton pregnancy; 95% CI 10.6-12.2, and 3.4 in multiple pregnancy; 95% CI 2.4-4.9). Maternal drug use is associated with an increased risk of intrauterine fetal death independent of placental abruption. In singleton pregnancies, maternal drug dependence is associated with an increased risk of placental abruption.

Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size.

PubMed

Ahlsson, Fredrik; Diderholm, Barbro; Ewald, Uwe; Jonsson, Björn; Forslund, Anders; Stridsberg, Mats; Gustafsson, Jan

2013-05-01

The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation. Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique. Median (range) rate of glucose production was 805 (653-1337) μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110-576) μmol/min. HOMA insulin resistance averaged 1.5 ± 0.75 and estimated fetal weights ranged between 2670 and 4175 g (-0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2 ± 2.5mg/L and median level of leptin was 47.1 (9.9-58.0) μg/L. Adiponectin concentrations (7.2 ± 2.5mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r=-0.50, p<0.035, r=-0.77, p<0.001, r=-0.67, p<0.002, and r=-0.51, p<0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r=0.76, p<0.001 and r=0.73, p<0.001, respectively. There was no correlation between maternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure. The inverse correlations between levels of maternal adiponectin and insulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Longitudinal changes in gestational weight gain and the association with intrauterine fetal growth.

PubMed

Hinkle, Stefanie N; Johns, Alicia M; Albert, Paul S; Kim, Sungduk; Grantz, Katherine L

2015-07-01

Total pregnancy weight gain has been associated with infant birthweight; however, most prior studies lacked repeat ultrasound measurements. Understanding of the longitudinal changes in maternal weight gain and intrauterine changes in fetal anthropometrics is limited. Prospective data from 1314 Scandinavian singleton pregnancies at high-risk for delivering small-for-gestational-age (SGA) were analyzed. Women had ≥1 (median 12) antenatal weight measurements. Ultrasounds were targeted at 17, 25, 33, and 37 weeks of gestation. Analyses involved a multi-step process. First, trajectories were estimated across gestation for maternal weight gain and fetal biometrics [abdominal circumference (AC, mm), biparietal diameter (BPD, mm), femur length (FL, mm), and estimated fetal weight (EFW, g)] using linear mixed models. Second, the association between maternal weight changes (per 5 kg) and corresponding fetal growth from 0 to 17, 17 to 28, and 28 to 37 weeks was estimated for each fetal parameter adjusting for prepregnancy body mass index, height, parity, chronic diseases, age, smoking, fetal sex, and weight gain up to the respective period as applicable. Third, the probability of fetal SGA, EFW <10th percentile, at the 3rd ultrasound was estimated across the spectrum of maternal weight gain rate by SGA status at the 2nd ultrasound. From 0 to 17 weeks, changes in maternal weight were most strongly associated with changes in BPD [β=0.51 per 5 kg (95%CI 0.26, 0.76)] and FL [β=0.46 per 5 kg (95%CI 0.26, 0.65)]. From 17 to 28 weeks, AC [β=2.92 per 5 kg (95%CI 1.62, 4.22)] and EFW [β=58.7 per 5 kg (95%CI 29.5, 88.0)] were more strongly associated with changes in maternal weight. Increased maternal weight gain was significantly associated with a reduced probability of intrauterine SGA; for a normal weight woman with SGA at the 2nd ultrasound, the probability of fetal SGA with a weight gain rate of 0.29 kg/w (10th percentile) was 59%, compared to 38% with a rate of 0.67 kg/w (90th percentile). Among women at high-risk for SGA, maternal weight gain was associated with fetal growth throughout pregnancy, but had a differential relationship with specific biometrics across gestation. For women with fetal SGA identified mid-pregnancy, increased antenatal weight gain was associated with a decreased probability of fetal SGA approximately 7 weeks later. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Macroscopic placental changes associated with fetal and maternal events in diabetes mellitus

PubMed Central

Salge, Ana Karina Marques; Rocha, Karlla Morgana Nunes; Xavier, Raphaela Maioni; Ramalho, Wilzianne Silva; Rocha, Érika Lopes; Guimarães, Janaína Valadares; Silva, Renata Calciolari Rossi e; Siqueira, Karina Machado; Abdalla, Douglas Reis; Michelin, Márcia Antoniazzi; Murta, Eddie Fernando Candido

2012-01-01

OBJECTIVES: The current study sought to identify macroscopic placental changes associated with clinical conditions in women with or without diabetes and their newborns. METHODS: The study population consisted of 62 pregnant women clinically diagnosed with diabetes and 62 healthy women (control group). RESULTS: Among the subjects with diabetes, 43 women (69.3%) were diagnosed with gestational diabetes mellitus, 15 had diabetes mellitus I (24.2%), and four had diabetes mellitus II (6.5%). The mean age of the women studied was 28.5±5.71 years, and the mean gestational age of the diabetic women was 38.51 weeks. Of the 62 placentas from diabetic pregnancies, 49 (79%) maternal surfaces and 59 (95.2%) fetal surfaces showed abnormalities, including calcium and fibrin deposits, placental infarction, hematoma, and fibrosis. A statistical association was found between newborn gender and fetal and maternal placental changes (p = 0.002). The mean weight of the newborns studied was 3,287±563 g for women with diabetes mellitus, 3,205±544 g for those with gestational diabetes mellitus, 3,563±696 g for those with diabetes mellitus II, and 3,095±451 g for those with diabetes mellitus I. CONCLUSIONS: Infarction, hematoma, calcification, and fibrin were found on the maternal and fetal placental surfaces in women with diabetes. Women with gestational diabetes and post-term infants had more calcium deposits on the maternal placental surface as compared to those with type I and type II diabetes. PMID:23070348

The impact of unemployment cycles on child and maternal health in Argentina.

PubMed

Wehby, George L; Gimenez, Lucas G; López-Camelo, Jorge S

2017-03-01

The purpose of this study is to examine the effects of economic cycles in Argentina on infant and maternal health between 1994 and 2006, a period that spans the major economic crisis in 1999-2002. We evaluate the effects of province-level unemployment rates on several infant health outcomes, including birth weight, gestational age, fetal growth rate, and hospital discharge status after birth in a sample of 15,000 infants born in 13 provinces. Maternal health and healthcare outcomes include acute and chronic illnesses, infectious diseases, and use of prenatal visits and technology. Regression models control for hospital and year fixed effects and province-specific time trends. Unemployment rise reduces fetal growth rate particularly among high educated parents. Also, maternal poverty-related infectious diseases increase, although reporting of acute illnesses declines (an effect more pronounced among low educated parents). There is also some evidence for reduced access to prenatal care and technology among less educated parents with higher unemployment. Unemployment rise in Argentina has adversely affected certain infant and maternal health outcomes, but several measures show no evidence of significant change.

Maternal pre-gravid body mass index and adiposity influence umbilical cord gene expression at term in AGA infants

USDA-ARS?s Scientific Manuscript database

While maternal obesity is associated with unfavorable maternal and fetal outcomes, the influence of maternal obesity on fetal gene expression is less clear. Umbilical cords (UC) from 12 lean (pre-gravid BMI < 25) and 10 overweight/obese (OB, pre-gravid BMI =25) women without gestational diabetes wer...

Assessment of the concordance among 2-tier, 3-tier, and 5-tier fetal heart rate classification systems.

PubMed

Gyamfi Bannerman, Cynthia; Grobman, William A; Antoniewicz, Leah; Hutchinson, Maria; Blackwell, Sean

2011-09-01

In 2008, a National Institute of Child Health and Human Development/Society for Maternal-Fetal Medicine-sponsored workshop on electronic fetal monitoring recommended a new fetal heart tracing interpretation system. Comparison of this 3-tier system with other systems is lacking. Our purpose was to determine the relationships between fetal heart rate categories for the 3 existing systems. Three Maternal-Fetal Medicine specialists reviewed 120 fetal heart rates. All tracings were from term, singleton pregnancies with known umbilical artery pH. The fetal heart rates were classified by a 2-tier, 3-tier, and 5-tier system. Each Maternal-Fetal Medicine examiner reviewed 120 fetal heart rate segments. When compared with the 2-tier system, 0%, 54%, and 100% tracings in categories 1, 2, and 3 were "nonreassuring." There was strong concordance between category 1 and "green" as well as category 3 and "red" tracings. The 3-tier and 5-tier systems were similar in fetal heart rate interpretations for tracings that were either very normal or very abnormal. Whether one system is superior to the others in predicting fetal acidemia remains unknown. Copyright © 2011 Mosby, Inc. All rights reserved.

Maternal melatonin selectively inhibits cortisol production in the primate fetal adrenal gland

PubMed Central

Torres-Farfan, Claudia; Richter, Hans G; Germain, Alfredo M; Valenzuela, Guillermo J; Campino, Carmen; Rojas-García, Pedro; Forcelledo, María Luisa; Torrealba, Fernando; Serón-Ferré, María

2004-01-01

We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal cortisol production. A functional G-protein-coupled MT1 membrane-bound melatonin receptor was detected in 90% gestation capuchin monkey fetal adrenals by (a) 2-[125I] iodomelatonin binding (Kd, 75.7 ± 6.9 pm; Bmax, 2.6 ± 0.4 fmol (mg protein)−1), (b) cDNA identification, and (c) melatonin inhibition of adrenocorticotrophic hormone (ACTH)- and corticotrophin-releasing hormone (CRH)-stimulated cortisol but not of dehydroepiandrosterone sulphate (DHAS) production in vitro. Melatonin also inhibited ACTH-induced 3β-hydroxysteroid dehydrogenase mRNA expression. To assess the physiological relevance of these findings, we next studied the effect of chronic maternal melatonin suppression (induced by exposure to constant light during the last third of gestation) on maternal plasma oestradiol during gestation and on plasma cortisol concentration in the 4- to 6-day-old newborn. Constant light suppressed maternal melatonin without affecting maternal plasma oestradiol concentration, consistent with no effect on fetal DHAS, the precursor of maternal oestradiol. However, newborns from mothers under constant light condition had twice as much plasma cortisol as newborns from mothers maintained under a normal light–dark schedule. Newborns from mothers exposed to chronic constant light and daily melatonin replacement had normal plasma cortisol concentration. Our results support a role of maternal melatonin in fetal and neonatal primate cortisol regulation. PMID:14673186

Fetal growth in women with homozygous sickle cell disease: an observational study.

PubMed

Thame, Minerva M; Osmond, Clive; Serjeant, Graham R

2013-09-01

To assess fetal growth and whether lower birthweight to mothers with homozygous sickle cell (SS) disease is related to maternal body composition or to clinical events in pregnancy. A prospective study of 41 pregnant women with SS disease and 41 women with a normal (AA) phenotype attending the antenatal clinic, University Hospital of the West Indies, Kingston, Jamaica. Maternal anthropometry, body composition and fetal sonographic measurements were assessed at 15, 25, and 35 weeks' gestation from December 2005 to April 2008. Birth measurements were performed within 24h of delivery. Differences between maternal genotypes and between their offspring were assessed using 2-sample t-tests. Multiple linear regression was used to control for baby's gender and gestational age at delivery. Fetal growth was compared in SS mothers with and without admission for sickle-related complications including bone pain crisis, acute chest syndrome, pregnancy-induced hypertension and urinary tract infection. Mothers with SS disease had lower weight, body fat, fat mass and lean body mass throughout pregnancy but correlation with birth size did not reach statistical significance. Sonographically, babies of SS mothers had smaller abdominal circumference, femoral length and a lower estimated fetal weight at 35 weeks. Birth measurements confirm lower birthweight, crown-heel length and head circumference but the differences were no longer significant after adjustment for baby gender and gestational age at delivery. Bone pain crisis in pregnancy was associated with a significantly reduced crown-heel length at birth. Lower birthweight in babies of mothers with SS disease is largely the result of the lower gestational age. Fetal sonography showed no growth differences by maternal genotype until 35 weeks' gestation and a reduced crown-heel length in offspring of SS mothers was associated with bone pain crises in pregnancy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Progesterone from maternal circulation binds to progestin receptors in fetal brain.

PubMed

Wagner, Christine K; Quadros-Mennella, Princy

2017-06-01

Steroid hormones activate nuclear receptors which, as transcription factors, can regulate critical aspects of neural development. Many regions of the rat forebrain, midbrain and hindbrain express progestin receptors (PR) during perinatal life, suggesting that progesterone may play an important role in the development of the brain. An immunohistochemical approach using two antibodies with differential recognition of ligand-bound PR was used to examine whether fetuses are exposed to maternal progesterone during pregnancy and whether progesterone from maternal circulation can bind to PR within the fetal brain. Findings demonstrate that maternal and fetal serum progesterone levels are positively correlated at the end of gestation, suggesting a common source of progesterone in mothers and fetuses (e.g., the maternal ovary). Additional findings suggest that administration of exogenous progesterone to mothers not only increases fetal serum progesterone levels within 2 h, but appears to increase ligand-bound PR in fetal brain. These findings suggest that progesterone of maternal origin may play a previously overlooked role in neural development. In addition, there are implications for the ongoing prophylactic use of synthetic progestins in pregnant women for the prevention of premature birth. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 767-774, 2017. © 2016 Wiley Periodicals, Inc.

Lipoprotein Profile Modifications during Gestation: A Current Approach to Cardiovascular risk surrogate markers and Maternal-fetal Unit Complications.

PubMed

Santos, Ana Paula Caires Dos; Couto, Ricardo David

2018-05-16

Several changes occur in lipid metabolism during gestation due to hormonal and metabolic changes, which are essential to satisfy the nutritional demands of the maternal-fetal unit development. The gestation shows two distinct periods that begin with fat accumulation, mainly in maternal adipose tissue, and the late phase, characterized by accelerated catabolism, with the increase of fatty acids in the circulation that causes hyperlipidemia, especially the one characterized as hypertriglyceridemia. Maternal hyperlipidemia may be associated with the development of maternal-fetal complications (preterm birth, preeclampsia, vascular complications) and the development of long-term cardiovascular disease. The cardiovascular risk may not only be related to lipoproteins cholesterol content, but also to the number and functionality of circulating lipoprotein particles. This review reports the major changes that occur in lipoprotein metabolism during pregnancy and that are associated with the development of dyslipidemias, lipoprotein atherogenic phenotype, and maternal-fetal unit complications. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Protecting the fetus against HIV infection: a systematic review of placental transfer of antiretrovirals.

PubMed

McCormack, Shelley A; Best, Brookie M

2014-11-01

Maternal-to-fetal transfer of antiretroviral drugs contributes to prevention of vertical transmission of HIV. This systematic review discusses published studies containing data pertaining to the pharmacokinetics of placental transfer of antiretrovirals in humans, including paired cord and maternal plasma samples collected at the time of delivery as well as ex vivo placental perfusion models. Articles pertaining to placental transfer of antiretrovirals were identified from PubMed, from references of included articles, and from US Department of Health and Human Services Panel on Treatment of HIV-infected Pregnant Women and Prevention of Perinatal Transmission guidelines. Articles from non-human animal models or that had no original maternal-to-fetal transfer data were excluded. PRISMA guidelines were followed. A total of 103 published studies were identified. Data across studies appeared relatively consistent for the nucleoside reverse transcriptase inhibitors (NRTIs) and the non-nucleotide reverse transcriptase inhibitors (NNRTIs), with cord to maternal ratios approaching 1 for many of these agents. The protease inhibitors atazanavir and lopinavir exhibited consistent maternal-to-fetal transfer across studies, although the transfer may be influenced by variations in drug-binding proteins. The protease inhibitors indinavir, nelfinavir, and saquinavir exhibited unreliable placental transport, with cord blood concentrations that were frequently undetectable. Limited data, primarily from case reports, indicate that darunavir and raltegravir provide detectable placental transfer. These findings appear consistent with current guidelines of using two NRTIs plus an NNRTI, atazanavir/ritonavir, or lopinavir/ritonavir to maximize placental transfer as well as to optimally suppress maternal viral load. Darunavir/ritonavir and raltegravir may reasonably serve as second-line agents.

Geographical variation in relationships between parental body size and offspring phenotype at birth

PubMed Central

Leary, Sam; Fall, Caroline; Osmond, Clive; Lovel, Hermione; Campbell, Doris; Eriksson, Johan; Forrester, Terrence; Godfrey, Keith; Hill, Jacqui; Jie, Mi; Law, Catherine; Newby, Rachel; Robinson, Sian; Yajnik, Chittaranjan

2009-01-01

Background Size and body proportions at birth are partly determined by maternal body composition, but most studies of mother-baby relationships have only considered the effects of maternal height and weight on offspring birthweight, and few have examined the size of effects. Paternal size and body composition also play a role, primarily through the fetal genome, although few studies have investigated relationships with neonatal phenotype. Methods Data from the UK, Finland, India, Sri Lanka, China, DR Congo, Nigeria and Jamaica were used to investigate the effects of maternal measures including estimates of muscle and fat (derived at 30-weeks gestation, N=16 418), and also paternal size (N=3 733) on neonatal phenotype, for singleton, liveborn, term births. Results After accounting for variation in maternal size and shape across populations, differences in neonatal phenotype were markedly reduced. Mother-baby relationships were similar across populations, although some were stronger in developing countries. Maternal height was generally the strongest predictor of neonatal length, maternal head circumference of neonatal head circumference, and maternal skinfold thickness of neonatal skinfolds. Relationships with maternal arm muscle area were generally weak. Data from fathers were limited to height and body mass index, but when compared with maternal height and body mass index, paternal effects were weaker in most studies. Conclusions Differences in maternal body composition account for a large part of the geographical variation in neonatal phenotype. The size of the effects of all maternal measures on neonatal phenotype suggests that nutrition at every stage of the mother's life cycle may influence fetal growth. Further research is needed into father-baby relationships and the genetic mechanisms which influence fetal growth. PMID:16929411

[Effect of Music Intervention on Maternal Anxiety and Fetal Heart Rate Pattern During Non-Stress Test].

PubMed

Oh, Myung Ok; Kim, Young Jeoum; Baek, Cho Hee; Kim, Ju Hee; Park, No Mi; Yu, Mi Jeong; Song, Han Sol

2016-06-01

The purpose of this cross-over experimental study was to examine effects of music intervention on maternal anxiety, fetal heart rate pattern and testing time during non-stress tests (NST) for antenatal fetal assessment. Sixty pregnant women within 28 to 40 gestational weeks were randomly assigned to either the experimental group (n=30) or control group (n=30). Music intervention was provided to pregnant women in the experimental group during NST. Degree of maternal anxiety and fetal heart rate pattern were our primary outcomes. State-trait anxiety inventory, blood pressure, pulse rate, and changes in peripheral skin temperature were assessed to determine the degree of maternal anxiety. Baseline fetal heart rate, frequency of acceleration in fetal heart rate, fetal movement test and testing time for reactive NST were assessed to measure the fetal heart rate pattern. The experimental group showed significantly lower scores in state anxiety than the control group. There were no significant differences in systolic blood pressure and pulse rate between the two groups. Baseline fetal heart rate was significantly lower in the experimental group than in the control group. Frequency of acceleration in fetal heart rate was significantly increased in the experimental group compared to the control group. There were no significant differences in fetal movement and testing time for reactive NST between the two groups. Present results suggest that music intervention could be an effective nursing intervention for alel viating anxiety during non-stress test.

Maternal hypothyroxinemia during pregnancy and growth of the fetal and infant head.

PubMed

van Mil, Nina H; Steegers-Theunissen, Régine P M; Bongers-Schokking, Jacoba J; El Marroun, Hanan; Ghassabian, Akhgar; Hofman, Albert; Jaddoe, Vincent W V; Visser, Theo J; Verhulst, Frank C; de Rijke, Yolanda B; Steegers, Eric A P; Tiemeier, Henning

2012-12-01

Severe maternal thyroid dysfunction during pregnancy affects fetal brain growth and corticogenesis. This study focused on the effect of maternal hypothyroxinemia during early pregnancy on growth of the fetal and infant head. In a population-based birth cohort, we assessed thyroid status in early pregnancy (median 13.4, 90% range 10.8-17.2), in 4894 women, and measured the prenatal and postnatal head size of their children at 5 time points. Hypothyroxinemia was defined as normal thyroid-stimulating hormone levels and free thyroxine-4 concentrations below the 10th percentile. Statistical analysis was performed using linear generalized estimating equation. Maternal hypothyroxinemia was associated with larger fetal and infant head size (overall estimate β: 1.38, 95% confidence interval 0.56; 2.19, P = .001). In conclusion, in the general population, even small variations in maternal thyroid function during pregnancy may affect the developing head of the young child.

Partition of environmental chemicals between maternal and fetal blood and tissues.

PubMed

Needham, Larry L; Grandjean, Philippe; Heinzow, Birger; Jørgensen, Poul J; Nielsen, Flemming; Patterson, Donald G; Sjödin, Andreas; Turner, Wayman E; Weihe, Pal

2011-02-01

Passage of environmental chemicals across the placenta has important toxicological consequences, as well as for choosing samples for analysis and for interpreting the results. To obtain systematic data, we collected in 2000 maternal and cord blood, cord tissue, placenta, and milk in connection with births in the Faroe Islands, where exposures to marine contaminants is increased. In 15 sample sets, we measured a total of 87 environmental chemicals, almost all of which were detected both in maternal and fetal tissues. The maternal serum lipid-based concentrations of organohalogen compounds averaged 1.7 times those of cord serum, 2.8 times those of cord tissue and placenta, and 0.7 those of milk. For organohalogen compounds detectable in all matrices, a high degree of correlation between concentrations in maternal serum and the other tissues investigated was generally observed (r(2) > 0.5). Greater degree of chlorination resulted in lower transfer from maternal serum into milk. Concentrations of pentachlorbenzene, γ-hexachlorocyclohexane, and several polychlorinated biphenyl congeners with low chlorination were higher in fetal samples and showed poor correlation with maternal levels. Perfluorinated compounds occurred in lower concentrations in cord serum than in maternal serum. Cadmium, lead, mercury, and selenium were all detected in fetal samples, but only mercury showed close correlations among concentrations in different matrices. Although the environmental chemicals examined pass through the placenta and are excreted into milk, partitions between maternal and fetal samples are not uniform.

Gastrointestinal and pancreatic hormones in the human fetus and mother at 18-21 weeks of gestation.

PubMed

Adrian, T E; Soltesz, G; MacKenzie, I Z; Bloom, S R; Aynsley-Green, A

1995-01-01

Several gastrointestinal hormones appear to play an important developmental role in the newborn, particularly in preterm neonates. Although the cells producing these peptides develop towards the end of the first trimester, fetal secretion of these regulatory peptides has not hitherto been demonstrated. Using samples collected by fetoscopy at 19-21 weeks of gestation we have measured concentrations of several gastrointestinal and pancreatic hormones. Maternal venous and amniotic fluid hormone concentrations were measured simultaneously. Concentrations of the pancreatic hormones, insulin, glucagon and pancreatic polypeptide (PP) were similar in fetal and maternal blood. Gastrin and motilin were present in the fetal circulation but at about 30% (p < 0.05) and 60% (p < 0.01) of the maternal levels, respectively. In contrast, enteroglucagon concentrations were more than twofold higher in the fetal circulation compared with maternal levels (p < 0.05). Concentrations of gastric inhibitory polypeptide (GIP) in fetal blood were higher than levels in maternal blood but not significantly. Concentrations of GIP (p < 0.001) were higher in the amniotic fluid than the fetal circulation. Gastrin and glucagon levels were similar in amniotic fluid and fetal blood. In contrast, PP and motilin were present in amniotic fluid, but at lower concentrations than in fetal blood. Enteroglucagon was not detectable in amniotic fluid. In conclusion, several alimentary hormones are secreted in the fetus at midterm. Since these peptides have trophic, secretory and motor effects on the gut, it is likely that these regulatory peptides are involved in the functional development of the fetal intestine.

Role of inflammatory proteins S100A8 and S100A9 in pathophysiology of recurrent early pregnancy loss.

PubMed

Nair, R R; Khanna, A; Singh, K

2013-09-01

Altered expression of inflammatory molecule at the maternal fetal interface is associated with early pregnancy loss. S100A8 and S100A9 are inflammatory proteins and they exhibit cytokine like function enhancing leukocyte recruitment to the inflammatory site. Reports from mouse model suggest the role of S100A8 with the vasculature of the decidual tissue and leukocyte recruitment during early pregnancy. Hence we hypothesized that maternal overexpression of S100A8 & S100A9 might increase the recruitment of inflammatory leukocytes in maternal-fetal interface resulting in uteroplacental perfusion deficiency, development of thrombotic events, and placental hypoxia, eventually embryo abortion. In the present study we investigated altered expression of S100A8 and S100A9 in 25 recurrent early pregnancy loss (REPL) patients compared to 40 induced abortion subjects as controls. S100A8 and S100A9 mRNA were evaluated using semi-quantitative RT-PCR and quantitative real-time PCR. To determine if differential expression pattern of these transcripts is translated to protein western blot analysis was performed.S100A8 and S100A9 mRNA and protein level were significantly increased in endometrial decidua tissue (p < 0.05) of REPL patients as compared to controls. This is the first report predicting the role of inflammatory molecules S100A8 & S100A9 in REPL. It opens a new perspective for understanding significance of S100A8 and S100A9 in pregnancy maintenance and outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

Does maternal-fetal transfer of creatine occur in pregnant sheep?

PubMed

Baharom, Syed; De Matteo, Robert; Ellery, Stacey; Della Gatta, Paul; Bruce, Clinton R; Kowalski, Greg M; Hale, Nadia; Dickinson, Hayley; Harding, Richard; Walker, David; Snow, Rodney J

2017-07-01

Our aim was to determine the disposition of creatine in ovine pregnancy and whether creatine is transferred across the placenta from mother to fetus. Pregnant ewes received either 1 ) a continuous intravenous infusion of creatine monohydrate or saline from 122 to 131 days gestation, with maternal and fetal arterial blood and amniotic fluid samples collected daily for creatine analysis and fetal tissues collected at necropsy at 133 days for analysis of creatine content, or 2 ) a single systemic bolus injection of [ 13 C]creatine monohydrate at 130 days of gestation, with maternal and fetal arterial blood, uterine vein blood, and amniotic fluid samples collected before and for 4 h after injection and analyzed for creatine, creatine isotopic enrichment, and guanidinoacetic acid (GAA; precursor of creatine) concentrations. Presence of the creatine transporter-1 (SLC6A8) and l-arginine:glycine amidinotransferase (AGAT; the enzyme synthesizing GAA) proteins were determined by Western blots of placental cotyledons. The 10-day creatine infusion increased maternal plasma creatine concentration three- to fourfold ( P < 0.05) without significantly changing fetal arterial, amniotic fluid, fetal tissues, or placental creatine content. Maternal arterial 13 C enrichment was increased ( P < 0.05) after bolus [ 13 C]creatine injection without change of fetal arterial 13 C enrichment. SLC6A8 and AGAT proteins were identified in placental cotyledons, and GAA concentration was significantly higher in uterine vein than maternal artery plasma. Despite the presence of SLC6A8 protein in cotyledons, these results suggest that creatine is not transferred from mother to fetus in near-term sheep and that the ovine utero-placental unit releases GAA into the maternal circulation. Copyright © 2017 the American Physiological Society.

Estimates of the Burden of Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children

PubMed Central

Seale, Anna C; Bianchi-Jassir, Fiorella; Russell, Neal J; Kohli-Lynch, Maya; Tann, Cally J; Hall, Jenny; Madrid, Lola; Blencowe, Hannah; Cousens, Simon; Baker, Carol J; Bartlett, Linda; Cutland, Clare; Gravett, Michael G; Heath, Paul T; Ip, Margaret; Le Doare, Kirsty; Madhi, Shabir A; Rubens, Craig E; Saha, Samir K; Schrag, Stephanie J; Sobanjo-ter Meulen, Ajoke; Vekemans, Johan; Lawn, Joy E

2017-01-01

Abstract Background We aimed to provide the first comprehensive estimates of the burden of group B Streptococcus (GBS), including invasive disease in pregnant and postpartum women, fetal infection/stillbirth, and infants. Intrapartum antibiotic prophylaxis is the current mainstay of prevention, reducing early-onset infant disease in high-income contexts. Maternal GBS vaccines are in development. Methods For 2015 live births, we used a compartmental model to estimate (1) exposure to maternal GBS colonization, (2) cases of infant invasive GBS disease, (3) deaths, and (4) disabilities. We applied incidence or prevalence data to estimate cases of maternal and fetal infection/stillbirth, and infants with invasive GBS disease presenting with neonatal encephalopathy. We applied risk ratios to estimate numbers of preterm births attributable to GBS. Uncertainty was also estimated. Results Worldwide in 2015, we estimated 205000 (uncertainty range [UR], 101000–327000) infants with early-onset disease and 114000 (UR, 44000–326000) with late-onset disease, of whom a minimum of 7000 (UR, 0–19000) presented with neonatal encephalopathy. There were 90000 (UR, 36000–169000) deaths in infants <3 months age, and, at least 10000 (UR, 3000–27000) children with disability each year. There were 33000 (UR, 13000–52000) cases of invasive GBS disease in pregnant or postpartum women, and 57000 (UR, 12000–104000) fetal infections/stillbirths. Up to 3.5 million preterm births may be attributable to GBS. Africa accounted for 54% of estimated cases and 65% of all fetal/infant deaths. A maternal vaccine with 80% efficacy and 90% coverage could prevent 107000 (UR, 20000–198000) stillbirths and infant deaths. Conclusions Our conservative estimates suggest that GBS is a leading contributor to adverse maternal and newborn outcomes, with at least 409000 (UR, 144000–573000) maternal/fetal/infant cases and 147000 (UR, 47000–273000) stillbirths and infant deaths annually. An effective GBS vaccine could reduce disease in the mother, the fetus, and the infant. PMID:29117332

Maternal exercise, season and sex modify the daily fetal heart rate rhythm.

