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

Prospective assessment of early fetal loss using an immunoenzymometric screening assay for detection of urinary human chorionic gonadotropin.

PubMed

Taylor, C A; Overstreet, J W; Samuels, S J; Boyers, S P; Canfield, R E; O'Connor, J F; Hanson, F W; Lasley, B L

1992-06-01

To develop an economical, nonradiometric immunoenzymometric assay (IEMA) for the detection of urinary human chorionic gonadotropin (hCG) in studies of early fetal loss. To be effective, the IEMA must have a sensitivity equal to the standard immunoradiometric assay (IRMA) and sufficient specificity to eliminate the need for screening most nonconceptive cycles with the expensive and labor-intensive IRMA. Two different assays were used to measure hCG in daily early morning urine samples from potential conceptive cycles. Women undergoing donor artificial insemination (AI) were evaluated in a prospective study. Ninety-two women volunteers were selected on the basis of apparent normal reproductive health. Artificial insemination with nonfrozen donor semen was performed by cervical cup twice each menstrual cycle at 48-hour intervals, and daily urine samples were self-collected throughout the menstrual cycle. An IEMA was developed to detect urinary hCG using the same antibodies as in the standard IRMA; a study was designed to determine whether this nonradiometric assay could successfully detect the early fetal loss that was detected by the IRMA. Of 224 menstrual cycles analyzed by both assays, a total of six early fetal losses were detected by the IRMA. When the tentative screening rule was set to allow all six of these losses and 95% of future losses to be detected by the IEMA, an additional 34 false-positive results were detected by the IEMA. The specificity of the IEMA with this rule was calculated to be 84%. An IEMA based on the same antibodies used for the standard IRMA can serve as an efficient screening assay for the detection of early fetal loss. When the IEMA is used in this manner, nearly 80% of screened menstrual cycles can be eliminated without further testing by the IRMA.

Fetal Brain Behavior and Cognitive Development.

ERIC Educational Resources Information Center

Joseph, R.

2000-01-01

Presents information on prenatal brain development, detailing the functions controlled by the medulla, pons, and midbrain, and the implications for cognitive development. Concludes that fetal cognitive motor activity, including auditory discrimination, orienting, the wake-sleep cycle, fetal heart rate accelerations, and defensive reactions,…

Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra.

PubMed

Shen, Joel; Overland, Maya; Sinclair, Adriane; Cao, Mei; Yue, Xuan; Cunha, Gerald; Baskin, Laurence

We recently described a two-step process of urethral plate canalization and urethral fold fusion to form the human penile urethra. Canalization ("opening zipper") opens the solid urethral plate into a groove, and fusion ("closing zipper") closes the urethral groove to form the penile urethra. We hypothesize that failure of canalization and/or fusion during human urethral formation can lead to hypospadias. Herein, we use scanning electron microscopy (SEM) and analysis of transverse serial sections to better characterize development of the human fetal penile urethra as contrasted to the development of the human fetal clitoris. Eighteen 7-13 week human fetal external genitalia specimens were analyzed by SEM, and fifteen additional human fetal specimens were sectioned for histologic analysis. SEM images demonstrate canalization of the urethral/vestibular plate in the developing male and female external genitalia, respectively, followed by proximal to distal fusion of the urethral folds in males only. The fusion process during penile development occurs sequentially in multiple layers and through the interlacing of epidermal "cords". Complex epithelial organization is also noted at the site of active canalization. The demarcation between the epidermis of the shaft and the glans becomes distinct during development, and the epithelial tag at the distal tip of the penile and clitoral glans regresses as development progresses. In summary, SEM analysis of human fetal specimens supports the two-zipper hypothesis of formation of the penile urethra. The opening zipper progresses from proximal to distal along the shaft of the penis and clitoris into the glans in identical fashion in both sexes. The closing zipper mechanism is active only in males and is not a single process but rather a series of layered fusion events, uniquely different from the simple fusion of two epithelial surfaces as occurs in formation of the palate and neural tube. Copyright © 2016 International Society

The role of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment.

PubMed

Ohara, Noriyuki; Tsujino, Taro; Maruo, Takeshi

2004-11-01

To review the literature on the roles of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment. MEDLINE was searched for English-language papers published from 1971 to 2003, using the key words "brain," "hypothyroidism," "placenta," "pregnancy," "threatened abortion," "thyroid hormone," "thyroid hormone receptor," "thyroid hormone replacement therapy," "thyroid hormone-responsive gene," and "trophoblast." Transplacental transfer of thyroid hormone occurs before the onset of fetal thyroid hormone secretion. Thyroid hormone receptors and iodothyronine deiodinases are present in the placenta and the fetal central nervous system early in pregnancy, and thyroid hormone plays a crucial role both in trophoblast function and fetal neurodevelopment. Maternal hypothyroxinemia is associated with a high rate of spontaneous abortion and long-term neuropsychological deficits in children born of hypothyroid mothers. Maternal iodine deficiency also causes a wide spectrum of neuropsychological disorders in children, ranging from subclinical deficits in cognitive motor and auditory functions to hypothyroid-induced cognitive impairment in infants. However, these conditions are preventable when iodine supplementation is initiated before the second trimester. Although thyroid hormone replacement therapy is effective for reducing the adverse effects complicated by maternal hypothyroidism, the appropriate dose of thyroid hormone is mandatory in protecting the early stage of pregnancy. Close monitoring of maternal thyroid hormone status and ensuring adequate maternal thyroid hormone levels in early pregnancy are of great importance to prevent miscarriage and neuropsychological deficits in infants.

Fetal programming and early identification of newborns at high risk of free radical-mediated diseases.

PubMed

Perrone, Serafina; Santacroce, Antonino; Picardi, Anna; Buonocore, Giuseppe

2016-05-08

Nowadays metabolic syndrome represents a real outbreak affecting society. Paradoxically, pediatricians must feel involved in fighting this condition because of the latest evidences of developmental origins of adult diseases. Fetal programming occurs when the normal fetal development is disrupted by an abnormal insult applied to a critical point in intrauterine life. Placenta assumes a pivotal role in programming the fetal experience in utero due to the adaptive changes in structure and function. Pregnancy complications such as diabetes, intrauterine growth restriction, pre-eclampsia, and hypoxia are associated with placental dysfunction and programming. Many experimental studies have been conducted to explain the phenotypic consequences of fetal-placental perturbations that predispose to the genesis of metabolic syndrome, obesity, diabetes, hyperinsulinemia, hypertension, and cardiovascular disease in adulthood. In recent years, elucidating the mechanisms involved in such kind of process has become the challenge of scientific research. Oxidative stress may be the general underlying mechanism that links altered placental function to fetal programming. Maternal diabetes, prenatal hypoxic/ischaemic events, inflammatory/infective insults are specific triggers for an acute increase in free radicals generation. Early identification of fetuses and newborns at high risk of oxidative damage may be crucial to decrease infant and adult morbidity.

Diet reduction to requirements in obese/overfed ewes from early gestation prevents glucose/insulin dysregulation and returns fetal adiposity and organ development to control levels

PubMed Central

Tuersunjiang, Nuermaimaiti; Odhiambo, John F.; Long, Nathan M.; Shasa, Desiree R.; Nathanielsz, Peter W.

2013-01-01

Obesity at conception and excess gestational weight gain pose significant risks for adverse health consequences in human offspring. This study evaluated the effects of reducing dietary intake of obese/overfed ewes beginning in early gestation on fetal development. Sixty days prior to conception, ewes were assigned to a control diet [CON: 100% of National Research Council (NRC) recommendations], a diet inducing maternal obesity (MO: 150% of NRC recommendations), or a maternal obesity intervention diet (MOI: 150% of NRC recommendations to day 28 of gestation, then 100% NRC) until necropsy at midgestation (day 75) or late (day 135) gestation. Fetal size and weight, as well as fetal organ weights, were greater (P < 0.05) at midgestation in MO ewes than those of CON and MOI ewes. By late gestation, whereas fetal size and weight did not differ among dietary groups, cardiac ventricular weights and wall thicknesses as well as liver and perirenal fat weights remained elevated in fetuses from MO ewes compared with those from CON and MOI ewes. MO ewes and fetuses exhibited elevated (P < 0.05) plasma concentrations of triglycerides, cholesterol, insulin, glucose, and cortisol at midgestation compared with CON and MOI ewes and fetuses. In late gestation, whereas plasma triglycerides and cholesterol, insulin, and cortisol remained elevated in MO vs. CON and MOI ewes and fetuses, glucose concentrations were elevated in both MO and MOI fetuses compared with CON fetuses, which was associated with elevated placental GLUT3 expression in both groups. These data are consistent with the concept that reducing maternal diet of obese/overfed ewes to requirements from early gestation can prevent subsequent alterations in fetal growth, adiposity, and glucose/insulin dynamics. PMID:23921140

Diet reduction to requirements in obese/overfed ewes from early gestation prevents glucose/insulin dysregulation and returns fetal adiposity and organ development to control levels.

PubMed

Tuersunjiang, Nuermaimaiti; Odhiambo, John F; Long, Nathan M; Shasa, Desiree R; Nathanielsz, Peter W; Ford, Stephen P

2013-10-01

Obesity at conception and excess gestational weight gain pose significant risks for adverse health consequences in human offspring. This study evaluated the effects of reducing dietary intake of obese/overfed ewes beginning in early gestation on fetal development. Sixty days prior to conception, ewes were assigned to a control diet [CON: 100% of National Research Council (NRC) recommendations], a diet inducing maternal obesity (MO: 150% of NRC recommendations), or a maternal obesity intervention diet (MOI: 150% of NRC recommendations to day 28 of gestation, then 100% NRC) until necropsy at midgestation (day 75) or late (day 135) gestation. Fetal size and weight, as well as fetal organ weights, were greater (P < 0.05) at midgestation in MO ewes than those of CON and MOI ewes. By late gestation, whereas fetal size and weight did not differ among dietary groups, cardiac ventricular weights and wall thicknesses as well as liver and perirenal fat weights remained elevated in fetuses from MO ewes compared with those from CON and MOI ewes. MO ewes and fetuses exhibited elevated (P < 0.05) plasma concentrations of triglycerides, cholesterol, insulin, glucose, and cortisol at midgestation compared with CON and MOI ewes and fetuses. In late gestation, whereas plasma triglycerides and cholesterol, insulin, and cortisol remained elevated in MO vs. CON and MOI ewes and fetuses, glucose concentrations were elevated in both MO and MOI fetuses compared with CON fetuses, which was associated with elevated placental GLUT3 expression in both groups. These data are consistent with the concept that reducing maternal diet of obese/overfed ewes to requirements from early gestation can prevent subsequent alterations in fetal growth, adiposity, and glucose/insulin dynamics.

Noninvasive monitoring of fetal growth and development in the Siberian polecat (Mustela eversmanni)

USGS Publications Warehouse

Wimsatt, Jeffrey; Johnson, Jay D.; Wrigley, Robert H.; Biggins, Dean E.; Godbey, Jerry L.

1998-01-01

The Siberian polecat (Mustela eversmanni) is the preferred species to assess procedures and establish normative values for application in the related and endangered black-footed ferret (Mustela nigripes). This study was undertaken to physically, ultrasonographically, and radiographically evaluate fetal development in a spontaneously breeding captive Siberian polecat population. Ultrasonographically, fetal sac enlargement allowed presumptive preg nancy detection as early as 12 days of gestation, the fetal pole was the first definitive sign of pregnancy at about 18 days of gestation, when the fetal heart beat also appeared, and definitive pregnancy detection by ultrasound was essentially 100% accurate after 18 days. The estimation of fetal number by ultrasound was less reliable than by radiography, as it is in other litter-bearing species. Crown-rump growth, organ differentiation, and calcification patterns resembled those of domestic carnivores except that comparable developmental stages in polecats occurred at dispro portionately later times, suggesting that young Siberian polecats are delivered in a less developed state. Careful palpation permitted detection of pregnancy after day 17 but with less certainty than with ultrasound. Radiographic evaluation was insensitive and of limited value for pregnancy detection until near term. Litter number and fetal detail were difficult to assess until ossification could be observed, 3-6 days before parturition.

Noninvasive monitoring of fetal growth and development in the Siberian polecat (Mustela eversmanni).

PubMed

Wimsatt, J; Johnson, J D; Wrigley, R H; Biggins, D E; Godbey, J L

1998-12-01

The Siberian polecat (Mustela eversmanni) is the preferred species to assess procedures and establish normative values for application in the related and endangered black-footed ferret (Mustela nigripes). This study was undertaken to physically, ultrasonographically, and radiographically evaluate fetal development in a spontaneously breeding captive Siberian polecat population. Ultrasonographically, fetal sac enlargement allowed presumptive pregnancy detection as early as 12 days of gestation, the fetal pole was the first definitive sign of pregnancy at about 18 days of gestation, when the fetal heart beat also appeared, and definitive pregnancy detection by ultrasound was essentially 100% accurate after 18 days. The estimation of fetal number by ultrasound was less reliable than by radiography, as it is in other litter-bearing species. Crown-rump growth, organ differentiation, and calcification patterns resembled those of domestic carnivores except that comparable developmental stages in polecats occurred at disproportionately later times, suggesting that young Siberian polecats are delivered in a less developed state. Careful palpation permitted detection of pregnancy after day 17 but with less certainty than with ultrasound. Radiographic evaluation was insensitive and of limited value for pregnancy detection until near term. Litter number and fetal detail were difficult to assess until ossification could be observed, 3-6 days before parturition.

Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review).

PubMed

Agrogiannis, Georgios D; Sifakis, Stavros; Patsouris, Efstratios S; Konstantinidou, Anastasia E

2014-08-01

The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre‑implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development.

Improving Metabolic Health in Obese Male Mice via Diet and Exercise Restores Embryo Development and Fetal Growth

PubMed Central

McPherson, Nicole O.; Bakos, Hassan W.; Owens, Julie A.; Setchell, Brian P.; Lane, Michelle

2013-01-01

Paternal obesity is now clearly associated with or causal of impaired embryo and fetal development and reduced pregnancy rates in humans and rodents. This appears to be a result of reduced blastocyst potential. Whether these adverse embryo and fetal outcomes can be ameliorated by interventions to reduce paternal obesity has not been established. Here, male mice fed a high fat diet (HFD) to induce obesity were used, to determine if early embryo and fetal development is improved by interventions of diet (CD) and/or exercise to reduce adiposity and improve metabolism. Exercise and to a lesser extent CD in obese males improved embryo development rates, with increased cell to cell contacts in the compacting embryo measured by E-cadherin in exercise interventions and subsequently, increased blastocyst trophectoderm (TE), inner cell mass (ICM) and epiblast cell numbers. Implantation rates and fetal development from resulting blastocysts were also improved by exercise in obese males. Additionally, all interventions to obese males increased fetal weight, with CD alone and exercise alone, also increasing fetal crown-rump length. Measures of embryo and fetal development correlated with paternal measures of glycaemia, insulin action and serum lipids regardless of paternal adiposity or intervention, suggesting a link between paternal metabolic health and subsequent embryo and fetal development. This is the first study to show that improvements to metabolic health of obese males through diet and exercise can improve embryo and fetal development, suggesting such interventions are likely to improve offspring health. PMID:23977045

Universal characteristics of evolution and development are inherent in fetal autonomic brain maturation.

PubMed

Schmidt, Alexander; Schukat-Talamazzini, Ernst G; Zöllkau, Janine; Pytlik, Adelina; Leibl, Sophia; Kumm, Kathrin; Bode, Franziska; Kynass, Isabelle; Witte, Otto W; Schleussner, Ekkehard; Schneider, Uwe; Hoyer, Dirk

2018-07-01

Adverse prenatal environmental influences to the developing fetus are associated with mental and cardiovascular disease in later life. Universal developmental characteristics such as self-organization, pattern formation, and adaptation in the growing information processing system have not yet been sufficiently analyzed with respect to description of normal fetal development and identification of developmental disturbances. Fetal heart rate patterns are the only non-invasive order parameter of the developing autonomic brain available with respect to the developing complex organ system. The objective of the present study was to investigate whether universal indices, known from evolution and phylogeny, describe the ontogenetic fetal development from 20 weeks of gestation onwards. By means of a 10-fold cross-validated data-driven multivariate regression modeling procedure, relevant indices of heart rate variability (HRV) were explored using 552 fetal heart rate recordings, each lasting over 30 min. We found that models which included HRV indices of increasing fluctuation amplitude, complexity and fractal long-range dependencies largely estimated the maturation age (coefficients of determination 0.61-0.66). Consideration of these characteristics in prenatal care may not only have implications for early identification of developmental disturbances, but also for the development of system-theory-based therapeutic strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

Hypoxia and fetal heart development.

PubMed

Patterson, A J; Zhang, L

2010-10-01

Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although "normal" hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes fetal programming of abnormality in the heart's development. The altered expression pattern of cardioprotective genes such as protein kinase c epsilon, heat shock protein 70, and endothelial nitric oxide synthase, likely predispose the developing heart to increased vulnerability to ischemia and reperfusion injury later in life. The events underlying the long-term changes in gene expression are not clear, but likely involve variation in epigenetic regulation.

Subspecies differences in early fetal development and plasma pregnancy-associated glycoprotein concentrations in cattle.

PubMed

Mercadante, P M; Waters, K M; Mercadante, V R G; Lamb, G C; Elzo, M A; Johnson, S E; Rae, D O; Yelich, J V; Ealy, A D

2013-08-01

.9 ng/mL; P = 0.005). In conclusion, these studies determined that the Bos taurus × Bos indicus genotype impacts fetal size and rate of fetal development by 7 wk of gestation. Plasma PAG concentrations were increased in cattle with Bos indicus genetics in 2 of 3 studies, suggesting that genotype is one of several determinants of PAG production and secretion in cattle.

Biomechanics of Early Cardiac Development

PubMed Central

Goenezen, Sevan; Rennie, Monique Y.

2012-01-01

Biomechanics affect early cardiac development, from looping to the development of chambers and valves. Hemodynamic forces are essential for proper cardiac development, and their disruption leads to congenital heart defects. A wealth of information already exists on early cardiac adaptations to hemodynamic loading, and new technologies, including high resolution imaging modalities and computational modeling, are enabling a more thorough understanding of relationships between hemodynamics and cardiac development. Imaging and modeling approaches, used in combination with biological data on cell behavior and adaptation, are paving the road for new discoveries on links between biomechanics and biology and their effect on cardiac development and fetal programming. PMID:22760547

Safe fetal platelet genotyping: new developments.

PubMed

Le Toriellec, Emilie; Chenet, Christophe; Kaplan, Cecile

2013-08-01

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is due to maternal alloimmunization against fetal platelet (PLT) antigens. Antenatal management strategies have been developed to avoid complications such as intracranial hemorrhage. The aim of this study was to set up two reliable, noninvasive fetal genotyping assays to determine the fetal risk in pregnancies in which the father is heterozygous for the offending antigen. This study focused on human PLT antigen (HPA)-1, the most frequently implicated antigen in FNAIT in Caucasians. Two assays based on cell-free fetal DNA extracted from maternal blood samples and on real-time polymerase chain reaction (QPCR) were developed: an allele-specific QPCR specifically targeting the polymorphic sequence in HPA-1 and the study of the variation in the high-resolution melting curve of amplicons containing the polymorphic region. All results from the 49 samples obtained from 29 pregnant women were consistent with expectations. Six women were compatible with their fetuses (three HPA-1aa women and three HPA-1bb women), 41 HPA-1bb women were incompatible with their fetuses, as were two HPA-1aa women. Two fetal PLT genotyping assays on maternal blood samples proved to be reliable as of 15 weeks of gestation, thereby avoiding invasive techniques such as amniocentesis. © 2012 American Association of Blood Banks.

Effects of glucocorticoid treatment given in early or late gestation on growth and development in sheep.

PubMed

Li, S; Sloboda, D M; Moss, T J M; Nitsos, I; Polglase, G R; Doherty, D A; Newnham, J P; Challis, J R G; Braun, T

2013-04-01

Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40-42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.

Antenatal Workup of Early Megacystis and Selection of Candidates for Fetal Therapy.

PubMed

Fontanella, Federica; Duin, Leonie; Adama van Scheltema, Phebe N; Cohen-Overbeek, Titia E; Pajkrt, Eva; Bekker, Mireille; Willekes, Christine; Bax, Caroline J; Oepkes, Dick; Bilardo, Catia M

2018-05-17

To investigate the best criteria for discriminating fetuses with isolated posterior urethral valves from those theoretically not eligible for fetal treatment because of complex megacystis, high chance of spontaneous resolution, and urethral atresia. A retrospective national study was conducted in fetuses with megacystis detected before 17 weeks' gestation (early megacystis). In total, 142 cases with fetal megacystis were included in the study: 52 with lower urinary tract obstruction, 29 with normal micturition at birth, and 61 with miscellaneous syndromal associations, chromosomal and multiple structural abnormalities (complex megacystis). Only a nuchal translucency > 95th centile, and not a longitudinal bladder diameter ≤15 mm (p = 0.24), significantly increased the risk of complex megacystis (p < 0.01). Cases with a high chance of spontaneous resolution were identified by using the cut-off of 12 mm, as demonstrated in a previous study, and the finding of an associated umbilical cord cyst carried a high-risk of urethral atresia (odds ratio: 15; p = 0.026), an unfavorable condition for antenatal treatment. An algorithm encompassing these three criteria demonstrated good accuracy in selecting fetuses theoretically eligible for fetal treatment (specificity 73%; sensitivity 92%). Cases theoretically eligible for early fetal therapy are those with normal nuchal translucency, a longitudinal bladder diameter > 12 mm, and without ultrasound evidence of umbilical cord cysts. © 2018 The Author(s) Published by S. Karger AG, Basel.

Uterine artery blood flow, fetal hypoxia and fetal growth

PubMed Central

Browne, Vaughn A.; Julian, Colleen G.; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G.

2015-01-01

Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100–4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success. PMID:25602072

Mapping fetal brain development in utero using magnetic resonance imaging: the Big Bang of brain mapping.

PubMed

Studholme, Colin

2011-08-15

The development of tools to construct and investigate probabilistic maps of the adult human brain from magnetic resonance imaging (MRI) has led to advances in both basic neuroscience and clinical diagnosis. These tools are increasingly being applied to brain development in adolescence and childhood, and even to neonatal and premature neonatal imaging. Even earlier in development, parallel advances in clinical fetal MRI have led to its growing use as a tool in challenging medical conditions. This has motivated new engineering developments encompassing optimal fast MRI scans and techniques derived from computer vision, the combination of which allows full 3D imaging of the moving fetal brain in utero without sedation. These promise to provide a new and unprecedented window into early human brain growth. This article reviews the developments that have led us to this point, examines the current state of the art in the fields of fast fetal imaging and motion correction, and describes the tools to analyze dynamically changing fetal brain structure. New methods to deal with developmental tissue segmentation and the construction of spatiotemporal atlases are examined, together with techniques to map fetal brain growth patterns.

Hypoxia: From Placental Development to Fetal Programming.

PubMed

Fajersztajn, Lais; Veras, Mariana Matera

2017-10-16

Hypoxia may influence normal and different pathological processes. Low oxygenation activates a variety of responses, many of them regulated by hypoxia-inducible factor 1 complex, which is mostly involved in cellular control of O 2 consumption and delivery, inhibition of growth and development, and promotion of anaerobic metabolism. Hypoxia plays a significant physiological role in fetal development; it is involved in different embryonic processes, for example, placentation, angiogenesis, and hematopoiesis. More recently, fetal hypoxia has been associated directly or indirectly with fetal programming of heart, brain, and kidney function and metabolism in adulthood. In this review, the role of hypoxia in fetal development, placentation, and fetal programming is summarized. Hypoxia is a basic mechanism involved in different pregnancy disorders and fetal health developmental complications. Although there are scientific data showing that hypoxia mediates changes in the growth trajectory of the fetus, modulates gene expression by epigenetic mechanisms, and determines the health status later in adulthood, more mechanistic studies are needed. Furthermore, if we consider that intrauterine hypoxia is not a rare event, and can be a consequence of unavoidable exposures to air pollution, nutritional deficiencies, obesity, and other very common conditions (drug addiction and stress), the health of future generations may be damaged and the incidence of some diseases will markedly increase as a consequence of disturbed fetal programming. Birth Defects Research 109:1377-1385, 2017.© 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Study of the development of fetal baboon brain using magnetic resonance imaging at 3 Tesla

PubMed Central

Liu, Feng; Garland, Marianne; Duan, Yunsuo; Stark, Raymond I.; Xu, Dongrong; Dong, Zhengchao; Bansal, Ravi; Peterson, Bradley S.; Kangarlu, Alayar

2008-01-01

Direct observational data on the development of the brains of human and nonhuman primates is on remarkably scant, and most of our understanding of primate brain development is extrapolated from findings in rodent models. Magnetic resonance imaging (MRI) is a promising tool for the noninvasive, longitudinal study of the developing primate brain. We devised a protocol to scan pregnant baboons serially at 3 T for up to 3 h per session. Seven baboons were scanned 1–6 times, beginning as early as 56 days post-conceptional age, and as late as 185 days (term ~185 days). Successful scanning of the fetal baboon required careful animal preparation and anesthesia, in addition to optimization of the scanning protocol. We successfully acquired maps of relaxation times (T1 and T2) and high-resolution anatomical images of the brains of fetal baboons at multiple time points during the course of gestation. These images demonstrated the convergence of gray and white matter contrast near term, and furthermore demonstrated that the loss of contrast at that age is a consequence of the continuous change in relaxation times during fetal brain development. These data furthermore demonstrate that maps of relaxation times have clear advantages over the relaxation time weighted images for the tracking of the changes in brain structure during fetal development. This protocol for in utero MRI of fetal baboon brains will help to advance the use of nonhuman primate models to study fetal brain development longitudinally. PMID:18155925

Effects of chronic carbon monoxide exposure on fetal growth and development in mice

PubMed Central

2011-01-01

Background Carbon monoxide (CO) is produced endogenously, and can also be acquired from many exogenous sources: ie. cigarette smoking, automobile exhaust. Although toxic at high levels, low level production or exposure lends to normal physiologic functions: smooth muscle cell relaxation, control of vascular tone, platelet aggregation, anti- inflammatory and anti-apoptotic events. In pregnancy, it is unclear at what level maternal CO exposure becomes toxic to the fetus. In this study, we hypothesized that CO would be embryotoxic, and we sought to determine at what level of chronic CO exposure in pregnancy embryo/fetotoxic effects are observed. Methods Pregnant CD1 mice were exposed to continuous levels of CO (0 to 400 ppm) from conception to gestation day 17. The effect on fetal/placental growth and development, and fetal/maternal CO concentrations were determined. Results Maternal and fetal CO blood concentrations ranged from 1.12- 15.6 percent carboxyhemoglobin (%COHb) and 1.0- 28.6%COHb, respectively. No significant difference was observed in placental histological morphology or in placental mass with any CO exposure. At 400 ppm CO vs. control, decreased litter size and fetal mass (p < 0.05), increased fetal early/late gestational deaths (p < 0.05), and increased CO content in the placenta and the maternal spleen, heart, liver, kidney and lung (p < 0.05) were observed. Conclusions Exposure to levels at or below 300 ppm CO throughout pregnancy has little demonstrable effect on fetal growth and development in the mouse. PMID:22168775

Placental hormones, nutrition, and fetal development.