PubMed

Sletten, J; Cornelissen, G; Assmus, J; Kiserud, T; Albrechtsen, S; Kessler, J

2018-05-13

The knowledge on biological rhythms is rapidly expanding. We aimed to define the longitudinal development of the daily (24-hour) fetal heart rate rhythm in an unrestricted, out-of-hospital setting and to examine the effects of maternal physical activity, season and fetal sex. We recruited 48 women with low-risk singleton pregnancies. Using a portable monitor for continuous fetal electrocardiography, fetal heart rate recordings were obtained around gestational weeks 24, 28, 32 and 36. Daily rhythms in fetal heart rate and fetal heart rate variation were detected by cosinor analysis; developmental trends were calculated by population-mean cosinor and multilevel analysis. For the fetal heart rate and fetal heart rate variation, a significant daily rhythm was present in 122/123 (99.2%) and 116/121 (95.9%) of the individual recordings respectively. The rhythms were best described by combining cosine waves with periods of 24 and 8 hours. With increasing gestational age, the magnitude of the fetal heart rate rhythm increased, and the peak of the fetal heart rate variation rhythm shifted from a mean of 14:25 (24 weeks) to 20:52 (36 weeks). With advancing gestation, the rhythm-adjusted mean value of the fetal heart rate decreased linearly in females (P < .001) and nonlinearly in males (quadratic function, P = .001). At 32 and 36 weeks, interindividual rhythm diversity was found in male fetuses during higher maternal physical activity and during the summer season. The dynamic development of the daily fetal heart rate rhythm during the second half of pregnancy is modified by fetal sex, maternal physical activity and season. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Distortion of maternal-fetal angiotensin II type 1 receptor allele transmission in pre-eclampsia.

PubMed Central

Morgan, L; Crawshaw, S; Baker, P N; Brookfield, J F; Broughton Pipkin, F; Kalsheker, N

1998-01-01

OBJECTIVE: To investigate the fetal angiotensin II type 1 receptor genotype in pre-eclampsia. DESIGN: Case-control study. POPULATION: Forty-one maternal-fetal pairs from pre-eclamptic pregnancies and 80 maternal-fetal pairs from normotensive pregnancies. METHODS: Maternal and fetal DNA was genotyped at three diallelic polymorphisms, at nucleotides 573, 1062, and 1166, in the coding exon of the angiotensin II type 1 receptor gene, and at a dinucleotide repeat polymorphism in its 3' flanking region. RESULTS: Allele and genotype frequencies at the four polymorphic regions investigated did not differ between pre-eclamptic and normotensive groups, in either fetal or maternal samples. Mothers heterozygous for the dinucleotide repeat allele designated A4 transmitted this allele to the fetus in 15 of 18 informative pre-eclamptic pregnancies and in eight of 26 normotensive pregnancies. This was greater than the expected probability in pre-eclamptic pregnancies (p=0.04) and less than expected in normotensive pregnancies (p<0.005). The 573T variant, which is in partial linkage disequilibrium with the A4 allele, showed a similar distortion of maternal-fetal transmission. CONCLUSION: Angiotensin II type 1 receptor gene expression in the fetus may contribute to the aetiology of pre-eclampsia. It is unclear whether susceptibility is conferred by the fetal genotype acting alone, or by allele sharing by mother and fetus. Possible mechanisms for the effect of the angiotensin II type 1 receptor gene are suggested by the association of the 573T variant with low levels of surface receptor expression on platelets. If receptor expression is similarly genetically determined in the placenta, responsiveness to angiotensin II may be affected, with the potential to influence placentation or placental prostaglandin secretion. PMID:9719367

Deficient maternal zinc intake-but not folate-is associated with lower fetal heart rate variability.

PubMed

Spann, Marisa N; Smerling, Jennifer; Gustafsson, Hanna; Foss, Sophie; Altemus, Margaret; Monk, Catherine

2015-03-01

Few studies of maternal prenatal diet and child development examine micronutrient status in relation to fetal assessment. Twenty-four-hour dietary recall of zinc and folate and 20min of fetal heart rate were collected from 3rd trimester pregnant adolescents. Deficient zinc was associated with less fetal heart rate variability. Deficient folate had no associations with HRV. Neither deficient zinc nor deficient folate was related to fetal heart rate. These findings, from naturalistic observation, are consistent with emerging data on prenatal zinc supplementation using a randomized control design. Taken together, the findings suggest that maternal prenatal zinc intake is an important and novel factor for understanding child ANS development. Copyright © 2015. Published by Elsevier Ireland Ltd.

Placental Adaptations in Growth Restriction

PubMed Central

Zhang, Song; Regnault, Timothy R.H.; Barker, Paige L.; Botting, Kimberley J.; McMillen, Isabella C.; McMillan, Christine M.; Roberts, Claire T.; Morrison, Janna L.

2015-01-01

The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR) is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions. PMID:25580812

Achieving Strong Teamwork Practices in Hospital Labor and Delivery Units

DTIC Science & Technology

2010-01-01

measures Maternal deaths 750 Uterine rupture 100 Unplanned maternal admission to ICU 65 Return to OR/L&D 40 3rd- or 4th-degree perineal laceration 5 Maternal...maternal lacerations ) Site 5 Improvement in communication due to team huddles/briefs at morning shift change None reported Debriefs have matured...practices, including a review of oxy- tocin use, use of standardized protocols, an exam for electronic fetal monitoring, and lowering surgical-site

Maternal thyroid function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China.

PubMed

Su, Pu-Yu; Huang, Kun; Hao, Jia-Hu; Xu, Ye-Qin; Yan, Shuang-Qin; Li, Tao; Xu, Yuan-Hong; Tao, Fang-Biao

2011-10-01

There are a few prospective population-based cohort studies evaluating the effects of maternal thyroid dysfunctions on fetal and infant developments, but they are inconsistent. The objective of the study was to investigate the effects of maternal thyroid dysfunction on fetal and infant development. The study was nested within a prospective population-based China-Anhui Birth Defects and Child Development study. A total of 1017 women with singleton pregnancies participated in this study. Maternal serum samples in the first 20 wk of pregnancy were tested for thyroid hormones (TSH and free T(4)). Pregnant women were classified by hormone status into percentile categories based on laboratory assay and were compared accordingly. Outcomes included fetal loss, malformation, birth weight, preterm delivery, fetal stress, neonatal death, and infant development. Clinical hypothyroidism was associated with increased fetal loss, low birth weight, and congenital circulation system malformations; the adjusted odds ratios [95% confidence interval (CI)] were 13.45 (2.54-71.20), 9.05 (1.01-80.90), and 10.44 (1.15-94.62), respectively. Subclinical hypothyroidism was associated with increased fetal distress, preterm delivery, poor vision development, and neurodevelopmental delay; the adjusted odds ratios (95% CI) were 3.65 (1.44-9.26), 3.32 (1.22-9.05), 5.34 (1.09-26.16), and 10.49 (1.01-119.19), respectively. Isolated hypothyroxinemia was related to fetal distress, small for gestational age, and musculoskeletal malformations; the adjusted odds ratios (95% CI) were 2.95 (1.08-8.05), 3.55 (1.01-12.83), and 9.12 (1.67-49.70), respectively. Isolated hyperthyroxinemia was associated with spontaneous abortion; the adjusted odds ratio (95% CI) was 6.02 (1.25-28.96). Clinical hyperthyroidism was associated with hearing dysplasia; the adjusted odds ratio (95% CI) was 12.14 (1.22-120.70). Thyroid dysfunction in the first 20 wk of pregnancy may result in fetal loss and dysplasia and some congenital malformations.

Semi-automatic segmentation of the placenta into fetal and maternal compartments using intravoxel incoherent motion MRI

NASA Astrophysics Data System (ADS)

You, Wonsang; Andescavage, Nickie; Zun, Zungho; Limperopoulos, Catherine

2017-03-01

Intravoxel incoherent motion (IVIM) magnetic resonance imaging is an emerging non-invasive technique that has been recently applied to quantify in vivo global placental perfusion. We propose a robust semi-automated method for segmenting the placenta into fetal and maternal compartments from IVIM data, using a multi-label image segmentation algorithm called `GrowCut'. Placental IVIM data were acquired on a 1.5T scanner from 16 healthy pregnant women between 21-37 gestational weeks. The voxel-wise perfusion fraction was then estimated after non-rigid image registration. The seed regions of the fetal and maternal compartments were determined using structural T2-weighted reference images, and improved progressively through an iterative process of the GrowCut algorithm to accurately encompass fetal and maternal compartments. We demonstrated that the placental perfusion fraction decreased in both fetal (-0.010/week) and maternal compartments (-0.013/week) while their relative difference (ffetal-fmaternal) gradually increased with advancing gestational age (+0.003/week, p=0.065). Our preliminary results show that the proposed method was effective in distinguishing placental compartments using IVIM.

RAT PLACENTATION: AN EXPERIMENTAL MODEL FOR INVESTIGATING THE HEMOCHORIAL MATERNAL-FETAL INTERFACE

PubMed Central

Soares, Michael J.; Chakraborty, Damayanti; Rumi, M.A. Karim; Konno, Toshihiro; Renaud, Stephen J.

2011-01-01

The rat possesses hemochorial placentation with deep intrauterine trophoblast cell invasion and trophoblast-directed uterine spiral artery remodeling; features shared with human placentation. Recognition of these similarities spurred the establishment of in vitro and in vivo research methods using the rat as an animal model to address mechanistic questions regarding development of the hemochorial placenta. The purpose of this review is to provide the requisite background to help move the rat to the forefront in placentation research. PMID:22284666

Identification of the First Receptor for a Pregnancy Specific Glycoprotein. Tetraspanins Find Their Ligand

DTIC Science & Technology

2001-04-13

correlates with intrauterine growth retardat ion. preeclampsia and fetal hypoxia [6, 7. 72]. 12 Furthermore. a chronic reduction in expression of PSG...maternal interface in nomlal pregnancies in mice and humans (28). Decreased concent rations of I L· I 0 in serum have been assoc iated with preeclampsia and...l 0 may have a dual role in regulating trophoblast invasion, because decreased production oflL-1 a is associated with preeclampsia , wh ich is

[GESTASTRES cohort study protocol on the effects of stress during pregnancy by measuring the cortisol in women's and newborn's hair].

PubMed

Caparros-Gonzalez, Rafael A; García-García, Inmaculada; Mariñas-Lirola, Juan Carlos; Peralta-Ramírez, Maria Isabel

2018-04-16

The aim was to present the longitudinal study protocol on the effects of perinatal stress from conception to one year of age. Stress is associated to psychopathological, cardiovascular and inmunological diseases. During pregnancy, the activation of the Hipotalamic-Pituitary-Adrenal results in an increased release of cortisol. Stress during pregnancy is related to maternal, fetal and infant negative outcomes that can last a lifetime. Nevertheless, contradictory findings have been reported. In this longitudinal study maternal stress is assessed from a sample of 807 pregnant women through hair cortisol levels and psychological question- naires during the three trimesters of pregnancy. Besides, associa- tions with the new-borns´ hair cortisol levels, temperament and neurodevelopment at age 6 and 12 months are assessed. Sociode- mographic, obstetrics, delivery, fetal and newborn development variables are included in analysis. Findings will be able to pro- vide a better understanding of perinatal stress and will improve maternal, fetal and infant outcomes.

Quantification of fetal and total circulatory DNA in maternal plasma samples before and after size fractionation by agarose gel electrophoresis.

PubMed

Hromadnikova, I; Zejskova, L; Doucha, J; Codl, D

2006-11-01

Fetal extracellular DNA is mainly derived from apoptotic bodies of trophoblast. Recent studies have shown size differences between fetal and maternal extracellular DNA. We have examined the quantification of fetal (SRY gene) and total (GLO gene) extracellular DNA in maternal plasma in different fractions (100-300, 300-500, 500-700, 700-900, and >900 bp) after size fractionation by agarose gel electrophoresis. DNA was extracted from maternal plasma samples from 11 pregnant women carrying male foetuses at the 16th week of gestation. Fetal circulatory DNA was mainly detected in the 100-300 bp fraction with the median concentration being 14.4 GE/ml. A lower median amount of 4.9 GE/ml was also found in the 300-500 bp fraction. Circulatory DNA extracted from the 100-300 bp fraction contained 4.2 times enriched fetal DNA when compared with unseparated DNA sample. Fetal DNA within the 300-500 bp fraction was 2.5 times enriched. Circulatory fetal DNA is predominantly present in a fraction with molecular size <500 bp, which can be used for the detection of paternally inherited alleles. However, the usage of size-separated DNA is not suitable for routine clinical applications because of risk of contamination.

Fetal-maternal erythrocyte distribution

MedlinePlus

... under the skin) Infection (a slight risk any time the skin is broken) Alternative Names Kleihauer-Betke stain; Flow cytometry - fetal-maternal erythrocyte distribution; Rh incompatibility - erythrocyte distribution References Chernecky CC, Berger ...

[Active management of labor with cesarean index 6.4% and very good materno-fetal outcome].

PubMed

Crespo Ruiz, Eliodoro; Rodríguez Fernández, Jesús Javier

2002-11-01

The objective of this study is to reduce the incidence of cesarean section and to evaluate the impact on fetal-maternal morbidity and mortality by strictly following the guidelines of the National Health Office (Secretaria de Salud) at the Hospital of Gynecology and Obstetrics of Garza Garcia in Nuevo Leon, Mexico. A prospective and observational study was made. All the patients who culminated their pregnancy on Saturdays and Sundays between 7:00 and 19:00 hrs, in the period June 2000 to June 2001, were included in this study. The incidence of Cesarean sections and its impact on maternal-fetal morbidity and mortality were observed. A total of 798 patients were included in the study. The total number of newborns was 801. The age average was of 23.4 years (14 years-40 years). Of the 798 patients, 280 (35.1%) presented dystocia at vaginal delivery, 467 patients (58.5%) had an eutocic vaginal delivery and 51 patients (6.4%) went through a Caesarean section. The Apgar scores were: 8 at the first minute and 9 at the fifth minute for 681 neonates (85.01%); and 7/9 for 53 (6.6%). According to the results obtained in the present study we can conclude that the incidence of Cesarean section can be reduced by strictly following the guidelines of the National Health Office without affecting the maternal-fetal morbidity and mortality.

Simultaneous monitoring of maternal and fetal heart rate variability during labor in relation with fetal gender.

PubMed

Gonçalves, Hernâni; Fernandes, Diana; Pinto, Paula; Ayres-de-Campos, Diogo; Bernardes, João

2017-11-01

Male gender is considered a risk factor for several adverse perinatal outcomes. Fetal gender effect on fetal heart rate (FHR) has been subject of several studies with contradictory results. The importance of maternal heart rate (MHR) monitoring during labor has also been investigated, but less is known about the effect of fetal gender on MHR. The aim of this study is to simultaneously assess maternal and FHR variability during labor in relation with fetal gender. Simultaneous MHR and FHR recordings were obtained from 44 singleton term pregnancies during the last 2 hr of labor (H 1, H 2 ). Heart rate tracings were analyzed using linear (time- and frequency-domain) and nonlinear indices. Both linear and nonlinear components were considered in assessing FHR and MHR interaction, including cross-sample entropy (cross-SampEn). Mothers carrying male fetuses (n = 22) had significantly higher values for linear indices related with MHR average and variability and sympatho-vagal balance, while the opposite occurred in the high-frequency component and most nonlinear indices. Significant differences in FHR were only observed in H 1 with higher entropy values in female fetuses. Assessing the differences between FHR and MHR, statistically significant differences were obtained in most nonlinear indices between genders. A significantly higher cross-SampEn was observed in mothers carrying female fetuses (n = 22), denoting lower synchrony or similarity between MHR and FHR. The variability of MHR and the synchrony/similarity between MHR and FHR vary with respect to fetal gender during labor. These findings suggest that fetal gender needs to be taken into account when simultaneously monitoring MHR and FHR. © 2017 Wiley Periodicals, Inc.

Adverse maternal outcomes associated with fetal macrosomia: what are the risk factors beyond birthweight?

PubMed Central

2013-01-01

Background To identify risk factors, beyond fetal weight, associated with adverse maternal outcomes in delivering infants with a birthweight of 4000 g or greater, and to quantify their role in maternal complications. Methods All women (n = 1564) with singleton pregnancies who attempted vaginal delivery and delivered infants weighing at least 4000 g, in two French tertiary care centers from 2005 to 2008, were included in our study. The studied outcome was maternal complications defined as composite item including the occurrence of a third- or fourth-degree perineal laceration, or the occurrence of severe postpartum hemorrhage requiring the use of prostaglandins, uterine artery embolization, internal iliac artery ligation or haemostatic hysterectomy, or the occurrence of blood transfusion. Univariate analysis, multivariable logistic regression and estimation of attributable risk were used. Results Maternal complications were increased in Asian women (adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 1.1–9.3, Attributable risk (AR): 3%), in prolonged labor (aOR = 1.9 [95% CI; 1.1–3.4], AR = 12%) and in cesarean delivery during labor (aOR = 2.2 [95% CI; 1.3–3.9], AR = 17%). Delivering infants with a birthweight > 4500 g also increased the occurrence of maternal complications (aOR = 2.7 [95% CI; 1.4–5.1]) but with an attributable risk of only 10%. Multiparous women with a previous delivery of a macrosomic infant were at lower risk of maternal complications (aOR = 0.5 [95% CI; 0.2–0.9]). Conclusion In women delivering infants with a birthweight of 4000 g or greater, some maternal characteristics as well as labor parameters may worsen maternal outcome beyond the influence of increased fetal weight. PMID:23565692

The introduction of the absolute risk for the detection of fetal aneuploidies in the first-trimester screening.

PubMed

Padula, Francesco; Laganà, Antonio Simone; Vitale, Salvatore Giovanni; D'Emidio, Laura; Coco, Claudio; Giannarelli, Diana; Cariola, Maria; Favilli, Alessandro; Giorlandino, Claudio

2017-05-01

Maternal age is a crucial factor in fetal aneuploidy screening, resulting in an increased rate of false-positive cases in older women and false-negative cases in younger women. The absolute risk (AR) is the simplest way to eliminate the background maternal age risk, as it represents the amount of improvement of the combined risk from the maternal background risk. The aim of this work is to assess the performance of the AR in the combined first-trimester screening for aneuploidies. A retrospective validation of the AR in the combined first-trimester screening for fetal aneuploidies, in an unselected population at Altamedica Fetal-Maternal Medical Center in Rome, between March 2007 and December 2008. Of 3845 women included in the study, we had a complete follow-up on 2984. We evaluated that an AR < 3 would individuate 22 of 23 cases of aneuploidy with a detection rate of 95.7% (95%CI 87.3-100), a false-positive rate of 8.7% (95%CI 7.7-9.7) and a false-negative rate of 4.3% (95%CI 0-12.7). In our study, the AR ameliorates the detection rate for aneuploidy. Further research and a prospective study on a larger population would help us to improve the AR in detecting most cases of aneuploidy.

Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation

PubMed Central

Lofthouse, E. M.; Perazzolo, S.; Brooks, S.; Crocker, I. P.; Glazier, J. D.; Johnstone, E. D.; Panitchob, N.; Sibley, C. P.; Widdows, K. L.; Sengers, B. G.

2015-01-01

Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [14C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [14C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14, and 18 ml/min for 1 h each. At each maternal flow rate, fetal flow rates were set at 3, 6, and 9 ml/min for 20 min each. Appearance of [14C]phenylalanine was measured in the maternal and fetal venous exudates. Computational modeling of phenylalanine transfer was undertaken to allow comparison of the experimental data with predicted phenylalanine uptake and transfer under different initial assumptions. Placental uptake (mol/min) of [14C]phenylalanine increased with maternal, but not fetal, flow. Delivery (mol/min) of [14C]phenylalanine to the fetal circulation was not associated with fetal or maternal flow. The absence of a relationship between placental phenylalanine uptake and net flux of phenylalanine to the fetal circulation suggests that factors other than flow or transporter-mediated uptake are important determinants of phenylalanine transfer. These observations could be explained by tight regulation of free amino acid levels within the placenta or properties of the facilitated transporters mediating phenylalanine transport. We suggest that amino acid metabolism, primarily incorporation into protein, is controlling free amino acid levels and, thus, placental transfer. PMID:26676251

Iodine-Induced Fetal Hypothyroidism: Diagnosis and Treatment with Intra-Amniotic Levothyroxine.

PubMed

Hardley, Macy T; Chon, Andrew H; Mestman, Jorge; Nguyen, Caroline T; Geffner, Mitchell E; Chmait, Ramen H

2018-05-23

Iodine is necessary for fetal thyroid development. Excess maternal intake of iodine can cause fetal hypothyroidism due to the inability to escape from the Wolff-Chaikoff effect in utero. We report a case of fetal hypothyroid goiter secondary to inadvertent excess maternal iodine ingestion from infertility supplements. The fetus was successfully treated with intra-amniotic levothyroxine injections. Serial fetal blood sampling confirmed fetal escape from the Wolff-Chaikoff effect in the mid third trimester. Early hearing test and neurodevelopmental milestones were normal. Intra-amniotic treatment of fetal hypothyroidism may decrease the rate of impaired neurodevelopment and sensorineural hearing loss. © 2018 S. Karger AG, Basel.

Prenatal diagnosis of fetal encephalomalacia after maternal diabetic ketoacidosis.

PubMed

Love, Rozalyn; Lee, Amy; Matiasek, April; Carter, William; Ylagan, Marissa

2014-11-01

Introduction Encephalomalacia in a developing fetus is a rare and devastating neurological finding on radiologic imaging. Maternal diabetic ketoacidosis (DKA) can lead to metabolic and vascular derangements which can cause fetal encephalomalacia. Case We report the case of a 27-year-old pregnant woman with White's Class C diabetes mellitus who presented in the 25th week of gestation with DKA. Four weeks after her discharge, marked fetal cerebral ventriculomegaly was noted on ultrasound. A subsequent fetal magnetic resonance imaging (MRI) demonstrated extensive, symmetric cystic encephalomalacia, primarily involving both cerebral hemispheres. The pregnancy was continued with close fetal and maternal surveillance. The patient underwent a repeat cesarean delivery in her 37th week. The infant had a 1 month neonatal intensive care unit stay with care rendered by a multiple disciplinary team of pediatric subspecialists. The postnatal course was complicated by global hypotonia, poor feeding, delayed development and ultimately required anticonvulsants for recurrent seizures. He died at the age of 9 months from aspiration during a seizure. Discussion Although the maternal mortality from DKA has declined, DKA still confers significant neurological fetal morbidity to its survivors.

Prenatal Diagnosis of Fetal Encephalomalacia after Maternal Diabetic Ketoacidosis

PubMed Central

Love, Rozalyn; Lee, Amy; Matiasek, April; Carter, William; Ylagan, Marissa

2014-01-01

Introduction Encephalomalacia in a developing fetus is a rare and devastating neurological finding on radiologic imaging. Maternal diabetic ketoacidosis (DKA) can lead to metabolic and vascular derangements which can cause fetal encephalomalacia. Case We report the case of a 27-year-old pregnant woman with White's Class C diabetes mellitus who presented in the 25th week of gestation with DKA. Four weeks after her discharge, marked fetal cerebral ventriculomegaly was noted on ultrasound. A subsequent fetal magnetic resonance imaging (MRI) demonstrated extensive, symmetric cystic encephalomalacia, primarily involving both cerebral hemispheres. The pregnancy was continued with close fetal and maternal surveillance. The patient underwent a repeat cesarean delivery in her 37th week. The infant had a 1 month neonatal intensive care unit stay with care rendered by a multiple disciplinary team of pediatric subspecialists. The postnatal course was complicated by global hypotonia, poor feeding, delayed development and ultimately required anticonvulsants for recurrent seizures. He died at the age of 9 months from aspiration during a seizure. Discussion Although the maternal mortality from DKA has declined, DKA still confers significant neurological fetal morbidity to its survivors. PMID:25452892

Management of pregnancies complicated by anti-Fy(a) alloimmunization.

PubMed

Hughes, Laura H; Rossi, Karen Q; Krugh, David W; O'Shaughnessy, Richard W

2007-10-01

The objective was to evaluate the management and outcome of patients with anti-Fy(a) at the Ohio State University. A database search for patients with pregnancies complicated only by anti-Fy(a) from 1959 to 2004. Collected information included maternal testing, fetal therapy, and neonatal outcomes. The final data set included 18 pregnancies in 15 women where anti-Fy(a) was the only maternal alloantibody present and the fetus was Fy(a) antigen-positive. Maternal antibody titers of at least 32 and optical density at 450 nm values in modified Liley Zone IIB or III identified all fetuses or neonates with significant hemolytic disease (2/18, 11%). No fetuses had hydrops, and there were no deaths attributed to hemolytic disease of the fetus and newborn. Anti-Fy(a) has the potential to lead to significant fetal hemolysis. Management guidelines developed for D sensitization are appropriate for pregnancies complicated by anti-Fy(a) alloimmunization.

Maternal nutritional programming of fetal adipose tissue development: differential effects on messenger ribonucleic acid abundance for uncoupling proteins and peroxisome proliferator-activated and prolactin receptors.

PubMed

Bispham, J; Gardner, D S; Gnanalingham, M G; Stephenson, T; Symonds, M E; Budge, H

2005-09-01

Maternal nutrient restriction at specific stages of gestation has differential effects on fetal development such that the offspring are programmed to be at increased risk of a range of adult diseases, including obesity. We investigated the effect of maternal nutritional manipulation through gestation on fetal adipose tissue deposition in conjunction with mRNA abundance for uncoupling protein (UCP)1 and 2, peroxisome proliferator-activated receptors (PPAR)alpha and gamma, together with long and short forms of the prolactin receptor (PRLR). Singleton-bearing ewes were either nutrient restricted (3.2-3.8 MJ day(-1) metabolizable energy) or fed to appetite (8.7-9.9 MJ day(-1)) over the period of maximal placental growth, i.e. between 28 and 80 d gestation. After 80 d gestation, ewes were either fed to calculated requirements, (6.7-7.5 MJ day(-1)), or to appetite (8.0-10.9 MJ day(-1)). At term, offspring of nutrient-restricted ewes possessed more adipose tissue, an adaptation that was greatest in those born to mothers that fed to requirements in late gestation. This was accompanied by an increased mRNA abundance for UCP2 and PPARalpha, an adaptation not seen in mothers re-fed to appetite. Maternal nutrition had no effect on mRNA abundance for UCP1, PPARgamma, or PRLR. Irrespective of maternal nutrition, mRNA abundance for UCP1 was positively correlated with PPARgamma and the long and short forms of PRLR, indicating that these factors may act together to ensure that UCP1 abundance is maximized in the newborn. In conclusion, we have shown, for the first time, differential effects of maternal nutrition on key regulatory components of fetal fat metabolism.

Zika virus infection in pregnancy: a systematic review of disease course and complications.

PubMed

Chibueze, Ezinne C; Tirado, Veronika; Lopes, Katharina da Silva; Balogun, Olukunmi O; Takemoto, Yo; Swa, Toshiyuki; Dagvadorj, Amarjargal; Nagata, Chie; Morisaki, Naho; Menendez, Clara; Ota, Erika; Mori, Rintaro; Oladapo, Olufemi T

2017-02-28

To characterize maternal Zika virus (ZIKV) infection and complement the evidence base for the WHO interim guidance on pregnancy management in the context of ZIKV infection. We searched the relevant database from inception until March 2016. Two review authors independently screened and assessed full texts of eligible reports and extracted data from relevant studies. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) and the National Institute of Health (NIH) tool for observational studies and case series/reports, respectively. Among 142 eligible full-text articles, 18 met the inclusion criteria (13 case series/reports and five cohort studies). Common symptoms among pregnant women with suspected/confirmed ZIKV infection were fever, rash, and arthralgia. One case of Guillain-Barré syndrome was reported among ZIKV-infected mothers, no other case of severe maternal morbidity or mortality reported. Complications reported in association with maternal ZIKV infection included a broad range of fetal and newborn neurological and ocular abnormalities; fetal growth restriction, stillbirth, and perinatal death. Microcephaly was the primary neurological complication reported in eight studies, with an incidence of about 1% among newborns of ZIKV infected women in one study. Given the extensive and variable fetal and newborn presentations/complications associated with prenatal ZIKV infection, and the dearth of information provided, knowledge gaps are evident. Further research and comprehensive reporting may provide a better understanding of ZIKV infection in pregnancy and attendant maternal/fetal complications. This knowledge could inform the creation of effective and evidence-based strategies, guidelines and recommendations aimed at the management of maternal ZIKV infection. Adherence to current best practice guidelines for prenatal care among health providers is encouraged, in the context of maternal ZIKV infection.

Is Fetal Growth Restriction Associated with a More Severe Maternal Phenotype in the Setting of Early Onset Pre-Eclampsia? A Retrospective Study

PubMed Central

Weiler, Jane; Tong, Stephen; Palmer, Kirsten R.