PubMed

Mulay, S; Browne, C A; Varma, D R; Solomon, S

1980-02-01

Fetal growth retardation due to maternal malnutrition is widespread especially in the Third World. Little is known about the mechanisms that regulate the growth of the fetus and placenta during protein malnutrition. It is known that the placental size and levels of circulating placental hormones such as human chorionic gonadotrophins (hCG), human placental lactogen (hPL), and estrogens are affected by the nutritional status of the mother. There is suggestive evidence that during malnutrition, hPL may increase lipolysis and exert a glucose sparing effect in the mother, thereby promoting glucose availability to the fetus. We have studied the influence of dietary protein deficiency on the binding of dexamethasone to the specific cytosol receptors in adult and fetal tissues. A low protein diet in adult male rats is associated with a decrease in dexamethasone binding to liver cytosol receptors. On the other hand, protein deprivation in pregnant female rats leads to an increase in dexamethasone binding to liver cytosol receptors of both the mother and fetus. However, the influences of maternal protein deprivation on dexamethasone receptors in the fetal liver and lungs are not similar. At 21 days gestation the binding of dexamethasone to fetal lung receptors of protein-deficient mothers is lower than that in the controls. These differences at a critical time in the fetal lung development indicate that a fall in receptors for dexamethasone may lead to impaired phospholipid synthesis in fetuses of protein-deficient mothers and point to the importance of nutritional factors in the biochemistry of fetal development.

Linear and nonlinear features of fetal heart rate on the assessment of fetal development in the course of pregnancy and the impact of fetal gender.

PubMed

Spyridou, K; Chouvarda, I; Hadjileontiadis, L; Maglaveras, N

2018-01-30

This work aims to investigate the impact of gestational age and fetal gender on fetal heart rate (FHR) tracings. Different linear and nonlinear parameters indicating correlation or complexity were used to study the influence of fetal age and gender on FHR tracings. The signals were recorded from 99 normal pregnant women in a singleton pregnancy at gestational ages from 28 to 40 weeks, before the onset of labor. There were 56 female fetuses and 43 male. Analysis of FHR shows that the means as well as measures of irregularity of FHR, such as approximate entropy and algorithmic complexity, decrease as gestation progresses. There were also indications that mutual information and multiscale entropy were lower in male fetuses in early pregnancy. Fetal age and gender seem to influence FHR tracings. Taking this into consideration would improve the interpretation of FHR monitoring.

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

Central vagal sensory and motor connections: human embryonic and fetal development.

PubMed

Cheng, Gang; Zhou, Xiangtian; Qu, Jia; Ashwell, Ken W S; Paxinos, G

2004-07-30

The embryonic and fetal development of the nuclear components and pathways of vagal sensorimotor circuits in the human has been studied using Nissl staining and carbocyanine dye tracing techniques. Eight fetal brains ranging from 8 to 28 weeks of development had DiI (1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate) inserted into either the thoracic vagus nerve at the level of the sternal angle (two specimens of 8 and 9 weeks of gestation) or into vagal rootlets at the surface of the medulla (at all other ages), while a further five were used for study of cytoarchitectural development. The first central labeling resulting from peripheral application of DiI to the thoracic vagus nerve was seen at 8 weeks. By 9 weeks, labeled bipolar cells at the ventricular surface around the sulcus limitans (sl) were seen after DiI application to the thoracic vagus nerve. Subnuclear organization as revealed by both Nissl staining and carbocyanine dye tracing was found to be advanced at a relatively early fetal age, with afferent segregation in the medial Sol apparent at 13 weeks and subnuclear organization of efferent magnocellular divisions of dorsal motor nucleus of vagus nerve noticeable at the same stage. The results of the present study also confirm that vagal afferents are distributed to the dorsomedial subnuclei of the human nucleus of the solitary tract, with particular concentrations of afferent axons in the gelatinosus subnucleus. These vagal afferents appeared to have a restricted zone of termination from quite early in development (13 weeks) suggesting that there is no initial exuberance in the termination field of vagal afferents in the developing human nucleus of the solitary tract. On the other hand, the first suggestion of afferents invading 10N from the medial Sol was not seen until 20 weeks and was not well developed until 24 weeks, suggesting that direct monosynaptic connections between the sensory and effector components of the vagal

Thyroid hormones and fetal brain development.

PubMed

Pemberton, H N; Franklyn, J A; Kilby, M D

2005-08-01

Thyroid hormones are intricately involved in the developing fetal brain. The fetal central nervous system is sensitive to the maternal thyroid status. Critical amounts of maternal T3 and T4 must be transported across the placenta to the fetus to ensure the correct development of the brain throughout ontogeny. Severe mental retardation of the child can occur due to compromised iodine intake or thyroid disease. This has been reported in areas of the world with iodine insufficiency, New Guinea, and also in mother with thyroid complications such as hypothyroxinaemia and hyperthyroidism. The molecular control of thyroid hormones by deiodinases for the activation of thyroid hormones is critical to ensure the correct amount of active thyroid hormones are temporally supplied to the fetus. These hormones provide timing signals for the induction of programmes for differentiation and maturation at specific stages of development. Understanding these molecular mechanisms further will have profound implications in the clinical management of individuals affected by abnormal maternal of fetal thyroid status.

STORY AND HISTORY IN FETAL BEHAVIOR RESEARCH.

PubMed

Brakke, Karen

2015-09-01

In their monograph, DiPietro, Costigan, and Voegtline present an important and thoughtful portrait of low-risk fetal development during the last trimester of gestation, and they also pay tribute to the Fels Longitudinal Study investigators' early work in this area. In this commentary, the history and legacy of the Fels Institute is further explored within the broader context of fetal research, and DiPietro et al.'s findings are placed in alignment with contemporary dynamic systems' theoretical approaches that emphasize longitudinal analysis of emergent behavior and process during early development. The commentary puts forth the assertion that the work reported by DiPietro and her colleagues tells a story that sets the stage for a new generation of technology-enhanced and culturally expanded investigations of fetal behavior. © 2015 The Society for Research in Child Development, Inc.

Fetal body weight and the development of the control of the cardiovascular system in fetal sheep.

PubMed

Frasch, M G; Müller, T; Wicher, C; Weiss, C; Löhle, M; Schwab, K; Schubert, H; Nathanielsz, P W; Witte, O W; Schwab, M

2007-03-15

Reduced birth weight predisposes to cardiovascular diseases in later life. We examined in fetal sheep at 0.76 (n = 18) and 0.87 (n = 17) gestation whether spontaneously occurring variations in fetal weight affect maturation of autonomic control of cardiovascular function. Fetal weights at both gestational ages were grouped statistically in low (LW) and normal weights (NW) (P < 0.01). LW fetuses were within the normal weight span showing minor growth dysproportionality at 0.76 gestation favouring heart and brain, with a primary growth of carcass between 0.76 and 0.87 gestation (P < 0.05). While twins largely contributed to LW fetuses, weight differences between singletons and twins were absent at 0.76 and modest at 0.87 gestation, underscoring the fact that twins belong to normality in fetal sheep not constituting a major malnutritive condition. Mean fetal blood pressure (FBP) of all fetuses was negatively correlated to fetal weight at 0.76 but not 0.87 gestation (P < 0.05). At this age, FBP and baroreceptor reflex sensitivity were increased in LW fetuses (P < 0.05), suggesting increased sympathetic activity and immaturity of circulatory control. Development of vagal modulation of fetal heart rate depended on fetal weight (P < 0.01). These functional associations were largely independent of twin pregnancies. We conclude, low fetal weight within the normal weight span is accompanied by a different trajectory of development of sympathetic blood pressure and vagal heart rate control. This may contribute to the development of elevated blood pressure in later life. Examination of the underlying mechanisms and consequences may contribute to the understanding of programming of cardiovascular diseases.

First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model.

PubMed

Lo, Jamie O; Schabel, Matthias C; Roberts, Victoria H J; Wang, Xiaojie; Lewandowski, Katherine S; Grant, Kathleen A; Frias, Antonio E; Kroenke, Christopher D

2017-03-01

throughout the placenta and reveal gradients in blood deoxyhemoglobin concentration that range from highly oxygenated blood (long T 2 *) proximal to spiral arteries to highly deoxygenated blood (short T 2 *). Distributions of T 2 *throughout the placenta show significant global reduction in T 2 * (and hence high blood deoxyhemoglobin concentration) in ethanol-exposed vs control animals at gestational day 110 (P=.02). Fetal brain measurements indicated impaired growth and development at gestational day 110, but less so at gestational day 135 in ethanol-exposed vs control animals. Chronic first-trimester ethanol exposure significantly reduces placental perfusion and oxygen supply to the fetal vasculature later in pregnancy. These perturbations of placental function are associated with fetal growth impairments. However, differences between ethanol-exposed and control animals in placental function and fetal developmental outcomes were smaller at gestational day 135 than at gestational day 110. These findings are consistent with placental adaptation to early perturbations that allow for compensated placental function and maintenance of fetal growth. Copyright © 2017 Elsevier Inc. All rights reserved.

Sertoli Cell Wt1 Regulates Peritubular Myoid Cell and Fetal Leydig Cell Differentiation during Fetal Testis Development.

PubMed

Wen, Qing; Wang, Yuqian; Tang, Jixin; Cheng, C Yan; Liu, Yi-Xun

2016-01-01

Sertoli cells play a significant role in regulating fetal testis compartmentalization to generate testis cords and interstitium during development. The Sertoli cell Wilms' tumor 1 (Wt1) gene, which encodes ~24 zinc finger-containing transcription factors, is known to play a crucial role in fetal testis cord assembly and maintenance. However, whether Wt1 regulates fetal testis compartmentalization by modulating the development of peritubular myoid cells (PMCs) and/or fetal Leydig cells (FLCs) remains unknown. Using a Wt1-/flox; Amh-Cre mouse model by deleting Wt1 in Sertoli cells (Wt1SC-cKO) at embryonic day 14.5 (E14.5), Wt1 was found to regulate PMC and FLC development. Wt1 deletion in fetal testis Sertoli cells caused aberrant differentiation and proliferation of PMCs, FLCs and interstitial progenitor cells from embryo to newborn, leading to abnormal fetal testis interstitial development. Specifically, the expression of PMC marker genes α-Sma, Myh11 and Des, and interstitial progenitor cell marker gene Vcam1 were down-regulated, whereas FLC marker genes StAR, Cyp11a1, Cyp17a1 and Hsd3b1 were up-regulated, in neonatal Wt1SC-cKO testes. The ratio of PMC:FLC were also reduced in Wt1SC-cKO testes, concomitant with a down-regulation of Notch signaling molecules Jag 1, Notch 2, Notch 3, and Hes1 in neonatal Wt1SC-cKO testes, illustrating changes in the differentiation status of FLC from their interstitial progenitor cells during fetal testis development. In summary, Wt1 regulates the development of FLC and interstitial progenitor cell lineages through Notch signaling, and it also plays a role in PMC development. Collectively, these effects confer fetal testis compartmentalization.

Maternal hair testing for the assessment of fetal exposure to drug of abuse during early pregnancy: Comparison with testing in placental and fetal remains.

PubMed

Falcon, M; Pichini, S; Joya, J; Pujadas, M; Sanchez, A; Vall, O; García Algar, O; Luna, A; de la Torre, R; Rotolo, M C; Pellegrini, M

2012-05-10

Drug use by pregnant women in the first trimester of pregnancy and subsequent fetal exposure during early gestation can be assessed only by repetitive/systematic maternal blood/urine analysis or segmental hair analysis. No evidence of any relationship between maternal/fetal exposure during this specific period of gestation has been demonstrated to date in a human model. To clarify drugs toxicokinetics and transplacental passage during early pregnancy, the presence of the most widely used recreational drugs of abuse and metabolites was investigated in the proximal 4cm hair segments of women undergoing voluntary termination of pregnancy (n=280) during the 12th week of gestation and the results were compared to those from placenta and fetal tissue samples in order to verify whether maternal hair testing can reflect fetal exposure and, if so, to what extent. Hair, placenta and fetal remains were analyzed by validated gas chromatography mass spectrometry assays. Eighty one positive hair samples were identified: 60 were positive for cannabis (74.1%), 28 for cocaine (34.6%), 7 for opiates (8.6%), 3 for MDMA (3.7%) and 18.5% were positive for more than one drug. The positive hair test results were confirmed in placenta/fetal tissues in 10 cases out of 60 for cannabis (16. 7%); in 7 out of 28 for cocaine (25%); and none for the 6 opiates positive cases and 3 MDMA cases, respectively. Drugs/metabolites in hair of pregnant women can be used as biomarkers of past drug use (repetitive or sporadic), although the use is not always reflected in fetal/placental tissues. There are several possible hypotheses to explain the results: (1) the use occurred before the start of pregnancy, (2) past sporadic consumption which could be measured in hair but not in fetal and placental remains because of the narrow window of drug detection in placental/fetal tissues; (3) the sensitivity of the analytical methods was not high enough for the detection of the minute amount of drugs of abuse and

A health priority for developing countries: the prevention of chronic fetal malnutrition.

PubMed

Villar, J; Altobelli, L; Kestler, E; Beliźan, J

1986-01-01

A prospective study of 3557 consecutively born neonates from a lower middle class district in Guatemala City documented a 23.8% incidence of intrauterine growth retardation due to fetal malnutrition. Those infants whose weights are below the 10th percentile of a sex- and race-specific birthweight and gestational age distribution, based on a developed country population, were considered to manifest intrauterine growth retardation. Ponderal index values were then used to further classify this population as having chronic fetal malnutrition (above the 10th percentile of the standard distribution) or subacute fetal malnutrition (below the 10th percentile); the incidences of these conditions were 79.1% and 20.8%, respectively. The results of numerous studies carried out in various populations suggest that developing countries have a higher incidence of chronically malnourished infants within the intrauterine growth retardation population, while subacute fetal malnutrition is more prevalent in developed countries. Moreover, it has been shown that chronically malnourished infants do not recover from their intrauterine damage and score the lowest in mental development tests even up to school age. They remain lighter, shorter, and with a smaller head circumference until at least 3 years of age. Based on the incidence rates ascertained in this study, it can be estimated that at least 2 million infants born each year in Latin America are at risk of chronic intrauterine growth retardation. Screening programs are needed to identify at-risk mothers early in pregnancy so that medical and nutritional interventions can be implemented.

Fetal effects of psychoactive drugs.

PubMed

Salisbury, Amy L; Ponder, Kathryn L; Padbury, James F; Lester, Barry M

2009-09-01

Psychoactive drug use by pregnant women has the potential to effect fetal development; the effects are often thought to be drug-specific and gestational age dependent. This article describes the effects of three drugs with similar molecular targets that involve monoaminergic transmitter systems: cocaine, methamphetamine, and selective serotonin re-uptake inhibitors (SSRIs) used to treat maternal depression during pregnancy. We propose a possible common epigenetic mechanism for their potential effects on the developing child. We suggest that exposure to these substances acts as a stressor that affects fetal programming, disrupts fetal placental monoamine transporter expression and alters neuroendocrine and neurotransmitter system development. We also discuss neurobehavioral techniques that may be useful in the early detection of the effects of in utero drug exposure.

Fetal Neurobehavioral Development.

ERIC Educational Resources Information Center

DiPietro, Janet A.; And Others

1996-01-01

Investigated the ontogeny of fetal autonomic, motoric, state, and interactive functioning in 31 healthy fetuses from 20 weeks through term. Found that male fetuses were more active than female fetuses, and that greater maternal stress appraisal was associated with reduced fetal heart rate variability. Found that an apparent period of…

Molecular genetics in fetal neurology.

PubMed

Huang, Jin; Wah, Isabella Y M; Pooh, Ritsuko K; Choy, Kwong Wai

2012-12-01

Brain malformations, particularly related to early brain development, are a clinically and genetically heterogeneous group of fetal neurological disorders. Fetal cerebral malformation, predominantly of impaired prosencephalic development namely agenesis of the corpus callosum and septo-optic dysplasia, is the main pathological feature in fetus, and causes prominent neurodevelopmental retardation, and associated with congenital facial anomalies and visual disorders. Differential diagnosis of brain malformations can be extremely difficult even through magnetic resonance imaging. Advances in genomic and molecular genetics technologies have led to the identification of the sonic hedgehog pathways and genes critical to the normal brain development. Molecular cytogenetic and genetic studies have identified numeric and structural chromosomal abnormalities as well as mutations in genes important for the etiology of fetal neurological disorders. In this review, we update the molecular genetics findings of three common fetal neurological abnormalities, holoprosencephaly, lissencephaly and agenesis of the corpus callosum, in an attempt to assist in perinatal and prenatal diagnosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Murine fetal echocardiography.

PubMed

Kim, Gene H

2013-02-15

Transgenic mice displaying abnormalities in cardiac development and function represent a powerful tool for the understanding the molecular mechanisms underlying both normal cardiovascular function and the pathophysiological basis of human cardiovascular disease. Fetal and perinatal death is a common feature when studying genetic alterations affecting cardiac development. In order to study the role of genetic or pharmacologic alterations in the early development of cardiac function, ultrasound imaging of the live fetus has become an important tool for early recognition of abnormalities and longitudinal follow-up. Noninvasive ultrasound imaging is an ideal method for detecting and studying congenital malformations and the impact on cardiac function prior to death. It allows early recognition of abnormalities in the living fetus and the progression of disease can be followed in utero with longitudinal studies. Until recently, imaging of fetal mouse hearts frequently involved invasive methods. The fetus had to be sacrificed to perform magnetic resonance microscopy and electron microscopy or surgically delivered for transillumination microscopy. An application of high-frequency probes with conventional 2-D and pulsed-wave Doppler imaging has been shown to provide measurements of cardiac contraction and heart rates during embryonic development with databases of normal developmental changes now available. M-mode imaging further provides important functional data, although, the proper imaging planes are often difficult to obtain. High-frequency ultrasound imaging of the fetus has improved 2-D resolution and can provide excellent information on the early development of cardiac structures.

Fetal programming in meat production.

PubMed

Du, Min; Wang, Bo; Fu, Xing; Yang, Qiyuan; Zhu, Mei-Jun

2015-11-01

Nutrient fluctuations during the fetal stage affects fetal development, which has long-term impacts on the production efficiency and quality of meat. During the early development, a pool of mesenchymal progenitor cells proliferate and then diverge into either myogenic or adipogenic/fibrogenic lineages. Myogenic progenitor cells further develop into muscle fibers and satellite cells, while adipogenic/fibrogenic lineage cells develop into adipocytes, fibroblasts and resident fibro-adipogenic progenitor cells. Enhancing the proliferation and myogenic commitment of progenitor cells during fetal development enhances muscle growth and lean production in offspring. On the other hand, promoting the adipogenic differentiation of adipogenic/fibrogenic progenitor cells inside the muscle increases intramuscular adipocytes and reduces connective tissue, which improves meat marbling and tenderness. Available studies in mammalian livestock, including cattle, sheep and pigs, clearly show the link between maternal nutrition and the quantity and quality of meat production. Similarly, chicken muscle fibers develop before hatching and, thus, egg and yolk sizes and hatching temperature affect long-term growth performance and meat production of chicken. On the contrary, because fishes are able to generate new muscle fibers lifelong, the impact of early nutrition on fish growth performance is expected to be minor, which requires further studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Course-, dose-, and stage-dependent toxic effects of prenatal dexamethasone exposure on fetal articular cartilage development.

PubMed

Chen, Ze; Zhao, Zhe; Li, Yunzepeng; Zhang, Xingyu; Li, Bin; Chen, Liaobin; Wang, Hui

2018-04-01

Dexamethasone, a synthetic long-acting glucocorticoid, is routinely used for treating mothers at risk for preterm delivery. However, intrauterine overexposure to glucocorticoids induces low birth weight and cartilage dysplasia in offspring. Also, the "critical window" and safe dose of this treatment are largely unknown. This study investigated the course-, dose-, and stage-dependent toxic effects and the possible mechanisms of prenatal dexamethasone exposure (PDE) on fetal development and articular cartilage development. Pregnant mice (C57BL/6) received subcutaneous injection of dexamethasone (0.8 mg/kg d) once on gestational day (GD) 15 or once a day from GD 15 to 17, or received various doses of dexamethasone (0, 0.2, 0.8, and 1.2 mg/kg d) on GD 15-17, or received dexamethasone (0.8 mg/kg d) at early stage (GD 12-14) or late stage of pregnancy (GD 15-17). Offspring's knee joints were harvested at birth for morphological analyses and detection of gene expression. Repeated PDE significantly suppressed fetal and articular cartilage development, which were characterized by decreased body weight and body length, coarse articular cartilage surfaces, and reduced gene and protein expression of Col2a1 and aggrecan. For those newborns treated with repeated PDE at different doses, the toxic effects on fetal and articular cartilage development were observed at doses of 0.8 and 1.2 mg/kg d, whereas no obvious toxic effects were observed at the dose of 0.2 mg/kg d. Moreover, PDE at 0.8 mg/kg d during the early embryonic stage induced stronger toxic effects on fetal and articular cartilage development, compared with PDE during the late embryonic stage. Detection of gene expression showed that the TGFβ signaling pathway in the articular cartilage was down-regulated after PDE. Taken together, PDE induces fetal developmental toxicity and articular cartilage developmental toxicity in a course-, dose-, and stage-dependent manner. Copyright © 2018 Elsevier B

Embryologic and Fetal Development of the Human Eyelid

PubMed Central

Abdulhafez, Mohamed H.; Fouad, Yousef A.; Dutton, Jonathan J.

2016-01-01

Purpose: To review the recent data about eyelid morphogenesis, and outline a timeline for eyelid development from the very early stages during embryonic life till final maturation of the eyelid late in fetal life. Methods: The authors extensively review major studies detailing human embryologic and fetal eyelid morphogenesis. These studies span almost a century and include some more recent cadaver studies. Numerous studies in the murine model have helped to better understand the molecular signals that govern eyelid embryogenesis. The authors summarize the current findings in molecular biology, and highlight the most significant studies in mice regarding the multiple and interacting signaling pathways involved in regulating normal eyelid morphogenesis. Results: Eyelid morphogenesis involves a succession of subtle yet strictly regulated morphogenetic episodes of tissue folding, proliferation, contraction, and even migration, which may occur simultaneously or in succession. Conclusions: Understanding the extraordinary process of building eyelid tissue in embryonic life, and deciphering its underlying signaling machinery has far reaching clinical implications beyond understanding the developmental abnormalities involving the eyelids, and may pave the way for achieving scar-reducing therapies in adult mammalian wounds, or control the spread of malignancies. PMID:27124372

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

Fetal programming of sexual development and reproductive function.

PubMed

Zambrano, Elena; Guzmán, Carolina; Rodríguez-González, Guadalupe L; Durand-Carbajal, Marta; Nathanielsz, Peter W

2014-01-25

The recent growth of interest in developmental programming of physiological systems has generally focused on the cardiovascular system (especially hypertension) and predisposition to metabolic dysfunction (mainly obesity and diabetes). However, it is now clear that the full range of altered offspring phenotypes includes impaired reproductive function. In rats, sheep and nonhuman primates, reproductive capacity is altered by challenges experienced during critical periods of development. This review will examine available experimental evidence across commonly studied experimental species for developmental programming of female and male reproductive function throughout an individual's life-course. It is necessary to consider events that occur during fetal development, early neonatal life and prior to and during puberty, during active reproductive life and aging as reproductive performance declines. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component.

PubMed

Merialdi, Mario; Widmer, Mariana; Gülmezoglu, Ahmet Metin; Abdel-Aleem, Hany; Bega, George; Benachi, Alexandra; Carroli, Guillermo; Cecatti, Jose Guilherme; Diemert, Anke; Gonzalez, Rogelio; Hecher, Kurt; Jensen, Lisa N; Johnsen, Synnøve L; Kiserud, Torvid; Kriplani, Alka; Lumbiganon, Pisake; Tabor, Ann; Talegawkar, Sameera A; Tshefu, Antoinette; Wojdyla, Daniel; Platt, Lawrence

2014-05-02

In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide. This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/- 1 week) to be performed by trained ultrasonographers.The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications. The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use of the Child Growth Standards.

WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component

PubMed Central

2014-01-01

Background In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide. Methods This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/− 1 week) to be performed by trained ultrasonographers. The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications. Discussion The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use

Impact of fetal death reporting requirements on early neonatal and fetal mortality rates and racial disparities.

PubMed

Tyler, Crystal P; Grady, Sue C; Grigorescu, Violanda; Luke, Barbara; Todem, David; Paneth, Nigel

2012-01-01

Racial disparities in infant and neonatal mortality vary substantially across the U.S. with some states experiencing wider disparities than others. Many factors are thought to contribute to these disparities, but state differences in fetal death reporting have received little attention. We examined whether such reporting requirements may explain national variation in neonatal and fetal mortality rates and racial disparities. We used data on non-Hispanic white and non-Hispanic black infants from the U.S. 2000-2002 linked birth/infant death and fetal death records to determine the degree to which state fetal death reporting requirements explain national variation in neonatal and fetal mortality rates and racial disparities. States were grouped depending upon whether they based the lower limit for fetal death reporting on birthweight alone, gestational age alone, both birthweight and gestational age, or required reporting of all fetal deaths. Traditional methods and the fetuses-at-risk approach were used to calculate mortality rates, 95% confidence intervals, and relative and absolute racial disparity measures in these four groups. States with birthweight-alone fetal death thresholds substantially underreported fetal deaths at lower gestations and slightly overreported neonatal deaths at older gestations. This finding was reflected by these states having the highest neonatal mortality rates and disparities, but the lowest fetal mortality rates and disparities. Using birthweight alone as a reporting threshold may promote some shift of fetal deaths to newborn deaths, contributing to racial disparities in neonatal mortality. The adoption of a uniform national threshold for reporting fetal deaths could reduce systematic differences in live birth and fetal death reporting.

Development and Function of the Human Fetal Adrenal Cortex: A Key Component in the Feto-Placental Unit

PubMed Central

Ishimoto, Hitoshi

2011-01-01

Continuous efforts have been devoted to unraveling the biophysiology and development of the human fetal adrenal cortex, which is structurally and functionally unique from other species. It plays a pivotal role, mainly through steroidogenesis, in the regulation of intrauterine homeostasis and in fetal development and maturation. The steroidogenic activity is characterized by early transient cortisol biosynthesis, followed by its suppressed synthesis until late gestation, and extensive production of dehydroepiandrosterone and its sulfate, precursors of placental estrogen, during most of gestation. The gland rapidly grows through processes including cell proliferation and angiogenesis at the gland periphery, cellular migration, hypertrophy, and apoptosis. Recent studies employing modern technologies such as gene expression profiling and laser capture microdissection have revealed that development and/or function of the fetal adrenal cortex may be regulated by a panoply of molecules, including transcription factors, extracellular matrix components, locally produced growth factors, and placenta-derived CRH, in addition to the primary regulator, fetal pituitary ACTH. The role of the fetal adrenal cortex in human pregnancy and parturition appears highly complex, probably due to redundant and compensatory mechanisms regulating these events. Mounting evidence indicates that actions of hormones operating in the human feto-placental unit are likely mediated by mechanisms including target tissue responsiveness, local metabolism, and bioavailability, rather than changes only in circulating levels. Comprehensive study of such molecular mechanisms and the newly identified factors implicated in adrenal development should help crystallize our understanding of the development and physiology of the human fetal adrenal cortex. PMID:21051591

Delayed rotation of the cerebellar vermis: a pitfall in early second-trimester fetal magnetic resonance imaging.

PubMed

Pinto, J; Paladini, D; Severino, M; Morana, G; Pais, R; Martinetti, C; Rossi, A

2016-07-01

We describe two cases in which delayed rotation of the cerebellar vermis simulated a Dandy-Walker malformation (DWM) on early second-trimester magnetic resonance imaging (MRI). Two pregnant women with suspected fetal posterior fossa anomaly on ultrasound examination underwent fetal MRI at 21 (Case 1) and 19 (Case 2) weeks' gestation. In both cases, upward rotation of the cerebellar vermis was noted; on midsagittal imaging, the brainstem-vermis angle was 28° and 43°, respectively, while cerebellar morphometry showed a reduced vermian anteroposterior diameter compared to reference data. The posterior fossa appeared to be mildly enlarged, while all other findings were normal. Follow-up MRI at 28 + 3 weeks' gestation (Case 1) and at 1 postnatal year (Case 2) showed completely normal findings. Both children had normal psychomotor development and neurological examinations at 1 year of age. Incomplete rotation of the cerebellar vermis can be a physiological finding on early second-trimester fetal MRI examination and can simulate DWM or other forms of cerebellar hypoplasia. Embryologically, delayed permeabilization of Blake's pouch could account for the delayed vermian rotation. Follow-up imaging at a later gestational age is crucial to ensure that this condition is not over-reported and to avoid the potential risk of unnecessary pregnancy interruption. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Fetal programming as a predictor of adult health or disease: the need to reevaluate fetal heart function.

PubMed

Miranda, Joana O; Ramalho, Carla; Henriques-Coelho, Tiago; Areias, José Carlos

2017-11-01

Epidemiologic and experimental evidence suggests that adverse stimuli during critical periods in utero permanently alters organ structure and function and may have persistent consequences for the long-term health of the offspring. Fetal hypoxia, maternal malnutrition, or ventricular overloading are among the major adverse conditions that can compromise cardiovascular development in early life. With the heart as a central organ in fetal adaptive mechanisms, a deeper understanding of the fetal cardiovascular physiology and of the echocardiographic tools to assess both normal and stressed pregnancies would give precious information on fetal well-being and hopefully may help in early identification of special risk groups for cardiovascular diseases later in life. Assessment of cardiac function in the fetus represents an additional challenge when comparing to children and adults, requiring advanced training and a critical approach to properly acquire and interpret functional parameters. This review summarizes the basic fetal cardiovascular physiology and the main differences from the mature postnatal circulation, provides an overview of the particularities of echocardiographic evaluation in the fetus, and finally proposes an integrated view of in utero programming of cardiovascular diseases later in life, highlighting priorities for future clinical research.

Sudden Unexpected Death in Fetal Life Through Early Childhood

PubMed Central

Kinney, Hannah C.; Willinger, Marian

2016-01-01

In March 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop entitled “Sudden Unexpected Death in Fetal Life Through Early Childhood: New Opportunities.” Its objective was to advance efforts to understand and ultimately prevent sudden deaths in early life, by considering their pathogenesis as a potential continuum with some commonalities in biological origins or pathways. A second objective of this meeting was to highlight current issues surrounding the classification of sudden infant death syndrome (SIDS), and the implications of variations in the use of the term “SIDS” in forensic practice, and pediatric care and research. The proceedings reflected the most current knowledge and understanding of the origins and biology of vulnerability to sudden unexpected death, and its environmental triggers. Participants were encouraged to consider the application of new technologies and “omics” approaches to accelerate research. The major advances in delineating the intrinsic vulnerabilities to sudden death in early life have come from epidemiologic, neural, cardiac, metabolic, genetic, and physiologic research, with some commonalities among cases of unexplained stillbirth, SIDS, and sudden unexplained death in childhood observed. It was emphasized that investigations of sudden unexpected death are inconsistent, varying by jurisdiction, as are the education, certification practices, and experience of death certifiers. In addition, there is no practical consensus on the use of “SIDS” as a determination in cause of death. Major clinical, forensic, and scientific areas are identified for future research. PMID:27230764

Region-, age-, and sex-specific effects of fetal diazepam exposure on the postnatal development of neurosteroids

PubMed Central

Kellogg, Carol K.; Kenjarski, Thomas P.; Pleger, Gloria L.; Frye, Cheryl A.

2013-01-01

Fetal exposure to diazepam (DZ), a positive modulator of GABAA receptors and an agonist at mitochondrial benzodiazine receptors, induces long-term neural and behavioral effects. This study evaluated whether the early manipulation influenced the normal development of brain levels of neurosteroids or altered steroid action at GABAA receptors. Pregnant dams were injected over gestation days 14 through 20 with DZ (2.5 mg/kg) or the vehicle. Male and female offspring were analyzed at five postnatal ages. The levels of progesterone (P), dihydroprogesterone (DHP), 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP), testosterone (T), dihydrotestosterone, and 5α-androstan-3α,17β diol were measured in the cerebral cortex and diencephalon. The results indicated that development of brain steroid levels and the impact of fetal DZ exposure were region- and sex-specific. Age-related changes in brain steroids did not mirror associated changes in circulating P and T. Age regulated the levels of all 3 progestins in the cerebral cortex, and fetal DZ exposure interacted with the development of P and DHP. The development of 3α,5α-THP in the cortex was markedly influenced by sex, with levels in males decreasing over postnatal development whereas they increased over postpubertal development in females. An adolescent surge in T levels was observed in male cortex and fetal DZ exposure prevented that surge. Steroid levels in the diencephalon were altered by age mainly in females, and DZ exposure had little effect in this region. The data support region-specific regulation of brain steroid synthesis. Only in the cerebral cortex are relevant mechanisms readily modifiable by fetal DZ exposure. However, neither sex nor fetal DZ exposure altered the response of GABAA receptors in adult cortex to neurosteroid. PMID:16376310

Effects of intratracheal budesonide during early postnatal life on lung maturity of premature fetal rabbits.

PubMed

Li, Ling; Yang, Chen; Feng, Xiuliang; Du, Yongping; Zhang, Zhihong; Zhang, Yueping

2018-01-01

This study aimed to study the effects of intratracheal instillation of budesonide on lung maturity of premature fetal rabbits. The developmental pattern of pulmonary alveoli in rabbits is similar to that in humans. Fetal rabbits were taken out from female rabbits on the 28th day of pregnancy (full term = 31 days) by cesarean section (c-section). The fetal rabbits were divided into four groups: control (normal saline, NS), budesonide (budesonide, BUD), calf pulmonary surfactant for injection (pulmonary surfactant, PS), and calf pulmonary surfactant + budesonide for injection (pulmonary surfactant + budesonide, PS + BUD). All premature rabbits were kept warm after c-section. After 15-min autonomous respiration, a tracheal cannula was implemented for instilling NS, BUD, PS, and PS + BUD. The morphology of lung tissues of premature fetal rabbits was analyzed using optical and electron microscopes. Surfactant protein B (SP-B) mRNA and protein levels in lung tissues were determined using polymerase chain reaction and Western blotting, respectively. Intratracheal instillation of BUD could increase the alveolar area of the fetal rabbits (P < 0.01), decrease the alveolar wall thickness (P < 0.01), and increase the mean density of lamellar bodies (P < 0.05) and SP-B protein levels in type II epithelial cells of pulmonary alveoli (P < 0.05). Intratracheal instillation of BUD during early postnatal life is effective in promoting alveolarization and increasing SP-B expression, the pro-pulmonary maturity of BUD combined with PS is superior to that of BUD or PS alone. However, the long-term effect of BUD on lung development needs further exploration. © 2017 Wiley Periodicals, Inc.

Fetal Research

NASA Astrophysics Data System (ADS)

Hansen, John T.; Sladek, John R.

1989-11-01

This article reviews some of the significant contributions of fetal research and fetal tissue research over the past 20 years. The benefits of fetal research include the development of vaccines, advances in prenatal diagnosis, detection of malformations, assessment of safe and effective medications, and the development of in utero surgical therapies. Fetal tissue research benefits vaccine development, assessment of risk factors and toxicity levels in drug production, development of cell lines, and provides a source of fetal cells for ongoing transplantation trials. Together, fetal research and fetal tissue research offer tremendous potential for the treatment of the fetus, neonate, and adult.

TGFβ2 regulates hypothalamic Trh expression through the TGFβ inducible early gene-1 (TIEG1) during fetal development

PubMed Central

Martínez-Armenta, Miriam; de León-Guerrero, Sol Díaz; Catalán, Ana; Alvarez-Arellano, Lourdes; Uribe, Rosa Maria; Subramaniam, Malayannan; Charli, Jean-Louis; Pérez-Martínez, Leonor

2015-01-01

The hypothalamus regulates the homeostasis of the organism by controlling hormone secretion from the pituitary. The molecular mechanisms that regulate the differentiation of the hypothalamic thyrotropin-releasing hormone (TRH) phenotype are poorly understood. We have previously shown that Klf10 or TGFβ inducible early gene-1 (TIEG1) is enriched in fetal hypothalamic TRH neurons. Here, we show that expression of TGFβ isoforms (1–3) and both TGFβ receptors (TβRI and II) occurs in the hypothalamus concomitantly with the establishment of TRH neurons during late embryonic development. TGFβ2 induces Trh expression via a TIEG1 dependent mechanism. TIEG1 regulates Trh expression through an evolutionary conserved GC rich sequence on the Trh promoter. Finally, in mice deficient in TIEG1, Trh expression is lower than in wild type animals at embryonic day 17. These results indicate that TGFβ signaling, through the upregulation of TIEG1, plays an important role in the establishment of Trh expression in the embryonic hypothalamus. PMID:25448845

Remodelling of the bovine placenta: Comprehensive morphological and histomorphological characterization at the late embryonic and early accelerated fetal growth stages.

PubMed

Estrella, Consuelo Amor S; Kind, Karen L; Derks, Anna; Xiang, Ruidong; Faulkner, Nicole; Mohrdick, Melina; Fitzsimmons, Carolyn; Kruk, Zbigniew; Grutzner, Frank; Roberts, Claire T; Hiendleder, Stefan

2017-07-01

Placental function impacts growth and development with lifelong consequences for performance and health. We provide novel insights into placental development in bovine, an important agricultural species and biomedical model. Concepti with defined genetics and sex were recovered from nulliparous dams managed under standardized conditions to study placental gross morphological and histomorphological parameters at the late embryo (Day48) and early accelerated fetal growth (Day153) stages. Placentome number increased 3-fold between Day48 and Day153. Placental barrier thickness was thinner, and volume of placental components, and surface areas and densities were higher at Day153 than Day48. We confirmed two placentome types, flat and convex. At Day48, there were more convex than flat placentomes, and convex placentomes had a lower proportion of maternal connective tissue (P < 0.01). However, this was reversed at Day153, where convex placentomes were lower in number and had greater volume of placental components (P < 0.01- P < 0.001) and greater surface area (P < 0.001) than flat placentomes. Importantly, embryo (r = 0.50) and fetal (r = 0.30) weight correlated with total number of convex but not flat placentomes. Extensive remodelling of the placenta increases capacity for nutrient exchange to support rapidly increasing embryo-fetal weight from Day48 to Day153. The cellular composition of convex placentomes, and exclusive relationships between convex placentome number and embryo-fetal weight, provide strong evidence for these placentomes as drivers of prenatal growth. The difference in proportion of maternal connective tissue between placentome types at Day48 suggests that this tissue plays a role in determining placentome shape, further highlighting the importance of early placental development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of maternal thyroid hormones during gestation on fetal brain development

PubMed Central

Moog, Nora K.; Entringer, Sonja; Heim, Christine; Wadhwa, Pathik D.; Kathmann, Norbert; Buss, Claudia

2015-01-01

Thyroid hormones (TH) play an obligatory role in many fundamental processes underlying brain development and maturation. The developing embryo/fetus is dependent on maternal supply of TH. The fetal thyroid gland does not commence THs synthesis until mid gestation, and the adverse consequences of severe maternal TH deficiency on offspring neurodevelopment are well established. Recent evidence suggests that even more moderate forms of maternal thyroid dysfunction, particularly during early gestation, may have a long-lasting influence on child cognitive development and risk of neurodevelopmental disorders. Moreover, these observed alterations appear to be largely irreversible after birth. It is, therefore, important to gain a better understanding of the role of maternal thyroid dysfunction on offspring neurodevelopment in terms of the nature, magnitude, time-specificity, and context-specificity of its effects. With respect to the issue of context specificity, it is possible that maternal stress and stress-related biological processes during pregnancy may modulate maternal thyroid function. The possibility of an interaction between the thyroid and stress systems in the context of fetal brain development has, however, not been addressed to date. We begin this review with a brief overview of TH biology during pregnancy and a summary of the literature on its effect on the developing brain. Next, we consider and discuss whether and how processes related to maternal stress and stress biology may interact with and modify the effects of maternal thyroid function on offspring brain development. We synthesize several research areas and identify important knowledge gaps that may warrant further study. The scientific and public health relevance of this review relates to achieving a better understanding of the timing, mechanisms and contexts of thyroid programming of brain development, with implications for early identification of risk, primary prevention and intervention. PMID

Fetal myosin immunoreactivity in human dystrophic muscle.

PubMed

Schiaffino, S; Gorza, L; Dones, I; Cornelio, F; Sartore, S

1986-01-01

We report immunofluorescence observations on normal and dystrophic human muscle using an antibody (anti-bF) raised against bovine fetal myosin and specific for fetal myosin heavy chains. In rat skeletal muscle, anti-bF was previously found to react selectively with myosin isoforms expressed during fetal and early postnatal development and in regenerating muscles. Anti-bF stained most fibers in human fetal and neonatal muscle, whereas only nuclear chain fibers of muscle spindles were labeled in normal adult muscle. In muscle biopsies from patients with Duchenne's muscular dystrophy, numerous extrafusal fibers were stained: some were small regenerating fibers, others were larger fibers presumably resulting from previous regenerative events. Fetal myosin immunoreactivity in Duchenne's dystrophy appears to reflect the reexpression of fetal-specific myosin isoforms and provides a new valuable tool for identifying regenerating fibers and following their destiny in dystrophic muscle.

Placental vascular dysfunction, fetal and childhood growth, and cardiovascular development: the generation R study.

PubMed

Gaillard, Romy; Steegers, Eric A P; Tiemeier, Henning; Hofman, Albert; Jaddoe, Vincent W V

2013-11-12

Suboptimal fetal nutrition may influence early growth and cardiovascular development. We examined whether umbilical and uterine artery resistance indices, as measures of feto-placental and utero-placental vascular function, respectively, are associated with fetal and childhood growth and cardiovascular development. This study was embedded in a population-based prospective cohort study among 6716 mothers and their children. Umbilical artery pulsatility index and uterine artery resistance index and fetal growth were measured in third trimester. Childhood growth was repeatedly assessed from birth to the age of 6 years. We measured body fat distribution, left ventricular mass, and blood pressure at the age of 6 years. Higher third trimester umbilical and uterine artery vascular resistance were associated with lower fetal length and weight growth in third trimester resulting in a smaller size at birth among boys and girls (P values < 0.05). These differences in length and weight growth became smaller from the age of 6 months onwards, but were still present at the age of 6 years. Higher third trimester umbilical artery vascular resistance, but not uterine artery vascular resistance, was associated with higher childhood body mass index, total fat mass, android/gynoid fat mass ratio, and systolic blood pressure, and with a lower left ventricular mass (P values<0.05). These associations were not explained by birth weight. Stronger associations tended to be present among girls as compared with boys. Higher third trimester feto-placental vascular resistance, but not utero-placental vascular resistance, was associated with slower fetal growth rates and cardiovascular adaptations in childhood.

The effect of Ramadan fasting on fetal development.

PubMed

Karateke, Atilla; Kaplanoglu, Mustafa; Avci, Fazil; Kurt, Raziye Keskin; Baloglu, Ali

2015-01-01

To evaluate the effects of Ramadan fasting on fetal development and outcomes of pregnancy. We performed this study in Antakya State Hospital of Obstetrics and Child Care, between 28 June 2014 and 27 July 2014 (during the month of Ramadan). A total of two hundred forty healthy pregnant women who were fasting during Ramadan, were included in the groups. The three groups were divided according to the trimesters. The each group was consisted of 40 healthy pregnant women with fasting and 40 healthy pregnant women without fasting. For evaluating the effects of Ramadan on fetus, ultrasonography was performed on all pregnant women in the beginning and the end of Ramadan. We used the essential parameters for the following measurements: increase of fetal biparietal diameter (BPD), increase of fetal femur length (FL), increase of estimated fetal body weight (EFBW), fetal biophysical profile (BPP), amniotic fluid index (AFI), and umbilical artery systole/diastole (S/D) ratio. No significant difference was found between the two groups for the fetal age, maternal weight gain (kilogram), estimated fetal weight gain (EFWG), fetal BPP, AFI, and umbilical artery S/D ratio. On the other hand, a statistically significant increase was observed in maternal weight in the second and third trimesters and a significant increase was observed in the amniotic fluid index in second trimester. In Ramadan there was no bad fetal outcome between pregnant women with fasting and pregnant women without fasting. Pregnant women who want to be with fast, should be examined by doctors, adequately get breakfast before starting to fast and after the fasting take essential calori and hydration. More comprehensive randomized studies are needed to explain the effects of fasting on the pregnancy and fetal outcomes.

Histone acetyltransferase activity of MOF is required for adult but not early fetal hematopoiesis in mice

PubMed Central

Valerio, Daria G.; Xu, Haiming; Eisold, Meghan E.; Woolthuis, Carolien M.; Pandita, Tej K.

2017-01-01

K(lysine) acetyltransferase 8 (KAT8, also known as MOF) mediates the acetylation of histone H4 at lysine 16 (H4K16ac) and is crucial for murine embryogenesis. Lysine acetyltransferases have been shown to regulate various stages of normal hematopoiesis. However, the function of MOF in hematopoietic stem cell (HSC) development has not yet been elucidated. We set out to study the role of MOF in general hematopoiesis by using a Vav1-cre–induced conditional murine Mof knockout system and found that MOF is critical for hematopoietic cell maintenance and HSC engraftment capacity in adult hematopoiesis. Rescue experiments with a MOF histone acetyltransferase domain mutant illustrated the requirement for MOF acetyltransferase activity in the clonogenic capacity of HSCs and progenitors. In stark contrast, fetal steady-state hematopoiesis at embryonic day (E) 14.5 was not affected by homozygous Mof deletion despite dramatic loss of global H4K16ac. Hematopoietic defects start manifesting in late gestation at E17.5. The discovery that MOF and its H4K16ac activity are required for adult but not early and midgestational hematopoiesis supports the notion that multiple chromatin regulators may be crucial for hematopoiesis at varying stages of development. MOF is therefore a developmental-stage–specific chromatin regulator found to be essential for adult but not early fetal hematopoiesis. PMID:27827827

Predicting the intrauterine fetal death of fetuses with cystic hygroma in early pregnancy.

PubMed

Shimura, Mai; Ishikawa, Hiroshi; Nagase, Hiromi; Mochizuki, Akihiko; Sekiguchi, Futoshi; Koshimizu, Naho; Itai, Toshiyuki; Odagami, Mizuha

2018-01-11

We investigated whether it was possible to predict the prognosis of fetuses with cystic hygroma in early pregnancy based on the degree of neck thickening. We retrospectively analyzed 57 singleton pregnancies with fetuses with cystic hygroma who were examined before the 22nd week of pregnancy. The fetuses were categorized according to the outcome, structural abnormalities at birth, and chromosomal abnormalities. Here, we proposed a new sonographic predictor with which we assessed neck thickening by dividing the width of the neck thickening by the biparietal diameter, which is expressed as the cystic hygroma width/biparietal diameter ratio. The median cystic hygroma width/biparietal diameter ratio in the intrauterine fetal death group (0.51) was significantly higher than that in the live birth group (0.27). No significant difference in the median cystic hygroma width/biparietal diameter ratio was found between the structural abnormalities group at birth and the no structural abnormalities group, and no significant difference in the median cystic hygroma width/biparietal diameter ratio was found between the chromosomal abnormality group and the no chromosomal abnormality group. We used receiver operating characteristic analysis to evaluate the cystic hygroma width/biparietal diameter ratio to predict intrauterine fetal death. When the cystic hygroma width/biparietal diameter ratio cut-off value was 0.5, intrauterine fetal death could be predicted with a sensitivity of 52.9% and a specificity of 100%. It is possible to predict intrauterine fetal death in fetuses with cystic hygroma in early pregnancy if cystic hygroma width/biparietal diameter ratio is measured. However, even if cystic hygroma width/biparietal diameter ratio is measured, predicting the presence or absence of a structural abnormality at birth or a chromosomal abnormality is difficult. © 2018 Japanese Teratology Society.

Fetal Neurobehavioral Development: A Tale of Two Cities.

ERIC Educational Resources Information Center

DiPietro, Janet A.; Caulfield, Laura; Costigan, Kathleen A.; Merialdi, Mario; Nguyen, Ruby H. N.; Zavaleta, Nelly; Gurewitsch, Edith D.

2004-01-01

Longitudinal neurobehavioral development was examined in 237 fetuses of low-risk pregnancies from 2 distinct populations-Baltimore, Maryland, and Lima, Peru-at 20, 24, 28, 32, 36, and 38 weeks gestation. Data were based on digitized Doppler-based fetal heart rate (FHR) and fetal movement (FM). In both groups, FHR declined while variability,…

Maternal nutrient restriction in early gestation upregulates myogenic genes in cattle fetal muscle tissue

USDA-ARS?s Scientific Manuscript database

Prenatal myogenesis is a critical factor in determining the muscle growth potential of cattle. We hypothesized that maternal nutrient restriction during early gestation would alter the transcriptome of fetal primordial muscle tissue in cattle. A total of 14 Angus-cross heifers were estrus synchroniz...

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

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

Evidence of cardiac involvement in the fetal inflammatory response syndrome: disruption of gene networks programming cardiac development in nonhuman primates.

PubMed

Mitchell, Timothy; MacDonald, James W; Srinouanpranchanh, Sengkeo; Bammler, Theodor K; Merillat, Sean; Boldenow, Erica; Coleman, Michelle; Agnew, Kathy; Baldessari, Audrey; Stencel-Baerenwald, Jennifer E; Tisoncik-Go, Jennifer; Green, Richard R; Gale, Michael J; Rajagopal, Lakshmi; Adams Waldorf, Kristina M

2018-04-01

Most early preterm births are associated with intraamniotic infection and inflammation, which can lead to systemic inflammation in the fetus. The fetal inflammatory response syndrome describes elevations in the fetal interleukin-6 level, which is a marker for inflammation and fetal organ injury. An understanding of the effects of inflammation on fetal cardiac development may lead to insight into the fetal origins of adult cardiovascular disease. The purpose of this study was to determine whether the fetal inflammatory response syndrome is associated with disruptions in gene networks that program fetal cardiac development. We obtained fetal cardiac tissue after necropsy from a well-described pregnant nonhuman primate model (pigtail macaque, Macaca nemestrina) of intrauterine infection (n=5) and controls (n=5). Cases with the fetal inflammatory response syndrome (fetal plasma interleukin-6 >11 pg/mL) were induced by either choriodecidual inoculation of a hypervirulent group B streptococcus strain (n=4) or intraamniotic inoculation of Escherichia coli (n=1). RNA and protein were extracted from fetal hearts and profiled by microarray and Luminex (Millipore, Billerica, MA) for cytokine analysis, respectively. Results were validated by quantitative reverse transcriptase polymerase chain reaction. Statistical and bioinformatics analyses included single gene analysis, gene set analysis, Ingenuity Pathway Analysis (Qiagen, Valencia, CA), and Wilcoxon rank sum. Severe fetal inflammation developed in the context of intraamniotic infection and a disseminated bacterial infection in the fetus. Interleukin-6 and -8 in fetal cardiac tissues were elevated significantly in fetal inflammatory response syndrome cases vs controls (P<.05). A total of 609 probe sets were expressed differentially (>1.5-fold change, P<.05) in the fetal heart (analysis of variance). Altered expression of select genes was validated by quantitative reverse transcriptase polymerase chain reaction that included

Fetal and post-natal lung defects reveal a novel and required role for Fgf8 in lung development

PubMed Central

Yu, Shibin; Poe, Bryan; Schwarz, Margaret; Elliot, Sarah; Albertine, Kurt H.; Fenton, Stephen; Garg, Vidu; Moon, Anne M.