2011-01-01

Background Both pre-eclampsia and fetal growth restriction are thought to result from abnormal placental implantation in early pregnancy. Consistent with this shared pathophysiology, it is not uncommon to see growth restriction further confound the course of pre-eclampsia and vice versa. It has been previously suggested that superimposed growth restriction is associated with a more severe pre-eclamptic phenotype, however this has not been a consistent finding. Therefore, we set out to determine whether the presence of fetal growth restriction among women with severe early-onset pre-eclampsia was associated with more severe maternal disease compared to those without a growth-restricted fetus. Methods and Findings We undertook a retrospective cohort study of women presenting to a tertiary hospital with severe early-onset pre-eclampsia (<34 weeks' gestation) between 2005–2009. We collected clinical data, including severity of pre-eclampsia, maternal and neonatal outcomes. Of 176 cases of severe pre-eclampsia, 39% (n = 68) were further complicated by fetal growth restriction. However, no significant difference was seen in relation to the severity of pre-eclampsia between those with or without a growth-restricted baby. The presence of concomitant growth restriction was however associated with a significantly increased risk of stillbirth (p = 0.003) and total perinatal mortality (p = 0.02). Conclusions The presence of fetal growth restriction among women with severe early-onset pre-eclampsia is not associated with increased severity of maternal disease. However the incidence of stillbirth and perinatal death is significantly increased in this sub-population. PMID:22046419

Applicability of initial optimal maternal and fetal electrocardiogram combination vectors to subsequent recordings

NASA Astrophysics Data System (ADS)

Yan, Hua-Wen; Huang, Xiao-Lin; Zhao, Ying; Si, Jun-Feng; Liu, Tie-Bing; Liu, Hong-Xing

2014-11-01

A series of experiments are conducted to confirm whether the vectors calculated for an early section of a continuous non-invasive fetal electrocardiogram (fECG) recording can be directly applied to subsequent sections in order to reduce the computation required for real-time monitoring. Our results suggest that it is generally feasible to apply the initial optimal maternal and fetal ECG combination vectors to extract the fECG and maternal ECG in subsequent recorded sections.

Maternal hemodynamics, fetal biometry and Dopplers in pregnancies followed up for suspected fetal growth restriction.

PubMed

Roberts, Llinos A; Ling, Hua Zen; Poon, Liona; Nicolaides, Kypros H; Kametas, Nikos A

2018-04-01

To assess whether in a cohort of patients with small for gestational age (SGA) foetuses with estimated fetal weight ≤10 th percentile, maternal hemodynamics, fetal biometry and Dopplers at presentation, can predict the subsequent development of abnormal fetal Dopplers or delivery with birthweight <3 rd percentile. The study population comprised of 86 singleton pregnancies with SGA fetuses presenting at a median gestational age of 32 (range 26-35) weeks. We measured maternal cardiac function with a non-invasive transthoracic bioreactance monitor (NICOM, Cheetah), mean arterial pressure, fetal biometry, umbilical artery (UA), middle cerebral artery (MCA) and uterine artery (UT) pulsatility index (PI) and the deepest vertical pool (DVP) of amniotic fluid. Z-scores of these variables were calculated based on reported reference ranges and the values were compared between those with evidence of abnormal fetal Dopplers at presentation (group 1), those that developed abnormal Dopplers in subsequent visits (group 2) and those who did not develop abnormal Dopplers throughout pregnancy (group 3). Abnormal fetal Dopplers were defined as UAPI >95 th percentile, or MCA PI <5 th percentile. Differences in measured variables at presentation were also compared between pregnancies delivering a baby with birthweight <3 rd and ≥3 rd percentile. Multivariate logistic regression analysis was used to determine significant predictors of birthweight <3 rd percentile and evolution from normal fetal Dopplers to abnormal fetal Dopplers in groups 2 and 3. In the study population 14 (16%) cases were in group 1, 19 (22%) in group 2 and 53 (62%) in group 3. The birthweight was <3 rd percentile in 39 (45%) cases and ≥3 rd percentile in 47 (55%). In the study groups, compared to normal populations, there was decreased cardiac output and stroke volume and increased peripheral vascular resistance and mean arterial pressure (MAP) and the deviations from normal were most marked in group 1. Pregnancies with a birthweight <3 rd , compared to those ≥3 rd percentile, had higher deviations from normal in fetal biometry, maternal cardiac output, stroke volume, heart rate and peripheral vascular resistance and UT-PI. Multivariate logistic regression analysis demonstrated that in the prediction of birth weight ≤3 rd percentile, maternal hemodynamics provided significant improvement to the prediction provided by maternal demographics, fetal biometry and UT-PI, UA-PI and MCA-PI (difference between AUCs 0.18, 95% CI 0.06-0.29, p=0.002). In contrast, there was no significant independent contribution from maternal hemodynamics in the prediction of subsequent abnormal fetal Dopplers. In pregnancies with SGA fetuses there is decreased maternal cardiac output and stroke volume and increased peripheral vascular resistance and MAP and the deviations from normal are most marked in cases of redistribution in the fetal circulation and reduced amniotic fluid volume. This article is protected by copyright. All rights reserved.

A placenta clinic approach to the diagnosis and management of fetal growth restriction.

PubMed

Kingdom, John C; Audette, Melanie C; Hobson, Sebastian R; Windrim, Rory C; Morgen, Eric

2018-02-01

Effective detection and management of fetal growth restriction is relevant to all obstetric care providers. Models of best practice to care for these patients and their families continue to evolve. Since much of the disease burden in fetal growth restriction originates in the placenta, the concept of a multidisciplinary placenta clinic program, managed primarily within a maternal-fetal medicine division, has gained popularity. In this context, fetal growth restriction is merely one of many placenta-related disorders that can benefit from an interdisciplinary approach, incorporating expertise from specialist perinatal ultrasound and magnetic resonance imaging, reproductive genetics, neonatal pediatrics, internal medicine subspecialties, perinatal pathology, and nursing. The accurate diagnosis and prognosis for women with fetal growth restriction is established by comprehensive clinical review and detailed sonographic evaluation of the fetus, combined with uterine artery Doppler and morphologic assessment of the placenta. Diagnostic accuracy for placenta-mediated fetal growth restriction may be enhanced by quantification of maternal serum biomarkers including placenta growth factor alone or combined with soluble fms-like tyrosine kinase-1. Uterine artery Doppler is typically abnormal in most instances of early-onset fetal growth restriction and is associated with coexistent preeclampsia and underlying maternal vascular malperfusion pathology of the placenta. By contrast, rare but potentially more serious underlying placental diagnoses, such as massive perivillous fibrinoid deposition, chronic histiocytic intervillositis, or fetal thrombotic vasculopathy, may be associated with normal uterine artery Doppler waveforms. Despite minor variations in placental size, shape, and cord insertion, placental function remains, largely normal in the general population. Consequently, morphologic assessment of the placenta is not currently incorporated into current screening programs for placental complications. However, placental ultrasound can be diagnostic in the context of fetal growth restriction, for example in Breus' mole and triploidy, which in turn may enhance diagnosis and management. Several examples are illustrated in our figures and supplementary videos. Recent advances in the ability of multiparameter screening and intervention programs to reduce the risk of severe preeclampsia will likely increase efforts to deliver similar improvements for women at risk of fetal growth restriction. Placental pathology is important because the underlying pathologies associated with fetal growth restriction have a wide range of recurrence risks. Rare conditions such as massive perivillous fibrinoid deposition or chronic histolytic intervillositis may recur in >50% of subsequent pregnancies. Postpartum care in a placenta-focused program can provide effective counseling for modifiable maternal risk factors, and can assist in planning future pregnancy care based on the pathologic basis of fetal growth restriction. Copyright © 2017 Elsevier Inc. All rights reserved.

3,3'-Diiodothyronine sulfate excretion in maternal urine reflects fetal thyroid function in sheep.

PubMed

Wu, S Y; Huang, W S; Fisher, D A; Florsheim, W H; Kashiwai, K; Polk, D H

2001-09-01

We have shown that there is significant fetal-to-maternal transfer of sulfated metabolites of thyroid hormone after fetal infusion of a pharmacologic amount of 3,3',5-triiodothyronine (T(3)) or sulfated T(3) in late pregnancy in sheep (Am J Physiol 277:E915, 1999). The transferred iodothyronine sulfoconjugate, i.e. 3,3'-diiodothyronine sulfate (T(2)S), of fetal origin appears in maternal sheep urine. The present study was carried out to assess the contribution of T(2)S of fetal origin to the urinary pool in ewes. Eighteen date-bred ewes (mean gestational age of 115 d) and their twin fetuses were divided into four groups. In group I (control, n = 5), both ewes (M) and their fetuses (F) were sham operated for thyroidectomy (Tx). In group II, the ewes (MTx, n = 4) and, in group III, the fetuses (FTx, n = 4) were subjected to Tx. In group IV (MTx.FTx, n = 5), both the ewe and fetus had Tx. After 10-12 d, fetal and/or maternal hypothyroidism were confirmed by serum thyroxine (<15 nmol/L) measurements. In addition, we infused radioactive T(3) without disturbing the T(3) pool in three singleton near-term fetuses and assessed the amount of radioactive iodothyronine that appeared in maternal urine (MU). After infusing [(125)I-3'],3,5-T(3) via fetal vein to the near-term normal fetuses, radioactive T(2)S was identified as the major metabolite in MU by HPLC and T(2)S-specific antibody. MU T(2)S excretion (pmol/mmol creatinine) was significantly reduced by FTx and MTx.FTx but not by MTx. In addition, positive correlations (p < 0.01) were found between MU T(2)S excretion and fetal serum thyroxine and T(3) concentrations but not with maternal serum thyroxine or T(3) levels. T(2)S of fetal origin contributes significantly to the MU pool.

Maternal Infection Requiring Hospitalization during Pregnancy and Autism Spectrum Disorders

ERIC Educational Resources Information Center

Atladottir, Hjordis O.; Thorsen, Poul; Ostergaard, Lars; Schendel, Diana E.; Lemcke, Sanne; Abdallah, Morsi; Parner, Erik T.

2010-01-01

Exposure to prenatal infection has been suggested to cause deficiencies in fetal neurodevelopment. In this study we included all children born in Denmark from 1980, through 2005. Diagnoses of autism spectrum disorders (ASDs) and maternal infection were obtained through nationwide registers. Data was analyzed using Cox proportional hazards…

Factors associated with higher oxytocin requirements in labor.

PubMed

Frey, Heather A; Tuuli, Methodius G; England, Sarah K; Roehl, Kimberly A; Odibo, Anthony O; Macones, George A; Cahill, Alison G

2015-09-01

To identify clinical characteristics associated with high maximum oxytocin doses in women who achieve complete cervical dilation. A retrospective nested case-control study was performed within a cohort of all term women at a single center between 2004 and 2008 who reached the second stage of labor. Cases were defined as women who had a maximum oxytocin dose during labor >20 mu/min, while women in the control group had a maximum oxytocin dose during labor of ≤20 mu/min. Exclusion criteria included no oxytocin administration during labor, multiple gestations, major fetal anomalies, nonvertex presentation, and prior cesarean delivery. Multiple maternal, fetal, and labor factors were evaluated with univariable analysis and multivariable logistic regression. Maximum oxytocin doses >20 mu/min were administered to 108 women (3.6%), while 2864 women received doses ≤20 mu/min. Factors associated with higher maximum oxytocin dose after adjusting for relevant confounders included maternal diabetes, birthweight >4000 g, intrapartum fever, administration of magnesium, and induction of labor. Few women who achieve complete cervical dilation require high doses of oxytocin. We identified maternal, fetal and labor factors that characterize this group of parturients.

NK cell-derived IL-10 is critical for DC-NK cell dialogue at the maternal-fetal interface.

PubMed

Blois, Sandra M; Freitag, Nancy; Tirado-González, Irene; Cheng, Shi-Bin; Heimesaat, Markus M; Bereswill, Stefan; Rose, Matthias; Conrad, Melanie L; Barrientos, Gabriela; Sharma, Surendra

2017-05-19

DC-NK cell interactions are thought to influence the development of maternal tolerance and de novo angiogenesis during early gestation. However, it is unclear which mechanism ensures the cooperative dialogue between DC and NK cells at the feto-maternal interface. In this article, we show that uterine NK cells are the key source of IL-10 that is required to regulate DC phenotype and pregnancy success. Upon in vivo expansion of DC during early gestation, NK cells expressed increased levels of IL-10. Exogenous administration of IL-10 was sufficient to overcome early pregnancy failure in dams treated to achieve simultaneous DC expansion and NK cell depletion. Remarkably, DC expansion in IL-10 -/- dams provoked pregnancy loss, which could be abrogated by the adoptive transfer of IL-10 +/+ NK cells and not by IL-10 -/- NK cells. Furthermore, the IL-10 expressing NK cells markedly enhanced angiogenic responses and placental development in DC expanded IL-10 -/- dams. Thus, the capacity of NK cells to secrete IL-10 plays a unique role facilitating the DC-NK cell dialogue during the establishment of a healthy gestation.

Choline Supplementation Normalizes Fetal Adiposity and Reduces Lipogenic Gene Expression in a Mouse Model of Maternal Obesity

PubMed Central

Jack-Roberts, Chauntelle; Joselit, Yaelle; Nanobashvili, Khatia; Bretter, Rachel; Malysheva, Olga V.; Caudill, Marie A.; Saxena, Anjana; Axen, Kathleen; Gomaa, Ahmed

2017-01-01

Maternal obesity increases fetal adiposity which may adversely affect metabolic health of the offspring. Choline regulates lipid metabolism and thus may influence adiposity. This study investigates the effect of maternal choline supplementation on fetal adiposity in a mouse model of maternal obesity. C57BL/6J mice were fed either a high-fat (HF) diet or a control (NF) diet and received either 25 mM choline supplemented (CS) or control untreated (CO) drinking water for 6 weeks before timed-mating and throughout gestation. At embryonic day 17.5, HF feeding led to higher (p < 0.05) percent total body fat in fetuses from the HFCO group, while the choline supplemented HFCS group did not show significant difference versus the NFCO group. Similarly, HF feeding led to higher (p < 0.05) hepatic triglyceride accumulation in the HFCO but not the HFCS fetuses. mRNA levels of lipogenic genes such as Acc1, Fads1, and Elovl5, as well as the transcription factor Srebp1c that favors lipogenesis were downregulated (p < 0.05) by maternal choline supplementation in the HFCS group, which may serve as a mechanism to reduce fat accumulation in the fetal liver during maternal HF feeding. In summary, maternal choline supplementation improves indices of fetal adiposity in obese dams at late gestation. PMID:28820499

Choline Supplementation Normalizes Fetal Adiposity and Reduces Lipogenic Gene Expression in a Mouse Model of Maternal Obesity.

PubMed

Jack-Roberts, Chauntelle; Joselit, Yaelle; Nanobashvili, Khatia; Bretter, Rachel; Malysheva, Olga V; Caudill, Marie A; Saxena, Anjana; Axen, Kathleen; Gomaa, Ahmed; Jiang, Xinyin

2017-08-18

Maternal obesity increases fetal adiposity which may adversely affect metabolic health of the offspring. Choline regulates lipid metabolism and thus may influence adiposity. This study investigates the effect of maternal choline supplementation on fetal adiposity in a mouse model of maternal obesity. C57BL/6J mice were fed either a high-fat (HF) diet or a control (NF) diet and received either 25 mM choline supplemented (CS) or control untreated (CO) drinking water for 6 weeks before timed-mating and throughout gestation. At embryonic day 17.5, HF feeding led to higher ( p < 0.05) percent total body fat in fetuses from the HFCO group, while the choline supplemented HFCS group did not show significant difference versus the NFCO group. Similarly, HF feeding led to higher ( p < 0.05) hepatic triglyceride accumulation in the HFCO but not the HFCS fetuses. mRNA levels of lipogenic genes such as Acc1 , Fads1 , and Elovl5 , as well as the transcription factor Srebp1c that favors lipogenesis were downregulated ( p < 0.05) by maternal choline supplementation in the HFCS group, which may serve as a mechanism to reduce fat accumulation in the fetal liver during maternal HF feeding. In summary, maternal choline supplementation improves indices of fetal adiposity in obese dams at late gestation.

Fetal QRS detection and heart rate estimation: a wavelet-based approach.

PubMed

Almeida, Rute; Gonçalves, Hernâni; Bernardes, João; Rocha, Ana Paula

2014-08-01

Fetal heart rate monitoring is used for pregnancy surveillance in obstetric units all over the world but in spite of recent advances in analysis methods, there are still inherent technical limitations that bound its contribution to the improvement of perinatal indicators. In this work, a previously published wavelet transform based QRS detector, validated over standard electrocardiogram (ECG) databases, is adapted to fetal QRS detection over abdominal fetal ECG. Maternal ECG waves were first located using the original detector and afterwards a version with parameters adapted for fetal physiology was applied to detect fetal QRS, excluding signal singularities associated with maternal heartbeats. Single lead (SL) based marks were combined in a single annotator with post processing rules (SLR) from which fetal RR and fetal heart rate (FHR) measures can be computed. Data from PhysioNet with reference fetal QRS locations was considered for validation, with SLR outperforming SL including ICA based detections. The error in estimated FHR using SLR was lower than 20 bpm for more than 80% of the processed files. The median error in 1 min based FHR estimation was 0.13 bpm, with a correlation between reference and estimated FHR of 0.48, which increased to 0.73 when considering only records for which estimated FHR > 110 bpm. This allows us to conclude that the proposed methodology is able to provide a clinically useful estimation of the FHR.

Minimal alteration in the ratio of circulatory fetal DNA to fetal corticotropin-releasing hormone mRNA level in preeclampsia.

PubMed

Zhong, Xiao Yan; Holzgreve, Wolfgang; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Gupta, Anurag Kumar; Huppertz, Berthold; Hahn, Sinuhe

2006-01-01

We have recently observed that fetal DNA and fetal corticotropin-releasing hormone (CRH) mRNA are associated with in vitro generated syncytiotrophoblast-derived microparticles, and that the ratio of fetal DNA to mRNA (CRH) varied according to whether the particles were derived by predominantly apoptotic, apo-necrotic or necrotic pathways. Hence, we examined whether these ratios varied in maternal plasma samples taken from normotensive and preeclamptic pregnancies in vivo. Maternal plasma samples were collected from 18 cases with preeclampsia and 29 normotensive term controls. Circulatory fetal CRH mRNA and DNA levels were quantified by real-time PCR and RT-PCR. Circulatory fetal mRNA and fetal DNA levels were significantly elevated in the preeclampsia study group when compared to normotensive controls. Alterations in the fetal mRNA to DNA ratio between the study and control groups were minimal, even when stratified into early (<34 weeks of gestation) and late (>34 weeks of gestation) onset preeclampsia. Our data suggest that although circulatory fetal DNA and mRNA levels are significantly elevated in preeclampsia, the ratios in maternal plasma are not dramatically altered. Copyright 2006 S. Karger AG, Basel.

Epigenetic approaches for the detection of fetal DNA in maternal plasma

PubMed Central

Tsui, Dana WY; Chiu, Rossa WK

2010-01-01

The presence of fetal DNA in the plasma of pregnant women has opened up new possibilities for noninvasive prenatal diagnosis. Over the past decades, different types of fetal markers have been developed, initially based on discriminative genetic markers such as male-specific signals or paternally-inherited polymorphisms, and gradually evolved to the detection of fetal-specific transcripts or epigenetic signatures. This development has extended the coverage of the application of cell-free fetal DNA to essentially all pregnancies, regardless of the gender of the fetus or its polymorphic status. In this review, we present an overview of the development of noninvasive prenatal diagnosis through epigenetics. We introduce the basis of how fetal DNA could be detected from a large background of maternal DNA in maternal plasma based on fetal-specific DNA methylation patterns. We evaluate the methodologies involved and discuss the factors that affect the robustness of the detection. We review the progress in adopting fetal epigenetic markers for noninvasive prenatal assessment of fetal chromosomal aneuploidies and pregnancy-associated disorders. We conclude with comments on the future directions regarding the search for new fetal epigenetic markers and the clinical implementation of epigenetic approaches for noninvasive prenatal diagnosis. PMID:21327153

A prospective study of maternal carboxyhemoglobin and preeclampsia risk

PubMed Central

Rudra, Carole B.; Williams, Michelle A.; Schiff, Melissa A.; Koenig, Jane Q.; Dills, Russell; Yu, Jianbo

2009-01-01

Summary We aimed to measure the relation between early-pregnancy maternal carboxyhemoglobin and subsequent preeclampsia risk. We conducted a nested case-control analysis using data from a western Washington State cohort study (1996–2004). We measured maternal whole blood carboxyhemoglobin in 128 women who developed preeclampsia and 419 normotensive controls (mean gestational age at blood draw, 14.8 weeks). After adjustment for confounders, high (≥1%) versus low (<0.7%) carboxyhemoglobin odds ratios [OR] and 95% confidence intervals [CI] were 4.09 [1.30, 12.9] in parous women, 0.53 [0.23, 1.26] in nulliparous women, and 1.11 [0.55, 2.25] in the overall study population (parity interaction p=0.01). The influence of parity on the association was unexpected. The association between high carboxyhemoglobin and preeclampsia risk in parous women implicates hypoxia at the fetal-maternal interface as a pathogenic mechanism. These results also suggest that the etiology of the disease may differ according to parity. PMID:20078828

A prospective study of maternal carboxyhaemoglobin and pre-eclampsia risk.

PubMed

Rudra, Carole B; Williams, Michelle A; Schiff, Melissa A; Koenig, Jane Q; Dills, Russell; Yu, Jianbo

2010-01-01

We aimed to measure the relationship between early-pregnancy maternal carboxyhaemoglobin and subsequent pre-eclampsia risk. A nested case-control analysis was conducted using data from a western Washington State cohort study (1996-2004). We measured maternal whole blood carboxyhaemoglobin in 128 women who developed pre-eclampsia and 419 normotensive controls (mean gestational age at blood draw, 14.8 weeks). After adjustment for confounders, high (>/=1%) vs. low (<0.7%) carboxyhaemoglobin odds ratios [OR] and 95% confidence intervals [CI] were 4.09 [1.30, 12.9] in multiparous women, 0.53 [0.23, 1.26] in primiparae and 1.11 [0.55, 2.25] in the overall study population (parity interaction P = 0.01). The influence of parity on the association was unexpected. The association between high carboxyhaemoglobin and pre-eclampsia risk in multiparae implicates hypoxia at the fetal-maternal interface as a pathogenic mechanism. These results also suggest that the aetiology of the disease may differ according to parity.

Is pregnancy over 45 with very high parity related with adverse maternal and fetal outcomes?

PubMed

Kale, A; Kuyumcuoğlu, U; Güzel, A

2009-01-01

To examine whether very high parity and age over 45 years are related with adverse maternal and fetal outcomes. This study was carried out at the Department of Obstetrics and Gynecology from January 1, 2007 to December 31, 2007. Sixty-one pregnant women were enrolled in this prospective study. Mothers were classified in two groups: the study group (n = 23) included women with very high parity over 45 years of age (age > 45 and > or = 10 previous live births), and a control group (n = 38) included women with high parity between 40-45 years of age (between 40-45 years and 5-9 previous live births). Hypertensive disorders complicating pregnancy, preterm labor, breech presentation, cesarean section ratio, mean APGAR scores, birthweight, fetal sex, fetal macrosomia, and early neonatal death were compared within groups. Six (26%) patients in the study group and 12 (31.5%) patients in the control group had hypertensive disorders of pregnancies (p > 0.05). Twelve (52.1%) patients in the study group and 22 (57.8%) patients in the control group had preterm labor (p > 0.05). One (4%) patient in the study group and two (5.2%) patients in the control group had breech presentation during delivery (p > 00.5). Twelve (52.1%) patients in the study group and 21 (55.2%) patients in the control group had cesarean operations (p > 0.05). Mean APGAR scores (at 1 min and 5 min), mean birthweight, fetal sex ratio, fetal macrosomia ratio, and early neonatal death ratio due to prematurity were not statistically significant in the study group as compared with the control group. It is generally assumed that women with advanced age have an increased risk for complications during pregnancy. However, prospective population-based studies do not exist and available publications give conflicting views. Based on our results, we hypothesized that cases aged 45 or over with very high parity are not always related with adverse maternal and fetal outcomes.

Maternal pomegranate juice attenuates maternal inflammation-induced fetal brain injury by inhibition of apoptosis, neural nitric oxide synthase and NF-κB in a rat model.

PubMed

Ginsberg, Yuval; Khatib, Nizar; Saadi, Noor; Ross, Michael G; Weinr, Zeev; Beloosesky, Ron

2018-04-27

Maternal inflammation is a risk factor for neonatal brain injury and future neurological deficits. Pomegranates have been shown to exhibit anti-inflammatory, anti-apoptotic and anti-oxidant activities. We hypothesized that pomegranate juice (POM) may attenuate fetal brain injury in a rat model of maternal inflammation. Pregnant rats (24 total) were randomized for i.p. LPS (100 ug/kg) or saline at time 0 at 18 days of gestation. From day 11 of gestation, 12 dams were provided ad libitum access to drinking water, and 12 dams were provided ad libitum access to drinking water with pomegranate juice (5cc per day), resulting in 4 groups of 6 dams (SAL/SAL, POM/SAL, SAL/LPS, POM/LPS). All dams were sacrificed 4 hours following the injection and maternal blood and fetal brains were collected from the 4 treatment groups. Maternal IL-6 serum levels and fetal brain caspase 3 active form (af), NF-kB p65, neuronal nitric oxide synthase (phospho-nNOS) and pro-inflammatory cytokine levels were determined by ELISA and western blot. Maternal LPS significantly increased maternal serum IL-6 levels (6039 ± 1039 vs 66 ± 46pg/ml; p < 0.05) and fetal brain caspase 3 af, NF-kB p65, phospho-nNOS and the pro-inflammatory cytokines compared to the control group (caspase 3 af 0.26 ± 0.01 vs. 0.20 ± 0.01 u; NF-κB p65 0.24 ± 0.01 vs. 0.1 ± 0.01 u; phospho-nNOS 0.23 ± 0.01 vs. 0.11 ± 0.01 u; IL-6 0.25 ± 0.01 vs. 0.09 ± 0.01 u; TNFα 0.26 ± 0.01 vs. 0.12 ± 0.01 u; CCL2 0.23 ± 0.01 vs. 0.1 ± 0.01 u). Maternal supplementation of POM to LPS exposed dams (POM/LPS) significantly reduced maternal serum IL-6 levels (3059± 1121pg/ml, fetal brain: caspase 3 af (0.2 ± 0.01 u), NF-κB p65 (0.22 ± 0.01 u), phospho-nNOS (0.19 ± 0.01 u) as well as the brain pro-inflammatory cytokines (IL-6, TNFα and CCL2) compared to LPS group. Maternal POM supplementation may attenuate maternal-inflammation-induced fetal brain injury. POM neuroprotective effects might be secondary to the suppression of both the maternal inflammatory response and inhibition of fetal brain apoptosis, neuronal nitric oxide synthase and NF-kB activation. Copyright © 2018. Published by Elsevier Inc.

Congenital heart disease linked to maternal autoimmunity against cardiac myosin.

PubMed

Cole, Charles R; Yutzey, Katherine E; Brar, Anoop K; Goessling, Lisa S; Van Vickle-Chavez, Sarah J; Cunningham, Madeleine W; Eghtesady, Pirooz

2014-05-01

Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti-β-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal-fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.

Rare Sequence Variation in the Genome Flanking a Short Tandem Repeat Locus Can Lead to a Question of “Nonmaternity”

PubMed Central

Deucher, Anne; Chiang, Tsoyu; Schrijver, Iris

2010-01-01

Typing of STR (short tandem repeat) alleles is used in a variety of applications in clinical molecular pathology, including evaluations for maternal cell contamination. Using a commercially available STR typing assay for maternal cell contamination performed in conjunction with prenatal diagnostic testing, we were posed with apparent nonmaternity when the two fetal samples did not demonstrate the expected maternal allele at one locus. By designing primers external to the region amplified by the primers from the commercial assay and by performing direct sequencing of the resulting amplicon, we were able to determine that a guanine to adenine sequence variation led to primer mismatch and allele dropout. This explained the apparent null allele shared between the maternal and fetal samples. Therefore, although rare, allele dropout must be considered whenever unexplained homozygosity at an STR locus is observed. PMID:20203001

Determinants and outcome of fetal macrosomia in a Nigerian tertiary hospital.

PubMed

Olokor, Oghenefegor Edwin; Onakewhor, Joseph Ubini; Aderoba, Adeniyi Kolade

2015-01-01

To determine the incidence and risk factors of fetal macrosomia and maternal and perinatal outcome. This was a 1-year prospective case-control study of singleton pregnancies in a Nigerian tertiary hospital. Only women who gave consent were recruited for the study. The maternal and perinatal outcomes in women who delivered macrosomic infants (birth weight ≥ 4000 g) were compared with the next consecutive delivery of normal birth weight (2500-3999 g) infants. The total deliveries for the study period were 2437, of which 135 were macrosomic babies. The incidence of fetal macrosomia was 5.5%. The mean birth weights of macrosomic and nonmacrosomic babies were 4.26 ± 0.29 kg and 3.20 ± 0.38 kg, respectively, P = 0.000. Mothers with macrosomic babies were more likely to be older (P = 0.047), of higher parity (0.001), taller (P = 0.007), and weighed more at delivery (P = 0.000). Previous history of fetal macrosomia (P = 0.000) and maternal diabetes (P = 0.007) were factors strongly associated with the delivery of macrosomic infants. Pregnancies associated with fetal macrosomia had increased duration of labor (P = 0.007), interventional deliveries (P = 0.000), shoulder dystocia, and genital laceration (P = 0.000). There was no significant difference in the incidence of primary postpartum hemorrhage (P = 0.790), birth asphyxia, and perinatal mortality (P = 0.197). Fetal macrosomia is associated with maternal and fetal morbidities. The presence of the observed risk factors should elicit the suspicion of a macrosomic fetus and the need for appropriate management to reduce maternal and fetal morbidities.

Effect of maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and farrowing characteristics in pigs.