2016-01-01

The fibroblast growth factor, FGF8, has been shown to be essential for vertebrate cardiovascular, craniofacial, brain and limb development. Here we report that Fgf8 function is required for normal progression through the late fetal stages of lung development that culminate in alveolar formation. Budding, lobation and branching morphogenesis are unaffected in early stage Fgf8 hypomorphic and conditional mutant lungs. Excess proliferation during fetal development disrupts distal airspace formation, mesenchymal and vascular remodeling, and Type I epithelial cell differentiation resulting in postnatal respiratory failure and death. Our findings reveal a previously unknown, critical role for Fgf8 function in fetal lung development and suggest that this factor may also contribute to postnatal alveologenesis. Given the high number of premature infants with alveolar dysgenesis and lung dysplasia, and the accumulating evidence that short-term benefits of available therapies may be outweighed by long term detrimental effects on postnatal alveologenesis, the therapeutic implications of identifying a factor or pathway that can be targeted to stimulate normal alveolar development are profound. PMID:20727874

Body composition during fetal development and infancy through the age of 5 years

PubMed Central

Toro-Ramos, T; Paley, C; Pi-Sunyer, FX; Gallagher, D

2015-01-01

Fetal body composition is an important determinant of body composition at birth, and it is likely to be an important determinant at later stages in life. The purpose of this work is to provide a comprehensive overview by presenting data from previously published studies that report on body composition during fetal development in newborns and the infant/child through 5 years of age. Understanding the changes in body composition that occur both in utero and during infancy and childhood, and how they may be related, may help inform evidence-based practice during pregnancy and childhood. We describe body composition measurement techniques from the in utero period to 5 years of age, and identify gaps in knowledge to direct future research efforts. Available literature on chemical and cadaver analyses of fetal studies during gestation is presented to show the timing and accretion rates of adipose and lean tissues. Quantitative and qualitative aspects of fetal lean and fat mass accretion could be especially useful in the clinical setting for diagnostic purposes. The practicality of different pediatric body composition measurement methods in the clinical setting is discussed by presenting the assumptions and limitations associated with each method that may assist the clinician in characterizing the health and nutritional status of the fetus, infant and child. It is our hope that this review will help guide future research efforts directed at increasing the understanding of how body composition in early development may be associated with chronic diseases in later life. PMID:26242725

Stereological study of developing glomerular forms during human fetal kidney development.

PubMed

Dakovic Bjelakovic, Marija; Vlajkovic, Slobodan; Petrovic, Aleksandar; Bjelakovic, Marko; Antic, Milorad

2018-05-01

Human fetal kidney development is a complex and stepwise process. The number, shape, size and distribution of glomeruli provide important information on kidney organization. The aim of this study was to quantify glomerular developing forms during human fetal kidney development using stereological methods. Kidney tissue specimens of 40 human fetuses with gestational ages ranging from 9 to 40 weeks were analyzed. Specimens were divided into eight groups based on gestational age, each corresponding to 1 lunar month. Stereological methods were used at the light microscopy level to estimate volume, surface and numerical density of the glomerular developing forms. During gestation, nephrogenesis continually advanced, and the number of nephrons increased. Volume, surface and numerical densities of vesicular forms and S-shaped bodies decreased gradually in parallel with gradual increases in estimated stereological parameters for vascularized glomeruli. Volume density and surface density of vascularized glomeruli increased gradually during fetal kidney development, and numerical density increased until the seventh lunar month. A relative decrease in vascularized glomeruli per unit volume of cortex occurred during the last 3 lunar months. Nephrogenesis began to taper off by 32 weeks and was completed by 36 weeks of gestation. The last sample in which we observed vesicles was from a fetus aged 32 weeks, and the last sample with S-shaped bodies was from a fetus aged 36 weeks. The present study is one of few quantitative studies conducted on human kidney development. Knowledge of normal human kidney morphogenesis during development could be important for future medical practice. Events occurring during fetal life may have significant consequences later in life.

Paternal low protein diet programs preimplantation embryo gene expression, fetal growth and skeletal development in mice.

PubMed

Watkins, Adam J; Sirovica, Slobodan; Stokes, Ben; Isaacs, Mark; Addison, Owen; Martin, Richard A

2017-06-01

Defining the mechanisms underlying the programming of early life growth is fundamental for improving adult health and wellbeing. While the association between maternal diet, offspring growth and adult disease risk is well-established, the effect of father's diet on offspring development is largely unknown. Therefore, we fed male mice an imbalanced low protein diet (LPD) to determine the impact on post-fertilisation development and fetal growth. We observed that in preimplantation embryos derived from LPD fed males, expression of multiple genes within the central metabolic AMPK pathway was reduced. In late gestation, paternal LPD programmed increased fetal weight, however, placental weight was reduced, resulting in an elevated fetal:placental weight ratio. Analysis of gene expression patterns revealed increased levels of transporters for calcium, amino acids and glucose within LPD placentas. Furthermore, placental expression of the epigenetic regulators Dnmt1 and Dnmt3L were increased also, coinciding with altered patterns of maternal and paternal imprinted genes. More strikingly, we observed fetal skeletal development was perturbed in response to paternal LPD. Here, while offspring of LPD fed males possessed larger skeletons, their bones comprised lower volumes of high mineral density in combination with reduced maturity of bone apatite. These data offer new insight in the underlying programming mechanisms linking poor paternal diet at the time of conception with the development and growth of his offspring. Copyright © 2017 Elsevier B.V. All rights reserved.

Uterine and placenta characteristics during early vascular development in the pig from day 22 to 42 of gestation.

PubMed

Wright, Elane C; Miles, Jeremy R; Lents, Clay A; Rempel, Lea A

2016-01-01

Insufficient placenta development is one of the primary causes of fetal death and reduced fetal growth after 35 days of gestation. Between day 22 and 42 the placenta consists of a central highly vascular placenta (HVP), adjacent to the fetus, a less vascular placenta (LVP), on either side of the fetus, and necrotic tips (NT). The objective of this study was to comprehensively evaluate uterine-placenta characteristics during early gestation in the gilt and determine time points and physiological changes. Gilts (n=25) were artificially inseminated at first detection of estrus (day 0) and 24h later, and harvested at 22, 27, 32, 37 or 42 days of gestation. Litter size, 12.1±3.4, was similar for all days of gestation. Fetal and placenta weight increased with day of gestation. The greatest increase in placenta weight occurred between 37 and 42 days of gestation. The LVP zones had no measurable fold formation until day 27. Necrotic tips became apparent after 27 days of gestation. Unoccupied areas of the uterus developed folds with changes in endometrial cell size and morphology from day 32 to 42 of gestation. Limited changes occurred in either fetal growth or placenta weight from day 27 through 32 of gestation; however, significant morphological changes occur at the maternal-fetal interface, demonstrating the dynamic architecture of the developing porcine placenta during early gestation. This work establishes fundamental time points in placenta development corresponding to fetal growth and microfold formation that may influence fetal growth and impact fetal survival. Published by Elsevier B.V.

Coincidence of pollen season with the first fetal trimester together with early pet exposure is associated with sensitization to cat and dog allergens in early childhood: A Finnish population-based study.

PubMed

Pyrhönen, K; Kulmala, P; Näyhä, S

2018-03-01

Children whose 11th fetal week falls in pollen season (spring) reportedly have an increased risk of sensitization to food allergens. No such finding has been reported for pet allergens. The aim of the study was to (i) evaluate the incidence of pet (dog and cat) sensitization according to the season of the 11th fetal week and (ii) whether the association between pet exposure and respective sensitization is modified by the coincidence of the 11th fetal week with pollen season. The study population comprised all children (born between 2001 and 2006) in the province of South Karelia, Finland (N = 5920). Their data of immunoglobulin E antibodies and skin prick tests to pet allergens (N = 538) were collected from patient records and linked with questionnaire data on pet exposure. The seasonal incidence peak of cat sensitization was observed in children whose 11th fetal week occurred in June (7.4%) and that of dog sensitization in April (3.8%) and June (4.7%). The relative rate (RR) for cat sensitization was 2.92 (95% CI 1.40-6.08) in children with cat exposure alone, 8.53 (4.07-17.86) in children with cat and fetal pollen exposures and 0.61 (0.20-1.83) in children exposed to pollen alone, compared with children without these exposures. The respective RRs for dog sensitization were 2.17 (1.13-4.19), 4.40 (2.19-8.83) and 1.65 (0.77-3.53). Coincidence of the first fetal trimester with pollen season strengthens the association between pet exposure and respective sensitization. Pollen exposure at early pregnancy may deviate immune system towards Th2-type reactivity promoting development of specific allergy in case allergen exposure occurred. Therefore, primary prevention of allergic diseases may need to begin during early pregnancy. © 2017 John Wiley & Sons Ltd.

Professionals' views of fetal-monitoring support the development of devices to provide objective longer-term assessment of fetal wellbeing.

PubMed

Brown, Rebecca; Johnstone, Edward D; Heazell, Alexander E P

2016-01-01

Continuous longer-term fetal monitoring has been proposed to address limitations of current technologies in the detection of fetal compromise. We aimed to assess professionals' views regarding current fetal-monitoring techniques and proposed longer-term continuous fetal monitoring. A questionnaire was designed and validated to assess obstetricians' and midwives' use of current fetal-monitoring techniques and their views towards continuous monitoring. 125 of 173 received responses (72% obstetricians, 28% midwives) were analysed. Professionals had the strongest views about supporting evidence for the most commonly employed fetal-monitoring techniques (maternal awareness of fetal movements, ultrasound assessment of fetal growth and umbilical artery Doppler). 45.1% of professionals agreed that a continuous monitoring device would be beneficial (versus 28.7% who disagreed); this perceived benefit was not influenced by professionals' views regarding current techniques or professional background. Professionals have limited experience of continuous fetal monitoring, but most respondents believed that it would increase maternal anxiety (64.3%) and would have concerns with its use in clinical practice (81.7%). Continuous fetal monitoring would be acceptable to the majority of professionals. However, development of these technologies must be accompanied by extended examination of professionals' and women's views to determine barriers to its introduction.

Histone acetyltransferase activity of MOF is required for adult but not early fetal hematopoiesis in mice.

PubMed

Valerio, Daria G; Xu, Haiming; Eisold, Meghan E; Woolthuis, Carolien M; Pandita, Tej K; Armstrong, Scott A

2017-01-05

K(lysine) acetyltransferase 8 (KAT8, also known as MOF) mediates the acetylation of histone H4 at lysine 16 (H4K16ac) and is crucial for murine embryogenesis. Lysine acetyltransferases have been shown to regulate various stages of normal hematopoiesis. However, the function of MOF in hematopoietic stem cell (HSC) development has not yet been elucidated. We set out to study the role of MOF in general hematopoiesis by using a Vav1-cre-induced conditional murine Mof knockout system and found that MOF is critical for hematopoietic cell maintenance and HSC engraftment capacity in adult hematopoiesis. Rescue experiments with a MOF histone acetyltransferase domain mutant illustrated the requirement for MOF acetyltransferase activity in the clonogenic capacity of HSCs and progenitors. In stark contrast, fetal steady-state hematopoiesis at embryonic day (E) 14.5 was not affected by homozygous Mof deletion despite dramatic loss of global H4K16ac. Hematopoietic defects start manifesting in late gestation at E17.5. The discovery that MOF and its H4K16ac activity are required for adult but not early and midgestational hematopoiesis supports the notion that multiple chromatin regulators may be crucial for hematopoiesis at varying stages of development. MOF is therefore a developmental-stage-specific chromatin regulator found to be essential for adult but not early fetal hematopoiesis. © 2017 by The American Society of Hematology.

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.

Interleukin-7 negatively regulates the development of mature T cells in fetal thymus organ cultures.

PubMed

DeLuca, Dominick; Clark, Dawn R

2002-05-01

We added antibody specific for interleukin-7 (IL-7) to chimeric fetal thymus organ cultures (FTOC) to investigate the involvement of this cytokine at distinct stages of T cell development. We report that the neutralization of IL-7 early in fetal T cell development results in a decrease in the production of mature CD4 or CD8 ('single positive', SP) or CD4/8 negative ('double negative', DN) T cell phenotypes, as defined by their expression of CD3. This loss of T cell development was not complete, but it did include the development of gammadelta T cells. However, if IL-7 was neutralized at later stages of FTOC, the production of CD4/8 positive ('double positive', DP) T cells was increased, and if the addition of the antibody was delayed further, the production of mature SP T cells was increased. This last result could be extended to both alphabeta and gammadelta T cells. These data suggested that IL-7 played a negative regulatory role in the development of progressively mature T cells. Tissue sections of FTOC showed that IL-7 was expressed in the subcapsular region of the tissue where immature T cells reside. However, IL-7 was not detected in the medullary region where mature T cells are located. These data suggest that IL-7 not only supports the development of immature fetal T cells, but it may inhibit the development of mature T cells. The production of mature fetal T cells may, therefore, be delayed until their precursors enter the medullary microenvironment, where IL-7 production is low. In this way, T cells may be prevented from maturing until negative selection or anergy events eliminate or inactivate autoreactive clones.

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…

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.

Fetal Alcohol Syndrome and Fetal Alcohol Effects in Child Development.

ERIC Educational Resources Information Center

Pancratz, Diane R.

This literature review defines Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) and considers their causes, diagnoses, prevalence, and educational ramifications. Effects of alcohol during each of the trimesters of pregnancy are summarized. Specific diagnostic characteristics of FAS are listed: (1) growth deficiency, (2) a…

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.

Fetal environment and early age at natural menopause in a British birth cohort study

PubMed Central

Tom, Sarah E.; Cooper, Rachel; Kuh, Diana; Guralnik, Jack M.; Hardy, Rebecca; Power, Chris

2010-01-01

BACKGROUND Early life development may influence the timing of natural menopause through association with size of the initial follicle pool or early follicular loss. This study examines the relationships of birthweight, gestational age and birthweight standardized by gestational age with early menopause in the 1958 British birth cohort study. METHODS Study participants were over 2900 women with data on birthweight, gestational age (obtained at birth), menopausal status at age 44–45 years and potential confounding factors. Logistic regression was used to study relationships of birthweight, gestational age and birthweight standardized by gestational age with post-menopausal status by 44–45 years, with and without adjustments for confounding factors. RESULTS There was a U-shaped association between birthweight and menopausal status at 44–45 years: women at either extremes of birthweight (<2.5 and ≥4.0 kg) had increased odds of post-menopausal status compared with those weighing 3.0–3.49 kg [odds ratio (OR) = 1.91, 95% confidence interval (CI) 1.08, 3.38; 1.81, 95% CI 1.11, 2.97, respectively]. Women with higher birthweight standardized by gestational age (which indicates faster fetal growth rate) also had increased odds of being post-menopausal by 44–45 years (OR for fastest quarter versus second fastest quarter = 1.80; 95% CI 1.16, 2.81). These associations persisted after adjustment for socioeconomic position at birth, adult smoking status and use of oral contraceptives. CONCLUSIONS These findings suggest that variations in fetal environment may be associated with the timing of menopause. Given that extremes of birthweight and higher birthweight standardized by gestational age were associated with earlier age at menopause, mechanisms related to these characteristics that also regulate ovarian function should be investigated further. PMID:20047935

Development and morphogenesis of human wrist joint during embryonic and early fetal period

PubMed Central

Hita-Contreras, Fidel; Martínez-Amat, Antonio; Ortiz, Raúl; Caba, Octavio; Álvarez, Pablo; Prados, José C; Lomas-Vega, Rafael; Aránega, Antonia; Sánchez-Montesinos, Indalecio; Mérida-Velasco, Juan A

2012-01-01

The development of the human wrist joint has been studied widely, with the main focus on carpal chondrogenesis, ligaments and triangular fibrocartilage. However, there are some discrepancies concerning the origin and morphogenetic time-table of these structures, including nerves, muscles and vascular elements. For this study we used serial sections of 57 human embryonic (n = 30) and fetal (n = 27) specimens from O’Rahilly stages 17–23 and 9–14 weeks, respectively. The following phases in carpal morphogenesis have been established: undifferentiated mesenchyme (stage 17), condensated mesenchyme (stages 18 and 19), pre-chondrogenic (stages 19 and 20) and chondrogenic (stages 21 and over). Carpal chondrification and osteogenic processes are similar, starting with capitate and hamate (stage 19) and ending with pisiform (stage 22). In week 14, a vascular bud penetrates into the lunate cartilaginous mold, early sign of the osteogenic process that will be completed after birth. In stage 18, median, ulnar and radial nerves and thenar eminence appear in the hand plate. In stage 21, there are indications of the interosseous muscles, and in stage 22 flexor digitorum superficialis, flexor digitorum profundus and lumbrical muscles, transverse carpal ligament and collateral ligaments emerge. In stage 23, the articular disc, radiocarpal and ulnocarpal ligaments and deep palmar arterial arch become visible. Radiate carpal and interosseous ligaments appear in week 9, and in week 10, dorsal radiocarpal ligament and articular capsule are evident. Finally, synovial membrane is observed in week 13. We have performed a complete analysis of the morphogenesis of the structures of the human wrist joint. Our results present new data on nervous and arterial elements and provide the basis for further investigations on anatomical pathology, comparative morphology and evolutionary anthropology. PMID:22428933

Selective serotonin reuptake inhibitor exposure during early pregnancy and the risk of fetal major malformations: focus on paroxetine.

PubMed

Gentile, Salvatore; Bellantuono, Cesario

2009-03-01

To analyze all studies reporting primary data on the rate of fetal malformations after early in utero exposure to paroxetine, investigated either specifically or jointly with other antidepressant medications. Medical literature was identified through searches of MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library (1980 through September 2008). Search terms were pregnancy, antidepressants, SSRIs, paroxetine, and fetal malformations. Additional studies were identified from the reference lists of published articles. Twenty-five articles reporting primary data on the rate of fetal structural malformations following exposure to paroxetine or selective serotonin reuptake inhibitors as a group during the first trimester of pregnancy were electronically or manually selected. Studies on the teratogenic risk of paroxetine show a high degree of heterogeneity. Moreover, research studies performed with the same methodology and thus showing the same level of evidence report conflicting results. Given the inconsistency of the findings and limitations of the methodology of the published studies, the teratogenic potential of paroxetine that has been reported in some studies remains unproven. This relevant safety question is likely to remain unanswered until large, prospective studies are conducted. Such studies should be designed to include a control group of untreated mothers with similar psychiatric diagnosis so as to differentiate effects of drug exposure from impact of underlying mental disorder on the fetus. Moreover, further experimental studies are warranted to definitively assess clinical consequences of the impact on fetal development related to physiologic effects of prenatal paroxetine exposure on different maternal and fetal parameters. ©Copyright 2009 Physicians Postgraduate Press, Inc.

Thrombophilic disorders and fetal loss: a meta-analysis.

PubMed

Rey, Evelyne; Kahn, Susan R; David, Michèle; Shrier, Ian

2003-03-15

Our aim was to assess the strength of the controversial association between thrombophilia and fetal loss, and to examine whether it varies according to the timing or definition of fetal loss. We searched Medline and Current Contents for articles published between 1975 and 2002 and their references with terms denoting recurrent fetal and non-recurrent fetal loss combined with various thrombophilic disorders. We included in our meta-analysis case-control, cohort, and cross-sectional studies published in English, the methodological quality of which was rated as moderate or strong. Pooled odds ratios (OR) with 95% CI were generated by random effects models with Cochrane Review Manager software. We included 31 studies. Factor V Leiden was associated with early (OR 2.01, 95% CI 1.13-3.58) and late (7.83, 2.83-21.67) recurrent fetal loss, and late non-recurrent fetal loss (3.26, 1.82-5.83). Exclusion of women with other pathologies that could explain fetal loss strengthened the association between Factor V Leiden and recurrent fetal loss. Activated protein C resistance was associated with early recurrent fetal loss (3.48, 1.58-7.69), and prothrombin G20210A mutation with early recurrent (2.56, 1.04-.29) and late non-recurrent (2.30, 1.09-4.87) fetal loss. Protein S deficiency was associated with recurrent fetal loss (14.72, 0.99-218.01) and late non-recurrent fetal loss (7.39, 1.28-42.63). Methylenetetrahydrofolate mutation, protein C, and antithrombin deficiencies were not significantly associated with fetal loss. The magnitude of the association between thrombophilia and fetal loss varies, according to type of fetal loss and type of thrombophilia.

Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants

PubMed Central

Hellström, Ann; Ley, David; Hansen-Pupp, Ingrid; Hallberg, Boubou; Ramenghi, Luca A.; Löfqvist, Chatarina; Smith, Lois E. H.; Hård, Anna-Lena

2018-01-01

The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities. PMID:27603537

Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF

PubMed Central

De Kleer, Ismé; Henri, Sandrine; Post, Sijranke; Vanhoutte, Leen; De Prijck, Sofie; Deswarte, Kim; Malissen, Bernard; Hammad, Hamida; Lambrecht, Bart N.

2013-01-01

Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac–derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the steady-state AMF pool. Mature AMFs were undetectable before birth and only fully colonized the alveolar space by 3 d after birth. Before birth, F4/80hiCD11blo primitive macrophages and Ly6ChiCD11bhi fetal monocytes sequentially colonized the developing lung around E12.5 and E16.5, respectively. The first signs of AMF differentiation appeared around the saccular stage of lung development (E18.5). Adoptive transfer identified fetal monocytes, and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes transferred to the lung of neonatal mice acquired an AMF phenotype via defined developmental stages over the course of one week, and persisted for at least three months. Early AMF commitment from fetal monocytes was absent in GM-CSF–deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy rescued AMF development for weeks, although the resulting AMFs displayed an immature phenotype. This demonstrates that tissue-resident macrophages can also develop from fetal monocytes that adopt a stable phenotype shortly after birth in response to instructive cytokines, and then self-maintain throughout life. PMID:24043763

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.

Fetal well-being assessment in bovine near-term gestations: Current knowledge and future perspectives arising from comparative medicine

PubMed Central

Buczinski, Sébastien M.C.; Fecteau, Gilles; Lefebvre, Réjean C.; Smith, Lawrence C.

2007-01-01

Cloning technology is associated with multiple losses throughout pregnancy and in the neonatal period. Any maternal or fetal disease can compromise pregnancy. A paucity of data are available on bovine fetal well-being in late pregnancy; development of well-being assessment methods might augment early diagnosis of abnormal pregnancy or fetal distress, allowing early intervention. This review presents the current knowledge on fetal well-being based on bovine, ovine, equine, and human studies, as well as interesting research parameters that have been studied in other species and not yet investigated in cattle. Transabdominal ultrasonography allows for diagnosis of large placentomes and hydrallantois that frequently accompany clone pregnancies. Fetal inactivity or large hyperechoic particles imaged within the fetal annexes are associated with fetal distress or death, and should be reassessed to confirm compromised pregnancy. Measurements of different fetal parameters (thoracic aorta, metacarpal or metatarsal thickness) could be reliable tools for early detection of the large offspring syndrome commonly found in cloned calves. PMID:17334032

Elevated fetal steroidogenic activity in autism.

PubMed

Baron-Cohen, S; Auyeung, B; Nørgaard-Pedersen, B; Hougaard, D M; Abdallah, M W; Melgaard, L; Cohen, A S; Chakrabarti, B; Ruta, L; Lombardo, M V

2015-03-01

Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism.

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

Maturation of the developing human fetal prostate in a rodent xenograft model

PubMed Central

Saffarini, Camelia M.; McDonnell, Elizabeth V.; Amin, Ali; Spade, Daniel J.; Huse, Susan M.; Kostadinov, Stefan; Hall, Susan J.; Boekelheide, Kim

2015-01-01

Background Prostate cancer is the most commonly diagnosed non-skin cancer in men. The etiology of prostate cancer is unknown, although both animal and epidemiologic data suggest that early life exposures to various toxicants, may impact DNA methylation status during development, playing an important role. Methods We have developed a xenograft model to characterize the growth and differentiation of human fetal prostate implants (gestational age 12-24 weeks) that can provide new data on the potential role of early life stressors on prostate cancer. The expression of key immunohistochemical markers responsible for prostate maturation was evaluated, including p63, cytokeratin 18, α-smooth muscle actin, vimentin, caldesmon, Ki-67, prostate specific antigen, estrogen receptor-α, and androgen receptor. Xenografts were separated into epithelial and stromal compartments using laser capture microdissection (LCM), and the DNA methylation status was assessed in >480,000 CpG sites throughout the genome. Results Xenografts demonstrated growth and maturation throughout the 200 days of post-implantation evaluation. DNA methylation profiles of laser capture micro-dissected tissue demonstrated tissue-specific markers clustered by their location in either the epithelium or stroma of human prostate tissue. Differential methylated promoter region CpG-associated gene analysis revealed significantly more stromal than epithelial DNA methylation in the 30 and 90-day xenografts. Functional classification analysis identified CpG-related gene clusters in methylated epithelial and stromal human xenografts. Conclusion This study of human fetal prostate tissue establishes a xenograft model that demonstrates dynamic growth and maturation, allowing for future mechanistic studies of the developmental origins of later life proliferative prostate disease. PMID:24038131

Proinflammatory cytokines: a link between chorioamnionitis and fetal brain injury.

PubMed

Patrick, Lindsay A; Smith, Graeme N

2002-09-01

To review the etiology of impaired fetal neurodevelopment - in particular, the relationship between chorioamnionitis, cytokines, and cerebral palsy. A MEDLINE search was performed for all clinical and basic science studies published in the English literature from 1966 to 2002. Key words or phrases used were chorioamnionitis, cerebral palsy, fetal brain damage, fetal CNS injury, infection in pregnancy, proinflammatory cytokines in pregnancy, proinflammatory cytokines in infection, and preterm labour or birth. All relevant human and animal studies were included. Fetal brain injury remains a major cause of lifelong morbidity, incurring significant societal and health care costs. It has been postulated that chorioamnionitis stimulates maternal/fetal proinflammatory cytokine release, which is damaging to the developing fetal nervous system. Elevated cytokine concentrations may interfere with glial cell development and proliferation in the late second trimester of pregnancy, when the central nervous system is most vulnerable. Increasing numbers of epidemiological and basic science studies found through MEDLINE searches support this hypothesis. Treatment options aimed at etiologic factors may lead to improved neurodevelopmental outcomes. Clearly, some relationship exists between chorioamnionitis, cytokines, and the development of cerebral palsy, but the severity and duration of exposure required to produce fetal damage remains unknown. Future research addressing these issues may aid in clinical decision-making. As well, the elucidation of mechanisms of cytokine action may aid in early treatment options to prevent or limit development of fetal brain injury.

Spreading the Clinical Window for Diagnosing Fetal-Onset Hypogonadism in Boys

PubMed Central

Grinspon, Romina P.; Loreti, Nazareth; Braslavsky, Débora; Valeri, Clara; Schteingart, Helena; Ballerini, María Gabriela; Bedecarrás, Patricia; Ambao, Verónica; Gottlieb, Silvia; Ropelato, María Gabriela; Bergadá, Ignacio; Campo, Stella M.; Rey, Rodolfo A.

2014-01-01

In early fetal development, the testis secretes – independent of pituitary gonadotropins – androgens and anti-Müllerian hormone (AMH) that are essential for male sex differentiation. In the second half of fetal life, the hypothalamic–pituitary axis gains control of testicular hormone secretion. Follicle-stimulating hormone (FSH) controls Sertoli cell proliferation, responsible for testis volume increase and AMH and inhibin B secretion, whereas luteinizing hormone (LH) regulates Leydig cell androgen and INSL3 secretion, involved in the growth and trophism of male external genitalia and in testis descent. This differential regulation of testicular function between early and late fetal periods underlies the distinct clinical presentations of fetal-onset hypogonadism in the newborn male: primary hypogonadism results in ambiguous or female genitalia when early fetal-onset, whereas it becomes clinically undistinguishable from central hypogonadism when established later in fetal life. The assessment of the hypothalamic–pituitary–gonadal axis in male has classically relied on the measurement of gonadotropin and testosterone levels in serum. These hormone levels normally decline 3–6 months after birth, thus constraining the clinical evaluation window for diagnosing male hypogonadism. The advent of new markers of gonadal function has spread this clinical window beyond the first 6 months of life. In this review, we discuss the advantages and limitations of old and new markers used for the functional assessment of the hypothalamic–pituitary–testicular axis in boys suspected of fetal-onset hypogonadism. PMID:24847309

Early brain development toward shaping of human mind: an integrative psychoneurodevelopmental model in prenatal and perinatal medicine.

PubMed

Hruby, Radovan; Maas, Lili M; Fedor-Freybergh, P G

2013-01-01

The article introduces an integrative psychoneurodevelopmental model of complex human brain and mind development based on the latest findings in prenatal and perinatal medicine in terms of integrative neuroscience. The human brain development is extraordinarily complex set of events and could be influenced by a lot of factors. It is supported by new insights into the early neuro-ontogenic processes with the help of structural 3D magnetic resonance imaging or diffusion tensor imaging of fetal human brain. Various factors and targets for neural development including birth weight variability, fetal and early-life programming, fetal neurobehavioral states and fetal behavioral responses to various stimuli and others are discussed. Molecular biology reveals increasing sets of genes families as well as transcription and neurotropic factors together with critical epigenetic mechanisms to be deeply employed in the crucial neurodevelopmental events. Another field of critical importance is psychoimmuno-neuroendocrinology. Various effects of glucocorticoids as well as other hormones, prenatal stress and fetal HPA axis modulation are thought to be of special importance for brain development. The early postnatal period is characterized by the next intense shaping of complex competences, induced mainly by the very unique mother - newborn´s interactions and bonding. All these mechanisms serve to shape individual human mind with complex abilities and neurobehavioral strategies. Continuous research elucidating these special competences of human fetus and newborn/child supports integrative neuroscientific approach to involve various scientific disciplines for the next progress in human brain and mind research, and opens new scientific challenges and philosophic attitudes. New findings and approaches in this field could establish new methods in science, in primary prevention and treatment strategies, and markedly contribute to the development of modern integrative and personalized

The implications of iodine and its supplementation during pregnancy in fetal brain development.

PubMed

Puig-Domingo, Manel; Vila, Lluis

2013-05-01

Iodine is an essential trace element for life. Its biological effects are a consequence of its incorporation to the thyroid hormones, which play a crucial role in fetal organogenesis, and in particular in brain development. This takes place during early gestation and involves delicate targeting throughout the central nervous system, including adequate neuronal growth, migration and myelinization at different sites, such as the cerebral cortex and neocortex, visual and auditory cortex, hippocampus and cerebellum. Pregnancy is characterized by an increased demand of thyroid hormones by the feto-placental unit in order to fulfill the necessary requirements of thyroid hormone action for normal fetal development. Up until week 20, the fetal thyroid is not fully active and therefore is completely dependent on the maternal thyroxine supply. Thus, the maternal thyroid has to adapt to this situation by producing about 1.5 fold more thyroxine. This requires that enzymatic gland machinery works normally as well as an adequate iodine intake, the principal substrate for thyroid hormone synthesis. Biological consequences of iodine related maternal hypothyroxinemia are currently very well known, by both experimental models and by clinical and epidemiological evidences. The associated disturbances parallel the degree of maternal thyroxine deficiency, ranging from increased neonatal morbi-mortality and severe mental dysfunction, to hyperactivity, attention disorders and a substantial decrease of IQ of an irreversible nature in the progeny of mothers suffering a deprivation of iodine during pregnancy. As a consequence, iodine deficiency is the leading preventable cause of mental impaired function in the world, affecting as many as 2 billion people (35.2% of the entire population). Prevention of fetal iodine deficiency - a problem of pandemic proportions- is feasible, provided that an iodine supply of 200-300 μg/day to the mother is ensured, before and throughout gestation as well

Embryo-fetal development studies with the dietary supplement vinpocetine in the rat and rabbit.

PubMed

Catlin, Natasha; Waidyanatha, Suramya; Mylchreest, Eve; Miller-Pinsler, Lutfiya; Cunny, Helen; Foster, Paul; Sutherland, Vicki; McIntyre, Barry

2018-06-01

Dietary supplement and natural product use is increasing within the United States, resulting in growing concern for exposure in vulnerable populations, including young adults and women of child-bearing potential. Vinpocetine is a semisynthetic derivative of the Vinca minor extract, vincamine. Human exposure to vinpocetine occurs through its use as a dietary supplement for its purported nootropic and neuroprotective effects. To investigate the effects of vinpocetine on embryo-fetal development, groups of 25 pregnant Sprague-Dawley rats and 8 pregnant New Zealand White rabbits were orally administered 0, 5, 20, or 60 mg vinpocetine/kg and 0, 25, 75, 150, or 300 mg/kg daily from gestational day (GD) 6-20 and GD 7-28, respectively. Pregnant rats dosed with vinpocetine demonstrated dose-dependent increases in postimplantation loss, higher frequency of early and total resorptions, lower fetal body weights, and fewer live fetuses following administration of 60 mg/kg, in the absence of maternal toxicity. Additionally, the rat fetuses displayed dose-dependent increases in the incidences of ventricular septum defects and full supernumerary thoracolumbar ribs. Similarly, albeit at higher doses than the rats, pregnant rabbits administered vinpocetine displayed an increase in postimplantation loss and fewer live fetuses (300 mg/kg), in addition to significantly lower fetal body weights (≥75 mg/kg). In conclusion, vinpocetine exposure resulted in similar effects on embryo-fetal development in the rat and rabbit. The species differences in sensitivity and magnitude of response is likely attributable to a species difference in metabolism. Taken together, these data suggest a potential hazard for pregnant women who may be taking vinpocetine. © 2018 Wiley Periodicals, Inc.

Embryonic essential myosin light chain regulates fetal lung development in rats.

PubMed

Santos, Marta; Moura, Rute S; Gonzaga, Sílvia; Nogueira-Silva, Cristina; Ohlmeier, Steffen; Correia-Pinto, Jorge

2007-09-01

Congenital diaphragmatic hernia (CDH) is currently the most life-threatening congenital anomaly the major finding of which is lung hypoplasia. Lung hypoplasia pathophysiology involves early developmental molecular insult in branching morphogenesis and a late mechanical insult by abdominal herniation in maturation and differentiation processes. Since early determinants of lung hypoplasia might appear as promising targets for prenatal therapy, proteomics analysis of normal and nitrofen-induced hypoplastic lungs was performed at 17.5 days after conception. The major differentially expressed protein was identified by mass spectrometry as myosin light chain 1a (MLC1a). Embryonic essential MLC1a and regulatory myosin light chain 2 (MLC2) were characterized throughout normal and abnormal lung development by immunohistochemistry and Western blot. Disruption of MLC1a expression was assessed in normal lung explant cultures by antisense oligodeoxynucleotides. Since early stages of normal lung development, MLC1a was expressed in vascular smooth muscle (VSM) cells of pulmonary artery, and MLC2 was present in parabronchial smooth muscle and VSM cells of pulmonary vessels. In addition, early smooth muscle differentiation delay was observed by immunohistochemistry of alpha-smooth muscle actin and transforming growth factor-beta1. Disruption of MLC1a expression during normal pulmonary development led to significant growth and branching impairment, suggesting a role in branching morphogenesis. Both MLC1a and MLC2 were absent from hypoplastic fetal lungs during pseudoglandular stage of lung development, whereas their expression partially recovered by prenatal treatment with vitamin A. Thus, a deficiency in contractile proteins MLC1a and MLC2 might have a role among the early molecular determinants of lung hypoplasia in the rat model of nitrofen-induced CDH.

The role of pleiotrophin and β-catenin in fetal lung development

PubMed Central

2010-01-01

Mammalian lung development is a complex biological process, which is temporally and spatially regulated by growth factors, hormones, and extracellular matrix proteins. Abnormal changes of these molecules often lead to impaired lung development, and thus pulmonary diseases. Epithelial-mesenchymal interactions are crucial for fetal lung development. This paper reviews two interconnected pathways, pleiotrophin and Wnt/β-catenin, which are involved in fibroblast and epithelial cell communication during fetal lung development. PMID:20565841

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.

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice.

PubMed

Akers, Katherine G; Kushner, Steven A; Leslie, Ana T; Clarke, Laura; van der Kooy, Derek; Lerch, Jason P; Frankland, Paul W

2011-07-07

Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.

Elevated fetal steroidogenic activity in autism

PubMed Central

Baron-Cohen, S; Auyeung, B; Nørgaard-Pedersen, B; Hougaard, D M; Abdallah, M W; Melgaard, L; Cohen, A S; Chakrabarti, B; Ruta, L; Lombardo, M V

2015-01-01

Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism. PMID:24888361

Up Front, in Hope: The Value of Early Intervention for Children with Fetal Alcohol Syndrome.

ERIC Educational Resources Information Center

Harwood, Maureen; Kleinfeld, Judith Smilg

2002-01-01

Differentiates fetal alcohol syndrome (FAS) from fetal alcohol effects (FAE) and discusses difficulties in diagnosing these conditions. Describes the effects of FAS/FAE on young children, detailing impact on sensory processing, focusing attention, and cognitive development in infants, toddlers, and preschoolers. Presents suggestions for caregivers…

[Fetal and early trauma syndrome-FETS].

PubMed

Zoroastro, Gastón A

2006-01-01

This is a new clinical description for cases of children whose parents are among those who have disappeared and were given birth by women held prisoners and subjected to torture, humiliation and abuses. This description is considered a special case of early, and in many cases fetal distress. These children felt horror when they were violently separated from their parents immediately after being born in captivity or in early infancy during the last military dictatorship (1976-1983). Afterwards they were sold by their captors and raised as adoptive or as their own children by the purchasers. The fact that these cases be included in the existing WHO categories contained in CIE-10: Posttraumatic stress disorder, F43.1, is discussed as they show late responses on the part of the victims to situations of torture, terrorism and rape. However, it is clarified that cases in which the aftereffects of severe stress become evident after decades will have to be classified as Persistent personality disorders, after catastrophic experience, F62.0. It is concluded that it is necessary to consider FETS as a new combination of manifestations of the Persistent Personality Disorders due to its specific idiosyncratic characteristics that go beyond the available clinical descriptions, to its own etiophatic equation and to its recognizable pathognomonic identification. Its pathognomonic identification in some cases was useful to detect children with these alienated identity problems (understood as legally neglected and clinically alienated). Propedeutic and treatment aspects are mentioned in conjunction with the peculiarities of a therapy that restores the illegally deprived personality of these children, who nowadays are adults of approximately 25 to 29 years of age. Finally, a metapsychologic discussion is presented, which is about the resilience of the truth and the fact that when it is rejected it returns, thus constituting ethics of the truth.

Development and significance of a fetal electrocardiogram recorded by signal-averaged high-amplification electrocardiography.

PubMed

Hayashi, Risa; Nakai, Kenji; Fukushima, Akimune; Itoh, Manabu; Sugiyama, Toru

2009-03-01

Although ultrasonic diagnostic imaging and fetal heart monitors have undergone great technological improvements, the development and use of fetal electrocardiograms to evaluate fetal arrhythmias and autonomic nervous activity have not been fully established. We verified the clinical significance of the novel signal-averaged vector-projected high amplification ECG (SAVP-ECG) method in fetuses from 48 gravidas at 32-41 weeks of gestation and in 34 neonates. SAVP-ECGs from fetuses and newborns were recorded using a modified XYZ-leads system. Once noise and maternal QRS waves were removed, the P, QRS, and T wave intervals were measured from the signal-averaged fetal ECGs. We also compared fetal and neonatal heart rates (HRs), coefficients of variation of heart rate variability (CV) as a parasympathetic nervous activity, and the ratio of low to high frequency (LF/HF ratio) as a sympathetic nervous activity. The rate of detection of a fetal ECG by SAVP-ECG was 72.9%, and the fetal and neonatal QRS and QTc intervals were not significantly different. The neonatal CVs and LF/HF ratios were significantly increased compared with those in the fetus. In conclusion, we have developed a fetal ECG recording method using the SAVP-ECG system, which we used to evaluate autonomic nervous system development.

IS THERE A VIABILITY-VULNERABILITY TRADEOFF? SEX DIFFERENCES IN FETAL PROGRAMMING

PubMed Central

SANDMAN, CURT A; GLYNN, LAURA M; DAVIS, ELYSIA POGGI

2013-01-01

OBJECTIVE In this paper we evaluate the evidence for sex differences in fetal programming within the context of the proposed viability-vulnerability tradeoff. METHODS We briefly review the literature on the factors contributing to primary and secondary sex ratios. Sex differences in fetal programming are assessed by summarizing previously published sex difference findings from our group (6 studies) and also new analyses of previously published findings in which sex differences were not reported (6 studies). RESULTS The review and reanalysis of studies from our group are consistent with the overwhelming evidence of increasing risk for viability among males exposed to environmental adversity early in life. New evidence reported here support the argument that females, despite their adaptive agility, also are influenced by exposure to early adversity. Two primary conclusions are (i) female fetal exposure to psychobiological stress selectively influences fear/anxiety, and (ii) the effects of female fetal exposure to stress persist into preadolescence. These persisting effects are reflected in increased levels of anxiety, impaired executive function and neurological markers associated with these behaviors. CONCLUSIONS A tacit assumption is that females, with their adaptive flexibility early in gestation, escape the consequences of early life exposure to adversity. We argue that the consequences of male exposure to early adversity threatens their viability, effectively culling the weak and the frail and creating a surviving cohort of the fittest. Females adjust to early adversity with a variety of strategies, but their escape from the risk of early mortality and morbidity has a price of increased vulnerability expressed later in development. PMID:24119938

Bendectin and fetal development. A study of Boston City Hospital.

PubMed

Morelock, S; Hingson, R; Kayne, H; Dooling, E; Zuckerman, B; Day, N; Alpert, J J; Flowerdew, G

1982-01-15

As part of a prospective study investigating maternal characteristics and habits during pregnancy and their impact on fetal development, 1,690 mother/infant pairs were studied. Of the mothers, 375 reported using Bendectin during pregnancy. Multivariate analyses examining birth weight, length, head circumference, gestational age, and congenital malformations as dependent variables demonstrated no associations between Bendectin exposure and adverse fetal outcome.

The extracellular calcium-sensing receptor regulates human fetal lung development via CFTR

PubMed Central

Brennan, Sarah C.; Wilkinson, William J.; Tseng, Hsiu-Er; Finney, Brenda; Monk, Bethan; Dibble, Holly; Quilliam, Samantha; Warburton, David; Galietta, Luis J.; Kemp, Paul J.; Riccardi, Daniela

2016-01-01

Optimal fetal lung growth requires anion-driven fluid secretion into the lumen of the developing organ. The fetus is hypercalcemic compared to the mother and here we show that in the developing human lung this hypercalcaemia acts on the extracellular calcium-sensing receptor, CaSR, to promote fluid-driven lung expansion through activation of the cystic fibrosis transmembrane conductance regulator, CFTR. Several chloride channels including TMEM16, bestrophin, CFTR, CLCN2 and CLCA1, are also expressed in the developing human fetal lung at gestational stages when CaSR expression is maximal. Measurements of Cl−-driven fluid secretion in organ explant cultures show that pharmacological CaSR activation by calcimimetics stimulates lung fluid secretion through CFTR, an effect which in humans, but not mice, was also mimicked by fetal hypercalcemic conditions, demonstrating that the physiological relevance of such a mechanism appears to be species-specific. Calcimimetics promote CFTR opening by activating adenylate cyclase and we show that Ca2+-stimulated type I adenylate cyclase is expressed in the developing human lung. Together, these observations suggest that physiological fetal hypercalcemia, acting on the CaSR, promotes human fetal lung development via cAMP-dependent opening of CFTR. Disturbances in this process would be expected to permanently impact lung structure and might predispose to certain postnatal respiratory diseases. PMID:26911344

Structural development of human brain white matter from mid-fetal to perinatal stage

NASA Astrophysics Data System (ADS)

Ouyang, Austin; Yu, Qiaowen; Mishra, Virendra; Chalak, Lina; Jeon, Tina; Sivarajan, Muraleedharan; Jackson, Greg; Rollins, Nancy; Liu, Shuwei; Huang, Hao

2015-03-01

The structures of developing human brain white matter (WM) tracts can be effectively quantified by DTI-derived metrics, including fractional anisotropy (FA), mean, axial and radial diffusivity (MD, AD and RD). However, dynamics of WM microstructure during very early developmental period from mid-fetal to perinatal stage is unknown. It is difficult to accurately measure microstructural properties of these WM tracts due to severe contamination from cerebrospinal fluid (CSF). In this study, high resolution DTI of fetal brains at mid-fetal stage (20 weeks of gestation or 20wg), 19 brains in the middle of 3rd trimester (35wg) and 17 brains around term (40wg) were acquired. We established first population-averaged DTI templates at these three time points and extracted WM skeleton. 16 major WM tracts in limbic, projection, commissural and association tract groups were traced with DTI tractography in native space. The WM skeleton in the template space was inversely transformed back to the native space for measuring core WM microstructures of each individual tract. Continuous microstructural enhancement and volumetric increase of WM tracts were found from 20wg to 40wg. The microstructural enhancement from FA measurement is decelerated in late 3rd trimester compared to mid-fetal to middle 3rd trimester, while volumetric increase of prefrontal WM tracts is accelerated. The microstructural enhancement from 35wg to 40wg is heterogeneous among different tract groups with microstructures of association tracts undergoing most dramatic change. Besides decreases of RD indicating active myelination, the decrease of AD for most WM tracts during late 3rd trimester suggests axonal packing process.

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

Fetal heart and uterine contraction monitor (image)

MedlinePlus

The fetal heart monitor and uterine contraction monitor provide a continuous record of the baby's heart rate and the mother's contraction rate as labor progresses. This device can provide early warning of fetal distress.

Early fetal heart ultrasonography as additional indicator for chromosomopathies.

PubMed

Dmitrovic, A; Jeremic, K; Babic, U M; Perovic, M; Mihailovic, T; Opric, D; Zecevic, N; Gojnić-Dugalić, M

2016-01-01

First trial of estimating values of scans of fetal heart structures (FHS) in first trimester of pregnancy, as more primary facts of possible chromosomopathies. The study included 2,643 fetuses that were examined in first trimester of pregnancy on Sono CT convex (C5-2MHz), endovaginal (ev 8-4MHz), and linear transducers (L12-5MHz) during a period of eight years. Fetal heart was evaluated using appropriate software with broad-band transducers and color Doppler, Sono CT, and HD ZOOM technologies. The scan was performed by three experienced physicians. FHS were based on: left and right ventricle morphology; AV valves (atrioventricular) position and existence of primal ostium; relationship of left ventricle outflow tract (LVOT) and right ventricle outflow tract (RVOT) and great vessels on three vessel view (3VV) and estimation of ductal and aortic arch. Several developments, one being the ability to identify fetuses at risk for cardiac defects combining nuchal translucency (NT), ductus venosus (DV) Doppler, and evaluation of tricuspid regurgitation, have prompted reconsideration of the role of the first trimester prognostic factor of fetal evaluation. In low-risk pregnancies group, 36 (1.8%) fetuses were found to have congenital heart disease (CHD), and in high-risk pregnancies the number of fetuses with CHD was 75 (12%). Genetic amniocentesis or chorionic villus sampling (CVS) was performed in all fetuses with CHD. Forty-two (37.8%) fetuses with CHD were found to have chromosomal anomalies. Out of 111 fetuses with CHD 39 (35.1%) had an nuchal translucency (NT) above three mm. Out of 42 fetuses with chromosomal anomalies and CHD, 29 (69%) had an increased NT. Using first trimester fetal echosonography constitutes a further step in the earlier recognition of chromosomopathies, even in low risk groups. Still further steps are necessary as all facts of good clinical practice. In order to offer further benefits during pregnancies, improvements in diagnostics are still

Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

PubMed Central

2011-01-01

Background Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Results Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Conclusions Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development. PMID:21736737

BPI-fold (BPIF) containing/plunc protein expression in human fetal major and minor salivary glands.

PubMed

Alves, Daniel Berretta Moreira; Bingle, Lynne; Bingle, Colin David; Lourenço, Silvia Vanessa; Silva, Andréia Aparecida; Pereira, Débora Lima; Vargas, Pablo Agustin

2017-01-16

The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.

Primary cultures of astrocytes from fetal bovine brain.

PubMed

Ballarin, Cristina; Peruffo, Antonella

2012-01-01

We describe here a method to obtain primary cell cultures from the cerebral cortex and the hypothalamus of bovine fetuses. We report how tissue origin, developmental stages, and culture medium conditions influence cell differentiation and the prevalence of glial cells vs. neurons. We compare explants from early, middle, and late stages of development and two different fetal calf serum concentrations (1 and 10%) to identify the best conditions to obtain and grow viable astrocytes in culture. In addition, we describe how to cryopreserve and obtain viable cortical astrocytes from frozen fetal bovine brain samples.

Perinatal Psychoneuroimmunology: Protocols for the Study of Prenatal Stress and Its Effects on Fetal and Postnatal Brain Development.

PubMed

Frasch, Martin G; Baier, Carlos J; Antonelli, Marta C; Metz, Gerlinde A S

2018-01-01

Prenatal stress (PS) impacts early behavioral, neuroimmune, and cognitive development. Pregnant rat models have been very valuable in examining the mechanisms of such fetal programming. A newer pregnant sheep model of maternal stress offers the unique advantages of chronic in utero monitoring and manipulation. This chapter presents the techniques used to model single and multigenerational stress exposures and their pleiotropic effects on the offspring.

Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice.

PubMed

Zazara, Dimitra E; Perani, Clara V; Solano, María E; Arck, Petra C

2018-02-01

Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically. Whilst prenatal stress challenge did not profoundly affect lung development in male fetuses, it resulted in less extensive terminal sacs, surrounded by thicker mesenchymal tissue in female fetuses. Thus, prenatal stress disrupted fetal lung development sex-specifically. Interestingly, upon prenatal stress challenge, the airway hyperresponsiveness and eosinophilic inflammation- two hallmarks of asthma - were significantly increased in adult female offspring, whilst regulatory CD4+ T cells were reduced. These findings strongly underpin the sex-specific association between s challenged fetal development and a sex-specific altered severity of asthma in adult offspring. Our model now allows to identify maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth in response to challenges. Such identification then opens avenues for primary disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

STATs in Lung Development: Distinct Early and Late Expression, Growth Modulation and Signaling Dysregulation in Congenital Diaphragmatic Hernia.

PubMed

Piairo, Paulina; Moura, Rute S; Baptista, Maria João; Correia-Pinto, Jorge; Nogueira-Silva, Cristina

2018-01-01

Congenital diaphragmatic hernia (CDH) is a life-threatening developmental anomaly, intrinsically combining severe pulmonary hypoplasia and hypertension. During development, signal transducers and activators of transcription (STAT) are utilized to elicit cell growth, differentiation, and survival. We used the nitrofen-induced CDH rat model. At selected gestational time points, lungs were divided into two experimental groups, i.e., control or CDH. We performed immunohistochemistry and western blotting analysis to investigate the developmental expression profile of the complete family of STATs (STAT1-6), plus specific STATs activation (p-STAT3, p-STAT6) and regulation by SOCS (SOCS3) in normal lungs against those of diseased lungs. The normal fetal lung explants were treated with piceatannol (STAT3 inhibitor) in vitro followed by morphometrical analysis. Molecular profiling of STATs during the lung development revealed distinct early and late expression signatures. Experimental CDH altered the STATs expression, activation, and regulation in the fetal lungs. In particular, STAT3 and STAT6 were persistently over-expressed and early over-activated. Piceatannol treatment dose-dependently stimulated the fetal lung growth. These findings suggest that STATs play an important role during normal fetal lung development and CDH pathogenesis. Moreover, functionally targeting STAT signaling modulates fetal lung growth, which highlights that STAT3 and STAT6 signaling might be promising therapeutic targets in reducing or preventing pulmonary hypoplasia in CDH. © 2018 The Author(s). Published by S. Karger AG, Basel.