PubMed

Harris, E K; Berg, E P; Berg, E L; Vonnahme, K A

2013-02-01

Yorkshire gilts either remained in their individual stall from d 40 to term (CON; n = 7) or were subjected to exercise for 30 min 3 times per week from mid to late gestation (EX; n = 7) to determine the impact of increased maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and parturition. In parity 1, maternal body composition (10th rib back fat and LM area), maternal behavior, and farrowing characteristics were recorded. In parities 1 and 2, fetal growth, fetal heart rate, pulsatility index and resistance index, and umbilical blood flow were monitored beginning at d 39 of gestation continuing to d 81 of gestation. Exercise continued until d 104. Gilts allowed to exercise sat less (P < 0.01), stood more (P < 0.01), tended (P = 0.06) to lie down less, and had fewer postural changes (P < 0.01) compared with CON gilts. Umbilical blood flow increased (P < 0.01) in EX compared with CON gilts. Moreover, gilts had greater (P < 0.01) umbilical blood flow in their first parity compared with their second. Indices of vascular resistance were not affected (P ≥ 0.15) by maternal treatment; however, EX gilts reached peak pulsatility index earlier than CON gilts (56.2 vs. 64.3 ± 3.6 d). Fetal weights, piglet birth weights, placental weight, interval between piglet births, and blood lactate of newborn piglets were unaffected (P ≥ 0.15) by maternal treatment. Although maternal exercise during gestation in the pig increased umbilical blood flow and appeared to reduce maternal restlessness, impacts on offspring development in postnatal life are not known.

Maternal-fetal disposition of glyburide in pregnant mice is dependent on gestational age.

PubMed

Shuster, Diana L; Risler, Linda J; Liang, Chao-Kang J; Rice, Kenneth M; Shen, Danny D; Hebert, Mary F; Thummel, Kenneth E; Mao, Qingcheng

2014-08-01

Gestational diabetes mellitus is a major complication of human pregnancy. The oral clearance (CL) of glyburide, an oral antidiabetic drug, increases 2-fold in pregnant women during late gestation versus nonpregnant controls. In this study, we examined gestational age-dependent changes in maternal-fetal pharmacokinetics (PK) of glyburide and metabolites in a pregnant mouse model. Nonpregnant and pregnant FVB mice were given glyburide by retro-orbital injection. Maternal plasma was collected over 240 minutes on gestation days (gd) 0, 7.5, 10, 15, and 19; fetuses were collected on gd 15 and 19. Glyburide and metabolites were quantified using high-performance liquid chromatography-mass spectrometry, and PK analyses were performed using a pooled data bootstrap approach. Maternal CL of glyburide increased approximately 2-fold on gd 10, 15, and 19 compared with nonpregnant controls. Intrinsic CL of glyburide in maternal liver microsomes also increased as gestation progressed. Maternal metabolite/glyburide area under the curve ratios were generally unchanged or slightly decreased throughout gestation. Total fetal exposure to glyburide was <5% of maternal plasma exposure, and was doubled on gd 19 versus gd 15. Fetal metabolite concentrations were below the limit of assay detection. This is the first evidence of gestational age-dependent changes in glyburide PK. Increased maternal glyburide clearance during gestation is attributable to increased hepatic metabolism. Metabolite elimination may also increase during pregnancy. In the mouse model, fetal exposure to glyburide is gestational age-dependent and low compared with maternal plasma exposure. These results indicate that maternal glyburide therapeutic strategies may require adjustments in a gestational age-dependent manner if these same changes occur in humans. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Maternal-Fetal Disposition of Glyburide in Pregnant Mice Is Dependent on Gestational Age

PubMed Central

Shuster, Diana L.; Risler, Linda J.; Liang, Chao-Kang J.; Rice, Kenneth M.; Shen, Danny D.; Hebert, Mary F.; Thummel, Kenneth E.

2014-01-01

Gestational diabetes mellitus is a major complication of human pregnancy. The oral clearance (CL) of glyburide, an oral antidiabetic drug, increases 2-fold in pregnant women during late gestation versus nonpregnant controls. In this study, we examined gestational age–dependent changes in maternal-fetal pharmacokinetics (PK) of glyburide and metabolites in a pregnant mouse model. Nonpregnant and pregnant FVB mice were given glyburide by retro-orbital injection. Maternal plasma was collected over 240 minutes on gestation days (gd) 0, 7.5, 10, 15, and 19; fetuses were collected on gd 15 and 19. Glyburide and metabolites were quantified using high-performance liquid chromatography–mass spectrometry, and PK analyses were performed using a pooled data bootstrap approach. Maternal CL of glyburide increased approximately 2-fold on gd 10, 15, and 19 compared with nonpregnant controls. Intrinsic CL of glyburide in maternal liver microsomes also increased as gestation progressed. Maternal metabolite/glyburide area under the curve ratios were generally unchanged or slightly decreased throughout gestation. Total fetal exposure to glyburide was <5% of maternal plasma exposure, and was doubled on gd 19 versus gd 15. Fetal metabolite concentrations were below the limit of assay detection. This is the first evidence of gestational age–dependent changes in glyburide PK. Increased maternal glyburide clearance during gestation is attributable to increased hepatic metabolism. Metabolite elimination may also increase during pregnancy. In the mouse model, fetal exposure to glyburide is gestational age–dependent and low compared with maternal plasma exposure. These results indicate that maternal glyburide therapeutic strategies may require adjustments in a gestational age–dependent manner if these same changes occur in humans. PMID:24898265

Influenza and its treatment during pregnancy: A review.

PubMed

Ghulmiyyah, L M; Alame, M M; Mirza, F G; Zaraket, H; Nassar, A H

2015-01-01

The influenza viral infection has dramatic effects during pregnancy on the mother and the fetus. We present a review article on the prevention and treatment recommendations of influenza infection in pregnant women, and the effects of antiviral medications on maternal-fetal outcomes. This viral infection not only leads to miscarriages, preterm deliveries and a high maternal mortality rate, but it also poses negative risks to the fetus including small-for-gestational age infants, and admissions to neonatal intensive care units. Vaccination is the most effective strategy for preventing influenza infection during pregnancy whereby can protect both maternal and fetal immunities. The safety profiles of antiviral drugs during pregnancy are limited. Available risk-benefit evidence has indicated that pregnant women with suspected or confirmed influenza should receive prompt antiviral therapy where these medications reduce the risk of complications among pregnant women, and attenuate the teratogenic effects of the influenza infection. Post-exposure prophylaxis is not recommended for most pregnant women, but it may be prescribed in pandemic settings, particularly to non-vaccinated women. Although some ex vivo models for pharmacokinetic studies have revealed that the transplacental transfer of oseltamivir to fetal circuits may occur, there is no evidence of adverse fetal outcomes as a result of most in utero exposures to neuraminidase inhibitors. Due to the large number of confounding variables, large, population-based studies are needed to assess the association between in utero oseltamivir exposure and fetal outcome.

Epigenetic changes in fetal hypothalamic energy regulating pathways are associated with maternal undernutrition and twinning

PubMed Central

Begum, Ghazala; Stevens, Adam; Smith, Emma Bolton; Connor, Kristin; Challis, John R. G.; Bloomfield, Frank; White, Anne

2012-01-01

Undernutrition during pregnancy is implicated in the programming of offspring for the development of obesity and diabetes. We hypothesized that maternal programming causes epigenetic changes in fetal hypothalamic pathways regulating metabolism. This study used sheep to examine the effect of moderate maternal undernutrition (60 d before to 30 d after mating) and twinning to investigate changes in the key metabolic regulators proopiomelanocortin (POMC) and the glucocorticoid receptor (GR) in fetal hypothalami. Methylation of the fetal hypothalamic POMC promoter was reduced in underfed singleton, fed twin, and underfed twin groups (60, 73, and 63% decrease, respectively). This was associated with reduced DNA methyltransferase activity and altered histone methylation and acetylation. Methylation of the hypothalamic GR promoter was decreased in both twin groups and in maternally underfed singleton fetuses (52, 65, and 55% decrease, respectively). This correlated with changes in histone methylation and acetylation and increased GR mRNA expression in the maternally underfed singleton group. Alterations in GR were hypothalamic specific, with no changes in hippocampi. Unaltered levels of OCT4 promoter methylation indicated gene-specific effects. In conclusion, twinning and periconceptional undernutrition are associated with epigenetic changes in fetal hypothalamic POMC and GR genes, potentially resulting in altered energy balance regulation in the offspring.—Begum, G., Stevens, A., Smith, E. B., Connor, K., Challis, J. R. G., Bloomfield, F., White, A. Epigenetic changes in fetal hypothalamic energy regulating pathways are associated with maternal undernutrition and twinning. PMID:22223754

Chronic hypoxia alters maternal uterine and fetal hemodynamics in the full-term pregnant guinea pig.

PubMed

Turan, Sifa; Aberdeen, Graham W; Thompson, Loren P

2017-10-01

Placental hypoxia is associated with maternal hypertension, placental insufficiency, and fetal growth restriction. In the pregnant guinea pig, prenatal hypoxia during early gestation inhibits cytotrophoblast invasion of spiral arteries, increases maternal blood pressure, and induces fetal growth restriction. In this study the impact of chronic maternal hypoxia on fetal heart structure was evaluated using four-dimensional echocardiography with spatiotemporal image correlation and tomographic ultrasound, and uterine and umbilical artery resistance/pulsatility indexes and fetal heart function were evaluated using pulsed-wave Doppler ultrasound. Pregnant guinea pigs were exposed to normoxia ( n = 7) or hypoxia (10.5% O 2 , n = 9) at 28-30 days gestation, which was maintained until full term (65 days). At full term, fetal heart structure and outflow tracts were evaluated in the four-chamber view. Fetal heart diastolic function was assessed by E wave-to-A wave diastolic filling ratios (E/A ratios) of both ventricles and systolic function by the myocardial performance index (or Tie) of left ventricles of normoxic ( n = 21) and hypoxic ( n = 17) fetuses. There were no structural abnormalities in fetal hearts. However, hypoxia induced asymmetric fetal growth restriction and increased the placental/fetal weight compared with normoxic controls. Hypoxia increased Doppler resistance and pulsatility indexes in the uterine, but not umbilical, arteries, had no effect on the Tie index, and increased the E/A ratio in left, but not right, ventricles. Thus, prolonged hypoxia, starting at midgestation, increases uterine artery resistance and generates fetal growth restriction at full term. Furthermore, the enhanced cardiac diastolic filling with no changes in systolic function or umbilical artery resistance suggests that the fetal guinea pig systemic circulation undergoes a compensated, adaptive response to prolonged hypoxia exposure. Copyright © 2017 the American Physiological Society.

In utero glucocorticoid exposure reduced fetal skeletal muscle mass in rats independent of effects on maternal nutrition

USDA-ARS?s Scientific Manuscript database

Maternal stress and undernutrition can occur together and expose the fetus to high glucocorticoid (GLC) levels during this vulnerable period. To determine the consequences of GLC exposure on fetal skeletal muscle independently of maternal food intake, groups of timed-pregnant Sprague-Dawley rats (n ...

Widespread differential maternal and paternal genome effects on fetal bone phenotype at mid-gestation.

PubMed

Xiang, Ruidong; Lee, Alice M C; Eindorf, Tanja; Javadmanesh, Ali; Ghanipoor-Samami, Mani; Gugger, Madeleine; Fitzsimmons, Carolyn J; Kruk, Zbigniew A; Pitchford, Wayne S; Leviton, Alison J; Thomsen, Dana A; Beckman, Ian; Anderson, Gail I; Burns, Brian M; Rutley, David L; Xian, Cory J; Hiendleder, Stefan

2014-11-01

Parent-of-origin-dependent (epi)genetic factors are important determinants of prenatal development that program adult phenotype. However, data on magnitude and specificity of maternal and paternal genome effects on fetal bone are lacking. We used an outbred bovine model to dissect and quantify effects of parental genomes, fetal sex, and nongenetic maternal effects on the fetal skeleton and analyzed phenotypic and molecular relationships between fetal muscle and bone. Analysis of 51 bone morphometric and weight parameters from 72 fetuses recovered at day 153 gestation (54% term) identified six principal components (PC1-6) that explained 80% of the variation in skeletal parameters. Parental genomes accounted for most of the variation in bone wet weight (PC1, 72.1%), limb ossification (PC2, 99.8%), flat bone size (PC4, 99.7%), and axial skeletal growth (PC5, 96.9%). Limb length showed lesser effects of parental genomes (PC3, 40.8%) and a significant nongenetic maternal effect (gestational weight gain, 29%). Fetal sex affected bone wet weight (PC1, p < 0.0001) and limb length (PC3, p < 0.05). Partitioning of variation explained by parental genomes revealed strong maternal genome effects on bone wet weight (74.1%, p < 0.0001) and axial skeletal growth (93.5%, p < 0.001), whereas paternal genome controlled limb ossification (95.1%, p < 0.0001). Histomorphometric data revealed strong maternal genome effects on growth plate height (98.6%, p < 0.0001) and trabecular thickness (85.5%, p < 0.0001) in distal femur. Parental genome effects on fetal bone were mirrored by maternal genome effects on fetal serum 25-hydroxyvitamin D (96.9%, p < 0.001) and paternal genome effects on alkaline phosphatase (90.0%, p < 0.001) and their correlations with maternally controlled bone wet weight and paternally controlled limb ossification, respectively. Bone wet weight and flat bone size correlated positively with muscle weight (r = 0.84 and 0.77, p < 0.0001) and negatively with muscle H19 expression (r = -0.34 and -0.31, p < 0.01). Because imprinted maternally expressed H19 regulates growth factors by miRNA interference, this suggests muscle-bone interaction via epigenetic factors. © 2014 American Society for Bone and Mineral Research.

The World Health Organization fetal growth charts: concept, findings, interpretation, and application.

PubMed

Kiserud, Torvid; Benachi, Alexandra; Hecher, Kurt; Perez, Rogelio González; Carvalho, José; Piaggio, Gilda; Platt, Lawrence D

2018-02-01

Ultrasound biometry is an important clinical tool for the identification, monitoring, and management of fetal growth restriction and development of macrosomia. This is even truer in populations in which perinatal morbidity and mortality rates are high, which is a reason that much effort is put onto making the technique available everywhere, including low-income societies. Until recently, however, commonly used reference ranges were based on single populations largely from industrialized countries. Thus, the World Health Organization prioritized the establishment of fetal growth charts for international use. New fetal growth charts for common fetal measurements and estimated fetal weight were based on a longitudinal study of 1387 low-risk pregnant women from 10 countries (Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) that provided 8203 sets of ultrasound measurements. The participants were characterized by median age 28 years, 58% nulliparous, normal body mass index, with no socioeconomic or nutritional constraints (median caloric intake, 1840 calories/day), and had the ability to attend the ultrasound sessions, thus essentially representing urban populations. Median gestational age at birth was 39 weeks, and birthweight was 3300 g, both with significant differences among countries. Quantile regression was used to establish the fetal growth charts, which also made it possible to demonstrate a number of features of fetal growth that previously were not well appreciated or unknown: (1) There was an asymmetric distribution of estimated fetal weight in the population. During early second trimester, the distribution was wider among fetuses <50th percentile compared with those above. The pattern was reversed in the third trimester, with a notably wider variation >50th percentile. (2) Although fetal sex, maternal factors (height, weight, age, and parity), and country had significant influence on fetal weight (1-4.5% each), their effect was graded across the percentiles. For example, the positive effect of maternal height on fetal weight was strongest on the lowest percentiles and smallest on the highest percentiles for estimated fetal weight. (3) When adjustment was made for maternal covariates, there was still a significant effect of country as covariate that indicated that ethnic, cultural, and geographic variation play a role. (4) Variation between populations was not restricted to fetal size because there were also differences in growth trajectories. (5) The wide physiologic ranges, as illustrated by the 5th-95th percentile for estimated fetal weight being 2205-3538 g at 37 weeks gestation, signify that human fetal growth under optimized maternal conditions is not uniform. Rather, it has a remarkable variation that largely is unexplained by commonly known factors. We suggest this variation could be part of our common biologic strategy that makes human evolution extremely successful. The World Health Organization fetal growth charts are intended to be used internationally based on low-risk pregnancies from populations in Africa, Asia, Europe, and South America. We consider it prudent to test and monitor whether the growth charts' performance meets the local needs, because refinements are possible by a change in cut-offs or customization for fetal sex, maternal factors, and populations. In the same line, the study finding of variations emphasizes the need for carefully adjusted growth charts that reflect optimal local growth when public health issues are addressed. Copyright © 2017 Elsevier Inc. All rights reserved.

Placental Inflammation and Fetal Injury in a Rare Zika Case Associated With Guillain-Barré Syndrome and Abortion.

PubMed

Rabelo, Kíssila; Souza, Luiz J; Salomão, Natália G; Oliveira, Edson R A; Sentinelli, Lynna de Paula; Lacerda, Marcelle S; Saraquino, Pedro B; Rosman, Fernando C; Basílio-de-Oliveira, Rodrigo; Carvalho, Jorge J; Paes, Marciano V

2018-01-01

Zika virus (ZIKV) is an emerging virus involved in recent outbreaks in Brazil. The association between the virus and Guillain-Barré syndrome (GBS) or congenital disorders has raised a worldwide concern. In this work, we investigated a rare Zika case, which was associated with GBS and spontaneous retained abortion. Using specific anti-ZIKV staining, the virus was identified in placenta (mainly in Hofbauer cells) and in several fetal tissues, such as brain, lungs, kidneys, skin and liver. Histological analyses of the placenta and fetal organs revealed different types of tissue abnormalities, which included inflammation, hemorrhage, edema and necrosis in placenta, as well as tissue disorganization in the fetus. Increased cellularity (Hofbauer cells and TCD8 + lymphocytes), expression of local pro-inflammatory cytokines such as IFN-γ and TNF-α, and other markers, such as RANTES/CCL5 and VEGFR2, supported placental inflammation and dysfunction. The commitment of the maternal-fetal link in association with fetal damage gave rise to a discussion regarding the influence of the maternal immunity toward the fetal development. Findings presented in this work may help understanding the ZIKV immunopathogenesis under the rare contexts of spontaneous abortions in association with GBS.

The Elsevier Trophoblast Research Award Lecture: Importance of metzincin proteases in trophoblast biology and placental development: a focus on ADAM12.

PubMed

Aghababaei, Mahroo; Beristain, Alexander G

2015-04-01

Placental development is a highly regulated process requiring signals from both fetal and maternal uterine compartments. Within this complex system, trophoblasts, placental cells of epithelial lineage, form the maternal-fetal interface controlling nutrient, gas and waste exchange. The commitment of progenitor villous cytotrophoblasts to differentiate into diverse trophoblast subsets is a fundamental process in placental development. Differentiation of trophoblasts into invasive stromal- and vascular-remodeling subtypes is essential for uterine arterial remodeling and placental function. Inadequate placentation, characterized by defects in trophoblast differentiation, may underlie the earliest cellular events driving pregnancy disorders such as preeclampsia and fetal growth restriction. Molecularly, invasive trophoblasts acquire characteristics defined by profound alterations in cell-cell and cell-matrix adhesion, cytoskeletal reorganization and production of proteolytic factors. To date, most studies have investigated the importance of the matrix metalloproteinases (MMPs) and their ability to efficiently remodel components of the extracellular matrix (ECM). However, it is now becoming clear that besides MMPs, other related proteases regulate trophoblast invasion via mechanisms other than ECM turnover. In this review, we will summarize the current knowledge on the regulation of trophoblast invasion by members of the metzincin family of metalloproteinases. Specifically, we will discuss the emerging roles that A Disintegrin and Metalloproteinases (ADAMs) play in placental development, with a particular focus on the ADAM subtype, ADAM12. Copyright © 2015 Elsevier Ltd. All rights reserved.

Associations of maternal weight status prior and during pregnancy with neonatal cardio-metabolic markers at birth: The Healthy Start Study

PubMed Central

Lemas, Dominick J.; Brinton, John T.; Shapiro, Allison L. B.; Glueck, Deborah H.; Friedman, Jacob E.; Dabelea, Dana

2015-01-01

Background Maternal obesity increases adult offspring risk for cardiovascular disease; however the role of offspring adiposity in mediating this association remains poorly characterized. Objective To investigate the associations of maternal pre-pregnant body mass index (maternal BMI) and gestational weight gain (GWG) with neonatal cardio-metabolic markers independent of fetal growth and neonatal adiposity. Methods A total of 753 maternal-infant pairs from the Healthy Start study, a large multi-ethnic pre-birth observational cohort were used. Neonatal cardio-metabolic markers included cord blood glucose, insulin, glucose-to-insulin ratio (Glu/Ins), total and high-density lipoprotein cholesterol (HDL-c), triglycerides, free fatty acids and leptin. Maternal BMI was abstracted from medical records or self-reported. GWG was calculated as the difference between the first pre-pregnant weight and the last weight measurement before delivery. Neonatal adiposity (percent fat mass) was measured within 72 hours of delivery using whole body air displacement plethysmography. Results In covariate adjusted models, maternal BMI was positively associated with cord blood insulin (p=0.01) and leptin (p<0.001) levels and inversely associated with cord blood HDL-c (p=0.05) and Glu/Ins (p=0.003). Adjustment for fetal growth or neonatal adiposity attenuated the effect of maternal BMI on neonatal insulin, rendering the association non-significant. However, maternal BMI remained associated with higher leptin (p<0.0011), lower HDL-c (p=0.02) and Glu/Ins (p=0.05), independent of neonatal adiposity. GWG was positively associated with neonatal insulin (p=0.02), glucose (p=0.03) and leptin levels (p<0.001) and negatively associated with Glu/Ins (p=0.006). After adjusting for neonatal adiposity, GWG remained associated with higher neonatal glucose (p=0.02) and leptin levels (p=0.02) and lower Glu/Ins (p=0.048). Conclusions Maternal weight prior and/or during pregnancy is associated with neonatal cardio-metabolic makers including leptin, glucose, and HDL-c at delivery, independent of neonatal adiposity. Our results suggest that intrauterine exposure to maternal obesity influences metabolic processes beyond fetal growth and fat accretion. PMID:26055075

The placenta. Not just a conduit for maternal fuels.

PubMed

Hay, W W

1991-12-01

The placenta is a specialized organ of exchange that provides nutrients to and excretes waste products from the fetus. The exchange of nutrients between placenta and fetus involves three major mechanisms: 1) direct transfer of nutrients from the maternal to the fetal plasma, 2) placental consumption of nutrients, and 3) placental conversion of nutrients to alternate substrate forms. Although direct transfer has been considered the primary means by which placental-fetal exchange controls the supply of nutrients to the fetus and thereby fetal metabolism and growth, the considerable metabolic activity of the placenta provides a large and fundamentally important contribution to both the quality and quantity of nutrient substrates supplied to the fetus; e.g., placental O2 and glucose consumption rates approach or even exceed those of brain and tumor tissue. Other placental metabolic activities include glycolysis, gluconeogenesis, glycogenesis, oxidation, protein synthesis, amino acid interconversion, triglyceride synthesis, and chain lengthening or shortening of individual fatty acids. Thus, consideration of the metabolism of the placenta is essential for a more complete understanding of how the placenta regulates nutrient transfer to the fetus, fetal energy balance, and fetal growth.

Increasing Maternal Body Mass Index Is Associated with Systemic Inflammation in the Mother and the Activation of Distinct Placental Inflammatory Pathways1

PubMed Central

Aye, Irving L.M.H.; Lager, Susanne; Ramirez, Vanessa I.; Gaccioli, Francesca; Dudley, Donald J.; Jansson, Thomas; Powell, Theresa L.

2014-01-01

ABSTRACT Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated maternal cytokines and activation of placental p38-MAPK and STAT3 inflammatory pathways, without changes in fetal systemic inflammatory profile. Activation of p38-MAPK by MCP-1 and TNFalpha, and STAT3 by TNFalpha, suggests a link between elevated proinflammatory cytokines in maternal plasma and activation of placental inflammatory pathways. We suggest that inflammatory processes associated with elevated maternal BMI may influence fetal growth by altering placental function. PMID:24759787

Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways.

PubMed

Aye, Irving L M H; Lager, Susanne; Ramirez, Vanessa I; Gaccioli, Francesca; Dudley, Donald J; Jansson, Thomas; Powell, Theresa L

2014-06-01

Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated maternal cytokines and activation of placental p38-MAPK and STAT3 inflammatory pathways, without changes in fetal systemic inflammatory profile. Activation of p38-MAPK by MCP-1 and TNFalpha, and STAT3 by TNFalpha, suggests a link between elevated proinflammatory cytokines in maternal plasma and activation of placental inflammatory pathways. We suggest that inflammatory processes associated with elevated maternal BMI may influence fetal growth by altering placental function. © 2014 by the Society for the Study of Reproduction, Inc.

Influence of maternal hyperthyroidism in the rat on the expression of neuronal and astrocytic cytoskeletal proteins in fetal brain.

PubMed

Evans, I M; Pickard, M R; Sinha, A K; Leonard, A J; Sampson, D C; Ekins, R P

2002-12-01

Maternal hypothyroidism during pregnancy impairs brain function in human and rat offspring, but little is known regarding the influence of maternal hyperthyroidism on neurodevelopment. We have previously shown that the expression of neuronal and glial differentiation markers in fetal brain is compromised in hypothyroid rat dam pregnancies and have now therefore extended this investigation to hyperthyroid rat dams. Study groups comprised partially thyroidectomised dams, implanted with osmotic pumps infusing either vehicle (TX dams) or a supraphysiological dose of thyroxine (T4) (HYPER dams), and euthyroid dams infused with vehicle (N dams). Cytoskeletal protein abundance was determined in fetal brain at 21 days of gestation by immunoblot analysis. Relative to N dams, circulating total T4 levels were reduced to around one-third in TX dams but were doubled in HYPER dams. Fetal brain weight was increased in HYPER dams, whereas litter size and fetal body weight were reduced in TX dams. Glial fibrillary acidic protein expression was similar in HYPER and TX dams, being reduced in both cases relative to N dams. alpha-Internexin (INX) abundance was reduced in HYPER dams and increased in TX dams, whereas neurofilament 68 (NF68) exhibited increased abundance in HYPER dams. Furthermore, INX was inversely related to - and NF68 directly related to - maternal serum total T4 levels, independently of fetal brain weight. In conclusion, maternal hyperthyroidism compromises the expression of neuronal cytoskeletal proteins in late fetal brain, suggestive of a pattern of accelerated neuronal differentiation.

Low-level maternal exposure to nicotine associates with significant metabolic perturbations in second-trimester amniotic fluid.

PubMed

Fischer, S Taylor; Lili, Loukia N; Li, Shuzhao; Tran, ViLinh T; Stewart, Kim B; Schwartz, Charles E; Jones, Dean P; Sherman, Stephanie L; Fridovich-Keil, Judith L

2017-10-01

Decades of public health research have documented that smoking in pregnancy poses significant health risks to both mother and child. More recent studies have shown that even passive maternal exposure to secondhand smoke associates with negative birth outcomes. However, the mechanisms linking exposure to outcomes have remained obscure. As a first step toward defining the metabolic consequence of low-level nicotine exposure on fetal development, we conducted an untargeted metabolomic analysis of 81 paired samples of maternal serum and amniotic fluid collected from karyotypically normal pregnancies in the second trimester. By comparing the m/z and retention times of our mass spectral features with confirmed standards, we identified cotinine, a nicotine derivative, and used the calculated cotinine concentrations to classify our maternal serum samples into exposure groups using previously defined cut-offs. We found that cotinine levels consistent with low-level maternal exposure to nicotine associated with distinct metabolic perturbations, particularly in amniotic fluid. In fact, the metabolic effects in amniotic fluid of ostensibly low-level exposed mothers showed greater overlap with perturbations previously observed in the sera of adult smokers than did the perturbations observed in the corresponding maternal sera. Dysregulated fetal pathways included aspartate and asparagine metabolism, pyrimidine metabolism, and metabolism of other amino acids. We also observed a strong negative association between level of maternal serum cotinine and acetylated polyamines in the amniotic fluid. Combined, these results confirm that low-level maternal nicotine exposure, indicated by a maternal serum cotinine level of 2-10ng/mL, is associated with striking metabolic consequences in the fetal compartment, and that the affected pathways overlap those perturbed in the sera of adult smokers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of maternal exercises on biophysical fetal and maternal parameters: a transversal study

PubMed Central

dos Santos, Caroline Mombaque; dos Santos, Wendel Mombaque; Gallarreta, Francisco Maximiliano Pancich; Pigatto, Camila; Portela, Luiz Osório Cruz; de Morais, Edson Nunes

2016-01-01

ABSTRACT Objective To evaluate the acute effects of maternal and fetal hemodynamic responses in pregnant women submitted to fetal Doppler and an aerobic physical exercise test according to the degree of effort during the activity and the impact on the well-being. Methods Transversal study with low risk pregnant women, obtained by convenience sample with gestational age between 26 to 34 weeks. The participants carry out a progressive exercise test. Results After the exercise session, reduced resistance (p=0.02) and pulsatility indices (p=0.01) were identified in the umbilical artery; however, other Doppler parameters analyzed, in addition to cardiotocography and fetal biophysical profile did not achieve significant change. Maternal parameters obtained linear growth with activity, but it was not possible to establish a standard with the Borg scale, and oxygen saturation remained stable. Conclusion A short submaximal exercise had little effect on placental blood flow after exercise in pregnancies without complications, corroborating that healthy fetus maintains homeostasis even in situations that alter maternal hemodynamics. PMID:28076590

Endogenous lysophosphatidic acid participates in vascularisation and decidualisation at the maternal-fetal interface in the rat.

PubMed

Sordelli, Micaela S; Beltrame, Jimena S; Zotta, Elsa; Gomez, Natalia; Dmytrenko, Ganna; Sales, María Elena; Blois, Sandra M; Davio, Carlos; Martinez, Silvina Perez; Franchi, Ana M; Ribeiro, María L

2017-10-01

Lysophosphatidic acid (LPA) affects several female reproductive functions through G-protein-coupled receptors. LPA contributes to embryo implantation via the lysophospholipid LPA 3 receptor. In the present study we investigated the participation of endogenous LPA signalling through the LPA 3 receptor in vascularisation and decidualisation, two crucial events at the maternal-fetal interface. Pregnant rats were treated with diacylglycerol pyrophosphate (DGPP), a highly selective antagonist of LPA 3 receptors, on Day 5 of gestation. Pregnant rats received intrauterine (i.u.) injections of single doses of DGPP (0.1mgkg -1 ) in a total volume of 2μL in the left horn (treated horn) in the morning of GD5. DGPP treatment produced aberrant embryo spacing and increased embryo resorption. The LPA 3 receptor antagonist decreased the cross-sectional length of the uterine and arcuate arteries and induced histological anomalies in the decidua and placentas. Marked haemorrhagic processes, infiltration of immune cells and tissue disorganisation were observed in decidual and placental tissues from sites of resorption. The mRNA expression of three vascularisation markers, namely interleukin 10 (Il10), vascular endothelial growth factor (Vegfa) and vascular endothelial growth factor receptor 1 (Vegfr1), was reduced at sites of resorption from Day 8. The results show that the disruption of endogenous LPA signalling by blocking the LPA 3 receptor modified the development of uterine vessels with consequences in the formation of the decidua and placenta and in the growth of embryos.

Maternal and fetal outcome of pregnancy complicated by HELLP syndrome.

PubMed

Gasem, Turki; Al Jama, Fathia E; Burshaid, Sameera; Rahman, Jessica; Al Suleiman, Suleiman A; Rahman, Mohammad S

2009-12-01

The study evaluated the maternal and fetal outcome in 64 pregnancies complicated by HELLP syndrome. A retrospective analysis of the medical records was performed of patients with HELLP syndrome managed at this tertiary Obstetric unit between January 1996 and December 2005, who were admitted for preeclamsia/eclampsia and had documented evidence of hemolysis, elevated liver enzymes and low platelet count. Maternal and neonatal complications were recorded and analyzed. The incidence of HELLP syndrome in the study was 8.3%. Mean gestational age at delivery was 32.4 +/- 4.2 weeks and mean birth weight was 1851 +/- 810 g. Forty-two percent of the patients had deliveries <32 weeks and 28% IUGR. Respiratory distress syndrome was the main indication for NICU admissions (33.9%). The PNM rate was 20%. Maternal morbidity rate was 34%. The most common maternal complications were abruptio placentae (36.4%) and DIC (31.8%). There was no maternal death. Once the diagnosis of HELLP syndrome is confirmed, the management depends on several obstetric and maternal variables like gestational age, severity of laboratory abnormalities and fetal status. As soon as the maternal condition is stabilized and fetal assessment is obtained, prompt delivery of the fetus is indicated. It is not yet established whether expectant management in preterm pregnancies with HELLP syndrome would improve perinatal outcome.

Photon migration through fetal head in utero using continuous wave, near infrared spectroscopy: clinical and experimental model studies

NASA Astrophysics Data System (ADS)

Ramanujam, Nirmala; Vishnoi, Gargi; Hielscher, Andreas H.; Rode, Martha; Forouzan, Iraj; Chance, Britton

2000-04-01

Near infrared (NIR) measurements were made from the maternal abdomen (clinical studies) and laboratory tissue phantoms (experimental studies) to gain insight into photon migration through the fetal head in utero. Specifically, a continuous wave spectrometer was modified and employed to make NIR measurements at 760 and 850 nm, at a large (10 cm) and small (2.5/4 cm) source-detector separation, simultaneously, on the maternal abdomen, directly above the fetal head. A total of 19 patients were evaluated, whose average gestational age and fetal head depth, were 37 weeks +/- 3 and 2.25 cm +/- 0.7, respectively. At the large source-detector separation, the photons are expected to migrate through both the underlying maternal and fetal tissues before being detected at the surface, while at the short source-detector separation, the photons are expected to migrate primarily through the superficial maternal tissues before being detected. Second, similar NIR measurements were made on laboratory tissue phantoms, with variable optical properties and physical geometries. The variable optical properties were obtained using different concentrations of India ink and Intralipid in water, while the variable physical geometries were realized by employing glass containers of different shapes and sizes. Third, the NIR measurements, which were made on the laboratory tissue phantoms, were compared to the NIR measurements made on the maternal abdomen to determine which tissue phantom best simulates the photon migration path through the fetal head in utero. The results of the comparison were used to provide insight into the optical properties and physical geometry of the maternal and fetal tissues in the photon migration path.

Maternal nutrient deprivation induces sex-specific changes in thyroid hormone receptor and deiodinase expression in the fetal guinea pig brain

PubMed Central

Chan, Shiao Y; Andrews, Marcus H; Lingas, Rania; McCabe, Chris J; Franklyn, Jayne A; Kilby, Mark D; Matthews, Stephen G

2005-01-01

Thyroid hormone deprivation during fetal life has been implicated in neurodevelopmental morbidity. In humans, poor growth in utero is also associated with fetal hypothyroxinaemia. In guinea pigs, a short period (48 h) of maternal nutrient deprivation at gestational day (gd) 50 results in fetuses with hypothyroxinaemia and increased brain/body weight ratios. Thyroid hormone action is mediated by nuclear thyroid hormone receptors (TRs) and is dependent upon the prereceptor regulation of supply of triiodothyronine (T3) by deiodinase enzymes. Examination of fetal guinea pig brains using in situ hybridization demonstrated widespread expression of mRNAs encoding TRα1, α2 and β1, with regional colocalization of deiodinase type 2 (D2) mRNA in the developing forebrain, limbic structures, brainstem and cerebellum at gd52. With maternal nutrient deprivation, TRα1 and β1 mRNA expression was significantly increased in the male, but decreased in the female fetal hippocampus and cerebellum and other areas showing high TR expression under euthyroid conditions. Maternal nutrient deprivation resulted in elevated D2 mRNA expression in males and females. Deiodinase type 3 (D3) mRNA expression was confined to the shell of the nucleus accumbens, the posterior amygdalohippocampal area, brainstem and cerebellum, and did not change with maternal nutrient deprivation. In conclusion, maternal nutrient deprivation resulted in sex-specific changes in TR mRNA expression and a generalized increase in D2 mRNAs within the fetal brain. These changes may represent a protective mechanism to maintain appropriate thyroid hormone action in the face of fetal hypothyroxinaemia in order to optimize brain development. PMID:15878952

Maternal hypervitaminosis D reduces fetal bone mass and mineral acquisition and leads to neonatal lethality.

PubMed

Lieben, L; Stockmans, I; Moermans, K; Carmeliet, G

2013-11-01

Pregnancy challenges maternal calcium handling because sufficient calcium has to be transferred to the fetus to ensure fetal bone mass acquisition. 1,25(OH)2 vitamin D [1,25(OH)2D] is an important regulator of calcium homeostasis during adulthood, yet its role seems redundant for the maternal adaptations to pregnancy as well as during fetal development. However, not only deficiency but also excess of 1,25(OH)2D can be harmful and we therefore questioned whether high maternal 1,25(OH)2D levels may injure fetal development or neonatal outcome, as maternal-fetal transport of 1,25(OH)2D has been largely disputed. To this end, vitamin D receptor (VDR) null (Vdr(-/-)) females, displaying high 1,25(OH)2D levels, were mated with Vdr(+/-) males to obtain pregnancies with fetuses that are responsive (Vdr(+/-)) or resistant (Vdr(-/-)) to 1,25(OH)2D. Surprisingly, most of the Vdr(+/-) neonates died shortly after birth, whereas none of the Vdr(-/-). Mechanistically, we noticed that in Vdr(+/-) embryos, serum calcium levels were normal, but that skeletal calcium storage was reduced as evidenced by decreased mineralized bone mass as well as bone mineral content. More precisely, bone formation was decreased and the level of bone mineralization inhibitors was increased. This decreased fetal skeletal calcium storage may severely compromise calcium balance and survival at birth. In conclusion, these data indicate that high maternal 1,25(OH)2D levels are transferred across the placental barrier and adversely affect the total amount of calcium stored in fetal bones which is accompanied by neonatal death. © 2013 Elsevier Inc. All rights reserved.

MATERNAL HEIGHT AND PRE-PREGNANCY WEIGHT STATUS ARE ASSOCIATED WITH FETAL GROWTH PATTERNS AND NEWBORN SIZE.

PubMed

Pölzlberger, Eva; Hartmann, Beda; Hafner, Erich; Stümpflein, Ingrid; Kirchengast, Sylvia

2017-05-01

The impact of maternal height, pre-pregnancy weight status and gestational weight gain on fetal growth patterns and newborn size was analysed using a dataset of 4261 singleton term births taking place at the Viennese Danube Hospital between 2005 and 2013. Fetal growth patterns were reconstructed from three ultrasound examinations carried out at the 11th/12th, 20th/21th and 32th/33th weeks of gestation. Crown-rump length, biparietal diameter, fronto-occipital diameter, head circumference, abdominal transverse diameter, abdominal anterior-posterior diameter, abdominal circumference and femur length were determined. Birth weight, birth length and head circumference were measured immediately after birth. The vast majority of newborns were of normal weight, i.e. between 2500 and 4000 g. Maternal height showed a just-significant but weak positive association (r=0.03: p=0.039) with crown-rump length at the first trimester and with the majority of fetal parameters at the second trimester (r>0.06; p0.09; p0.08; p0.17; p0.13; p0.13; p<0.001), were significantly positively associated with newborn size. Some of these associations were quite weak and the statistical significance was mainly due to the large sample size. The association patterns between maternal height and pre-pregnancy weight status with fetal growth patterns (p<0.001), as well as newborn size (p<0.001), were independent of maternal age, nicotine consumption and fetal sex. In general, taller and heavier women gave birth to larger infants. This association between maternal size and fetal growth patterns was detectable from the first trimester onwards.

Maternal L-glutamine supplementation prevents prenatal alcohol exposure-induced fetal growth restriction in an ovine model.

PubMed

Sawant, Onkar B; Wu, Guoyao; Washburn, Shannon E

2015-06-01

Prenatal alcohol exposure is known to cause fetal growth restriction and disturbances in amino acid bioavailability. Alterations in these parameters can persist into adulthood and low birth weight can lead to altered fetal programming. Glutamine has been associated with the synthesis of other amino acids, an increase in protein synthesis and it is used clinically as a nutrient supplement for low birth weight infants. The aim of this study was to explore the effect of repeated maternal alcohol exposure and L-glutamine supplementation on fetal growth and amino acid bioavailability during the third trimester-equivalent period in an ovine model. Pregnant sheep were randomly assigned to four groups, saline control, alcohol (1.75-2.5 g/kg), glutamine (100 mg/kg, three times daily) or alcohol + glutamine. In this study, a weekend binge drinking model was followed where treatment was done 3 days per week in succession from gestational day (GD) 109-132 (normal term ~147). Maternal alcohol exposure significantly reduced fetal body weight, height, length, thoracic girth and brain weight, and resulted in decreased amino acid bioavailability in fetal plasma and placental fluids. Maternal glutamine supplementation successfully mitigated alcohol-induced fetal growth restriction and improved the bioavailability of glutamine and glutamine-related amino acids such as glycine, arginine, and asparagine in the fetal compartment. All together, these findings show that L-glutamine supplementation enhances amino acid availability in the fetus and prevents alcohol-induced fetal growth restriction.

Antenatal Testing – A Reevaluation

PubMed Central

Signore, Caroline; Freeman, Roger K.; Spong, Catherine Y.

2009-01-01

In August 2007, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health Office of Rare Diseases, the American College of Obstetricians and Gynecologists, and the American Academy of Pediatrics cosponsored a 2-day workshop to reassess the body of evidence supporting antepartum assessment of fetal well-being, identify key gaps in the evidence, and formulate recommendations for further research. Participants included experts in obstetrics and fetal physiology, and representatives from relevant stakeholder groups and organizations. This article is a summary of the discussions at the workshop, including synopses of oral presentations on the epidemiology of stillbirth and fetal neurological injury, fetal physiology, techniques for antenatal monitoring, and maternal and fetal indications for monitoring. Finally, a synthesis of recommendations for further research compiled from three breakout workgroups is presented. PMID:19300336

Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women.

PubMed

Lean, Samantha C; Heazell, Alexander E P; Dilworth, Mark R; Mills, Tracey A; Jones, Rebecca L

2017-08-29

Pregnancies in women of advanced maternal age (AMA) are susceptible to fetal growth restriction (FGR) and stillbirth. We hypothesised that maternal ageing is associated with utero-placental dysfunction, predisposing to adverse fetal outcomes. Women of AMA (≥35 years) and young controls (20-30 years) with uncomplicated pregnancies were studied. Placentas from AMA women exhibited increased syncytial nuclear aggregates and decreased proliferation, and had increased amino acid transporter activity. Chorionic plate and myometrial artery relaxation was increased compared to controls. AMA was associated with lower maternal serum PAPP-A and sFlt and a higher PlGF:sFlt ratio. AMA mice (38-41 weeks) at E17.5 had fewer pups, more late fetal deaths, reduced fetal weight, increased placental weight and reduced fetal:placental weight ratio compared to 8-12 week controls. Maternofetal clearance of 14 C-MeAIB and 3 H-taurine was reduced and uterine arteries showed increased relaxation. These studies identify reduced placental efficiency and altered placental function with AMA in women, with evidence of placental adaptations in normal pregnancies. The AMA mouse model complements the human studies, demonstrating high rates of adverse fetal outcomes and commonalities in placental phenotype. These findings highlight placental dysfunction as a potential mechanism for susceptibility to FGR and stillbirth with AMA.

Fetal vascular adaptation before and after treatment of severe maternal anemia in pregnancy.

PubMed

Ali, Eram; Kumar, Manisha; Naqvi, Sayyed E H; Trivedi, Shubha S; Singh, Anuradha

2016-06-01

To use color Doppler ultrasonography indices to study the effects on fetal circulation of treating severe maternal anemia. A prospective cohort study enrolled patients who were at 30-34weeks of pregnancy and had hemoglobin levels below 70g/L between November 1, 2011 and March 31, 2013 at a hospital in New Delhi, India. A control group consisting of patients with the same duration of pregnancy and with hemoglobin levels above 110g/L was included. Umbilical artery and middle cerebral artery velocimetry were performed using color Doppler ultrasonography at admission and after 4weeks and 6weeks of treatment. The maternal anemia cohort demonstrated a significantly lower middle cerebral artery resistance index and middle cerebral/umbilical artery resistance ratio (P<0.001) at admission. Following 4weeks of treatment for maternal anemia, significant increases in these parameters were observed (P<0.001). Fetuses of individuals with severe maternal anemia demonstrated altered cerebral and umbilical artery flows. Normal flows were restored following treatment of maternal anemia. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Predictive value of vaginal IL-6 and TNFα bedside tests repeated until delivery for the prediction of maternal-fetal infection in cases of premature rupture of membranes.

PubMed

Kayem, Gilles; Batteux, Frederic; Girard, Noémie; Schmitz, Thomas; Willaime, Marion; Maillard, Francoise; Jarreau, Pierre Henri; Goffinet, Francois

2017-04-01

Examine the predictive value for maternal-fetal infection of routine bedside tests detecting the proinflammatory cytokines, TNFα and IL-6, in the vaginal secretions of women with premature rupture of the membranes (PROM). This prospective two-center cohort study included all women hospitalized for PROM over a 2-year period. A bedside test assessed IL-6 and TNFα in vaginal secretions. Both centers routinely tested CRP and leukocytes, assaying both in maternal serum, and analyzed vaginal bacterial flora; all samples were repeated twice weekly until delivery. The study included 689 women. In cases of preterm PROM (PPROM) before 37 weeks (n=184), a vaginal sample positive for one or more bacteria was the only marker associated with early neonatal infection (OR 5.6, 95%CI; 2.0-15.7). Its sensitivity was 82% (95%CI; 62-94) and its specificity 56% (95%CI; 47-65). All positive markers of infection were associated with the occurrence of chorioamnionitis. In cases of PROM from 37 weeks onward (n=505), only CRP >5mg/dL was associated with early neonatal infection (OR=8.3, 95%CI; 1.1-65.4) or clinical chorioamnionitis (OR=6.8, 95%CI; 1.5-30.0). The sensitivity of CRP >5mg/dL was 91% (95%CI; 59-100) and its specificity 45% (95%CI; 40-51) for predicting early neonatal infection, and 89% (95%CI; 65-99) and 46% (95%CI; 41-51), respectively, for predicting clinical chorioamnionitis. The association of vaginal cytokines with maternal-fetal infection is weak and thus prevents their use as a good predictor of maternal-fetal infection. CRP and vaginal samples may be useful for identifying a group of women at low risk of infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Partitioning of glutamine synthesised by the isolated perfused human placenta between the maternal and fetal circulations☆

PubMed Central

Day, P.E.L.; Cleal, J.K.; Lofthouse, E.M.; Goss, V.; Koster, G.; Postle, A.; Jackson, J.M.; Hanson, M.A.; Jackson, A.A.; Lewis, R.M.

2013-01-01

Introduction Placental glutamine synthesis has been demonstrated in animals and is thought to increase the availability of this metabolically important amino acid to the fetus. Glutamine is of fundamental importance for cellular replication, cellular function and inter-organ nitrogen transfer. The objective of this study was to investigate the role of glutamate/glutamine metabolism by the isolated perfused human placenta in the provision of glutamine to the fetus. Methods Glutamate metabolism was investigated in the isolated dually perfused human placental cotyledon. U–13C-glutamate was used to investigate the movement of carbon and 15N-leucine to study movement of amino-nitrogen. Labelled amino acids were perfused via maternal or fetal arteries at defined flow rates. The enrichment and concentration of amino acids in the maternal and fetal veins were measured following 5 h of perfusion. Results Glutamate taken up from the maternal and fetal circulations was primarily converted into glutamine the majority of which was released into the maternal circulation. The glutamine transporter SNAT5 was localised to the maternal-facing membrane of the syncytiotrophoblast. Enrichment of 13C or 15N glutamine in placental tissue was lower than in either the maternal or fetal circulation, suggesting metabolic compartmentalisation within the syncytiotrophoblast. Discussion Placental glutamine synthesis may help ensure the placenta's ability to supply this amino acid to the fetus does not become limiting to fetal growth. Glutamine synthesis may also influence placental transport of other amino acids, metabolism, nitrogen flux and cellular regulation. Conclusions Placental glutamine synthesis may therefore be a central mechanism in ensuring that the human fetus receives adequate nutrition and is able to maintain growth. PMID:24183194

MATERNAL MIND-MINDEDNESS: RELATIONS WITH MATERNAL-FETAL ATTACHMENT AND STABILITY IN THE FIRST TWO YEARS OF LIFE: FINDINGS FROM AN AUSTRALIAN PROSPECTIVE STUDY.

PubMed

McMahon, Catherine; Camberis, Anna-Lisa; Berry, Sinead; Gibson, Frances

2016-01-01

Mind-mindedness captures a caregiver's attunement to his or her infant's mental states, and the tendency to interpret behavior as resulting from these mental states. The construct is assessed through analysis of maternal language during interaction or from mothers' use of mental state words when invited to describe their child. This study examined whether maternal-fetal attachment predicted maternal mind-mindedness, whether there was continuity in mind-mindedness over the first 2 postnatal years, and concordance for the two approaches to measurement. One hundred fifty women completed a questionnaire measure of maternal-fetal attachment in the third trimester of pregnancy and participated in home visits to assess maternal mind-mindedness when their infants were 7 months and 19 months of age. Path analysis showed that maternal-fetal attachment predicted indices of maternal mind-mindedness at 7 and 19 months; mothers who made more mind-related comments during play at 7 months also did so at 19 months, and mothers who made more mind-related comments during play at 19 months also used more mental state words when describing their child. Results suggest that a proclivity to mind-mindedness may be a caregiver characteristic that is present prior to birth and stable over time. © 2015 Michigan Association for Infant Mental Health.

Maternal KIR in combination with paternal HLA-C2 regulate human birth weight.

PubMed

Hiby, Susan E; Apps, Richard; Chazara, Olympe; Farrell, Lydia E; Magnus, Per; Trogstad, Lill; Gjessing, Håkon K; Carrington, Mary; Moffett, Ashley

2014-06-01

Human birth weight is subject to stabilizing selection; babies born too small or too large are less likely to survive. Particular combinations of maternal/fetal immune system genes are associated with pregnancies where the babies are ≤ 5th birth weight centile, specifically an inhibitory maternal KIR AA genotype with a paternally derived fetal HLA-C2 ligand. We have now analyzed maternal KIR and fetal HLA-C combinations at the opposite end of the birth weight spectrum. Mother/baby pairs (n = 1316) were genotyped for maternal KIR as well as fetal and maternal HLA-C. Presence of a maternal-activating KIR2DS1 gene was associated with increased birth weight in linear or logistic regression analyses of all pregnancies >5th centile (p = 0.005, n = 1316). Effect of KIR2DS1 was most significant in pregnancies where its ligand, HLA-C2, was paternally but not maternally inherited by a fetus (p = 0.005, odds ratio = 2.65). Thus, maternal KIR are more frequently inhibitory with small babies but activating with big babies. At both extremes of birth weight, the KIR associations occur when their HLA-C2 ligand is paternally inherited by a fetus. We conclude that the two polymorphic immune gene systems, KIR and HLA-C, contribute to successful reproduction by maintaining birth weight between two extremes with a clear role for paternal HLA.

Fetal response to maternal hunger and satiation - novel finding from a qualitative descriptive study of maternal perception of fetal movements.

PubMed

Bradford, Billie; Maude, Robyn

2014-08-26

Maternal perception of decreased fetal movements is a specific indicator of fetal compromise, notably in the context of poor fetal growth. There is currently no agreed numerical definition of decreased fetal movements, with the subjective perception of a decrease on the part of the mother being the most significant definition clinically. Both qualitative and quantitative aspects of fetal activity may be important in identifying the compromised fetus.Yet, how pregnant women perceive and describe fetal activity is under-investigated by qualitative means. The aim of this study was to explore normal fetal activity, through first-hand descriptive accounts by pregnant women. Using qualitative descriptive methodology, interviews were conducted with 19 low-risk women experiencing their first pregnancy, at two timepoints in their third trimester. Interview transcripts were later analysed using qualitative content analysis and patterns of fetal activity identified were then considered along-side the characteristics of the women and their birth outcomes. This paper focuses on a novel finding; the description by pregnant women of fetal behaviour indicative of hunger and satiation. Full findings will be presented in later papers. Most participants (74% 14 of 19) indicated mealtimes were a time of increased fetal activity. Eight participants provided detailed descriptions of increased activity around meals, with seven (37% 7 of 19) of these specifying increased fetal activity prior to meals or in the context of their own hunger. These movements were interpreted as a fetal demand for food often prompting the mother to eat. Interestingly, the women who described increased fetal activity in the context of hunger subsequently gave birth to smaller infants (mean difference 364 gm) than those who did not describe a fetal response to hunger. Food seeking behaviour may have a pre-birth origin. Maternal-fetal interaction around mealtimes could constitute an endocrine mediated communication, in the interests of maintaining optimal intrauterine conditions. Further research is warranted to explore this phenomenon and the potential influence of feeding on the temporal organisation of fetal activity in relation to growth.

Mother's educational level and fetal growth: the genesis of health inequalities.

PubMed

Silva, Lindsay M; Jansen, Pauline W; Steegers, Eric A P; Jaddoe, Vincent W V; Arends, Lidia R; Tiemeier, Henning; Verhulst, Frank C; Moll, Henriëtte A; Hofman, Albert; Mackenbach, Johan P; Raat, Hein

2010-10-01

Women of low socio-economic status (SES) give birth to lighter babies. It is unknown from which moment during pregnancy socio-economic differences in fetal weight can be observed, whether low SES equally affects different fetal-growth components, or what the effect of low SES is after taking into account mediating factors. In 3545 pregnant women participating in the Generation R Study, we studied the association of maternal educational level (high, mid-high, mid-low and low) as a measure of SES with fetal weight, head circumference, abdominal circumference and femur length. We did this before and after adjusting for potential mediators, including maternal height, pre-pregnancy body mass index and smoking. In fetuses of low-educated women relative to those of high-educated women, fetal growth was slower, leading to a lower fetal weight that was observable from late pregnancy onwards. In these fetuses, growth of the head [-0.16 mm/week; 95% confidence interval (CI): -0.25 to -0.07; P = 0.0004], abdomen (-0.10 mm/week; 95% CI: -0.21 to 0.01; P = 0.08) and femur (-0.03 mm/week; 95% CI: -0.05 to -0.006; P = 0.01) were all slower; from mid-pregnancy onwards, head circumference was smaller, and from late pregnancy onwards, femur length was also smaller. The negative effect of low education was greatest for head circumference (difference in standard deviation score in late pregnancy: -0.26; 95% CI: -0.36 to -0.15; P < 0.0001). This effect persevered even after adjustment for the potential mediators (adjusted difference: -0.14; 95% CI: -0.25 to -0.03; P = 0.01). Low maternal education is associated with a slower fetal growth and this effect appears stronger for growth of the head than for other body parts.

Use of cell-free DNA in the investigation of intrauterine fetal demise and miscarriage.

PubMed

Clark-Ganheart, Cecily A; Fries, Melissa H; Leifheit, Kathryn M; Jensen, Taylor J; Moreno-Ruiz, Nilda L; Ye, Peggy P; Jennings, Jacky M; Driggers, Rita W

2015-06-01

To estimate whether cell-free DNA is present in nonviable pregnancies and thus can be used in diagnostic evaluation in this setting. We conducted a prospective cohort study of 50 participants at MedStar Washington Hospital Center, Washington, DC, between June 2013 and January 2014. Included were women with pregnancies complicated by missed abortion or fetal demise. All gestational ages were considered for study participation. Participants with fetal demise were offered the standard workup for fetal death per the American College of Obstetricians and Gynecologists. Maternal blood samples were processed to determine the presence of cell-free DNA, the corresponding fetal fractions, and genetic abnormalities. Fifty samples from nonviable pregnancies were analyzed. The average clinical gestational age was 16.9 weeks (standard deviation 9.2). The mean maternal body mass index was 30.3 (standard deviation 9.1). Seventy-six percent (38/50) of samples yielded cell-free DNA results, that is, had fetal fractions within the detectable range of 3.7-65%. Among the 38, 76% (29) were classified as euploid, 21% (8) as trisomies, and 3% (1) as microdeletion. A cell-free DNA result was obtained more frequently at ultrasonographic gestational ages of 8 weeks or greater compared with less than 8 weeks (87.9% [n=29/33, 95% confidence interval (CI) 72.7-95.2; and 52.9%, n=9/17, 95% CI 31.0-73.8] of the time, respectively, P=.012). Time from demise was not associated with obtaining a result. Among nonviable pregnancies, cell-free DNA is present in the maternal plasma with fetal fractions greater than 3.7% in more than three fourths of cases after an ultrasonographic gestational age of 8 weeks. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01916928. III.

Maternal obesity upregulates fatty acid and glucose transporters and increases expression of enzymes mediating fatty acid biosynthesis in fetal adipose tissue depots.

PubMed

Long, N M; Rule, D C; Zhu, M J; Nathanielsz, P W; Ford, S P

2012-07-01

Maternal nutrient restriction leads to alteration in fetal adipose tissue, and offspring from obese mothers have an increased risk of developing obesity. We hypothesized that maternal obesity increases fetal adipogenesis. Multiparous ewes (Columbia/Rambouillet cross 3 to 5 yr of age) carrying twins were assigned to a diet of 100% (Control; CON; n = 4) or 150% (Obese; OB, n = 7) of NRC maintenance requirements from 60 d before conception until necropsy on d 135 of gestation. Maternal and fetal plasma were collected and stored at -80°C for glucose and hormone analyses. Fetal measurements were made at necropsy, and perirenal, pericardial, and subcutaneous adipose tissues were collected from 7 male twin fetuses per group and snap frozen at -80°C. Protein and mRNA expression of fatty acid translocase [cluster of differentiation (CD) 36], fatty acid transport proteins (FATP) 1 and 4, insulin-sensitive glucose transporter (GLUT-4), fatty acid synthase (FASN), and acetyl-coA carboxylase (ACC) was evaluated. Fetal weight was similar, but fetal carcass weight (FCW) was reduced (P < 0.05) in OB versus CON fetuses. Pericardial and perirenal adipose tissue weights were increased (P < 0.05) as a percentage of FCW in OB versus CON fetuses, as was subcutaneous fat thickness (P < 0.001). Average adipocyte diameter was greater (P < 0.01) in the perirenal fat and the pericardial fat (P = 0.06) in OB fetuses compared with CON fetuses. Maternal plasma showed no difference (P > 0.05) in glucose or other hormones, fetal plasma glucose was similar (P = 0.42), and cortisol, IGF-1, and thyroxine were reduced (P ≤ 0.05) in OB fetuses compared with CON fetuses. Protein and mRNA expression of CD 36, FATP 1 and 4, and GLUT-4 were increased (P ≤ 0.05) in all fetal adipose depots in OB versus CON fetuses. The mRNA expression of FASN and ACC was increased (P < 0.05) in OB vs. CON fetuses in all 3 fetal adipose tissue depots. Fatty acid concentrations were increased (P = 0.01) in the perirenal depot of OB versus CON fetuses, and specific fatty acid concentrations were altered (P < 0.05) in subcutaneous and pericardial adipose tissue because of maternal obesity. In conclusion, maternal obesity was associated with increased fetal adiposity, increased fatty acid and glucose transporters, and increased expression of enzymes mediating fatty acid biosynthesis in adipose depots. These alterations, if maintained into the postnatal period, could predispose the offspring to later obesity and metabolic disease.

The Influence of Maternal Early to Mid-Gestation Nutrient Restriction of Long Chain Polyunsaturated Fatty Acids in Fetal Sheep

USDA-ARS?s Scientific Manuscript database

The early to mid-gestational period (days 28-78) in sheep is the period of most rapid placental development. Maternal nutrient restriction (MNR) in this phase has negative consequences on fetal growth and development, predisposing the fetus to disease in adult life. The influence of MNR on fetal tis...

High-salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system.