Ibuprofen results in alterations of human fetal testis development

PubMed Central

Ben Maamar, Millissia; Lesné, Laurianne; Hennig, Kristin; Desdoits-Lethimonier, Christèle; Kilcoyne, Karen R.; Coiffec, Isabelle; Rolland, Antoine D.; Chevrier, Cécile; Kristensen, David M.; Lavoué, Vincent; Antignac, Jean-Philippe; Le Bizec, Bruno; Dejucq-Rainsford, Nathalie; Mitchell, Rod T.; Mazaud-Guittot, Séverine; Jégou, Bernard

2017-01-01

Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7–17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8–9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10–12 GW, or in second trimester xenografted testes (14–17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow ‘early window’ of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology. PMID:28281692

Extrinsic Factors Influencing Fetal Deformations and Intrauterine Growth Restriction

PubMed Central

Moh, Wendy; Graham, John M.; Wadhawan, Isha; Sanchez-Lara, Pedro A.

2012-01-01

The causes of intrauterine growth restriction (IUGR) are multifactorial with both intrinsic and extrinsic influences. While many studies focus on the intrinsic pathological causes, the possible long-term consequences resulting from extrinsic intrauterine physiological constraints merit additional consideration and further investigation. Infants with IUGR can exhibit early symmetric or late asymmetric growth abnormality patterns depending on the fetal stage of development, of which the latter is most common occurring in 70–80% of growth-restricted infants. Deformation is the consequence of extrinsic biomechanical factors interfering with normal growth, functioning, or positioning of the fetus in utero, typically arising during late gestation. Biomechanical forces play a critical role in the normal morphogenesis of most tissues. The magnitude and direction of force impact the form of the developing fetus, with a specific tissue response depending on its pliability and stage of development. Major uterine constraining factors include primigravida, small maternal size, uterine malformation, uterine fibromata, early pelvic engagement of the fetal head, aberrant fetal position, oligohydramnios, and multifetal gestation. Corrective mechanical forces similar to those that gave rise to the deformation to reshape the deformed structures are often used and should take advantage of the rapid postnatal growth to correct form. PMID:22888434

Fetal growth restriction: current knowledge.

PubMed

Nardozza, Luciano Marcondes Machado; Caetano, Ana Carolina Rabachini; Zamarian, Ana Cristina Perez; Mazzola, Jaqueline Brandão; Silva, Carolina Pacheco; Marçal, Vivian Macedo Gomes; Lobo, Thalita Frutuoso; Peixoto, Alberto Borges; Araujo Júnior, Edward

2017-05-01

Fetal growth restriction (FGR) is a condition that affects 5-10% of pregnancies and is the second most common cause of perinatal mortality. This review presents the most recent knowledge on FGR and focuses on the etiology, classification, prediction, diagnosis, and management of the condition, as well as on its neurological complications. The Pubmed, SCOPUS, and Embase databases were searched using the term "fetal growth restriction". Fetal growth restriction (FGR) may be classified as early or late depending on the time of diagnosis. Early FGR (<32 weeks) is associated with substantial alterations in placental implantation with elevated hypoxia, which requires cardiovascular adaptation. Perinatal morbidity and mortality rates are high. Late FGR (≥32 weeks) presents with slight deficiencies in placentation, which leads to mild hypoxia and requires little cardiovascular adaptation. Perinatal morbidity and mortality rates are lower. The diagnosis of FGR may be clinical; however, an arterial and venous Doppler ultrasound examination is essential for diagnosis and follow-up. There are currently no treatments to control FGR; the time at which pregnancy is interrupted is of vital importance for protecting both the mother and fetus. Early diagnosis of FGR is very important, because it enables the identification of the etiology of the condition and adequate monitoring of the fetal status, thereby minimizing risks of premature birth and intrauterine hypoxia.

Human cerebral organoids recapitulate gene expression programs of fetal neocortex development

PubMed Central

Camp, J. Gray; Badsha, Farhath; Florio, Marta; Kanton, Sabina; Gerber, Tobias; Wilsch-Bräuninger, Michaela; Lewitus, Eric; Sykes, Alex; Hevers, Wulf; Lancaster, Madeline; Knoblich, Juergen A.; Lachmann, Robert; Pääbo, Svante; Huttner, Wieland B.; Treutlein, Barbara

2015-01-01

Cerebral organoids—3D cultures of human cerebral tissue derived from pluripotent stem cells—have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and previously unidentified interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single-cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. PMID:26644564

Development of customized fetal growth charts in twins.

PubMed

Ghi, Tullio; Prefumo, Federico; Fichera, Anna; Lanna, Mariano; Periti, Enrico; Persico, Nicola; Viora, Elsa; Rizzo, Giuseppe

2017-05-01

Twin gestations are at significantly higher risk of fetal growth restriction in comparison with singletons. Using fetal biometric charts customized for obstetrical and parental characteristics may facilitate an accurate assessment of fetal growth. The objective of the study was to construct reference charts for the gestation of fetal biometric parameters stratified by chorionicity and customized for obstetrical and parental characteristics. Fetal biometric measurements obtained from serial ultrasound examinations in uncomplicated twin pregnancies delivering after 36 weeks of gestation were collected by 19 Italian fetal medicine units under the auspices of the Società Italiana di Ecografia Ostetrica e Ginecologica. The measurements acquired in each fetus at each examination included biparietal diameter, head circumference, abdominal circumference, and femur length. Multilevel linear regression models were used to adjust for the serial ultrasonographic measurements obtained and the clustering of each fetus in twin pregnancy. The impact of maternal and paternal characteristics (height, weight, ethnicity), parity, fetal sex, and mode of conception was also considered. Models for each parameter were stratified by fetal chorionicity and compared with our previously constructed growth curves for singletons. The data set included 1781 twin pregnancies (dichorionic, n = 1289; monochorionic diamniotic, n = 492) with 8923 ultrasonographic examinations with a median of 5 (range, 2-8) observations per pregnancy in dichorionic and 6 in (range, 2-11) monochorionic pregnancies. Growth curves of twin pregnancies differed from those of singletons, and differences were more marked in monochorionic twins and during the third trimester. A significant influence of parental characteristics was found. Curves of fetal biometric measurements in twins are influenced by parental characteristics. There is a reduction in the growth rate during the third trimester. The reference limits for

Maternal, fetal, and placental conditions associated with medically indicated late preterm and early term delivery: a retrospective study.

PubMed

Brown, H K; Speechley, K N; Macnab, J; Natale, R; Campbell, M K

2016-04-01

Our objectives were: (1) to examine the association between maternal, fetal, and placental phenotypes of preterm delivery and medically indicated early delivery of singletons during the late preterm and early term periods; and (2) to identify the specific maternal, fetal, and placental conditions associated with these early deliveries. Retrospective study. City of London and Middlesex County, Ontario, Canada. Singleton live deliveries, at 34-41 weeks of gestation to women in London and Middlesex. We obtained data from a city-wide perinatal database (2002-2011; n = 25 699). We used multinomial logistic regression for multivariable analyses. The outcome was the occurrence of medically indicated late preterm (34-36 weeks of gestation) and early term (37-38 weeks of gestation) delivery, versus delivery at full term (39-41 weeks of gestation). After controlling for confounding factors, all phenotypes were associated with increased odds of medically indicated late preterm and early term delivery. Within the maternal phenotype, chronic maternal medical conditions were associated with increased odds of medically indicated early term delivery (e.g. for gastrointestinal disease, adjusted odds ratio, aOR 1.72, 95% CI 1.47-2.00; for anaemia, aOR 1.40, 95% CI 1.20-1.63), but not late preterm delivery. The aetiology of medically indicated early delivery close to full term is heterogeneous. Patterns of associations suggest slightly different conditions underlying the late preterm and early term phenotypes, with chronic maternal medical conditions being associated with early term delivery but not with late preterm delivery. These results have implications for the prevention of early delivery as well as the identification of high-risk groups among those born early. The aetiology of medically indicated late preterm and early term delivery is heterogeneous. © 2015 Royal College of Obstetricians and Gynaecologists.

In utero exposure to chloroquine alters sexual development in the male fetal rat

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

Clewell, Rebecca A.; Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709; Pluta, Linda

Chloroquine (CQ), a drug that has been used extensively for the prevention and treatment of malaria, is currently considered safe for use during pregnancy. However, CQ has been shown to disrupt steroid homeostasis in adult rats and similar compounds, such as quinacrine, inhibit steroid production in the Leydig cell in vitro. To explore the effect of in utero CQ exposure on fetal male sexual development, pregnant Sprague-Dawley rats were given a daily dose of either water or chloroquine diphosphate from GD 16-18 by oral gavage. Chloroquine was administered as 200 mg/kg CQ base on GD 16, followed by two maintenancemore » doses of 100 mg/kg CQ base on GD 16 and 18. Three days of CQ treatment resulted in reduced maternal and fetal weight on GD 19 and increased necrosis and steatosis in the maternal liver. Fetal livers also displayed mild lipid accumulation. Maternal serum progesterone was increased after CQ administration. Fetal testes testosterone, however, was significantly decreased. Examination of the fetal testes revealed significant alterations in vascularization and seminiferous tubule development after short-term CQ treatment. Anogenital distance was not altered. Microarray and RT-PCR showed down-regulation of several genes associated with cholesterol transport and steroid synthesis in the fetal testes. This study indicates that CQ inhibits testosterone synthesis and normal testis development in the rat fetus at human relevant doses.« less

Effect of maternal smoking cessation before and during early pregnancy on fetal and childhood growth.

PubMed

Suzuki, Kohta; Sato, Miri; Zheng, Wei; Shinohara, Ryoji; Yokomichi, Hiroshi; Yamagata, Zentaro

2014-01-01

Maternal smoking during pregnancy is a major cause of intrauterine growth restriction and childhood obesity, but only a few studies have examined the association of smoking cessation before and during pregnancy with fetal and childhood growth. We examined this association in a prospective cohort study in Japan. Our study included children born between 1991 and 2006 and their mothers. Using a questionnaire, maternal smoking status was recorded at pregnancy. The anthropometric data of the children were collected during a medical check-up at age 3 years. Multiple linear and logistic regression models were used for data analysis stratified by sex. In total, 2663 mothers reported their smoking status during early pregnancy, and data were collected from 2230 (83.7%) children at age 3 years. Maternal smoking during pregnancy was associated with a significant reduction in birth weight (approximately 120-150 g). Body mass index at age 3 years was significantly higher among boys born to smoking mothers than among boys born to nonsmoking mothers. Maternal smoking during pregnancy was associated with overweight at age 3 years among boys (adjusted odds ratio, 2.4; 95% CI, 1.03-5.4). However, among women who stopped smoking in early pregnancy, there was no increase in the risks of a small for gestational age birth or childhood overweight at age 3 years. Children born to mothers who stopped smoking before or during early pregnancy had appropriate fetal and childhood growth.

Sonographic study of the development of fetal corpus callosum in a Chinese population.

PubMed

Zhang, Hai-chun; Yang, Jie; Chen, Zhong-ping; Ma, Xiao-yan

2009-02-01

The observation of fetal corpus callosum (CC) is important for the prenatal sonographic assessment of fetal central nervous system development. The aim of this study was to investigate the development of normal Chinese fetal CC. CC measurements were performed using high-resolution transabdominal sonography on 622 Chinese fetuses between 16 and 39 weeks' gestation. The correlation between CC size and gestational age was investigated. The fetal CC length increased in a linear fashion during pregnancy. The length of the CC as a function of gestational age was expressed by the following regression equation: length (mm) = -9.567 + 1.495 x gestational age (weeks) (r = 0.932, p < 0.001). Knowledge of normal CC appearance may help identify developmental anomalies and enable accurate prenatal counseling. (c) 2008 Wiley Periodicals, Inc.

Neurobehavioral determinants of nutritional security in fetal growth-restricted individuals.

PubMed

Portella, André Krumel; Silveira, Patrícia Pelufo

2014-12-01

Fetal growth restriction results from a failure to achieve a higher growth potential and has been associated with many maternal conditions, such as chronic diseases (infections, hypertension, and some cases of diabetes and obesity), exposures (tobacco smoke, drugs), and malnutrition. This early adversity induces a series of adaptive physiological responses aimed at improving survival, but imposing increased risk for developing chronic nontransmittable diseases (obesity, type II diabetes, cardiovascular disease) in the long term. Recently, mounting evidence has shown that fetal growth impairment is related to altered feeding behavior and preferences through the life course. When living in countries undergoing nutritional transition, in which individuals experience the coexistence of underweight and overweight problems (the "double burden of malnutrition"), fetal growth-restricted children can be simultaneously growth restricted and overweight-a double burden of malnutrition at the individual level. Considering food preferences as an important aspect of nutrition security, we will summarize the putative neurobiological mechanisms at the core of the relationship between fetal growth and nutrition security over the life course and the evidence linking early life adversity to later food preferences. © 2014 New York Academy of Sciences.

Adult brain and behavioral pathological markers of prenatal immune challenge during early/middle and late fetal development in mice.

PubMed

Meyer, Urs; Nyffeler, Myriel; Yee, Benjamin K; Knuesel, Irene; Feldon, Joram

2008-05-01

Maternal infection during pregnancy increases the risk for neurodevelopmental disorders such as schizophrenia and autism in the offspring. This association appears to be critically dependent on the precise prenatal timing. However, the extent to which distinct adult psychopathological and neuropathological traits may be sensitive to the precise times of prenatal immune activation remains to be further characterized. Here, we evaluated in a mouse model of prenatal immune challenge by the viral mimic, polyriboinosinic-polyribocytidilic acid (PolyIC), whether prenatal immune activation in early/middle and late gestation may influence the susceptibility to some of the critical cognitive, pharmacological, and neuroanatomical dysfunctions implicated in schizophrenia and autism. We revealed that PolyIC-induced prenatal immune challenge on gestation day (GD) 9 but not GD17 significantly impaired sensorimotor gating and reduced prefrontal dopamine D1 receptors in adulthood, whereas prenatal immune activation specifically in late gestation impaired working memory, potentiated the locomotor reaction to the NMDA-receptor antagonist dizocilpine, and reduced hippocampal NMDA-receptor subunit 1 expression. On the other hand, potentiation of the locomotor reaction to the dopamine-receptor agonist amphetamine and reduction in Reelin- and Parvalbumin-expressing prefrontal neurons emerged independently of the precise times of prenatal immune challenge. Our findings thus highlight that prenatal immune challenge during early/middle and late fetal development in mice leads to distinct brain and behavioral pathological symptom clusters in adulthood. Further examination and evaluation of in utero immune challenge at different times of gestation may provide important new insight into the neuroimmunological and neuropathological mechanisms underlying the segregation of different symptom clusters in heterogeneous neuropsychiatric disorders such as schizophrenia and autism.

Sex Moderates Associations between Prenatal Glucocorticoid Exposure and Human Fetal Neurological Development

ERIC Educational Resources Information Center

Glynn, Laura M.; Sandman, Curt A.

2012-01-01

Maternal cortisol levels (at 15, 19, 25, 31 and 37 weeks' gestation) and fetal movement response to vibroacoustic stimulation (VAS; at 25, 31 and 37 weeks) were assessed in 190 mother-fetus pairs. Fetuses showed a response to the VAS at 25 weeks and there was evidence of increasing maturation in the response at 31 and 37 weeks. Early elevations in…

Racial/ethnic standards for fetal growth: the NICHD Fetal Growth Studies.

PubMed

Buck Louis, Germaine M; Grewal, Jagteshwar; Albert, Paul S; Sciscione, Anthony; Wing, Deborah A; Grobman, William A; Newman, Roger B; Wapner, Ronald; D'Alton, Mary E; Skupski, Daniel; Nageotte, Michael P; Ranzini, Angela C; Owen, John; Chien, Edward K; Craigo, Sabrina; Hediger, Mary L; Kim, Sungduk; Zhang, Cuilin; Grantz, Katherine L

2015-10-01

Fetal growth is associated with long-term health yet no appropriate standards exist for the early identification of undergrown or overgrown fetuses. We sought to develop contemporary fetal growth standards for 4 self-identified US racial/ethnic groups. We recruited for prospective follow-up 2334 healthy women with low-risk, singleton pregnancies from 12 community and perinatal centers from July 2009 through January 2013. The cohort comprised: 614 (26%) non-Hispanic whites, 611 (26%) non-Hispanic blacks, 649 (28%) Hispanics, and 460 (20%) Asians. Women were screened at 8w0d to 13w6d for maternal health status associated with presumably normal fetal growth (aged 18-40 years; body mass index 19.0-29.9 kg/m(2); healthy lifestyles and living conditions; low-risk medical and obstetrical history); 92% of recruited women completed the protocol. Women were randomized among 4 ultrasonography schedules for longitudinal fetal measurement using the Voluson E8 (GE Healthcare, Milwaukee, WI). In-person interviews and anthropometric assessments were conducted at each visit; medical records were abstracted. The fetuses of 1737 (74%) women continued to be low risk (uncomplicated pregnancy, absent anomalies) at birth, and their measurements were included in the standards. Racial/ethnic-specific fetal growth curves were estimated using linear mixed models with cubic splines. Estimated fetal weight (EFW) and biometric parameter percentiles (5th, 50th, 95th) were determined for each gestational week and comparisons made by race/ethnicity, with and without adjustment for maternal and sociodemographic factors. EFW differed significantly by race/ethnicity >20 weeks. Specifically at 39 weeks, the 5th, 50th, and 95th percentiles were 2790, 3505, and 4402 g for white; 2633, 3336, and 4226 g for Hispanic; 2621, 3270, and 4078 g for Asian; and 2622, 3260, and 4053 g for black women (adjusted global P < .001). For individual parameters, racial/ethnic differences by order of detection were

Exposure of the developing heart to diabetic environment and early cardiac assessment: A review.

PubMed

Asoglu, Mehmet R; Gabbay-Benziv, Rinat; Turan, Ozhan M; Turan, Sifa

2018-02-01

Hyperglycemia during organogenesis is associated with an increased risk of congenital cardiac defects (CHDs). The pathophysiology leading to CHDs is not completely uncovered. However, elevated oxidative stress is considered to be the primary trigger that causes CHDs in fetuses of diabetic mothers. Maternal diabetes has been found to increase the risk for all types of CHDs. Diabetes may also impact the fetal cardiac performance at all gestational ages. Early detection of CHDs has certain advantages, such as making early decision about termination of pregnancy, enabling early genetic testing, and early reassurance if scan is normal. Combined transabdominal and transvaginal approach at 13-14 weeks of gestation is a reasonable strategy to assess fetal heart in diabetic women. Diagnostic accuracy of early fetal echocardiography has reached to above a reasonable cutoff when it is done in the late first trimester or early second trimester in the hands of expert sonographers. However, the literature is less certain to provide a firm conclusion about functional heart assessment in fetuses of diabetic mothers. © 2018 Wiley Periodicals, Inc.

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.

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm

PubMed Central

Aye, Christina Y L; Lewandowski, Adam J; Lamata, Pablo; Upton, Ross; Davis, Esther; Ohuma, Eric O; Kenworthy, Yvonne; Boardman, Henry; Wopperer, Samuel; Packham, Alice; Adwani, Satish; McCormick, Kenny; Papageorghiou, Aris T; Leeson, Paul

2017-01-01

Background Adults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development. Methods Cardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes. Results At birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001). Conclusion Preterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health. PMID:28399117

Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm.

PubMed

Aye, Christina Y L; Lewandowski, Adam J; Lamata, Pablo; Upton, Ross; Davis, Esther; Ohuma, Eric O; Kenworthy, Yvonne; Boardman, Henry; Wopperer, Samuel; Packham, Alice; Adwani, Satish; McCormick, Kenny; Papageorghiou, Aris T; Leeson, Paul

2017-07-01

BackgroundAdults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.MethodsCardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.ResultsAt birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).ConclusionPreterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health.

Thiamin deficiency on fetal brain development with and without prenatal alcohol exposure.

PubMed

Kloss, Olena; Eskin, N A Michael; Suh, Miyoung

2018-04-01

Adequate thiamin levels are crucial for optimal health through maintenance of homeostasis and viability of metabolic enzymes, which require thiamine as a co-factor. Thiamin deficiency occurs during pregnancy when the dietary intake is inadequate or excessive alcohol is consumed. Thiamin deficiency leads to brain dysfunction because thiamin is involved in the synthesis of myelin and neurotransmitters (e.g., acetylcholine, γ-aminobutyric acid, glutamate), and its deficiency increases oxidative stress by decreasing the production of reducing agents. Thiamin deficiency also leads to neural membrane dysfunction, because thiamin is a structural component of mitochondrial and synaptosomal membranes. Similarly, in-utero exposure to alcohol leads to fetal brain dysfunction, resulting in negative effects such as fetal alcohol spectrum disorder (FASD). Thiamin deficiency and prenatal exposure to alcohol could act synergistically to produce negative effects on fetal development; however, this area of research is currently under-studied. This minireview summarizes the evidence for the potential role of thiamin deficiency in fetal brain development, with or without prenatal exposure to alcohol. Such evidence may influence the development of new nutritional strategies for preventing or mitigating the symptoms of FASD.

Fetal Surgery

PubMed Central

Laberge, Jean-Martin

1986-01-01

Fetal surgery has come of age. For decades experimental fetal surgery proved essential in studying normal fetal physiology and development, and pathophysiology of congenital defects. Clinical fetal surgery started in the 1960s with intrauterine transfusions. In the 1970s, the advent of ultrasonography revolutionized fetal diagnosis and created a therapeutic vacuum. Fetal treatment, medical and surgical, is slowly trying to fill the gap. Most defects detected are best treated after birth, some requiring a modification in the time, mode and place of delivery for optimal obstetrical and neonatal care. Surgical intervention in utero should be considered for malformations that cause progressive damage to the fetus, leading to death or severe morbidity; that can be corrected or palliated in utero with a reasonable expectation of normal postnatal development; that cannot wait to be corrected after birth, even considering pre-term delivery; that are not accompanied by chromosomal or other major anomalies. At present, congenital hydronephrosis is the most common indication for fetal surgery, followed by obstructive hydrocephalus. Congenital diaphragmatic hernia also fulfills the criteria, but its correction poses more problems, and no clinical attempts have been reported so far. In the future many other malformations or diseases may become best treated in utero. The ethical and moral issues are complex and need to be discussed as clinical and experimental progress is made. PMID:21267309

Fetal behavioral teratology.

PubMed

Visser, Gerard H A; Mulder, Eduard J H; Tessa Ververs, F F

2010-10-01

Ultrasound studies of fetal motor behavior provide direct – in vivo – insight in the functioning of the motor component of the fetal central nervous system. In this article, studies are reviewed showing changes in the first timetable of appearance of fetal movements, changes in quality and/or quantity of movements and disturbances in the development of fetal behavioral states in case of endogenous malfunctions, maternal diseases and exogenous behavioral teratogens.

Fetal phonocardiography--past and future possibilities.

PubMed

Kovács, Ferenc; Horváth, Csaba; Balogh, Adám T; Hosszú, Gábor

2011-10-01

The paper presents an overview of the 15 year long development of fetal phonocardiography including the works on the applied signal processing methods for identification of sound components. Based on the improvements achieved on this field, the paper shows that beyond the traditional CTG test the phonocardiography may be successfully applied for long-term fetal measurements and home monitoring. In addition, by indication of heart murmurs based on a comprehensive analysis of the recorded heart sound congenital heart defects can also be detected together with additional features in the third trimester. This makes an early widespread screening possible combined with the prescribed CTG test even at home using a telemedicine system. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Imprinted gene expression in fetal growth and development.

PubMed

Lambertini, L; Marsit, C J; Sharma, P; Maccani, M; Ma, Y; Hu, J; Chen, J

2012-06-01

Experimental studies showed that genomic imprinting is fundamental in fetoplacental development by timely regulating the expression of the imprinted genes to overlook a set of events determining placenta implantation, growth and embryogenesis. We examined the expression profile of 22 imprinted genes which have been linked to pregnancy abnormalities that may ultimately influence childhood development. The study was conducted in a subset of 106 placenta samples, overrepresented with small and large for gestational age cases, from the Rhode Island Child Health Study. We investigated associations between imprinted gene expression and three fetal development parameters: newborn head circumference, birth weight, and size for gestational age. Results from our investigation show that the maternally imprinted/paternally expressed gene ZNF331 inversely associates with each parameter to drive smaller fetal size, while paternally imprinted/maternally expressed gene SLC22A18 directly associates with the newborn head circumference promoting growth. Multidimensional Scaling analysis revealed two clusters within the 22 imprinted genes which are independently associated with fetoplacental development. Our data suggest that cluster 1 genes work by assuring cell growth and tissue development, while cluster 2 genes act by coordinating these processes. Results from this epidemiologic study offer solid support for the key role of imprinting in fetoplacental development. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Fetal urology].

PubMed

Jakobovits, Akos; Jakobovits, Antal

2009-06-14

Although it becomes vitally important only after birth, renal function already plays significant role in maintaining fetal metabolic equilibrium. The kidneys significantly contribute to production of amniotic fluid. Adequate amount of amniotic fluid is needed to stimulate the intrauterine fetal respiratory activity. Intrauterine breathing is essential for lung development. As a result, oligohydramnion is conducive to pulmonary hypoplasia. The latter may lead to neonatal demise soon after birth. In extrauterine life kidneys eliminate nitrogen containing metabolic byproducts. Inadequate renal function results therefore lethal uremia. Integrity of ureters and the urethra is essential for the maintenance of renal function. Retention of urine causes degeneration of the functional units of the kidneys and ensuing deterioration of renal function. Intrauterine kidney puncture or shunt procedure may delay this process in some cases. On the other hand, once renal function has been damaged, no therapy can restart it. Certain anomalies of renal excretory pathways may also be associated with other congenital abnormalities, making the therapeutic efforts pointless. Presence of these associated intrauterine defects makes early pregnancy termination a management alternative, as well as it affects favorably perinatal mortality rates.