PubMed

Mao, Caiping; Liu, Rong; Bo, Le; Chen, Ningjing; Li, Shigang; Xia, Shuixiu; Chen, Jie; Li, Dawei; Zhang, Lubo; Xu, Zhice

2013-07-01

Intrauterine environments are related to fetal renal development and postnatal health. Influence of salty diets during pregnancy on renal functions and renin-angiotensin system (RAS) was determined in the ovine fetuses and offspring. Pregnant ewes were fed high-salt diet (HSD) or normal-salt diet (NSD) for 2 months during middle-to-late gestation. Fetal renal functions, plasma hormones, and mRNA and protein expressions of the key elements of renal RAS were measured in the fetuses and offspring. Fetal renal excretion of sodium was increased while urine volume decreased in the HSD group. Fetal blood urea nitrogen was increased, while kidney weight:body weight ratio decreased in the HSD group. The altered ratio was also observed in the offspring aged 15 and 90 days. Maternal and fetal plasma antidiuretic hormone was elevated without changes in plasma renin activity and Ang I levels, while plasma Ang II was decreased. The key elements of local renal RAS, including angiotensinogen, angiotensin converting enzyme (ACE), ACE2, AT1, and AT2 receptor expression in both mRNA and protein, except renin, were altered following maternal high salt intake. The results suggest that high intake of salt during pregnancy affected fetal renal development associated with an altered expression of the renal key elements of RAS, some alterations of fetal origins remained after birth as possible risks in developing renal or cardiovascular diseases.

Multiplex fluorescent PCR for noninvasive prenatal detection of fetal-derived paternally inherited diseases using circulatory fetal DNA in maternal plasma.

PubMed

Tang, Dong-ling; Li, Yan; Zhou, Xin; Li, Xia; Zheng, Fang

2009-05-01

To develop a fluorescent polymerase chain reaction (PCR) assay for the detection of circulating fetal DNA in maternal plasma and use the established multiplex in noninvasive prenatal genetic diagnosis and its further applications in forensic casework. The DNA template was extracted from 47 pregnant women and the whole blood samples from the stated biological fathers were used to detect genotype. Using multiplex fluorescent PCR at 16 different polymorphic short tandem repeat (STR) loci, maternal DNA extracted from plasma samples at early pregnancy, medium pregnancy and late pregnancy were used to detect genotype. Their husbands' DNA was also used for fetal genotype ascertainment. Multiplex fluorescent PCR with 16 polymorphic short tandem repeats revealed the presence of fetal DNA in all cases. Every pregnant women/husband pair was informative in at least 3 of 16 loci. The chances of detecting paternally inherited fetal alleles ranged from 66.67 to 94.12%. They are 66.67% in early pregnancy, 85.71% in medium pregnancy and 94.12% in late pregnancy. The accuracy of Multiplex PCR assay to detect fetal DNA was 100%. Circulating fetal DNA analysis can be used as a possible alternative tool in routine laboratory prenatal diagnosis in the near future; this highly polymorphic STR multiplex has greatly improved the chances of detecting paternally inherited fetal alleles compared with other fetal DNA detection systems that use fetus-derived Y sequences to detect only male fetal DNA in maternal plasma. Our proposed technique can be applied to both female and male fetuses, which provides a sensitive, accurate and efficient method for noninvasive prenatal genetic diagnosis and forensic casework.

Maternal exposure to hurricane destruction and fetal mortality.

PubMed

Zahran, Sammy; Breunig, Ian M; Link, Bruce G; Snodgrass, Jeffrey G; Weiler, Stephan; Mielke, Howard W

2014-08-01

The majority of research documenting the public health impacts of natural disasters focuses on the well-being of adults and their living children. Negative effects may also occur in the unborn, exposed to disaster stressors when critical organ systems are developing and when the consequences of exposure are large. We exploit spatial and temporal variation in hurricane behaviour as a quasi-experimental design to assess whether fetal death is dose-responsive in the extent of hurricane damage. Data on births and fetal deaths are merged with Parish-level housing wreckage data. Fetal outcomes are regressed on housing wreckage adjusting for the maternal, fetal, placental and other risk factors. The average causal effect of maternal exposure to hurricane destruction is captured by difference-in-differences analyses. The adjusted odds of fetal death are 1.40 (1.07-1.83) and 2.37 (1.684-3.327) times higher in parishes suffering 10-50% and >50% wreckage to housing stock, respectively. For every 1% increase in the destruction of housing stock, we observe a 1.7% (1.1-2.4%) increase in fetal death. Of the 410 officially recorded fetal deaths in these parishes, between 117 and 205 may be attributable to hurricane destruction and postdisaster disorder. The estimated fetal death toll is 17.4-30.6% of the human death toll. The destruction caused by Hurricanes Katrina and Rita imposed significant measurable losses in terms of fetal death. Postdisaster migratory dynamics suggest that the reported effects of maternal exposure to hurricane destruction on fetal death may be conservative. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Fetal Risks and Maternal Renal Complications in Pregnancy with Preexisting Chronic Glomerulonephritis.

PubMed

Li, Yuehong; Wang, Wei; Wang, Yujuan; Chen, Qi

2018-02-18

BACKGROUND Analysis the maternal and fetal risk predictors in pregnancy in conjunction with chronic glomerulonephritis (CGN) patients are helpful to understand the influence of kidney diseases on pregnancy and the effects of pregnancy on kidney diseases. The aim of this study was to determine the predictors of adverse maternal and fetal outcomes in CGN patients. MATERIAL AND METHODS Maternal and fetal outcomes in 64 pregnancies of CGN patients were retrospectively analyzed. We randomly selected 100 low-risk-pregnancy women without chronic kidney disease (CKD) at the same time as the control group. Clinical manifestations, laboratory data, medication, and outcomes during pregnancies of these patients were analyzed by univariate and logistic regression. RESULTS CGN patients were associated with higher adverse pregnancy outcomes versus general pregnancies. The gestational ages are shorter, and the incidence of preeclampsia, gestational hypertension, and abortion were increased. The rates of premature delivery, low birth weights, and intrauterine growth restriction were higher in the CGN group. Prenatal proteinuria and blood pressure were significantly increased compared with pre-pregnancy stage. Proteinuria (0.9±0.6 g/d vs. 0.5±0.3 g/d, P=0.032) and hypertension (6.9% vs. 3.4%, P=0.021) at 6 months after delivery were aggravated. Prenatal proteinuria ≥3.5 g/d (OR 12.22, 95%CI 3.16~47.32, P=0.001) was the maternal risk predictor in pregnancy. Prenatal blood pressure ≥160/110 mmHg (OR 8.97, 95%CI 1.69~47.53, P=0.010) and uric acid ≥363 μmol/L (OR 7.35, 95%CI 1.88~28.76, P=0.004) were the fetal risk predictors in pregnancy in conjunction with CGN patients. CONCLUSIONS Maternal-fetal risks are increased in pregnancies in conjunction with CGN patients. Prenatal proteinuria ≥3.5 g/d, BP ≥160/110 mmHg, and uric acid ≥363 μmol/L were the maternal and fetal risk predictors in pregnancy.

Maternal Obesity Accelerates Fetal Pancreatic Beta Cell but not Alpha Cell Development in the Sheep: Prenatal and Postnatal Consequences

USDA-ARS?s Scientific Manuscript database

Maternal obesity affects offspring weight, body composition and organ function, increasing diabetes and metabolic syndrome risk. We determined effects of maternal obesity and a high energy diet on fetal pancreatic development. Sixty days prior to breeding. ewes were assigned to control (C, 100% of N...

The Reversed Feto-Maternal Bile Acid Gradient in Intrahepatic Cholestasis of Pregnancy Is Corrected by Ursodeoxycholic Acid

PubMed Central

Geenes, Victoria; Lövgren-Sandblom, Anita; Benthin, Lisbet; Lawrance, Dominic; Chambers, Jenny; Gurung, Vinita; Thornton, Jim; Chappell, Lucy; Khan, Erum; Dixon, Peter; Marschall, Hanns-Ulrich; Williamson, Catherine

2014-01-01

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder associated with an increased risk of adverse fetal outcomes. It is characterised by raised maternal serum bile acids, which are believed to cause the adverse outcomes. ICP is commonly treated with ursodeoxycholic acid (UDCA). This study aimed to determine the fetal and maternal bile acid profiles in normal and ICP pregnancies, and to examine the effect of UDCA treatment. Matched maternal and umbilical cord serum samples were collected from untreated ICP (n = 18), UDCA-treated ICP (n = 46) and uncomplicated pregnancy (n = 15) cases at the time of delivery. Nineteen individual bile acids were measured using HPLC-MS/MS. Maternal and fetal serum bile acids are significantly raised in ICP compared with normal pregnancy (p = <0.0001 and <0.05, respectively), predominantly due to increased levels of conjugated cholic and chenodeoxycholic acid. There are no differences between the umbilical cord artery and cord vein levels of the major bile acid species. The feto-maternal gradient of bile acids is reversed in ICP. Treatment with UDCA significantly reduces serum bile acids in the maternal compartment (p = <0.0001), thereby reducing the feto-maternal transplacental gradient. UDCA-treatment does not cause a clinically important increase in lithocholic acid (LCA) concentrations. ICP is associated with significant quantitative and qualitative changes in the maternal and fetal bile acid pools. Treatment with UDCA reduces the level of bile acids in both compartments and reverses the qualitative changes. We have not found evidence to support the suggestion that UDCA treatment increases fetal LCA concentrations to deleterious levels. PMID:24421907

The reversed feto-maternal bile acid gradient in intrahepatic cholestasis of pregnancy is corrected by ursodeoxycholic acid.

PubMed

Geenes, Victoria; Lövgren-Sandblom, Anita; Benthin, Lisbet; Lawrance, Dominic; Chambers, Jenny; Gurung, Vinita; Thornton, Jim; Chappell, Lucy; Khan, Erum; Dixon, Peter; Marschall, Hanns-Ulrich; Williamson, Catherine

2014-01-01

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder associated with an increased risk of adverse fetal outcomes. It is characterised by raised maternal serum bile acids, which are believed to cause the adverse outcomes. ICP is commonly treated with ursodeoxycholic acid (UDCA). This study aimed to determine the fetal and maternal bile acid profiles in normal and ICP pregnancies, and to examine the effect of UDCA treatment. Matched maternal and umbilical cord serum samples were collected from untreated ICP (n = 18), UDCA-treated ICP (n = 46) and uncomplicated pregnancy (n = 15) cases at the time of delivery. Nineteen individual bile acids were measured using HPLC-MS/MS. Maternal and fetal serum bile acids are significantly raised in ICP compared with normal pregnancy (p = <0.0001 and <0.05, respectively), predominantly due to increased levels of conjugated cholic and chenodeoxycholic acid. There are no differences between the umbilical cord artery and cord vein levels of the major bile acid species. The feto-maternal gradient of bile acids is reversed in ICP. Treatment with UDCA significantly reduces serum bile acids in the maternal compartment (p = <0.0001), thereby reducing the feto-maternal transplacental gradient. UDCA-treatment does not cause a clinically important increase in lithocholic acid (LCA) concentrations. ICP is associated with significant quantitative and qualitative changes in the maternal and fetal bile acid pools. Treatment with UDCA reduces the level of bile acids in both compartments and reverses the qualitative changes. We have not found evidence to support the suggestion that UDCA treatment increases fetal LCA concentrations to deleterious levels.

Fetal growth in different racial groups.

PubMed Central

Alvear, J; Brooke, O G

1978-01-01

Three racial groups of mothers and their newborn babies-- North European 75, Negro 75, and "Indian" Asian 37--were matched for parity, gestational age, sex, maternal age, maternal smoking habits, and social class. Multiple anthropometric measurements, including skinfold thickness, limb circumferences, and various linear measurements were made on the mothers and their infants to determine the effects of race and smoking on fetal size. Indian-Asian mothers, though shorter and lighter than Europeans and Negroes, had similar skinfold thickness and weight: height2 ratios and gained as much weight during pregnancy. Their infants, however, were lighter than the others, and had smaller head and limb circumferences, although their linear measurements were the same. Negro and European infants were almost identical in size. We found no effect on any of the fetal measurements which could be attributed to smoking. PMID:626515

Maternal diets deficient in folic acid and related methyl donors modify mechanisms associated with lipid metabolism in the fetal liver of the rat.

PubMed

McNeil, Christopher J; Hay, Susan M; Rucklidge, Garry J; Reid, Martin D; Duncan, Gary J; Rees, William D

2009-11-01

Previously we have examined the effects of diets deficient in folic acid ( - F) or folate deficient with low methionine and choline ( - F LM LC) on the relative abundance of soluble proteins in the liver of the pregnant rat. In the present study we report the corresponding changes in the fetal liver at day 21 of gestation. The abundance of eighteen proteins increased when dams were fed the - F diet. When dams were fed the - F LM LC diet, thirty-three proteins increased and eight decreased. Many of the differentially abundant proteins in the fetal liver could be classified into the same functional groups as those previously identified in the maternal liver, namely protein synthesis, metabolism, lipid metabolism and proteins associated with the cytoskeleton and endoplasmic reticulum. The pattern was consistent with reduced cell proliferation in the - F LM LC group but not in the - F group. Metabolic enzymes associated with lipid metabolism changed in both the - F and - F LM LC groups. The mRNA for carnitine palmitoyl transferase were up-regulated and CD36 (fatty acid translocase) down-regulated in the - F group, suggesting increased mitochondrial oxidation of fatty acids as an indirect response to altered maternal lipid metabolism. In the - F LM LC group the mRNA for acetyl CoA carboxylase was down-regulated, suggesting reduced fatty acid synthesis. The mRNA for transcriptional regulators including PPARalpha and sterol response element-binding protein-1c were unchanged. These results suggest that an adequate supply of folic acid and the related methyl donors may benefit fetal development directly by improving lipid metabolism in fetal as well as maternal tissues.

Added value of cerebro-placental ratio and uterine artery Doppler at routine third trimester screening as a predictor of SGA and FGR in non-selected pregnancies.

PubMed

Rial-Crestelo, M; Martinez-Portilla, R J; Cancemi, A; Caradeux, J; Fernandez, L; Peguero, A; Gratacos, E; Figueras, Francesc

2018-03-04

The objective of this study is to determine the added value of cerebroplacental ratio (CPR) and uterine Doppler velocimetry at third trimester scan in an unselected obstetric population to predict smallness and growth restriction. We constructed a prospective cohort study of women with singleton pregnancies attended for routine third trimester screening (32 +0 -34 +6 weeks). Fetal biometry and fetal-maternal Doppler ultrasound examinations were performed by certified sonographers. The CPR was calculated as a ratio of the middle cerebral artery to the umbilical artery pulsatility indices. Both attending professionals and patients were blinded to the results, except in cases of estimated fetal weight < p10. The association between third trimester Doppler parameters and small for gestational age (SGA) (birth weight <10th centile) and fetal growth restriction (FGR) (birth weight below the third centile) was assessed by logistic regression, where the basal comparison was a model comprising maternal characteristics and estimated fetal weight (EFW). A total of 1030 pregnancies were included. The mean gestational age at scan was 33 weeks (SD 0.6). The addition of CPR and uterine Doppler to maternal characteristics plus EFW improved the explained uncertainty of the predicting models for SGA (15 versus 10%, p < .001) and FGR (12 versus 8%, p = .03). However, the addition of CPR and uterine Doppler to maternal characteristics plus EFW only marginally improved the detection rates for SGA (38 versus 34% for a 10% of false positives) and did not change the predictive performance for FGR. The added value of CPR and uterine Doppler at 33 weeks of gestation for detecting defective growth is poor.

Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity.

PubMed

Nam, Juha; Greenwald, Esther; Jack-Roberts, Chauntelle; Ajeeb, Tamara T; Malysheva, Olga V; Caudill, Marie A; Axen, Kathleen; Saxena, Anjana; Semernina, Ekaterina; Nanobashvili, Khatia; Jiang, Xinyin

2017-11-01

Maternal obesity increases placental transport of macronutrients, resulting in fetal overgrowth and obesity later in life. Choline participates in fatty acid metabolism, serves as a methyl donor and influences growth signaling, which may modify placental macronutrient homeostasis and affect fetal growth. Using a mouse model of maternal obesity, we assessed the effect of maternal choline supplementation on preventing fetal overgrowth and restoring placental macronutrient homeostasis. C57BL/6J mice were fed either a high-fat (HF, 60% kcal from fat) diet or a normal (NF, 10% kcal from fat) diet with a drinking supply of either 25 mM choline chloride or control purified water, respectively, beginning 4 weeks prior to mating until gestational day 12.5. Fetal and placental weight, metabolites and gene expression were measured. HF feeding significantly (P<.05) increased placental and fetal weight in the HF-control (HFCO) versus NF-control (NFCO) animals, whereas the HF choline-supplemented (HFCS) group effectively normalized placental and fetal weight to the levels of the NFCO group. Compared to HFCO, the HFCS group had lower (P<.05) glucose transporter 1 and fatty acid transport protein 1 expression as well as lower accumulation of glycogen in the placenta. The HFCS group also had lower (P<.05) placental 4E-binding protein 1 and ribosomal protein s6 phosphorylation, which are indicators of mechanistic target of rapamycin complex 1 activation favoring macronutrient anabolism. In summary, our results suggest that maternal choline supplementation prevented fetal overgrowth in obese mice at midgestation and improved biomarkers of placental macronutrient homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Maternal nutrient restriction during pregnancy impairs an endothelium-derived hyperpolarizing factor-like pathway in sheep fetal coronary arteries.

PubMed

Shukla, Praveen; Ghatta, Srinivas; Dubey, Nidhi; Lemley, Caleb O; Johnson, Mary Lynn; Modgil, Amit; Vonnahme, Kimberly; Caton, Joel S; Reynolds, Lawrence P; Sun, Chengwen; O'Rourke, Stephen T

2014-07-15

The mechanisms underlying developmental programming are poorly understood but may be associated with adaptations by the fetus in response to changes in the maternal environment during pregnancy. We hypothesized that maternal nutrient restriction during pregnancy alters vasodilator responses in fetal coronary arteries. Pregnant ewes were fed a control [100% U.S. National Research Council (NRC)] or nutrient-restricted (60% NRC) diet from days 50 to 130 of gestation (term = 145 days); fetal tissues were collected at day 130. In coronary arteries isolated from control fetal lambs, relaxation to bradykinin was unaffected by nitro-l-arginine (NLA). Iberiotoxin or contraction with KCl abolished the NLA-resistant response to bradykinin. In fetal coronary arteries from nutrient-restricted ewes, relaxation to bradykinin was fully suppressed by NLA. Large-conductance, calcium-activated potassium channel (BKCa) currents did not differ in coronary smooth muscle cells from control and nutrient-restricted animals. The BKCa openers, BMS 191011 and NS1619, and 14,15-epoxyeicosatrienoic acid [a putative endothelium-derived hyperpolarizing factor (EDHF)] each caused fetal coronary artery relaxation and BKCa current activation that was unaffected by maternal nutrient restriction. Expression of BKCa-channel subunits did not differ in fetal coronary arteries from control or undernourished ewes. The results indicate that maternal undernutrition during pregnancy results in loss of the EDHF-like pathway in fetal coronary arteries in response to bradykinin, an effect that cannot be explained by a decreased number or activity of BKCa channels or by decreased sensitivity to mediators that activate BKCa channels in vascular smooth muscle cells. Under these conditions, bradykinin-induced relaxation is completely dependent on nitric oxide, which may represent an adaptive response to compensate for the absence of the EDHF-like pathway. Copyright © 2014 the American Physiological Society.

Evaluation of developmental toxicity in rats exposed to the environmental estrogen bisphenol A during pregnancy.

PubMed

Kim, J C; Shin, H C; Cha, S W; Koh, W S; Chung, M K; Han, S S

2001-10-19

Bisphenol A (BPA) is an essential component of epoxy resins used in the lacquer lining of metal food cans, as a component of polycarbonates, and in dental sealants. The present study was conducted in an attempt to evaluate the adverse effects of the environmental estrogen BPA on initiation and maintenance of pregnancy and embryofetal development after maternal exposure during the entire period of pregnancy in Sprague-Dawley rats. The test chemical was administered by gavage to mated females from days 1 to 20 of gestation (sperm in varginal lavage = day 0) at dose levels of 0, 100, 300, and 1000 mg/kg. All females were subjected to caesarean section on day 21 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. In the 1000 mg/kg group, significant toxic effects including abnormal clinical signs, decreased maternal body weight and body weight gain, and reduced food consumption were observed in pregnant rats. An increase in pregnancy failure was also found in the successfully mated females. In addition, increased number of embryonal deaths, increased postimplantation loss, reduced litter size and fetal body weight, and decreased number of fetal ossification centers of several skeletal districts were seen. On the contrary, no significant changes induced by BPA were detected in the number of corpora lutea and implantation sites and by fetal morphological examinations. In the 300 mg/kg group, suppressed maternal body weight and body weight gain, decreased food intake and reduced body weight of male fetuses were seen. There were no adverse signs of either maternal toxicity or developmental toxicity in the 100 mg/kg group. It was concluded that BPA administration during the entire period of pregnancy in rats produced pregnancy failure, pre- and postimplantation loss, fetal developmental delay and severe maternal toxicity, but no embryo-fetal dysmorphogenesis at an oral exposure level of 1000 mg/kg.

Efficiency of the modified Sims maternal position in the rotation of persistent occiput posterior position during labor: A randomized clinical trial.

PubMed

Bueno-Lopez, Vanessa; Fuentelsaz-Gallego, Carmen; Casellas-Caro, Manel; Falgueras-Serrano, Ana Maria; Crespo-Berros, Silvia; Silvano-Cocinero, Ana Maria; Alcaine-Guisado, Carolina; Zamoro Fuentes, Manuela; Carreras, Elena; Terré-Rull, Carmen

2018-03-14

Fetal occiput posterior position in labor is associated with more painful and prolonged labor, and an increase in both maternal and fetal morbidity. The aim of this study is to assess whether the modified Sims position on the side of the fetal spine increases the rotation to occiput anterior position in women with epidural analgesia and a fetus in persistent occiput posterior (POP) position. This is an open, randomized controlled, clinical trial. One hundred and twenty women in labor with fetuses in POP position were included. The diagnosis was performed through digital vaginal examination and confirmed with an ultrasound scan. Women were randomized into the free position group or the modified Sims on the side of the fetal spine. The primary outcome was rotation to occiput anterior, and secondary outcomes were type of delivery, postpartum perineal condition, perinatal results, and maternal satisfaction. In pregnant women undergoing labor in the Sims position, fetuses in POP rotated to occiput anterior in 50.8% of cases, whilst in the free position group, the rotation occurred in 21.7% (P = .001). The rate of vaginal deliveries was higher in the Sims group compared with the free position group (84.7% vs 68.3%, P = .035). The modified Sims position is a maternal posture intervention efficient in POP rotation, which decreases cesarean delivery rate. It is a simple and noninvasive intervention, reproducible, and well tolerated by pregnant women. © 2018 Wiley Periodicals, Inc.

The Effect of Diabetes and Hypertension on the Placental Permeation of the Hydrophilic Drug, Ranitidine.

PubMed

Lalic-Popovic, Mladena; Paunkovic, Jovana; Grujic, Zorica; Golocorbin-Kon, Svetlana; Vasovic, Velibor; Al-Salami, Hani; Mikov, Momir

2016-12-01

Ranitidine is a hydrophilic weak base and an H 2 -receptor antagonist which is commonly used for gastroesophageal reflux, including during pregnancy. It has limited placental permeation and can be used as a pre-anesthetic antacid to prevent aspiration of acidic stomach contents. Recent studies suggest that diabetes and hypertension may influence placental permeation of hydrophilic drugs. Thus, this study aimed to investigate the influence of diabetes and hypertension on ranitidine's placental permeation in pregnant women. Forty one pregnant women all scheduled for elective cesarean section entered the study: healthy control (n = 15), with hypertension (n = 16) and with gestational diabetes (n = 10). All women received 50 mg of ranitidine intravenously. Three samples of maternal plasma (after ranitidine application, at delivery and after delivery), and two umbilical cord samples (arterial and venous blood) were collected and analyzed for ranitidine concentrations. Maternal pharmacokinetic parameter were calculated as well as feto:maternal and umbilical cord arterial to venous concentration ratios. Ranitidine maternal and umbilical cord (arterial and venous) concentrations were similar in all three groups and there were no difference between feto:maternal ratios nor volume of distribution, clearance and half life between the groups. Fetal concentrations are dependent on maternal concentrations in healthy and hypertensive women but not in diabetic women. Hypertension and diabetes did not affect fetal handling of ranitidine. Though hypertension and diabetes did not influence ranitidine placental permeation, it appears they altered time needed to achieve unity between maternal and fetal plasma. Copyright © 2016. Published by Elsevier Ltd.

Maternal and fetal effects of chocolate consumption during pregnancy: a systematic review.

PubMed

Latif, Rabia

2018-03-13

The purpose of this review is to explore the effects of chocolate consumption during pregnancy on fetus and mother herself. Randomized controlled trials/quasi-experimental/observational/controlled before and after studies involving chocolate/cocoa/cacao consumption (irrespective of type or dose, composition, exposure period, and method of administration) among pregnant women/animals; and measuring any outcome (beneficial or harmful) related to fetus or mother after chocolate exposure were included. Databases searched were PubMed, Web of Science and Scopus; between April and May 2017. Risk of bias within each human randomized controlled trial (RCT) and animals' experimental studies was evaluated by "The Cochrane Collaboration's tool" and SYRCLE's tool respectively. Fourteen human studies including a total of 6639 participants and nine animal studies were selected. Outcome variables investigated in human studies were maternal blood pressure, fetal heart rate, and striae gravidarum. Animal studies explored chocolate-induced teratogenicity and fetal metabolic derangements. Ten out of these 23 studies reported chocolate to be "beneficial"; five studies reported adverse effects, whereas eight studies declared chocolate as "neutral". Maternal chocolate intake has acute stimulatory effects on fetal reactivity and chronic blood pressure reducing effect in mothers. Chocolate is nonteratogenic and does not affect reproductive indices. Metabolic derangements in offsprings born to chocolate fed dams have been reported. Pregnant females must be careful about consumption of cocoa and chocolate. Future studies should be planned, keeping in view heterogeneities identified across the selected studies in this review.

Signal separation by nonlinear projections: The fetal electrocardiogram

NASA Astrophysics Data System (ADS)

Schreiber, Thomas; Kaplan, Daniel T.

1996-05-01

We apply a locally linear projection technique which has been developed for noise reduction in deterministically chaotic signals to extract the fetal component from scalar maternal electrocardiographic (ECG) recordings. Although we do not expect the maternal ECG to be deterministic chaotic, typical signals are effectively confined to a lower-dimensional manifold when embedded in delay space. The method is capable of extracting fetal heart rate even when the fetal component and the noise are of comparable amplitude. If the noise is small, more details of the fetal ECG, like P and T waves, can be recovered.

The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction.

PubMed

Groom, Katie M; David, Anna L

2018-02-01

Fetal growth restriction and related placental pathologies such as preeclampsia, stillbirth, and placental abruption are believed to arise in early pregnancy when inadequate remodeling of the maternal spiral arteries leads to persistent high-resistance and low-flow uteroplacental circulation. The consequent placental ischaemia, reperfusion injury, and oxidative stress are associated with an imbalance in angiogenic/antiangiogenic factors. Many interventions have centered on the prevention and/or treatment of preeclampsia with results pertaining to fetal growth restriction and small-for-gestational-age pregnancy often included as secondary outcomes because of the common pathophysiology. This renders the study findings less reliable for determining clinical significance. For the prevention of fetal growth restriction, a recent large-study level meta-analysis and individual patient data meta-analysis confirm that aspirin modestly reduces small-for-gestational-age pregnancy in women at high risk (relative risk, 0.90, 95% confidence interval, 0.81-1.00) and that a dose of ≥100 mg should be recommended and to start at or before 16 weeks of gestation. These findings support national clinical practice guidelines. In vitro and in vivo studies suggest that low-molecular-weight heparin may prevent fetal growth restriction; however, evidence from randomized control trials is inconsistent. A meta-analysis of multicenter trial data does not demonstrate any positive preventative effect of low-molecular-weight heparin on a primary composite outcome of placenta-mediated complications including fetal growth restriction (18% vs 18%; absolute risk difference, 0.6%; 95% confidence interval, 10.4-9.2); use of low-molecular-weight heparin for the prevention of fetal growth restriction should remain in the research setting. There are even fewer treatment options once fetal growth restriction is diagnosed. At present the only management option if the risk of hypoxia, acidosis, and intrauterine death is high is iatrogenic preterm birth, with the use of peripartum maternal administration of magnesium sulphate for neuroprotection and corticosteroids for fetal lung maturity, to prevent adverse neonatal outcomes. The pipeline of potential therapies use different strategies, many aiming to increase fetal growth by improving poor placentation and uterine blood flow. Phosphodiesterase type 5 inhibitors that potentiate nitric oxide availability such as sildenafil citrate have been extensively researched both in preclinical and clinical studies; results from the Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction consortium of randomized control clinical trials are keenly awaited. Targeting the uteroplacental circulation with novel therapeutics is another approach, the most advanced being maternal vascular endothelial growth factor gene therapy, which is being translated into the clinic via the doEs Vascular endothelial growth factor gene therapy safEly impRove outcome in seveRe Early-onset fetal growth reSTriction consortium. Other targeting approaches include nanoparticles and microRNAs to deliver drugs locally to the uterine arterial endothelium or trophoblast. In vitro and in vivo studies and animal models have demonstrated effects of nitric oxide donors, dietary nitrate, hydrogen sulphide donors, statins, and proton pump inhibitors on maternal blood pressure, uteroplacental resistance indices, and angiogenic/antiangiogenic factors. Data from human pregnancies and, in particular, pregnancies with fetal growth restriction remain very limited. Early research into melatonin, creatine, and N-acetyl cysteine supplementation in pregnancy suggests they may have potential as neuro- and cardioprotective agents in fetal growth restriction. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth.

PubMed

Rosario, Fredrick J; Kanai, Yoshikatsu; Powell, Theresa L; Jansson, Thomas

2015-08-01

To identify possible mechanisms linking obesity in pregnancy to increased fetal adiposity and growth, a unique mouse model of maternal obesity associated with fetal overgrowth was developed, and the hypothesis that maternal obesity causes up-regulation of placental nutrient transporter expression and activity was tested. C57BL/6J female mice were fed a control (C) or a high-fat/high-sugar (HF/HS) pelleted diet supplemented by ad libitum access to sucrose (20%) solution, mated, and studied at embryonic day 18.5. HF/HS diet increased maternal fat mass by 2.2-fold (P < 0.01) and resulted in glucose intolerance with normal fasting glucose. Maternal circulating insulin, leptin, and cholesterol were increased (P < 0.05) whereas total and high-molecular-weight adiponectin was decreased (P < 0.05). HF/HS diet increased fetal weight (+18%, P = 0.0005). In trophoblast plasma membranes (TPM) isolated from placentas of HF/HS-fed animals, protein expression of glucose transporter (GLUT) 1 and 3, sodium-coupled neutral amino acid transporter (SNAT) 2, and large neutral amino acid transporter 1 (LAT1) was increased. TPM System A and L amino acid transporter activity was increased in the HF/HS group. Up-regulation of specific placental nutrient transporter isoforms may constitute a mechanism underlying fetal overgrowth in maternal obesity. © 2015 The Obesity Society.

Prenatal stress and hemodynamics in pregnancy: a systematic review.

PubMed

Levine, Terri A; Alderdice, Fiona A; Grunau, Ruth E; McAuliffe, Fionnuala M

2016-10-01

Maternal prenatal stress is associated with preterm birth, intrauterine growth restriction, and developmental delay. However, the impact of prenatal stress on hemodynamics during pregnancy remains unclear. This systematic review was conducted in order to assess the quality of the evidence available to date regarding the relationship between prenatal stress and maternal-fetal hemodynamics. The PubMed/Medline, EMBASE, PsycINFO, Maternity and Infant Care, Trip, Cochrane Library, and CINAHL databases were searched using the search terms pregnancy; stress; fetus; blood; Doppler; ultrasound. Studies were eligible for inclusion if prenatal stress was assessed with standardized measures, hemodynamics was measured with Doppler ultrasound, and methods were adequately described. A specifically designed data extraction form was used. The methodological quality of included studies was assessed using well-accepted quality appraisal guidelines. Of 2532 studies reviewed, 12 met the criteria for inclusion. Six reported that prenatal stress significantly affects maternal or fetal hemodynamics; six found no significant association between maternal stress and circulation. Significant relationships between prenatal stress and uterine artery resistance (RI) and pulsatility (PI) indices, umbilical artery RI, PI, and systolic/diastolic ratio, fetal middle cerebral artery PI, cerebroplacental ratio, and umbilical vein volume blood flow were found. To date, there is limited evidence that prenatal stress is associated with changes in circulation. More carefully designed studies with larger sample sizes, repeated assessments across gestation, tighter control for confounding factors, and measures of pregnancy-specific stress will clarify this relationship.

Progression of ultrasound findings of fetal syphilis after maternal treatment.

PubMed

Rac, Martha W F; Bryant, Stefanie N; McIntire, Donald D; Cantey, Joseph B; Twickler, Diane M; Wendel, George D; Sheffield, Jeanne S

2014-10-01

The purpose of this study was to evaluate ultrasound findings of fetal syphilis and to describe their progression after maternal treatment. This was a retrospective cohort study from September 1981 to June 2011 of seropositive women after 18 weeks of gestation who had an ultrasound before treatment to evaluate for fetal syphilis. Only those women who received treatment after the initial ultrasound scan, but before delivery, were included. If the initial ultrasound scan was abnormal, serial sonography was performed until resolution of the abnormality or delivery. Patient demographics, ultrasound findings, stage of syphilis, delivery, and infant outcomes were recorded. Standard statistical analyses were performed. Kaplan-Meier estimates were constructed to estimate time to resolution. Two hundred thirty-five women met the inclusion criteria; 73 of them (30%) had evidence of fetal syphilis on initial ultrasound scan. Abnormalities included hepatomegaly (79%), placentomegaly (27%), polyhydramnios (12%), ascites (10%) and abnormal middle cerebral arterial Doppler assessment (33%). After treatment, middle cerebral arterial Doppler assessment abnormalities, ascites, and polyhydramnios resolved first, followed by placentomegaly and finally hepatomegaly. Infant outcomes were available for 173 deliveries; of these, 32 infants (18%) were diagnosed with congenital syphilis. Congenital syphilis was more common when antenatal ultrasound abnormalities were present (39% vs 12%; P < .001). Infant examination findings at delivery were similar between women with and without an abnormal pretreatment ultrasound scan. However, in those infants with congenital syphilis, hepatomegaly was the most frequent abnormality found, regardless of antenatal ultrasound findings. Sonographic signs of fetal syphilis confer a higher risk of congenital syphilis at delivery for all maternal stages. Hepatomegaly develops early and resolves last after antepartum treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2

PubMed Central

Hiby, Susan E.; Apps, Richard; Sharkey, Andrew M.; Farrell, Lydia E.; Gardner, Lucy; Mulder, Arend; Claas, Frans H.; Walker, James J.; Redman, Christopher C.; Morgan, Linda; Tower, Clare; Regan, Lesley; Moore, Gudrun E.; Carrington, Mary; Moffett, Ashley

2010-01-01

Many common disorders of pregnancy are attributed to insufficient invasion of the uterine lining by trophoblast, fetal cells that are the major cell type of the placenta. Interactions between fetal trophoblast and maternal uterine NK (uNK) cells — specifically interactions between HLA-C molecules expressed by the fetal trophoblast cells and killer Ig-like receptors (KIRs) on the maternal uNK cells — influence placentation in human pregnancy. Consistent with this, pregnancies are at increased risk of preeclampsia in mothers homozygous for KIR haplotype A (KIR AA). In this study, we have demonstrated that trophoblast expresses both paternally and maternally inherited HLA-C surface proteins and that maternal KIR AA frequencies are increased in affected pregnancies only when the fetus has more group 2 HLA-C genes (C2) than the mother. These data raise the possibility that there is a deleterious allogeneic effect stemming from paternal C2. We found that this effect also occurred in other pregnancy disorders (fetal growth restriction and recurrent miscarriage), indicating a role early in gestation for these receptor/ligand pairs in the pathogenesis of reproductive failure. Notably, pregnancy disorders were less frequent in mothers that possessed the telomeric end of the KIR B haplotype, which contains activating KIR2DS1. In addition, uNK cells expressed KIR2DS1, which bound specifically to C2+ trophoblast cells. These findings highlight the complexity and central importance of specific combinations of activating KIR and HLA-C in maternal-fetal immune interactions that determine reproductive success. PMID:20972337

Gamma-linoleic acid and ascorbate improves skeletal ossification in offspring of diabetic rats.

PubMed

Braddock, Rattana; Simán, C Martin; Hamilton, Katherine; Garland, Hugh O; Sibley, Colin P

2002-05-01

Maternal diabetes causes a range of complications in offspring, including reduced skeletal ossification. This study examined whether feeding gamma-linoleic acid (GLA) and ascorbate, alone or in combination, to diabetic pregnant rats improves skeletal development in their offspring. In addition, Ca(2+) concentration was monitored in maternal plasma and fetal tissue, as well as placental mRNA expression of calbindin-D(9k). Female rats rendered diabetic with streptozotocin were fed GLA (500 mg/kg/d), ascorbate (290 mg/kg/d), ascorbyl-GLA (790 mg/kg/d), or GLA and ascorbate (500 and 290 mg/kg/d, respectively) throughout pregnancy. Fetal skeletons were studied after alizarin red staining. Fewer ossification centers were observed in offspring of diabetic rats compared with offspring of control rats (68 +/- 4% of control, p = 0.01). An almost complete restoration of ossification occurred with all the treatments (92-95 +/- 3% of control). The effects of treatment on fetal ossification could not be explained by altered maternal plasma Ca(2+) concentrations or by mRNA expression of the placental Ca(2+)-transporting protein calbindin-D(9K). We conclude that GLA and/or ascorbate treatment was effective against diabetes-induced fetal ossification defects by a mechanism not related to placental Ca(2+) supply.

Influence of fetal birth weight on perinatal outcome in planned vaginal births.

PubMed

Temerinac, Dunja; Chen, Xi; Sütterlin, Marc; Kehl, Sven

2014-02-01

The aim of this study was to provide information for better obstetric counseling by analyzing the impact of fetal birth weight (BW) on fetal and maternal outcome when vaginal birth is planned in a university hospital. In this retrospective study from January 1st 2006 to December 31st 2011, 5,177 singleton, alive deliveries at or >37 gestational weeks were assessed with regard to the fetal BW when vaginal birth was attempted. The normal BW group was defined as ≥2,500 <4,500 g. For comparison, further BW groups were defined as: group 1 <2,500 g, group 2 ≥4,000 <4,250 g, group 3 ≥4,250 <4,500 g and group 4 ≥4,500 g. Outcome criteria were mode of delivery and perineal lacerations as well as the pH and base excess of the umbilical cord artery, the Apgar score after 5 min and occurrence of shoulder dystocia. The set of controlling variables included maternal height, maternal weight, maternal age, gestational age, neonatal sex and parity. Second stage caesarean section is significantly more likely when fetal BW is under 2,500 g (30.7 vs. 15.5 % in the normal BW group, odds ratio 3.01, 95 % confidence interval 2.03-4.46, p value < 0.001). Shoulder dystocia occurred significantly more often when fetal BW was over 4,250 g (group 3: odds ratio 4.95, 95 % confidence interval 1.74-14.10, p value 0.003, group 4: odds ratio 19.96, 95 % confidence interval 7.61-52.38, p value < 0.001). The risk of an Apgar score after 5 min below 7 increased, when fetal BW was below 2,500 g (odds ratio 9.28, 95 % confidence interval 3.15-27.35, p value < 0.001) or above 4,500 g (odds ratio 5.65, 95 % confidence interval 1.22-26.24, p value 0.027). All groups were comparable to the normal group regarding pH and base excess of the umbilical cord artery as well as the risk for severe (third and fourth degree) perineal lacerations. Although a fetal birth weight under 2,500 g and a birth weight over 4,250 g are associated with some risks, there is no general contraindication for an attempt to deliver vaginally in a university hospital with regard to fetal birth weight.

Circulating erythroblasts in maternal blood are not elevated before onset of preterm labor.

PubMed

Hoesli, Irene; Danek, Milan; Lin, Dexin; Li, Ying; Hahn, Sinuhe; Holzgreve, Wolfgang

2002-11-01

Preterm labor has recently been reported to be associated with an increased release of cell free fetal deoxyribonucleic acid (DNA) into the maternal circulation. We have previously observed increases in both fetal cell traffic and cell free fetal DNA in preeclamptic pregnancies. In this study, we investigated whether fetal cell traffic is also disturbed in pregnancies with preterm labor. In a case-control study, we examined 47 pregnancies complicated by preterm contractions that occurred between 20 and 34 weeks' gestation and an equal number of matched controls. Erythroblasts were enriched for by magnetic cell sorting and enumerated. These values were then correlated with subsequent pregnancy outcome. In the study group 16 patients delivered prematurely (subgroup A). The other 31 (subgroup B) delivered at term, as did all those in the control group. No significant difference was noted in erythroblast numbers between either one of the subgroups and the controls. Contrary to the reported increased levels of free fetal DNA in maternal serum, erythroblasts in maternal blood are not elevated significantly in pregnancies with threatened premature labor or in those that deliver preterm.

How competent are you (or your staff) with shoulder dystocia?

PubMed

Wright, M; Higgins, P G

1999-01-01

Shoulder dystocia-when the fetal head retracts or recoils against the maternal perineum ("turtle sign") and external rotation is not accomplished-occurs in approximately 1 of every 200 deliveries. It's often diagnosed after the emergence of the fetal head when delivery is prevented by impaction of the fetal shoulders within or above the maternal pelvis. When it occurs, shoulder dystocia is an obstetric emergency.

Influence of the magnesium aspartate hydrochloride administration to the maternal circuit on the aspartate concentration of the fetal circuit under in vitro perfusion of human placenta.

PubMed

Malek, A; Leiser, R

2009-01-01

Magnesium aspartate hydrochloride (Magnesiocard, Mg-Asp-HCl) is proposed as a substitute of magnesium sulfate for the treatment of preeclampsia and premature labor. After an i.v. administration of a dose equivalent to that used in the treatment of preeclampsia to nonpregnant volunteers, a 10-fold increase of aspartic acid (Asp) over the physiological level was observed. Animal experiments have demonstrated that highly increased fetal levels of acidic amino acids such as Asp could be associated with neurotoxic damage in the fetal brain. The influence of such an elevation of Asp concentration in the maternal circuit on the fetal level, using the in vitro perfusion model of human placenta, was investigated. After a control phase (2h), a therapeutic dose of Mg combined with Asp (Magnesiocard, Mg-Asp-HCl) was applied to the maternal circuit approaching 10 times the physiological level of Asp. The administration was performed in two different phases simulating either a peak of maximum concentration (bolus application, 2h) or a steady state level (initially added, 4h). In four experiments, during experimental phases (6h) a slow increase in concentration in the fetal circuit was seen for Mg, AIB (alpha-aminoisobutyric acid, artificial amino acid) and creatinine confirming previous observations. In contrast, no net transfer of Asp across the placenta was seen. A continuous decrease in the concentration of Asp on both maternal and fetal side suggests active uptake and metabolization by the placenta. Viability control parameters remained stable indicating the absence of an effect on placental metabolism, permeability and morphology. Elevation of Asp concentration up to 10 times the physiological level by the administration of Mg-Asp-HCl to the maternal circuit under in vitro perfusion conditions of human placenta has no influence on the fetal level of Asp suggesting no transfer of Asp from the maternal to fetal compartment. Therefore, the administration of Mg-Asp-HCl to preeclamptic patients would be beneficial for the patients without any impact on placental or fetal physiology.

Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Shows that Fetal Heart Rate Correlates with Maternal Glycemia.

PubMed

Cypryk, Katarzyna; Bartyzel, Lukasz; Zurawska-Klis, Monika; Mlynarski, Wojciech; Szadkowska, Agnieszka; Wilczynski, Jan; Nowakowska, Dorota; Wozniak, Lucyna A; Fendler, Wojciech

2015-09-01

Much evidence has shown that pregnancies in women with preexisting diabetes are affected by an increased risk of maternal and fetal adverse outcomes, probably linked to poor glycemic control. Despite great progress in medical care, the rate of stillbirths remains much higher in diabetes patients than in the general population. Recent technological advances in the field of glucose monitoring and noninvasive fetal heart rate monitoring made it possible to observe the fetal-maternal dependencies in a continuous manner. Fourteen type 1 diabetes patients were involved into the study and fitted with a blinded continuous glucose monitoring (CGM) recorder. Fetal electrocardiogram data were recorded using the Monica AN24™ device (Monica Healthcare Ltd., Nottingham, United Kingdom), the recordings of which were matched with CGM data. Statistical analysis was performed using a generalized mixed-effect logistic regression to account for individual factors. The mean number of paired data points per patient was 254±106, representing an observation period of 21.2±8.8 h. Mean glycemia equaled 5.64±0.68 mmol/L, and mean fetal heart rate was 135±6 beats/min. Higher glycemia correlated with fetal heart rate (R=0.32; P<0.0001) and was associated with higher odds of the fetus developing small accelerations (odds ratio=1.05; 95% confidence interval, 1.00-1.10; P=0.04). Elevated maternal glycemia of mothers with diabetes is associated with accelerations of fetal heart rate.

Monitoring of fetal radiation exposure during pregnancy.

PubMed

Chandra, Venita; Dorsey, Chelsea; Reed, Amy B; Shaw, Palma; Banghart, Dawn; Zhou, Wei

2013-09-01

One unique concern of vascular surgeons and trainees is radiation exposure associated with increased endovascular practice. The safety of childbearing is a particular worry for current and future women in vascular surgery. Little is known regarding actual fetal radiation exposure. This multi-institutional study aimed to evaluate the radiation dosages recorded on fetal dosimeter badges and compare them to external badges worn by the same cohort of women. All women who declared pregnancy with potential radiation exposure were required to wear two radiation monitors at each institution, one outside and the other inside the lead apron. Maternal (external) and fetal monitor dosimeter readings were analyzed. Maternal radiation exposures prior to, during, and postpregnancy were also assessed to determine any associated behavior modification. Eighty-one women declared pregnancy from 2008 to 2011 and 32 had regular radiation exposure during pregnancy. Maternal whole-body exposures ranged from 21-731 mrem. The average fetal dosimeter recordings for the cohort rounded to zero. Only two women had positive fetal dosimeter recordings; one had a single recording of 3 mrem and the other had a single recording of 7 mrem. There was no significant difference between maternal exposures prior to, during, and postpregnancy. Lack of knowledge of fetal radiation exposure has concerned many vascular surgeons, prompting them to wear double lead aprons during pregnancy, and perhaps prevented numerous other women from entering the field. Our study showed negligible radiation exposure on fetal monitoring suggesting that with the appropriate safety precautions, these concerns may be unwarranted. Published by Mosby, Inc.

Prognostic factors of premature closure of the ductus arteriosus in utero: a systematic literature review.

PubMed

Ishida, Hidekazu; Kawazu, Yukiko; Kayatani, Futoshi; Inamura, Noboru

2017-05-01

A number of case reports show various outcomes of premature closure of the ductus arteriosus in utero, including persistent pulmonary hypertension of the newborn and fetal or neonatal death; however, no study clarifies the clinical observations that are related to their prognoses. We aimed to clarify the prognostic factors of intrauterine ductal closure by a systematic literature review. Data sources We searched PubMed database (1975-2014) to identify case reports and studies on intrauterine closure of the ductus arteriosus, including maternal, fetal, and neonatal clinical information and their prognoses. We analysed the data of 116 patients from 39 articles. Of these, 12 (10.3%) died after birth or in utero. Fetal or neonatal death was significantly correlated with fetal hydrops (odds ratio=39.6, 95% confidence interval=4.6-47.8) and complete closure of the ductus arteriosus (odds ratio=5.5, 95% confidence interval=1.2-15.1). Persistent pulmonary hypertension was observed in 33 cases (28.4%), and was also correlated with fetal hydrops (odds ratio=4.2, 95% confidence interval=1.3-4.6) and complete closure of the ductus arteriosus (odds ratio=5.5, 95% confidence interval=1.6-6.0). Interestingly, maternal drug administration was not correlated with the risk of death and persistent pulmonary hypertension. Fetal hydrops and complete ductal closure are significant risk factors for both death and persistent pulmonary hypertension. Cardiac or neurological prognoses could be favourable if the patients overcome right heart failure during the perinatal period.

Fetal Programming and Cardiovascular Pathology

PubMed Central

Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira

2016-01-01

Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521

Maternal Obesity: Lifelong Metabolic Outcomes for Offspring from Poor Developmental Trajectories During the Perinatal Period.

PubMed

Zambrano, Elena; Ibáñez, Carlos; Martínez-Samayoa, Paola M; Lomas-Soria, Consuelo; Durand-Carbajal, Marta; Rodríguez-González, Guadalupe L

2016-01-01

The prevalence of obesity in women of reproductive age is increasing in developed and developing countries around the world. Human and animal studies indicate that maternal obesity adversely impacts both maternal health and offspring phenotype, predisposing them to chronic diseases later in life including obesity, dyslipidemia, type 2 diabetes mellitus, and hypertension. Several mechanisms act together to produce these adverse health effects including programming of hypothalamic appetite-regulating centers, increasing maternal, fetal and offspring glucocorticoid production, changes in maternal metabolism and increasing maternal oxidative stress. Effective interventions during human pregnancy are needed to prevent both maternal and offspring metabolic dysfunction due to maternal obesity. This review addresses the relationship between maternal obesity and its negative impact on offspring development and presents some maternal intervention studies that propose strategies to prevent adverse offspring metabolic outcomes. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Maternal and fetal safety of fluid-restrictive general anesthesia for endoscopic fetal surgery in monochorionic twin gestations.

PubMed

Duron, Vincent D; Watson-Smith, Debra; Benzuly, Scott E; Muratore, Christopher S; O'Brien, Barbara M; Carr, Stephen R; Luks, Francois I

2014-05-01

To review our experience with general anesthesia in endoscopic fetal surgery for twin-to-twin transfusion syndrome (TTTS), and to compare fetomaternal outcome before and after protocol implementation. Retrospective impact study. University-affiliated medical center. Data from 85 consecutive patients who underwent endoscopic laser ablation of placenta vessels for severe TTTS were studied. Outcomes were compared in patients before (2000-2007) and after (2008-2012) a change to strict intraoperative intravenous (IV) fluid and liberal vasopressor management. Perioperative parameters (IV fluid administration, vasopressor use, maternal hemoglobin [Hb] concentration); maternal complication rate (respiratory, hemorrhagic); pregnancy outcome; and fetal and neonatal survival were recorded. Patients in the early group (2000-2007; n = 55) received 1634 ± 949 mL of crystalloid fluid intraoperatively, compared with 485 ± 238 mL (P < 0.001; Student's t test) given to the late group (2008-2012; n = 30). Maternal pulmonary edema and any respiratory distress were seen in 5.5% and 12.7% of patients in the early group, respectively, and in none of the late group patients (P < 0.05; Chi-square analysis). A significant risk of maternal respiratory complications exists after general anesthesia for endoscopic fetal surgery. Judicious fluid management significantly decreases this risk. Copyright © 2014 Elsevier Inc. All rights reserved.

Maternal obesity reduces oxidative capacity in fetal skeletal muscle of Japanese macaques

PubMed Central

McCurdy, Carrie E.; Hetrick, Byron; Houck, Julie; Drew, Brian G.; Kaye, Spencer; Lashbrook, Melanie; Bergman, Bryan C.; Takahashi, Diana L.; Dean, Tyler A.; Gertsman, Ilya; Hansen, Kirk C.; Philp, Andrew; Hevener, Andrea L.; Chicco, Adam J.; Aagaard, Kjersti M.; Grove, Kevin L.; Friedman, Jacob E.

2016-01-01

Maternal obesity is proposed to alter the programming of metabolic systems in the offspring, increasing the risk for developing metabolic diseases; however, the cellular mechanisms remain poorly understood. Here, we used a nonhuman primate model to examine the impact of a maternal Western-style diet (WSD) alone, or in combination with obesity (Ob/WSD), on fetal skeletal muscle metabolism studied in the early third trimester. We find that fetal muscle responds to Ob/WSD by upregulating fatty acid metabolism, mitochondrial complex activity, and metabolic switches (CPT-1, PDK4) that promote lipid utilization over glucose oxidation. Ob/WSD fetuses also had reduced mitochondrial content, diminished oxidative capacity, and lower mitochondrial efficiency in muscle. The decrease in oxidative capacity and glucose metabolism was persistent in primary myotubes from Ob/WSD fetuses despite no additional lipid-induced stress. Switching obese mothers to a healthy diet prior to pregnancy did not improve fetal muscle mitochondrial function. Lastly, while maternal WSD alone led only to intermediary changes in fetal muscle metabolism, it was sufficient to increase oxidative damage and cellular stress. Our findings suggest that maternal obesity or WSD, alone or in combination, leads to programmed decreases in oxidative metabolism in offspring muscle. These alterations may have important implications for future health. PMID:27734025

Epigenetic changes in fetal hypothalamic energy regulating pathways are associated with maternal undernutrition and twinning.

PubMed

Begum, Ghazala; Stevens, Adam; Smith, Emma Bolton; Connor, Kristin; Challis, John R G; Bloomfield, Frank; White, Anne

2012-04-01

Undernutrition during pregnancy is implicated in the programming of offspring for the development of obesity and diabetes. We hypothesized that maternal programming causes epigenetic changes in fetal hypothalamic pathways regulating metabolism. This study used sheep to examine the effect of moderate maternal undernutrition (60 d before to 30 d after mating) and twinning to investigate changes in the key metabolic regulators proopiomelanocortin (POMC) and the glucocorticoid receptor (GR) in fetal hypothalami. Methylation of the fetal hypothalamic POMC promoter was reduced in underfed singleton, fed twin, and underfed twin groups (60, 73, and 63% decrease, respectively). This was associated with reduced DNA methyltransferase activity and altered histone methylation and acetylation. Methylation of the hypothalamic GR promoter was decreased in both twin groups and in maternally underfed singleton fetuses (52, 65, and 55% decrease, respectively). This correlated with changes in histone methylation and acetylation and increased GR mRNA expression in the maternally underfed singleton group. Alterations in GR were hypothalamic specific, with no changes in hippocampi. Unaltered levels of OCT4 promoter methylation indicated gene-specific effects. In conclusion, twinning and periconceptional undernutrition are associated with epigenetic changes in fetal hypothalamic POMC and GR genes, potentially resulting in altered energy balance regulation in the offspring.

Coding update of the SMFM definition of low risk for cesarean delivery from ICD-9-CM to ICD-10-CM.

PubMed

Armstrong, Joanne; McDermott, Patricia; Saade, George R; Srinivas, Sindhu K

2017-07-01

In 2015, the Society for Maternal-Fetal Medicine developed a low risk for cesarean delivery definition based on administrative claims-based diagnosis codes described by the International Classification of Diseases, Ninth Revision, Clinical Modification. The Society for Maternal-Fetal Medicine definition is a clinical enrichment of 2 available measures from the Joint Commission and the Agency for Healthcare Research and Quality measures. The Society for Maternal-Fetal Medicine measure excludes diagnosis codes that represent clinically relevant risk factors that are absolute or relative contraindications to vaginal birth while retaining diagnosis codes such as labor disorders that are discretionary risk factors for cesarean delivery. The introduction of the International Statistical Classification of Diseases, 10th Revision, Clinical Modification in October 2015 expanded the number of available diagnosis codes and enabled a greater depth and breadth of clinical description. These coding improvements further enhance the clinical validity of the Society for Maternal-Fetal Medicine definition and its potential utility in tracking progress toward the goal of safely lowering the US cesarean delivery rate. This report updates the Society for Maternal-Fetal Medicine definition of low risk for cesarean delivery using International Statistical Classification of Diseases, 10th Revision, Clinical Modification coding. Copyright © 2017. Published by Elsevier Inc.

Maternal serum pregnancy-associated plasma protein A and fetal nuchal translucency thickness for the prediction of fetal trisomies in early pregnancy.

PubMed

Brizot, M L; Snijders, R J; Bersinger, N A; Kuhn, P; Nicolaides, K H

1994-12-01

To determine if the risk for fetal trisomies during the first trimester of pregnancy can be derived by combining data from maternal serum pregnancy-associated plasma protein A (PAPP-A) and fetal nuchal translucency thickness. Pregnancy-associated plasma protein A was measured in samples from 87 singleton pregnancies with fetal chromosomal abnormalities (45 trisomy 21, 19 trisomy 18, eight trisomy 13, 11 sex chromosome aneuploidies, four triploidies) and 348 chromosomally normal controls at 10-13 weeks' gestation. Likelihood ratios for trisomies 21, 18, and 13 in relation to PAPP-A, in multiples of the normal median (MoM) for crown-rump length, were derived from the overlapping gaussian frequency distribution curves for normal and abnormal pregnancies. In the chromosomally normal group, maternal serum PAPP-A correlated significantly with fetal crown-rump length (r = 0.421, P < .0001). In the chromosomally abnormal group, the median PAPP-A was significantly lower than in the normal controls. The respective median values expressed in MoM for trisomies 21, 18, and 13 and other aneuploidies were 0.5 MoM (90% confidence interval [CI] 0.09-1.67, z = 6.0, P < .001), 0.17 MoM (90% CI 0.06-1.45, z = 6.6, P < .001), 0.25 MoM (90% CI 0.10-0.62, z = 4.5, P < .001), and 0.72 MoM (90% CI 0.09-2.48, z = 2.2, P < .05), respectively. There was no significant linear association between PAPP-A and fetal nuchal translucency thickness in either the chromosomally normal (r = -0.01, P = .89) or abnormal groups (r = -0.19, P = .08). The risks for fetal trisomies at 10-13 weeks' gestation can be derived by combining data on maternal age, maternal serum PAPP-A, and fetal nuchal translucency thickness.

In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis

PubMed Central

Connolly, Fiona; Rae, Michael T.; Späth, Katharina; Boswell, Lyndsey; McNeilly, Alan S.; Duncan, W. Colin

2015-01-01

Increased maternal androgen exposure during pregnancy programmes a polycystic ovary syndrome (PCOS)-like condition, with metabolic dysfunction, in adult female offspring. Other in utero exposures associated with the development of insulin resistance, such as intrauterine growth restriction and exposure to prenatal glucocorticoids, are associated with altered fetal gluconeogenesis. We therefore aimed to assess the effect of maternal androgenisation on the expression of PEPCK and G6PC in the ovine fetus. Pregnant Scottish Greyface sheep were treated with twice weekly testosterone propionate (TP; 100mg) or vehicle control from day 62 to day102 of gestation. At day 90 and day 112 fetal plasma and liver and kidney tissue was collected for analysis. PEPCK and G6PC expression were analysed by quantitative RT-PCR, immunohistochemistry and western blotting. PEPCK and G6PC were localised to fetal hepatocytes but maternal androgens had no effect on female or male fetuses. PEPCK and G6PC were also localised to the renal tubules and renal PEPCK (P<0.01) and G6PC (P = 0.057) were lower in females after prenatal androgenisation with no change in male fetuses. These tissue and sex specific observations could not be explained by alterations in fetal insulin or cortisol. The sexual dimorphism may be related to the increase in circulating estrogen (P<0.01) and testosterone (P<0.001) in females but not males. The tissue specific effects may be related to the increased expression of ESR1 (P<0.01) and AR (P<0.05) in the kidney when compared to the fetal liver. After discontinuation of maternal androgenisation female fetal kidney PEPCK expression normalised. These data further highlight the fetal and sexual dimorphic effects of maternal androgenisation, an antecedent to adult disease and the plasticity of fetal development. PMID:26148093

[Epidemiology of maternal-fetal group B streptococcal infections].