Fetal Testosterone, Socio-Emotional Engagement and Language Development

ERIC Educational Resources Information Center

Farrant, Brad M.; Mattes, Eugen; Keelan, Jeff A.; Hickey, Martha; Whitehouse, Andrew J. O.

2013-01-01

The present study investigated the relations among fetal testosterone, child socio-emotional engagement and language development in a sample of 467 children (235 boys) from the Western Australian Pregnancy Cohort (Raine) Study. Bioavailable testosterone concentration measured in umbilical cord blood taken at birth was found to be significantly…

Sildenafil Citrate in Fetal Growth Restriction

PubMed Central

Panda, Subrat; Das, Ananya; Md Nowroz, Hossain

2014-01-01

Background Pregnancies with early onset fetal growth restriction have poor perinatal outcome. Sildenafil citrate (PDE -5 inhibitor) as a vasodilator increases utero-placental blood flow and potentiates fetal growth. Case Presentation In this study, a case was examined and Sildenafil was administered for her. It was found that Sildenafil improved the uterine blood flow with a favorable fetal outcome at delivery. Conclusion Sildenafil, as a vasodilator has emerged as a potential management option in the treatment of Intra Uterine Growth Retardation (IUGR) and preeclampsia by later normalization in velocimetric profile. PMID:25202677

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

The effect of ambient air pollution during early pregnancy on fetal ultrasonic measurements during mid-pregnancy.

PubMed

Hansen, Craig A; Barnett, Adrian G; Pritchard, Gary

2008-03-01

Over the past decade there has been mounting evidence that ambient air pollution during pregnancy influences fetal growth. This study was designed to examine possible associations between fetal ultrasonic measurements collected from 15,623 scans (13-26 weeks gestation) and ambient air pollution during early pregnancy. We calculated mothers' average monthly exposures over the first 4 months of pregnancy for the following pollutants: particulate matter < 10 microm aerodynamic diameter (PM10), ozone, nitrogen dioxide, and sulfur dioxide. We examined associations with fetal femur length (FL), biparietal diameter (BPD), head circumference (HC), and abdominal circumference (AC). Final analyses included scans from only those women within 2 km of an air pollution monitoring site. We controlled for long-term trend, season, temperature, gestation, mother's age, socioeconomic status, and fetal sex. A reduction in fetal AC was associated with O3 during days 31-60 [-1.42 mm; 95% confidence interval (CI), -2.74 to -0.09], SO2 during days 61-90 (-1.67 mm; 95% CI, -2.94 to -0.40), and PM10 during days 91-120 (-0.78 mm; 95% CI, -1.49 to -0.08). Other results showed a reduction in BPD (-0.68 mm; 95% CI, -1.09 to -0.27) associated with SO2 during days 0-30, a reduction in HC (-1.02 mm; 95% CI, -1.78 to -0.26) associated with PM10 during days 91-120, and a reduction in FL associated with PM10 during days 0-30 (-0.28 mm; 95% CI, -0.48 to -0.08) and 91-120 (-0.23; 95% CI, -0.42 to -0.04). We found strong effects of ambient air pollution on ultrasound measures. Future research, including more individually detailed data, is needed to confirm our results.

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.

Ramadan fasting and pregnancy: implications for fetal development in summer season.

PubMed

Sakar, Mehmet Nafi; Gultekin, Huseyin; Demir, Bulent; Bakir, Vuslat Lale; Balsak, Deniz; Vuruskan, Erkut; Acar, Hicran; Yucel, Oguz; Yayla, Murat

2015-05-01

In the Islamic religion, Ramadan is a month in the year that is passed by fasting. Healthy adult individuals are prohibited to eat, drink, and smoke from sunrise to sunset. In the present study, our aim was to assess the relation of Ramadan fasting with fetal development and maternal-fetal Doppler indices in pregnant women. This is a prospective case-control study carried out in the month of Ramadan in 2013 (9 July-7 August). One hundred and six pregnant women at the second and third trimesters of pregnancy were enrolled into the study. The sample size of the fasting group was 83 and the non-fasting group sample size was also 83. Fetal biometric measurements, such as biparietal diameter, head circumference, abdominal circumference, femur length, estimated fetal weight, amniotic fluid index, and Doppler indices of both uterine and umbilical arteries were evaluated by gray scala and color Doppler ultrasound at the beginning and end of Ramadan. At the end of the Ramadan, increase in biparietal diameter, head circumference, and femur length showed a statistically significant difference from initial measurements (P<0.05). When fasting and non-fasting groups were compared separately, an increase in amniotic fluid index was statistically significant in the non-fasting group (P<0.05). We demonstrated some adverse effects of Ramadan fasting on fetal development. In the Islamic religion, pregnant individuals have the privilege of not fasting; therefore, they should consider postponing fasting to the postpartum period, especially in the summer season. If they are willing to do so, an appropriate nutritional program should be recommended.

Prenatal Foundations: Fetal Programming of Health and Development

ERIC Educational Resources Information Center

Davis, Elysia Poggi; Thompson, Ross A.

2014-01-01

The fetal programming and developmental origins of disease models suggest that experiences that occur before birth can have consequences for physical and mental health that persist across the lifespan. Development is more rapid during the prenatal period as compared to any other stage of life. This introductory article considers evidence that…

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.

Fetal Alcohol Spectrum Disorders.

PubMed

Williams, Janet F; Smith, Vincent C

2015-11-01

Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus. Copyright © 2015 by the American Academy of Pediatrics.

Non-invasive biomarkers of fetal brain development reflecting prenatal stress: An integrative multi-scale multi-species perspective on data collection and analysis.

PubMed

Frasch, Martin G; Lobmaier, Silvia M; Stampalija, Tamara; Desplats, Paula; Pallarés, María Eugenia; Pastor, Verónica; Brocco, Marcela A; Wu, Hau-Tieng; Schulkin, Jay; Herry, Christophe L; Seely, Andrew J E; Metz, Gerlinde A S; Louzoun, Yoram; Antonelli, Marta C

2018-05-30

Prenatal stress (PS) impacts early postnatal behavioural and cognitive development. This process of 'fetal programming' is mediated by the effects of the prenatal experience on the developing hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). We derive a multi-scale multi-species approach to devising preclinical and clinical studies to identify early non-invasively available pre- and postnatal biomarkers of PS. The multiple scales include brain epigenome, metabolome, microbiome and the ANS activity gauged via an array of advanced non-invasively obtainable properties of fetal heart rate fluctuations. The proposed framework has the potential to reveal mechanistic links between maternal stress during pregnancy and changes across these physiological scales. Such biomarkers may hence be useful as early and non-invasive predictors of neurodevelopmental trajectories influenced by the PS as well as follow-up indicators of success of therapeutic interventions to correct such altered neurodevelopmental trajectories. PS studies must be conducted on multiple scales derived from concerted observations in multiple animal models and human cohorts performed in an interactive and iterative manner and deploying machine learning for data synthesis, identification and validation of the best non-invasive detection and follow-up biomarkers, a prerequisite for designing effective therapeutic interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantification of Maternal Serum Cell-Free Fetal DNA in Early-Onset Preeclampsia

PubMed Central

Yu, Hong; Shen, Yanting; Ge, Qinyu; He, Youji; Qiao, Dongyan; Ren, Mulan; Zhang, Jianqiong

2013-01-01

The aim of this study was to determine whether the increased serum cell-free fetal DNA (cffDNA) level of gravidas developed into early-onset preeclampsia (EOPE) subsequently in the early second trimesters is related to prenatal screening markers. Serum was collected from 1011 gravidas. The level of cffDNA and prenatal screening markers were analyzed in 20 cases with EOPE and 20 controls. All fetuses were male. The maternal serum cffDNA level was assessed by amplification of the Y chromosome specific gene. Correlations between the variables were examined. (Logged) cffDNA in EOPE (median, 3.08; interquartile range, 2.93–3.68) was higher than controls (median, 1.79; interquartile range, 1.46–2.53). The increased level of (logged) cffDNA was correlated significantly with the increased human chorionic gonadotropin (HCG) level (r = 0.628, p < 0.001). Significant reciprocal correlations between cffDNA and babies’ birth weight as well as gestation weeks at delivery were noted (r = −0.516, p = 0.001; r = −0.623, p < 0.001, respectively). The sensitivity and specificity of cffDNA to discriminate between the EOPE cases and the controls were 90% and 85%, respectively. CffDNA is a potential marker for EOPE, which had a significant reciprocal correlation with babies’ birth weight and gestation weeks at delivery. Moreover, it may help in indicating the underlying hypoxic condition in the placenta. PMID:23567271

Unexpected fetal death during pregnancy--a problem of unrecognized fetal disorders during antenatal care?

PubMed

Künzel, Wolfgang; Misselwitz, Björn

2003-09-22

To investigate the causes of ante partum fetal death (APFD) and to evaluate the diagnostic methods for prevention. A population-based retrospective study was conducted in 293091 deliveries from 1996 to 2000 in the State of Hesse, Germany. The investigations focus on mortality of infants during pregnancy, separated between singletons of 37-42 weeks (n=361) and 23-36 weeks (n=550), and multiple births (n=76). In 44 cases, the gestational age was unknown and in 19 cases lower than 23 weeks or greater than 43 weeks. In total 1006 cases remained and were subject for evaluation. Perinatal mortality (PM) was 0.56%. APFD occurred in 1050 cases (0.3%), i.e. 63.5% of PM. Risk factors from the medical history during pregnancy could be identified in 515 cases (51.2%). Significant risk factors were social burden (odds ratio (OR) 58.3), diabetes mellitus (OR 5.4) and gestational diabetes (OR 2.1), psychological burden (OR 4.8), proteinuria (OR 2.8), maternal age (OR 1.7) and maternal smoking, depending on the number of cigarettes. The risk factors show a difference in significance, if related to the gestational age and multiple pregnancies. The contribution of malformations to APFD was 7.8%. There was however a number of unexpected fetal deaths with unidentified risk factors: n=415 (41.3%). In this group, fetal growth restriction was observed in 38.1%. Compared to control, APFD was three to five times higher in fetal growth retardation below the 10th percentile. Fetal death was closely related to fetal surveillance, i.e. the number of antenatal visits, ultrasound measurements, and fetal heart rate monitoring. Fetal ante partum fetal death can be reduced at least by 50%, if the available methods for fetal surveillance are employed aiming to detect indications of fetal oxygen deprivation at an early stage.

Fetal Onset of Aberrant Gene Expression Relevant to Pulmonary Carcinogenesis in Lung Adenocarcinoma Development Induced by In Utero Arsenic Exposure

PubMed Central

Shen, Jun; Liu, Jie; Xie, Yaxiong; Diwan, Bhalchandra A.; Waalkes, Michael P.

2009-01-01

Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-α (ER-α) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-β-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. in utero arsenic exposure also induced overexpression of α-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-α expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-α expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-α activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood. PMID:17077188

Fetal onset of aberrant gene expression relevant to pulmonary carcinogenesis in lung adenocarcinoma development induced by in utero arsenic exposure.

PubMed

Shen, Jun; Liu, Jie; Xie, Yaxiong; Diwan, Bhalchandra A; Waalkes, Michael P

2007-02-01

Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-alpha (ER-alpha) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-beta-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. In utero arsenic exposure also induced overexpression of alpha-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-alpha expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-alpha expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-alpha activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood.

Fetal magnetic resonance imaging (MRI): a tool for a better understanding of normal and abnormal brain development.

PubMed

Saleem, Sahar N

2013-07-01

Knowledge of the anatomy of the developing fetal brain is essential to detect abnormalities and understand their pathogenesis. Capability of magnetic resonance imaging (MRI) to visualize the brain in utero and to differentiate between its various tissues makes fetal MRI a potential diagnostic and research tool for the developing brain. This article provides an approach to understand the normal and abnormal brain development through schematic interpretation of fetal brain MR images. MRI is a potential screening tool in the second trimester of pregnancies in fetuses at risk for brain anomalies and helps in describing new brain syndromes with in utero presentation. Accurate interpretation of fetal MRI can provide valuable information that helps genetic counseling, facilitates management decisions, and guides therapy. Fetal MRI can help in better understanding the pathogenesis of fetal brain malformations and can support research that could lead to disease-specific interventions.

[Embryo-fetal diseases in multiple pregnancies].

PubMed

Colla, F; Alba, E; Grio, R

2001-04-01

Embryo-fetal diseases are the consequence of prenatal (progenetic and metagenetic or environmental) and intranatal (of a traumatic, infective, toxic nature) pathological factors. In multiple pregnancies this complex etiopathogenesis also includes an altered didymous embriogenesis. This study aimed to evaluate the pathologies affecting the fetus in multiple pregnancy, a special biological situation leading to the potential onset of severe fetal and neonatal damage. The authors studied 205 patients with multiple pregnancies, including 199 bigeminal, 5 trigeminal and 1 quadrigeminal, admitted to the Department B of the Obstetrics and Gynecological Clinic of Turin University between 1989-1999. Possible embyro-fetal damage was examined using a chronological criterion: namely following the development of the multiple fetuses from the zygotic to the neonatal phase. Pregnancies were biamniotic bichorionic in 54% of cases, biamniotic monochorionic in 45% and monochorionic monoamniotic in 1%. There were a total of 154 (79.38%) premature births out of 194 and neonatal birth weight was always SGA (small for gestational age). 66.84% of newborns were LBW (<2500 g) and 7.14% were VLBW (<1500 g). Fetal mortality (2.29%) was higher than early neonatal mortality (1.53%). Perinatal mortality (3.82%) was three times higher than in all neonates from the same period (1.03%). The severe embryo-fetal and neonatal damage found in multiple pregnancies is a clinical reality that calls for adequate diagnostic and therapeutic measures, and above all specific medical and social prevention to limit maternal pathogenic risks.

Schizophrenia Risk Variation in the NRG1 gene Exerts Effects on NRG1-IV Splicing During Fetal and Early Postnatal Human Neocortical Development

PubMed Central

Paterson, Clare; Wang, Yanhong; Kleinman, Joel E.; Law, Amanda J.

2015-01-01

OBJECTIVE Neuregulin 1 (NRG1) is a multifunctional neurotrophin and a critical mediator of neurodevelopment and risk for schizophrenia. NRG1 undergoes extensive alternative splicing, and association of brain NRG1-IV isoform expression with the schizophrenia-risk polymorphism, rs6994992, is a potential molecular mechanism of risk. Novel splice variants of NRG1-IV (NRG1-IVNV), with predicted unique signaling capabilities, have been cloned in fetal brain. Because the developmental expression and genetic regulation of NRG1-IVNV in human brain and relationship to schizophrenia is unknown, the authors investigated the temporal dynamics of NRG1-IVNV transcription, compared to the major NRG1 isoforms (types I-IV), across human prenatal and postnatal prefrontal cortical development and examined the association of rs6994992 with NRG1-IVNV expression. METHOD NRG1, types I-IV and NRG1-IVNV isoform expression was evaluated using quantitative real-time PCR in prefrontal cortex during human fetal brain development (14-39 weeks gestation: N=41) and postnatally through aging (age range 0-83 years: N=195). The association of rs6994992 genotype with NRG1-IVNV expression was determined. In-vitro assays were performed to determine the subcellular distribution and proteolytic processing of NRG1-IVNV isoforms. RESULTS Expression of NRG1, types I, II, III was temporally regulated during human prenatal and postnatal neocortical development and the trajectory of NRG1-IVNV was unique, being expressed from 16 weeks gestation until 3 years of age, after which it was undetectable. NRG1-IVNVs expression was associated with rs6994992 genotype, whereby homozygosity for the schizophrenia-risk allele (T) conferred lower cortical NRG1-IVNV levels. Finally, in-vitro cellular assays demonstrate that NRG1-IVNV is a novel nuclear enriched, truncated NRG1 protein that is resistant to proteolytic processing. CONCLUSION This study provides the first quantitative map of NRG1 isoform expression during human

Fetal Alcohol Effects in Children: Cognitive, Educational, and Behavioral Considerations.

ERIC Educational Resources Information Center

Horowitz, Sheldon

The effects of alcohol on the developing fetus are examined. Noted is the existence of both structural problems (such as microcephaly and cardiac anomalies) and behavioral problems (such as mental retardation and speech and language deficits). The potential damage of alcohol at a very early stage of fetal development is discussed. It is thought…

Development of prenatal lateralization: evidence from fetal mouth movements.

PubMed

Reissland, N; Francis, B; Aydin, E; Mason, J; Exley, K

2014-05-28

Human lateralized behaviors relate to the asymmetric development of the brain. Research of the prenatal origins of laterality is equivocal with some studies suggesting that fetuses exhibit lateralized behavior and other not finding such laterality. Given that by around 22weeks of gestation the left cerebral hemisphere compared to the right is significantly larger in both male and female fetuses we expected that the right side of the fetal face would show more movement with increased gestation. This longitudinal study investigated whether fetuses from 24 to 36weeks of gestation showed increasing lateralized behaviors during mouth opening and whether lateralized mouth movements are related to fetal age, gender and maternal self-reported prenatal stress. Following ethical approval, fifteen healthy fetuses (8 girls) of primagravid mothers were scanned four times from 24 to 36-gestation. Two types of mouth opening movements - upper lip raiser and mouth stretch - were coded in 60 scans for 10min. We modeled the proportion of right mouth opening for each fetal scan using a generalized linear mixed model, which takes account of the repeated measures design. There was a significant increase in the proportion of lateralized mouth openings over the period increasing by 11% for each week of gestational age (LRT change in deviance=10.92, 1df; p<0.001). No gender differences were found nor was there any effect of maternally reported stress on fetal lateralized mouth movements. There was also evidence of left lateralization preference in mouth movement, although no evidence of changes in lateralization bias over time. This longitudinal study provides important new insights into the development of lateralized mouth movements from 24 to 36 weeks of gestation. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Reproductive Toxicity of T Cells in Early Life: Abnormal Immune Development and Postnatal Diseases.

PubMed

Liu, Han-Xiao; Jiang, Aifang; Chen, Ting; Qu, Wen; Yan, Hui-Yi; Ping, Jie

2017-01-01

Immunity is a balanced status with adequate biological defenses to recognize and fight "non-self", as well as adequate tolerance to recognize "self". To maintain this immune homeostasis, a well-organized T cell immune network is required, which in part depends on the well-controlled development of alternative effector T cells, with different cytokine repertoires. Recent researches have pointed that developing fetal T cells network is a remarkably sensitive toxicological target for adverse factors in early life. Epidemiological and experimental studies showed an inseparable relationship between T cell developmental toxicity and immune diseases in adults. Considering that the inflammatory and immune disorders have become a growing health problem worldwide, increasing attention is now being paid to the T cell developmental toxicity. We propose that adverse factors may have programming effects on the crucial functions of immune system during early life which is critical for fetal T cell development and the establishment of the distinct T cell repertoires balance. The permanently disturbed intrathymic or peripheral T cell development may in turn lead to the immune disorders in later life. In this manuscript, we reviewed how adverse factors affected T cell development in early-life with the consequence of the immune dysfunction and immune diseases, and further elucidate the mechanisms. These mechanisms will be helpful in prevention and treatment of the increased prevalence of immune diseases by interfering those pathways. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Co-expression analysis of fetal weight-related genes in ovine skeletal muscle during mid and late fetal development stages

USDA-ARS?s Scientific Manuscript database

Muscle development and lipid metabolism play important roles during fetal development stages. The commercial Texel sheep are more muscular than the indigenous Ujumqin sheep which are fatter. We performed serial transcriptomics assays and systems biology analyses to investigate the dynamics of gene e...

Development of an assay for a biomarker of pregnancy and early fetal loss

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

Canfield, R.E.; O'Connor, J.F.; Birken, S.

1987-10-01

Human chorionic gonadotropin (hCG) is a glycoprotein hormone, secreted by the syncytiotrophoblast cells of the fertilized ovum, that enters the maternal circulation at the time of endometrial implantation. It is composed of two nonidentical subunits; ..cap alpha.. and ..beta.., with molecular weights of 14 kD and 23 kD, respectively. Human chorionic gonadotropin binds to the same receptor as hLH and displays the same biological response, namely, to stimulate the declining function of the corpus luteum to produce progestins and estrogen late in the menstrual cycle. The differences in the structures of hCG and hLH have been exploited to develop antibodiesmore » that can measure hCG specifically in the presence of hLH. Two-site antibody binding assays have been developed, based on a surface immunological concept of hCG epitopes, that involve four distinct regions to which antibodies against hCG can bind simultaneously. Antibody cooperative effects, in conjunction with kinetic advantages derived from the concentration factors by use of the sandwich assay technique (immunoradiometric assay, IRMA), have enabled development of extremely sensitive and specific measurement protocols for urinary hCG. The assay described herein permits the detection of pregnancy on an average 25.4 days after the first day of the preceding menses, as opposed to 29.5 days for conventional radioimmunoassay techniques. In addition, the greater sensitivity and specificity of this assay method has permitted the detection of episodes of fetal loss not detected by radioimmunoassay of urine specimens. A large scale epidemiological study is in progress using this assay technique as a way to identify pregnancies that are lost before becoming clinically apparent.« less

Fetal growth and risk of childhood asthma and allergic disease

PubMed Central

Tedner, S G; Örtqvist, A K; Almqvist, C

2012-01-01

Introduction Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. Objective This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. Methods PubMed-search on pre-defined terms and cross-references. Results Several studies have shown a correlation between low birth weight and/or gestational age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subsequent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that diseases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. Conclusion and clinical relevance Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases. PMID:22994341

The quality of fetal arm movements as indicators of fetal stress.

PubMed

Reissland, Nadja; Francis, Brian

2010-12-01

Although a number of studies have found that maternal stress affects the fetus, it is unclear whether jerky fetal movements observed on ultrasound scans are indicative of fetal stress, or whether they are part of normal development. The present study was designed to examine the relationship between jerky fetal arm movements in relation to fetal age and stress. Video recordings were made of routine ultrasound scans of 57 fetuses (age range 8 to 33 weeks) classified into three age groups: 1st trimester (8-12 weeks, N=9), 2nd trimester (13-24 weeks, N=38), and 3rd trimester (26-33 weeks, N=10). Following previous research on stress behaviour in neonates, a fetal index of stress was derived from frequency of hiccup, back arch and rhythmical mouthing. Results indicated that while stress level was unrelated to fetal age, jerkiness of arm movements was significantly associated with the fetal stress index but not age. Our findings suggest that jerky arm movements in fetuses are suggestive of fetal stress. Copyright © 2010 Elsevier Ltd. All rights reserved.

Apoptotic cell death correlates with ROS overproduction and early cytokine expression after hypoxia-ischemia in fetal lambs.

PubMed

Alonso-Alconada, Daniel; Hilario, Enrique; Álvarez, Francisco José; Álvarez, Antonia

2012-07-01

Despite advances in neonatology, the hypoxic-ischemic injury in the perinatal period remains the single most important cause of brain injury in the newborn, leading to death or lifelong sequelae. Using a sheep model of intrauterine asphyxia, we evaluated the correlation between reactive oxygen species (ROS) overproduction, cytokine expression, and apoptotic cell death. Fetal lambs were assigned to sham group, nonasphyctic animals; and hypoxia-ischemia (HI) group, lambs subjected to 60 minutes of HI) by partial cord occlusion and sacrificed 3 hours later. Different brain regions were separated to quantify the number of apoptotic cells and the same territories were dissociated for flow cytometry studies. Our results suggest that the overproduction of ROS and the early increase in cytokine production after HI in fetal lambs correlate in a significant manner with the apoptotic index, as well as with each brain region evaluated.

Periconceptional growth hormone treatment alters fetal growth and development in lambs.

PubMed

Koch, J M; Wilmoth, T A; Wilson, M E

2010-05-01

fetal growth and development. Lambs born to ewes treated with GH were larger at birth and had altered organ development, which may indicate that early maternal GH treatment may lead to permanent changes in the developing fetus. The ewe lambs maintained their growth performance to at least 100 d of postnatal life and appeared to have an altered GH axis, as demonstrated by the altered response to GHRH.

Commercialization and Industrial Development for the Fetal Hear Rate Monitor

NASA Technical Reports Server (NTRS)

Zahorian, Stephen

2000-01-01

The primary objectives for this task were to continue the development and testing of the NASA/ODU passive acoustic fetal heart rate monitor, with the goal of transferring the technology to the commercial sector. Areas of work included: 1. To assist in the development of a new hardware front end electronics box for the fetal heart rate monitor, so as to reduce the size of the electronics box, and also to provide for a "low-frequency" and "high-frequency" mode of operation. To make necessary changes in the operating software to support the two modes of operation. 2. To provide an option for a strip chart recording for the system, so that medical personnel could more easily make comparisons with ultra sound strip chart recordings. and 3. To help with continued testing of the system.

Upregulation of Cytokines Is Detected in the Placentas of Cattle Infected with Neospora caninum and Is More Marked Early in Gestation When Fetal Death Is Observed ▿

PubMed Central

Rosbottom, Anne; Gibney, E. Helen; Guy, Catherine S.; Kipar, Anja; Smith, Robert F.; Kaiser, Pete; Trees, Alexander J.; Williams, Diana J. L.

2008-01-01

The protozoan parasite Neospora caninum causes fetal death after experimental infection of pregnant cattle in early gestation, but the fetus survives a similar infection in late gestation. An increase in Th1-type cytokines in the placenta in response to the presence of the parasite has been implicated as a contributory factor to fetal death due to immune-mediated pathological alterations. We measured, using real-time reverse transcription-PCR and enzyme-linked immunosorbent assay, the levels of cytokines in the placentas of cattle experimentally infected with N. caninum in early and late gestation. After infection in early gestation, fetal death occurred, and the levels of mRNA of both Th1 and Th2 cytokines, including interleukin-2 (IL-2), gamma interferon (IFN-γ), IL-12p40, tumor necrosis factor alpha (TNF-α), IL-18, IL-10, and IL-4, were significantly (P < 0.01) increased by up to 1,000-fold. There was extensive placental necrosis and a corresponding infiltration of CD4+ T cells and macrophages. IFN-γ protein expression was also highly increased, and a modest increase in transforming growth factor β was detected. A much smaller increase in the same cytokines and IFN-γ protein expression, with minimal placental necrosis and inflammatory infiltration, occurred after N. caninum infection in late gestation when the fetuses survived. Comparison of cytokine mRNA levels in separated maternal and fetal placental tissue that showed maternal tissue was the major source of all cytokine mRNA except for IL-10 and TNF-α, which were similar in both maternal and fetal tissues. These results suggest that the magnitude of the cytokine response correlates with but is not necessarily the cause of fetal death and demonstrate that a polarized Th1 response was not evident in the placentas of N. caninum-infected cattle. PMID:18362132

Fetal Health Locus of Control Scale: Development and Validation.