PubMed

Ben Hamida Nouaili, E; Abidi, K; Chaouachi, S; Marrakchi, Z

2011-03-01

The aim of this study was to determine the incidence, risk factors, and outcome of maternal-fetal infection due to group B streptococcus. We identified all cases of maternal-fetal group B streptococcus infection between January 2003 and December 2007, from neonatal unit reports at the Charles Nicolle Hospital. Ninety cases were identified out of 17,922 live births, incidence 5 ‰ of which 2.3 ‰ of bacteremia. Twenty percent of all newborns were premature and 22.2% had a low birth weight. Peripartum maternal fever was recorded in 52.2% of cases and membrane rupture more than 12 hours before delivery occurred in 74.4%. Among the newborns, 45.6% were symptomatic at birth. Forty percent of group B streptococci were resistant to erythromycin and 3.3% with intermediate resistance to ampicillin. The global neonatal mortality after group B streptococcus infection was 3.3%. Maternal-fetal infection due to group B streptococcus is still frequent and continues to be a major cause of morbidity and mortality. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

[The role of oxidative stress in placental-related diseases of pregnancy].

PubMed

Jauniaux, E; Burton, G J

2016-10-01

In normal pregnancies, the earliest stages of development take place in a low oxygen (O 2 ) environment. This physiological hypoxia of the early gestational sac protects the developing fetus against the deleterious and teratogenic effects of O 2 free radicals. Oxidative stress is manifested at the maternal-fetal interface from early pregnancy onwards. In early pregnancy, a well-controlled oxidative stress plays a role in modulating placental development, functions and remodelling. Focal trophoblastic oxidative damage and progressive villous degeneration trigger the formation of the fetal membranes, which is an essential developmental step enabling vaginal delivery. Our data have demonstrated that the first trimester placenta in humans is histiotrophic and not haemochorial. The development and maintenance of a physiological O 2 gradient between the uterine and fetal circulations is also essential for placental functions, such as transport and hormonal synthesis. Pathological oxidative stress arises when the production of reactive O 2 species overwhelms the intrinsic anti-oxidant defences causing indiscriminate damage to biological molecules, leading to loss of function and cell death. We here review the role of oxidative stress in the pathophysiology of miscarriage, pre-eclampsia and fetal growth restriction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Performance of a wearable acoustic system for fetal movement discrimination

PubMed Central

Lai, Jonathan; Woodward, Richard; Alexandrov, Yuriy; ain Munnee, Qurratul; Lees, Christoph C.

2018-01-01

Fetal movements (FM) are a key factor in clinical management of high-risk pregnancies such as fetal growth restriction. While maternal perception of reduced FM can trigger self-referral to obstetric services, maternal sensation is highly subjective. Objective, reliable monitoring of fetal movement patterns outside clinical environs is not currently possible. A wearable and non-transmitting system capable of sensing fetal movements over extended periods of time would be extremely valuable, not only for monitoring individual fetal health, but also for establishing normal levels of movement in the population at large. Wearable monitors based on accelerometers have previously been proposed as a means of tracking FM, but such systems have difficulty separating maternal and fetal activity and have not matured to the level of clinical use. We introduce a new wearable system based on a novel combination of accelerometers and bespoke acoustic sensors as well as an advanced signal processing architecture to identify and discriminate between types of fetal movements. We validate the system with concurrent ultrasound tests on a cohort of 44 pregnant women and demonstrate that the garment is capable of both detecting and discriminating the vigorous, whole-body ‘startle’ movements of a fetus. These results demonstrate the promise of multimodal sensing for the development of a low-cost, non-transmitting wearable monitor for fetal movements. PMID:29734344

Performance of a wearable acoustic system for fetal movement discrimination.

PubMed

Lai, Jonathan; Woodward, Richard; Alexandrov, Yuriy; Ain Munnee, Qurratul; Lees, Christoph C; Vaidyanathan, Ravi; Nowlan, Niamh C

2018-01-01

Fetal movements (FM) are a key factor in clinical management of high-risk pregnancies such as fetal growth restriction. While maternal perception of reduced FM can trigger self-referral to obstetric services, maternal sensation is highly subjective. Objective, reliable monitoring of fetal movement patterns outside clinical environs is not currently possible. A wearable and non-transmitting system capable of sensing fetal movements over extended periods of time would be extremely valuable, not only for monitoring individual fetal health, but also for establishing normal levels of movement in the population at large. Wearable monitors based on accelerometers have previously been proposed as a means of tracking FM, but such systems have difficulty separating maternal and fetal activity and have not matured to the level of clinical use. We introduce a new wearable system based on a novel combination of accelerometers and bespoke acoustic sensors as well as an advanced signal processing architecture to identify and discriminate between types of fetal movements. We validate the system with concurrent ultrasound tests on a cohort of 44 pregnant women and demonstrate that the garment is capable of both detecting and discriminating the vigorous, whole-body 'startle' movements of a fetus. These results demonstrate the promise of multimodal sensing for the development of a low-cost, non-transmitting wearable monitor for fetal movements.

Maternal obesity downregulates myogenesis and beta-catenin signaling in fetal skeletal muscle.

PubMed

Tong, Jun F; Yan, Xu; Zhu, Mei J; Ford, Stephen P; Nathanielsz, Peter W; Du, Min

2009-04-01

Skeletal muscle is one of the primary tissues responsible for insulin resistance and type 2 diabetes (T2D). The fetal stage is crucial for skeletal muscle development. Obesity induces inflammatory responses, which might regulate myogenesis through Wnt/beta-catenin signaling. This study evaluated the effects of maternal obesity (>30% increase in body mass index) during pregnancy on myogenesis and the Wnt/beta-catenin and IKK/NF-kappaB pathways in fetal skeletal muscle using an obese pregnant sheep model. Nonpregnant ewes were assigned to a control group (C; fed 100% of National Research Council recommendations; n=5) or obesogenic (OB; fed 150% of National Research Council recommendations; n=5) diet from 60 days before to 75 days after conception (term approximately 148 days) when fetal semitendenosus skeletal muscle was sampled for analyses. Myogenic markers including MyoD, myogenin, and desmin contents were reduced in OB compared with C fetal semitendenosus, indicating the downregulation of myogenesis. The diameter of primary muscle fibers was smaller in OB fetal muscle. Phosphorylation of GSK3beta was reduced in OB compared with C fetal semitendenosus. Although the beta-catenin level was lower in OB than C fetal muscle, more beta-catenin was associated with FOXO3a in the OB fetuses. Moreover, we found phosphorylation levels of IKKbeta and RelA/p65 were both increased in OB fetal muscle. In conclusion, our data showed that myogenesis and the Wnt/beta-catenin signaling pathway were downregulated, which might be due to the upregulation of inflammatory IKK/NF-kappaB signaling pathways in fetal muscle of obese mothers.

Fetal Programming of Body Composition, Obesity, and Metabolic Function: The Role of Intrauterine Stress and Stress Biology

PubMed Central

Entringer, Sonja; Buss, Claudia; Swanson, James M.; Cooper, Dan M.; Wing, Deborah A.; Waffarn, Feizal; Wadhwa, Pathik D.

2012-01-01

Epidemiological, clinical, physiological, cellular, and molecular evidence suggests that the origins of obesity and metabolic dysfunction can be traced back to intrauterine life and supports an important role for maternal nutrition prior to and during gestation in fetal programming. The elucidation of underlying mechanisms is an area of interest and intense investigation. In this perspectives paper we propose that in addition to maternal nutrition-related processes it may be important to concurrently consider the potential role of intrauterine stress and stress biology. We frame our arguments in the larger context of an evolutionary-developmental perspective that supports roles for both nutrition and stress as key environmental conditions driving natural selection and developmental plasticity. We suggest that intrauterine stress exposure may interact with the nutritional milieu, and that stress biology may represent an underlying mechanism mediating the effects of diverse intrauterine perturbations, including but not limited to maternal nutritional insults (undernutrition and overnutrition), on brain and peripheral targets of programming of body composition, energy balance homeostasis, and metabolic function. We discuss putative maternal-placental-fetal endocrine and immune/inflammatory candidate mechanisms that may underlie the long-term effects of intrauterine stress. We conclude with a commentary of the implications for future research and clinical practice. PMID:22655178

Maternal and neonatal outcomes in labor and at delivery when long QT syndrome is present.

PubMed

Tanaka, Hiroaki; Katsuragi, Shinji; Tanaka, Kayo; Sawada, Masami; Iwanaga, Naoko; Yoshimatsu, Jun; Ikeda, Tomoaki

2016-01-01

Women during labor may be susceptible to torsades de pointes (TdP), which may cause the fetal condition to deteriorate. The aim of the present investigation was to analyze maternal and fetal outcomes during labor when long QT syndrome (LQTS) was present. We examined the maternal and neonatal outcomes of 25 pregnancies (18 women) with LQT between 1995 and 2012 at the Department of Perinatology, National Cardiovascular Center, Japan. Maternal and neonatal outcomes including cardiovascular events, cardiovascular events within a week after delivery, caesarean delivery rate, still births, preterm births, and non-reassuring fetal heart rate pattern (NRFHR) during labor were investigated. All the mothers survived, and no cardiovascular events occurred in labor or postpartum due to LQTS in either vaginal delivery or caesarean delivery. A total of 23 women (92%) had used beta blockers in this study. Caesarean delivery was performed due to NRFHR during labor in 5 pregnancies (20%). Delivery when LQTS is present has a low likelihood of cardiovascular events, but pregnancy with LQTS had a higher caesarean delivery rate due to NRFHR in labor. Most women used beta blockers in this study, and it is possible that beta blocker use prevents cardiovascular events during labor. NRFHR during labor may be related with inherited LQT through the mother.

Placental dysfunction in Suramin-treated rats: impact of maternal diabetes and effects of antioxidative treatment.

PubMed

Nash, Peppi; Olovsson, Matts; Eriksson, Ulf J

2005-04-01

The aim of the present study was to evaluate a rat model of placental dysfunction/preeclampsia in pregnancies complicated by maternal diabetes. A second objective was to evaluate the effects of vitamin E treatment in this model. Normal and streptozotocin-induced diabetic rats of two different strains (U and H) were given intraperitoneal (IP) injections of the angiogenesis inhibitor Suramin (Sigma Chemical Co, St Louis, MO) or saline in early pregnancy, and fed standard or vitamin E-enriched food. The outcome of pregnancy was evaluated on gestational day 20. In both rat strains Suramin caused fetal growth retardation, decreased placental blood flow, and increased placental concentration of the isoprostane 8-iso-PGF(2alpha). In the U rats Suramin also caused increased fetal resorption rate, increased maternal blood pressure, decreased renal blood flow, and diminished maternal growth. Diabetes caused severe maternal and fetal growth retardation, increased resorption rate, and increased placental 8-iso-PGF(2alpha) concentration independent of Suramin administration. The maternal and fetal effects of Suramin and diabetes were more pronounced in the U strain than in the H strain. Vitamin E treatment improved the status of Suramin-injected diabetic rats: in U rats the blood pressure increase was normalized; and in both U and H rats the decreased placental blood flow was marginally enhanced, and the increase in placental 8-iso-PGF(2alpha) was partly normalized by vitamin E. Suramin injections to pregnant rats cause a state of placental insufficiency, which in U rats resembles human preeclampsia. The induction of this condition is at least partly mediated by oxidative stress, and antagonized by antioxidative treatment. Maternal diabetes involves increased oxidative stress, and causes both maternal and fetal morbidity, which are only marginally affected by additional Suramin treatment.

Optimizing blood collection, transport and storage conditions for cell free DNA increases access to prenatal testing.

PubMed

Wong, David; Moturi, Sharmili; Angkachatchai, Vach; Mueller, Reinhold; DeSantis, Grace; van den Boom, Dirk; Ehrich, Mathias

2013-08-01

Fetal mutations and fetal chromosomal abnormalities can be detected by molecular analysis of circulating cell free fetal DNA (ccffDNA) from maternal plasma. This comprehensive study was aimed to investigate and verify blood collection and blood shipping conditions that enable Noninvasive Prenatal Testing. Specifically, the impact of shipping and storage on the stability and concentration of circulating cell-free DNA (ccfDNA) in Streck® Cell-Free DNA™ Blood Collection Tubes (Streck BCTs, Streck, Omaha NE). These BCTs were designed to minimize cellular degradation, and thus effectively prevent dilution of fetal ccf DNA by maternal genomic DNA, was evaluated. Peripheral venous maternal blood was collected into Streck BCTs to investigate four aspects of handling and processing conditions: (1) time from blood draw to plasma processing; (2) storage temperature; (3) mechanical stress; and (4) lot-to-lot tube variations. Maternal blood stored in Streck BCTs for up to 7 days at ambient temperature provides stable concentrations of ccffDNA. The amount of fetal DNA did not change over a broad range of storage temperatures (4°C, 23°C, 37°C, 40°C), but the amount of total (largely maternal) DNA increased in samples stored at 23°C and above, indicating maternal cell degradation and genomic DNA release at elevated temperatures. Shipping maternal blood in Streck BCTs, did not affect sample quality. Maternal plasma DNA stabilized for 0 to 7 days in Streck BCTs can be used for non-invasive prenatal molecular applications, when temperatures are maintained within the broad parameters assessed in this study. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Exercise in pregnancy. Part 1: Update on pathophysiology.

PubMed Central

Stevenson, L.

1997-01-01

OBJECTIVE: To review the current data regarding the safety of exercise in pregnancy. QUALITY OF EVIDENCE: MEDLINE search was limited to English literature between 1987 and 1995 with the key MeSH words exercise and pregnancy. Other sources included the Sports and Fitness Database between 1991 and 1995 and a manual search for relevant articles. Previous studies on the safety of exercise in pregnancy are limited in many ways and exhibit difficulties in controlling for confounding factors and in establishing associations while maintaining maternal and fetal safety. MAIN FINDINGS: Concerns about the effect of exercise on pregnancy include exercise-induced hyperthermia, birth weight changes, fetal heart rate responses, miscarriage, labour patterns, maternal injury, and maternal weight gain. Exercise during pregnancy also has many potential benefits. CONCLUSIONS: Important gaps in our knowledge of exercise and pregnancy remain. Available data suggest, however, that moderate exercise on a regular basis during a healthy pregnancy has minimal risk for women and their fetuses. PMID:9626428

Maternal choline supplementation: a nutritional approach for improving offspring health?

PubMed

Jiang, Xinyin; West, Allyson A; Caudill, Marie A

2014-05-01

The modulatory role of choline on the fetal epigenome and the impact of in utero choline supply on fetal programming and health are of great interest. Studies in animals and/or humans suggest that maternal choline supplementation during pregnancy benefits important physiologic systems such as offspring cognitive function, response to stress, and cerebral inhibition. Because alterations in offspring phenotype frequently coincide with epigenetic modifications and changes in gene expression, maternal choline supplementation may be a nutritional strategy to improve lifelong health of the child. Future studies are warranted to elucidate further the effect of choline on the fetal epigenome and to determine the level of maternal choline intake required for optimal offspring physiologic function. Copyright © 2014 Elsevier Ltd. All rights reserved.

Non-invasive fetal RHD genotyping for RhD negative women stratified into RHD gene deletion or variant groups: comparative accuracy using two blood collection tube types.

PubMed

Hyland, Catherine A; Millard, Glenda M; O'Brien, Helen; Schoeman, Elizna M; Lopez, Genghis H; McGowan, Eunike C; Tremellen, Anne; Puddephatt, Rachel; Gaerty, Kirsten; Flower, Robert L; Hyett, Jonathan A; Gardener, Glenn J

2017-12-01

Non-invasive fetal RHD genotyping in Australia to reduce anti-D usage will need to accommodate both prolonged sample transport times and a diverse population demographic harbouring a range of RHD blood group gene variants. We compared RHD genotyping accuracy using two blood sample collection tube types for RhD negative women stratified into deleted RHD gene haplotype and RHD gene variant cohorts. Maternal blood samples were collected into EDTA and cell-free (cf)DNA stabilising (BCT) tubes from two sites, one interstate. Automated DNA extraction and polymerase chain reaction (PCR) were used to amplify RHD exons 5 and 10 and CCR5. Automated analysis flagged maternal RHD variants, which were classified by genotyping. Time between sample collection and processing ranged from 2.9 to 187.5 hours. cfDNA levels increased with time for EDTA (range 0.03-138 ng/μL) but not BCT samples (0.01-3.24 ng/μL). For the 'deleted' cohort (n=647) all fetal RHD genotyping outcomes were concordant, excepting for one unexplained false negative EDTA sample. Matched against cord RhD serology, negative predictive values using BCT and EDTA tubes were 100% and 99.6%, respectively. Positive predictive values were 99.7% for both types. Overall 37.2% of subjects carried an RhD negative baby. The 'variant' cohort (n=15) included one novel RHD and eight hybrid or African pseudogene variants. Review for fetal RHD specific signals, based on one exon, showed three EDTA samples discordant to BCT, attributed to high maternal cfDNA levels arising from prolonged transport times. For the deleted haplotype cohort, fetal RHD genotyping accuracy was comparable for samples collected in EDTA and BCT tubes despite higher cfDNA levels in the EDTA tubes. Capacity to predict fetal RHD genotype for maternal carriers of hybrid or pseudogene RHD variants requires stringent control of cfDNA levels. We conclude that fetal RHD genotyping is feasible in the Australian environment to avoid unnecessary anti-D immunoglobulin prophylaxis. Copyright © 2017. Published by Elsevier B.V.

The influence of fetal sex in screening for trisomy 21 by fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation.

PubMed

Spencer, K; Ong, C Y; Liao, A W; Papademetriou, D; Nicolaides, K H

2000-08-01

In a study of 2923 normal pregnancies and 203 pregnancies affected by trisomy 21 we have shown a significant difference in the median MoM of the markers: fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A in the presence of a female fetus compared with a male fetus. For maternal serum free beta-hCG levels are higher by 15% if the fetus is chromosomally normal and by 11% if the fetus has trisomy 21. For maternal serum PAPP-A the levels in chromosomally normal fetuses are 10% higher in the presence of a female fetus and 13% higher if the fetus has trisomy 21. In contrast, fetal nuchal translucency is 3-4% lower in both chromosomally normal and trisomy 21 female fetuses. The consequence of such changes when screening for trisomy 21 will be a reduction in the detection rate in female fetuses by a factor of 1-2%. Correction of risk algorithms for fetal sex, however, is probably not feasible, since ultrasound detection of fetal sex is only 70-90% accurate in the 10-14 week period. Copyright 2000 John Wiley & Sons, Ltd.

Maternal and fetal response to fetal persistent infection with bovine viral diarrhea virus.

PubMed

Hansen, Thomas R; Smirnova, Natalia P; Van Campen, Hana; Shoemaker, Megan L; Ptitsyn, Andrey A; Bielefeldt-Ohmann, Helle

2010-10-01

Infection of naïve pregnant cows with non-cytopathic (ncp) bovine viral diarrhea virus (BVDV) results in transplacental infection of the fetus. Infection of the pregnant cow with ncp BVDV late in gestation (after day 150) results in transient infection (TI), as both the dam and fetus can mount an immune response to the virus. In contrast, if the fetus is infected with ncp BVDV early in gestation (before day 150), the fetal immune system is undeveloped and unable to recognize the virus as foreign. This results in induction of immune tolerance to the infecting BVDV strain and persistent infection (PI). Infection of naïve pregnant heifers with ncp BVDV2 on day 75 was hypothesized to induce differential gene expression in white blood cells of the dams and their fetuses, adversely affecting development and antiviral immune responses in PI fetuses. Gene expression differed in maternal blood cells in the presence of PI versus uninfected fetuses. PI adversely affected fetal development and antiviral responses, despite protective immune responses in the dam. Fetal PI with BVDV alters maternal immune function, compromises fetal growth and immune responses, and results in expression of maternal blood biomarkers that can be used to identify cows carrying PI fetuses.

The outcomes and risk factors of fetal bradycardia associated with external cephalic version.

PubMed

Suyama, Fumio; Ogawa, Kohei; Tazaki, Yukiko; Miwa, Terumi; Taniguchi, Kosuke; Nakamura, Noriyuki; Tanaka, Satomi; Tanigaki, Shinji; Sago, Haruhiko

2017-11-02

The objective of this study is to assess the outcomes and risk factors of fetal bradycardia after external cephalic version (ECV). We performed a retrospective study of women who underwent ECV after 35 weeks of gestation in 2010-2016. We assessed the birth outcomes, including umbilical cord artery pH, according to the duration of fetal bradycardia and the risk factors for bradycardia. Among 390 cases, 189 (48.5%) cases showed fetal bradycardia during or immediately after ECV. The duration of fetal bradycardia was <1 min (n = 82, 43.4%), <5 min (n = 168, 88.9%); and <10 min (n = 186, 98.4%). All cases showed a good prognosis. Fetal bradycardia lasting >10 min occurred in three cases; emergency cesarean section was performed in each case, with delivery after 12-4 min of bradycardia. Two of three cases showed low Apgar scores at 5 min, with an umbilical cord arterial pH of <7.1. Lower maternal BMI and a prolonged ECV procedure were significantly associated with bradycardia (p for trend: .016 and .015, respectively). Fetal bradycardia lasting >10 min after ECV was a risk factor for asphyxia. Thus, delivery should be completed within 10 min after bradycardia. A low maternal BMI and a prolonged ECV procedure were risk factors for bradycardia after ECV.

Group B Streptococcus β-hemolysin/Cytolysin Breaches Maternal-Fetal Barriers to Cause Preterm Birth and Intrauterine Fetal Demise in Vivo

PubMed Central

Randis, Tara M.; Gelber, Shari E.; Hooven, Thomas A.; Abellar, Rosanna G.; Akabas, Leor H.; Lewis, Emma L.; Walker, Lindsay B.; Byland, Leah M.; Nizet, Victor; Ratner, Adam J.

2014-01-01

Background. Maternal vaginal colonization with Streptococcus agalactiae (Group B Streptococcus [GBS]) is a precursor to chorioamnionitis, fetal infection, and neonatal sepsis, but the understanding of specific factors in the pathogenesis of ascending infection remains limited. Methods. We used a new murine model to evaluate the contribution of the pore-forming GBS β-hemolysin/cytolysin (βH/C) to vaginal colonization, ascension, and fetal infection. Results. Competition assays demonstrated a marked advantage to βH/C-expressing GBS during colonization. Intrauterine fetal demise and/or preterm birth were observed in 54% of pregnant mice colonized with wild-type (WT) GBS and 0% of those colonized with the toxin-deficient cylE knockout strain, despite efficient colonization and ascension by both strains. Robust placental inflammation, disruption of maternal-fetal barriers, and fetal infection were more frequent in animals colonized with WT bacteria. Histopathologic examination revealed bacterial tropism for fetal lung and liver. Conclusions. Preterm birth and fetal demise are likely the direct result of toxin-induced damage and inflammation rather than differences in efficiency of ascension into the upper genital tract. These data demonstrate a distinct contribution of βH/C to GBS chorioamnionitis and subsequent fetal infection in vivo and showcase a model for this most proximal step in GBS pathogenesis. PMID:24474814

Pregnancy Complications Associated With Maternal Hypothyroidism: A Systematic Review.

PubMed

Shinohara, Danielle Rosani; Santos, Thais da Silva; de Carvalho, Hayalla Corrêa; Lopes, Laíza Cristina Bahls; Günther, Luciene Setsuko Akimoto; Aristides, Sandra Mara Alessi; Teixeira, Jorge Juarez Vieira; Demarchi, Izabel Galhardo

2018-04-01

Hypothyroidism is one of the most prevalent diseases in pregnancy, but there is no consensus about its management in pregnant women. In this systematic review, we evaluated the association between pregnancy complications and treated or untreated maternal hypothyroidism. PubMed and reference lists were searched for the Medical Subject Headings terms "pregnancy complications" and "hypothyroidism." The eligibility criteria for inclusion in the study were an original study published between 2002 and 2013. Six reviewers independently selected the studies, and 3 extracted the data. Two reviewers assessed the risk of bias and quality of the studies. Eighteen studies were included in the systematic review. The most prevalent complications associated with maternal hypothyroidism were abortion, intrauterine fetal death, preterm delivery, and preeclampsia. The pregnancy outcome depended on the treatment that was received by the patient. Strong evidence indicates that maternal hypothyroidism is associated with maternal-fetal complications, but no consensus was found among the studies reviewed herein. The dose of levothyroxine that is required to maintain euthyroidism is still questioned, but studies have suggested that levothyroxine should be adjusted according to the gestational period and laboratory profile.

Amnioinfusion for relief of recurrent severe and moderate variable decelerations in labor.

PubMed

Regi, Annie; Alexander, Nancy; Jose, Ruby; Lionel, Jessie; Varghese, Lilly; Peedicayil, Abraham

2009-05-01

To determine whether intrapartum amnioinfusion (AI) relieves recurrent moderate and severe variable decelerations in laboring women with clear or grade I meconium-stained amniotic fluid and reduces cesarean section rate for fetal distress. A randomized controlled trial was conducted in labor unit of Christian Medical College Hospital, Vellore, India, between October 2003 and September 2004. Women were randomized to receive AI (group I) and not to receive it (group II). A total of 150 women (75 in each group) were included in the study. There was significant relief of variable decelerations in group I and no difference in overall cesarean section rate but significant reduction in cesarean section rate for fetal distress in group I, and significant reduction in cesarean section rate for fetal distress in nulliparous women of group I. Neonatal acidemia was also significantly reduced in the nulliparous women receiving AI. The duration of maternal postpartum hospital stay was significantly reduced in group I. There were no adverse maternal or neonatal outcomes. AI was a beneficial therapeutic intervention in women patients showing fetal distress in first stage of labor, and it reduced cesarean section for fetal distress and neonatal acidemia.

Wavelet-Based Adaptive Denoising of Phonocardiographic Records

DTIC Science & Technology

2001-10-25

phonocardiography, including the recording of fetal heart sounds on the maternal abdominal surface. Keywords - phonocardiography, wavelets, denoising, signal... fetal heart rate monitoring [2], [7], [8]. Unfortunately, heart sound records are very often disturbed by various factors, which can prohibit their...recorded the acoustic signals. The first microphone was inserted into the focus of a stethoscope and it recorded the acoustic signals of the heart ( heart

In utero exposure to cigarette chemicals induces sex-specific disruption of one-carbon metabolism and DNA methylation in the human fetal liver.

PubMed

Drake, Amanda J; O'Shaughnessy, Peter J; Bhattacharya, Siladitya; Monteiro, Ana; Kerrigan, David; Goetz, Sven; Raab, Andrea; Rhind, Stewart M; Sinclair, Kevin D; Meharg, Andrew A; Feldmann, Jörg; Fowler, Paul A

2015-01-29

Maternal smoking is one of the most important modifiable risk factors for low birthweight, which is strongly associated with increased cardiometabolic disease risk in adulthood. Maternal smoking reduces the levels of the methyl donor vitamin B12 and is associated with altered DNA methylation at birth. Altered DNA methylation may be an important mechanism underlying increased disease susceptibility; however, the extent to which this can be induced in the developing fetus is unknown. In this retrospective study, we measured concentrations of cobalt, vitamin B12, and mRNA transcripts encoding key enzymes in the 1-carbon cycle in 55 fetal human livers obtained from 11 to 21 weeks of gestation elective terminations and matched for gestation and maternal smoking. DNA methylation was measured at critical regions known to be susceptible to the in utero environment. Homocysteine concentrations were analyzed in plasma from 60 fetuses. In addition to identifying baseline sex differences, we found that maternal smoking was associated with sex-specific alterations of fetal liver vitamin B12, plasma homocysteine and expression of enzymes in the 1-carbon cycle in fetal liver. In the majority of the measured parameters which showed a sex difference, maternal smoking reduced the magnitude of that difference. Maternal smoking also altered DNA methylation at the imprinted gene IGF2 and the glucocorticoid receptor (GR/NR3C1). Our unique data strengthen studies linking in utero exposures to altered DNA methylation by showing, for the first time, that such changes are present in fetal life and in a key metabolic target tissue, human fetal liver. Furthermore, these data propose a novel mechanism by which such changes are induced, namely through alterations in methyl donor availability and changes in 1-carbon metabolism.

Magnetic resonance angiography of fetal vasculature at 3.0 T.

PubMed

Neelavalli, Jaladhar; Krishnamurthy, Uday; Jella, Pavan K; Mody, Swati S; Yadav, Brijesh K; Hendershot, Kelly; Hernandez-Andrade, Edgar; Yeo, Lami; Cabrera, Maria D; Haacke, Ewart M; Hassan, Sonia S; Romero, Roberto

2016-12-01

Magnetic resonance angiography has not been used much previously for visualizing fetal vessels in utero for reasons that include a contraindication for the use of exogenous contrast agents, maternal respiratory motion and fetal motion. In this work, we report the feasibility of using an appropriately modified clinical time-of-flight magnetic resonance imaging sequence for non-contrast angiography of human fetal and placental vessels at 3.0 T. Using this 2D angiography technique, it is possible to visualize fetal vascular networks in late pregnancy. • 3D-visualization of fetal vasculature is feasible using non-contrast MRA at 3.0 T. • Visualization of placental vasculature is also possible with this method. • Fetal MRA can serve as a vascular localizer for quantitative MRI studies. • This method can be extended to 1.5 T.