ERIC Educational Resources Information Center

Labs, Sharon M.; Wurtele, Sandy K.

1986-01-01

Describes development of the Fetal Health Locus of Control scale, the scale's utility in predicting maternal health-related behavior during pregnancy, normative data, and information on factor structure and internal consistency. Reports that cigarette and caffeine consumption during pregnancy, and women's intentions to participate in prepared…

Childhood cognitive development after fetal growth restriction.

PubMed

Llurba, E; Baschat, A A; Turan, O M; Harding, J; McCowan, L M

2013-04-01

To examine the relationship between prenatal umbilical artery (UA) and internal carotid artery (ICA) Doppler findings and cognitive development at 3 and 6 years in low-birth-weight children. This was a study of 209 low-birth-weight (< 10(th) centile) children born after 28 gestational weeks with UA resistance index (RI) measured within 2 weeks before delivery. Children with normal UA- and ICA-RI were defined as small-for-gestational age (SGA) and those with abnormal UA or ICA Doppler findings as having fetal growth restriction (FGR). Cognitive ability at 3 and 6 years' corrected age was assessed using the fourth edition of the Stanford-Binet Intelligence Scale (SBIS) and compared between SGA and FGR groups. An SBIS score < 85 was considered to indicate delayed development. The median gestational age at diagnosis of abnormal fetal growth was 36.6 (range, 28-41) weeks. There were 87 (41.6%) children classified as having FGR and 122 (58.4%) as SGA. The mean global SBIS score at 3 years was 109.4 (SD, 22.8) and at 6 years it was 110.5 (SD, 13.9). Overall, 22 (10.5%) children had delayed development at 3 years. Total SBIS scores and individual domain scores did not differ between FGR and SGA groups at 3 or 6 years and similar proportions in each group had delayed development. Abnormal prenatal UA and ICA Doppler findings are not associated with lower developmental scores in low-birth-weight children delivered in the third trimester of pregnancy. Copyright © 2013 ISUOG. Published by John Wiley & Sons, Ltd.

Convergence of Cortical, Thalamocortical, and Callosal Pathways during Human Fetal Development Revealed by Diffusion MRI Tractography.

PubMed

Wang, Rongpin; Wilkinson, Molly; Kane, Tara; Takahashi, Emi

2017-01-01

There has been evidence that during brain development, emerging thalamocortical (TC) and corticothalamic (CT) pathways converge in some brain regions and follow each other's trajectories to their final destinations. Corpus callosal (CC) pathways also emerge at a similar developmental stage, and are known to converge with TC pathways in specific cortical regions in mature brains. Given the functional relationships between TC and CC pathways, anatomical convergence of the two pathways are likely important for their functional integration. However, it is unknown (1) where TC and CT subcortically converge in the human brain, and (2) where TC and CC converge in the cortex of the human brain, due to the limitations of non-invasive methods. The goals of this study were to describe the spatio-temporal relationships in the development of the TC/CT and CC pathways in the human brain, using high-angular resolution diffusion MR imaging (HARDI) tractography. Emerging cortical, TC and CC pathways were identified in postmortem fetal brains ranging from 17 gestational weeks (GW) to 30 GW, as well as in vivo 34-40 GW newborns. Some pathways from the thalami were found to be converged with pathways from the cerebral cortex as early as 17 GW. Such convergence was observed mainly in anterior and middle regions of the brain until 21 GW. At 22 GW and onwards, posterior pathways from the thalami also converged with cortical pathways. Many CC pathways reached the full length up to the cortical surface as early as 17 GW, while pathways linked to thalami (not only TC axons but also including pathways linked to thalamic neuronal migration) reached the cortical surface at and after 20 GW. These results suggest that CC pathways developed earlier than the TC pathways. The two pathways were widespread at early stages, but by 40 GW they condensed and formed groups of pathways that projected to specific regions of the cortex and overlapped in some brain regions. These results suggest that HARDI

Convergence of Cortical, Thalamocortical, and Callosal Pathways during Human Fetal Development Revealed by Diffusion MRI Tractography

PubMed Central

Wang, Rongpin; Wilkinson, Molly; Kane, Tara; Takahashi, Emi

2017-01-01

There has been evidence that during brain development, emerging thalamocortical (TC) and corticothalamic (CT) pathways converge in some brain regions and follow each other's trajectories to their final destinations. Corpus callosal (CC) pathways also emerge at a similar developmental stage, and are known to converge with TC pathways in specific cortical regions in mature brains. Given the functional relationships between TC and CC pathways, anatomical convergence of the two pathways are likely important for their functional integration. However, it is unknown (1) where TC and CT subcortically converge in the human brain, and (2) where TC and CC converge in the cortex of the human brain, due to the limitations of non-invasive methods. The goals of this study were to describe the spatio-temporal relationships in the development of the TC/CT and CC pathways in the human brain, using high-angular resolution diffusion MR imaging (HARDI) tractography. Emerging cortical, TC and CC pathways were identified in postmortem fetal brains ranging from 17 gestational weeks (GW) to 30 GW, as well as in vivo 34–40 GW newborns. Some pathways from the thalami were found to be converged with pathways from the cerebral cortex as early as 17 GW. Such convergence was observed mainly in anterior and middle regions of the brain until 21 GW. At 22 GW and onwards, posterior pathways from the thalami also converged with cortical pathways. Many CC pathways reached the full length up to the cortical surface as early as 17 GW, while pathways linked to thalami (not only TC axons but also including pathways linked to thalamic neuronal migration) reached the cortical surface at and after 20 GW. These results suggest that CC pathways developed earlier than the TC pathways. The two pathways were widespread at early stages, but by 40 GW they condensed and formed groups of pathways that projected to specific regions of the cortex and overlapped in some brain regions. These results suggest that HARDI

Development of fetal and placental innate immune responses during establishment of persistent infection with bovine viral diarrhea virus.

PubMed

Smirnova, Natalia P; Webb, Brett T; Bielefeldt-Ohmann, Helle; Van Campen, Hana; Antoniazzi, Alfredo Q; Morarie, Susan E; Hansen, Thomas R

2012-08-01

Transplacental viral infections are dependent upon complex interactions between feto-placental and maternal immune responses and the stage of fetal development at which the infection occurs. Bovine viral diarrhea virus (BVDV) has the ability to cross the placenta and infect the fetus. Infection early in gestation with non-cytopathic (ncp) BVDV leads to persistent infection. Establishment of fetal persistent infection results in life-long viremia, virus-specific immunotolerance, and may have detrimental developmental consequences. We have previously shown that heifers infected experimentally with ncp BVDV type 2 on d. 75 of gestation had transient robust up-regulation of the type I interferon (IFN) stimulated genes (ISGs) 3-15 days after viral inoculation. Blood from persistently infected (PI) fetuses, collected 115 days post maternal infection, demonstrated moderate chronic up-regulation of ISGs. This infection model was used to delineate timing of the development of innate immune responses in the fetus and placenta during establishment of persistent infection. It was hypothesized that: (i) chronic stimulation of innate immune responses occurs following infection of the fetus and (ii) placental production of the type I IFN contributes to up-regulation of ISGs in PI fetuses. PI fetuses, generated by intranasal inoculation of pregnant heifers with ncp BVDV, and control fetuses from uninfected heifers, were collected via Cesarean sections on d. 82, 89, 97, 192, and 245 of gestation. Fetal viremia was confirmed starting on d. 89. Significant up-regulation of mRNA encoding cytosolic dsRNA sensors -RIG-I and MDA5 - was detected on d. 82-192. Detection of viral dsRNA by cytosolic sensors leads to the stimulation of ISGs, which was reflected in significant up-regulation of ISG15 mRNA in fetal blood on d. 89, 97, and 192. No difference in IFN-α and IFN-β mRNA concentration was found in fetal blood or caruncular tissue, while a significant increase in both IFN-α and IFN

Fetal electrocardiograph

NASA Astrophysics Data System (ADS)

Rios, Heriberto; Andrade, Armando; Puente, Ernestina; Lizana, Pablo R.; Mendoza, Diego

2002-11-01

The high intra-uterine death rate is due to failure in appropriately diagnosing some problems in the cardiobreathing system of the fetus during pregnancy. The electrocardiograph is one apparatus which might detect problems at an early stage. With electrodes located near the womb and uterus, in a way similar to the normal technique, the detection of so-called biopotential differences, caused by concentrations of ions, can be achieved. The fetal electrocardiograph is based on an ultrasound technique aimed at detecting intrauterine problems in pregnant women, because it is a noninvasive technique due to the very low level of ultrasound power used. With this system, the following tests can be done: Heart movements from the ninth week onwards; Rapid and safe diagnosis of intrauterine fetal death; Location and size of the placenta. The construction of the fetal electrocardiograph requires instrument level components directly mounted on the printed circuit board, in order to avoid stray capacitance in the cabling which prevents the detection of the E.C.G. activity. The low cost of the system makes it affordable to low budget institutions; in contrast, available commercial systems are priced in U.S. Dollars. (To be presented in Spanish.)

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.

Changes in Mechanics and Composition of Human Talar Cartilage Anlagen During Fetal Development

PubMed Central

Mahmoodian, Roza; Leasure, Jeremi; Philip, Phitha; Pleshko, Nancy; Capaldi, Franco; Siegler, Sorin

2011-01-01

Objective Fetal cartilage anlage provides a framework for endochondral ossification and organization into articular cartilage. We previously reported differences between mechanical properties of talar cartilage anlagen and adult articular cartilage. However, the underlying development-associated changes remain to be established. Delineation of the normal evolvement of mechanical properties and its associated compositional basis provides insight into the natural mechanisms of cartilage maturation. Our goal was to address this issue. Materials and methods Human fetal cartilage anlagen were harvested from the tali of normal stillborn fetuses from 20 to 36 weeks of gestational age. Data obtained from stress relaxation experiments conducted under confined and unconfined compression configurations were processed to derive the compressive mechanical properties. The compressive mechanical properties were extracted from a linear fit to the equilibrium response in unconfined compression, and by using the nonlinear biphasic theory to fit to the experimental data from the confined compression experiment, both in stress-relaxation. The molecular composition was obtained using FTIR, and spatial maps of tissue contents per dry weight were created using FTIR imaging. Correlative and regression analyses were performed to identify relationships between the mechanical properties and age, compositional properties and age, and mechanical versus compositional parameters. Results All of the compositional quantities and the mechanical properties excluding the Poisson’s ratio changed with maturation. Stiffness increased by a factor of ~2.5 and permeability decreased by 20% over the period studied. Collagen content and degree of collagen integrity increased with age by ~3-fold, while the proteoglycan content decreased by 18%. Significant relations were found between the mechanical and compositional properties. Conclusion The mechanics of fetal talar cartilage is related to its composition

Cloning and analysis of fetal ovary microRNAs in cattle.

PubMed

Tripurani, Swamy K; Xiao, Caide; Salem, Mohamed; Yao, Jianbo

2010-07-01

Ovarian folliculogenesis and early embryogenesis are complex processes, which require tightly regulated expression and interaction of a multitude of genes. Small endogenous RNA molecules, termed microRNAs (miRNAs), are involved in the regulation of gene expression during folliculogenesis and early embryonic development. To identify miRNAs in bovine oocytes/ovaries, a bovine fetal ovary miRNA library was constructed. Sequence analysis of random clones from the library identified 679 miRNA sequences, which represent 58 distinct bovine miRNAs. Of these distinct miRNAs, 42 are known bovine miRNAs present in the miRBase database and the remaining 16 miRNAs include 15 new bovine miRNAs that are homologous to miRNAs identified in other species, and one novel miRNA, which does not match any miRNAs in the database. The precursor sequences for 14 of the new 15 miRNAs as well as the novel miRNA were identified from the bovine genome database and their hairpin structures were predicted. Expression analysis of the 58 miRNAs in fetal ovaries in comparison to somatic tissue pools identified 8 miRNAs predominantly expressed in fetal ovaries. Further analysis of the eight miRNAs in germinal vesicle (GV) stage oocytes identified two miRNAs (bta-mir424 and bta-mir-10b), that are highly abundant in GV oocytes. Both miRNAs show similar expression patterns during oocyte maturation and preimplantation development of bovine embryos, being abundant in GV and MII stage oocytes, as well as in early stage embryos (until 16-cell stage). The amount of the novel miRNA is relatively small in oocytes and early cleavage embryos but greater in blastocysts, suggesting a role of this miRNA in blastocyst cell differentiation. Copyright 2010 Elsevier B.V. All rights reserved.

Maternal-fetal unit interactions and eutherian neocortical development and evolution

PubMed Central

Montiel, Juan F.; Kaune, Heidy; Maliqueo, Manuel

2013-01-01

The conserved brain design that primates inherited from early mammals differs from the variable adult brain size and species-specific brain dominances observed across mammals. This variability relies on the emergence of specialized cerebral cortical regions and sub-compartments, triggering an increase in brain size, areal interconnectivity and histological complexity that ultimately lies on the activation of developmental programs. Structural placental features are not well correlated with brain enlargement; however, several endocrine pathways could be tuned with the activation of neuronal progenitors in the proliferative neocortical compartments. In this article, we reviewed some mechanisms of eutherians maternal–fetal unit interactions associated with brain development and evolution. We propose a hypothesis of brain evolution where proliferative compartments in primates become activated by “non-classical” endocrine placental signals participating in different steps of corticogenesis. Changes in the inner placental structure, along with placenta endocrine stimuli over the cortical proliferative activity would allow mammalian brain enlargement with a concomitant shorter gestation span, as an evolutionary strategy to escape from parent-offspring conflict. PMID:23882189

EVERREST prospective study: a 6-year prospective study to define the clinical and biological characteristics of pregnancies affected by severe early onset fetal growth restriction.

PubMed

Spencer, Rebecca; Ambler, Gareth; Brodszki, Jana; Diemert, Anke; Figueras, Francesc; Gratacós, Eduard; Hansson, Stefan R; Hecher, Kurt; Huertas-Ceballos, Angela; Marlow, Neil; Marsál, Karel; Morsing, Eva; Peebles, Donald; Rossi, Carlo; Sebire, Neil J; Timms, John F; David, Anna L

2017-01-23

Fetal growth restriction (FGR) is a serious obstetric condition for which there is currently no treatment. The EVERREST Prospective Study has been designed to characterise the natural history of pregnancies affected by severe early onset FGR and establish a well phenotyped bio-bank. The findings will provide up-to-date information for clinicians and patients and inform the design and conduct of the EVERREST Clinical Trial: a phase I/IIa trial to assess the safety and efficacy of maternal vascular endothelial growth factor (VEGF) gene therapy in severe early onset FGR. Data and samples from the EVERREST Prospective Study will be used to identify ultrasound and/or biochemical markers of prognosis in pregnancies with an estimated fetal weight (EFW) <3rd centile between 20+0 and 26+6 weeks of gestation. This is a 6 year European multicentre prospective cohort study, recruiting women with a singleton pregnancy where the EFW is <3rd centile for gestational age and <600 g at 20+0 to 26+6 weeks of gestation. Detailed data are collected on: maternal history; antenatal, peripartum, and postnatal maternal complications; health economic impact; psychological impact; neonatal condition, progress and complications; and infant growth and neurodevelopment to 2 years of corrected age in surviving infants. Standardised longitudinal ultrasound measurements are performed, including: fetal biometry; uterine artery, umbilical artery, middle cerebral artery, and ductus venosus Doppler velocimetry; and uterine artery and umbilical vein volume blood flow. Samples of maternal blood and urine, amniotic fluid (if amniocentesis performed), placenta, umbilical cord blood, and placental bed (if caesarean delivery performed) are collected for bio-banking. An initial analysis of maternal blood samples at enrolment is planned to identify biochemical markers that are predictors for fetal or neonatal death. The findings of the EVERREST Prospective Study will support the development of a novel

A crucial role for maternal dietary methyl donor intake in epigenetic programming and fetal growth outcomes.

PubMed

McGee, Meghan; Bainbridge, Shannon; Fontaine-Bisson, Bénédicte

2018-06-01

The fetal origins of health and disease framework has identified extremes in fetal growth and birth weight as factors associated with the lifelong generation of chronic diseases such as obesity, diabetes, cardiovascular disease, and hypertension. Maternal nutrition plays a critical role in fetal and placental development, in part by providing the methyl groups required to establish the fetus's genome structure and function, notably through DNA methylation. The goal of this narrative review is to describe the role of maternal dietary methyl donor (methionine, folate, and choline) and cofactor (zinc and vitamins B2, B6, and B12) intake in one-carbon metabolism and DNA methylation in the fetus and placenta, as well as their impacts on fetal growth and lifelong health outcomes, with specific examples in animals and humans. Based on the available evidence, it is concluded that intake of different amounts of dietary methyl donors and cofactors during pregnancy may alter fetal growth and development, thus establishing a major link between early environmental exposure and disease development in the offspring later in life.

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.

Fetal programming of polycystic ovary syndrome

PubMed Central

Gur, Esra Bahar; Karadeniz, Muammer; Turan, Guluzar Arzu

2015-01-01

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women. Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development, possibly even during intrauterine life. This suggests that PCOS is either genetically-transmitted or is due to epigenetic alterations that develop in the intrauterine microenvironment. Although familial cases support the role of genetic factors, no specific genetic pattern has been defined in PCOS. Several candidate genes have been implicated in its pathogenesis, but none can specifically be implicated in PCOS development. Hypotheses based on the impact of the intrauterine environment on PCOS development can be grouped into two categories. The first is the “thrifty” phenotype hypothesis, which states that intrauterine nutritional restriction in fetuses causes decreased insulin secretion and, as a compensatory mechanism, insulin resistance. Additionally, an impaired nutritional environment can affect the methylation of some specific genes, which can also trigger PCOS. The second hypothesis postulates that fetal exposure to excess androgen can induce changes in differentiating tissues, causing the PCOS phenotype to develop in adult life. This review aimed to examine the role of fetal programming in development of PCOS. PMID:26185601

Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus.

PubMed

Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M; Sandman, Curt A

2009-10-01

Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.

Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys.

PubMed

Martinot, Amanda J; Abbink, Peter; Afacan, Onur; Prohl, Anna K; Bronson, Roderick; Hecht, Jonathan L; Borducchi, Erica N; Larocca, Rafael A; Peterson, Rebecca L; Rinaldi, William; Ferguson, Melissa; Didier, Peter J; Weiss, Deborah; Lewis, Mark G; De La Barrera, Rafael A; Yang, Edward; Warfield, Simon K; Barouch, Dan H

2018-05-17

The development of interventions to prevent congenital Zika syndrome (CZS) has been limited by the lack of an established nonhuman primate model. Here we show that infection of female rhesus monkeys early in pregnancy with Zika virus (ZIKV) recapitulates many features of CZS in humans. We infected 9 pregnant monkeys with ZIKV, 6 early in pregnancy (weeks 6-7 of gestation) and 3 later in pregnancy (weeks 12-14 of gestation), and compared findings with uninfected controls. 100% (6 of 6) of monkeys infected early in pregnancy exhibited prolonged maternal viremia and fetal neuropathology, including fetal loss, smaller brain size, and histopathologic brain lesions, including microcalcifications, hemorrhage, necrosis, vasculitis, gliosis, and apoptosis of neuroprogenitor cells. High-resolution MRI demonstrated concordant lesions indicative of deep gray matter injury. We also observed spinal, ocular, and neuromuscular pathology. Our data show that vascular compromise and neuroprogenitor cell dysfunction are hallmarks of CZS pathogenesis, suggesting novel strategies to prevent and to treat this disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Is MSAFP still a useful test for detecting open neural tube defects and ventral wall defects in the era of first-trimester and early second-trimester fetal anatomical ultrasounds?

PubMed

Roman, Ashley S; Gupta, Simi; Fox, Nathan S; Saltzman, Daniel; Klauser, Chad K; Rebarber, Andrei

2015-01-01

To evaluate whether maternal serum α-fetoprotein (MSAFP) improves the detection rate for open neural tube defects (ONTDs) and ventral wall defects (VWD) in patients undergoing first-trimester and early second-trimester fetal anatomical survey. A cohort of women undergoing screening between 2005 and 2012 was identified. All patients were offered an ultrasound at between 11 weeks and 13 weeks and 6 days of gestational age for nuchal translucency/fetal anatomy followed by an early second-trimester ultrasound at between 15 weeks and 17 weeks and 6 days of gestational age for fetal anatomy and MSAFP screening. All cases of ONTD and VWD were identified via query of billing and reporting software. Sensitivity and specificity for detection of ONTD/VWD were calculated, and groups were compared using the Fisher exact test, with p < 0.05 as significance. A total of 23,790 women met the criteria for inclusion. Overall, 15 cases of ONTD and 17 cases of VWD were identified; 100% of cases were diagnosed by ultrasound prior to 18 weeks' gestation; none were diagnosed via MSAFP screening (p < 0.001). First-trimester and early second-trimester ultrasound had 100% sensitivity and 100% specificity for diagnosing ONTD/VWD. Ultrasound for fetal anatomy during the first and early second trimester detected 100% of ONTD/VWD in our population. MSAFP is not useful as a screening tool for ONTD and VWD in the setting of this ultrasound screening protocol. © 2014 S. Karger AG, Basel.

Fetal bilateral renal agenesis, phocomelia, and single umbilical artery associated with cocaine abuse in early pregnancy.

PubMed

Kashiwagi, Maki; Chaoui, Rabih; Stallmach, Thomas; Hürlimann, Sandra; Lauper, Urs; Hebisch, Gundula

2003-11-01

Maternal cocaine abuse in pregnancy is associated with complications such as intrauterine growth retardation, abruptio placentae, and preterm delivery. We report what is, to our knowledge, the first published observation of fetal bilateral renal agenesis associated with a vascular disruption syndrome comprising upper limb reduction defect and a single umbilical artery following maternal cocaine abuse in early pregnancy. This constellation in a fetus aborted at 18 weeks extends the spectrum of complications possibly associated with cocaine abuse in pregnancy. Copyright 2003 Wiley-Liss, Inc.

Expression of Iroquois genes is up-regulated during early lung development in the nitrofen-induced pulmonary hypoplasia.

PubMed

Doi, Takashi; Lukošiūtė, Aušra; Ruttenstock, Elke; Dingemann, Jens; Puri, Prem

2011-01-01

Iroquois homeobox (Irx) genes have been implicated in the early lung morphogenesis of vertebrates. Irx1-3 and Irx5 gene expression is seen in fetal lung in rodents up to day (D) 18.5 of gestation. Fetal lung in Irx knockdown mice shows loss of mesenchyme and dilated airspaces, whereas nitrofen-induced hypoplastic lung displays thickened mesenchyme and diminished airspaces. We hypothesized that the Irx genes are up-regulated during early lung morphogenesis in the nitrofen-induced hypoplastic lung. Pregnant rats were exposed either to olive oil or nitrofen on D9. Fetal lungs harvested on D15 were divided into control and nitrofen groups; and the lungs harvested on D18 were divided into control, nitrofen without congenital diaphragmatic hernia (CDH[-]), and nitrofen with CDH (CDH[+]). Irx gene expression levels were analyzed by reverse transcriptase polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression of Irx family. Pulmonary Irx1-3 and Irx5 messenger RNA expression levels were significantly up-regulated in nitrofen group compared with controls at D15. On D15, Irx immunoreactivity was increased in nitrofen-induced hypoplastic lung compared with controls. Overexpression of Irx genes in the early lung development may cause pulmonary hypoplasia in the nitrofen CDH model by inducing lung dysmorphogenesis with thickened mesenchyme and diminished airspaces. Copyright © 2011 Elsevier Inc. All rights reserved.

Fetal pain, abortion, viability, and the Constitution.

PubMed

Cohen, I Glenn; Sayeed, Sadath

2011-01-01

In early 2010, the Nebraska state legislature passed a new abortion restricting law asserting a new, compelling state interest in preventing fetal pain. In this article, we review existing constitutional abortion doctrine and note difficulties presented by persistent legal attention to a socially derived viability construct. We then offer a substantive biological, ethical, and legal critique of the new fetal pain rationale. © 2011 American Society of Law, Medicine & Ethics, Inc.

Fetal heart rate patterns at 20 to 24 weeks gestation as recorded by fetal electrocardiography

PubMed Central

Hofmeyr, F; Groenewald, CA; Nel, DG; Myers, MM; Fifer, WP; Signore, C; Hankins, GDV; Odendaal, HJ

2014-01-01

Introduction With advancing technology it has become possible to accurately record and assess fetal heart rate (FHR) patterns from gestations as early as 20 weeks. The aim of our study was to describe early patterns of FHR, as recorded by transabdominal fetal electrocardiogram according to the Dawes-Redman criteria. Accordingly, short-term variability, basal heart rate, accelerations and decelerations were quantified at 20-24 weeks gestation among women with uncomplicated pregnancies. Methods This study was conducted in a subset of participants enrolled in a large prospective pregnancy cohort study. Our final data set consisted of 281 recordings of women with good perinatal outcomes that had undergone fetal electrocardiographic assessment as part of the Safe Passage Study. Results The success rate of the recordings was 95.4%. The mean frequency of small and large accelerations was 0.5 and 0.1 per 10 minutes respectively and that of small and large decelerations 0.3 and 0.008 per 10 minutes respectively. The mean and basal heart rates were both equal to 148.0 bpm at a median gestation of 161 days. The mean short term variation was 6.2 (SD 1.4) milliseconds and mean minute range 35.1 (SD 7.1) milliseconds. Conclusion The 20 to 24 week fetus demonstrates FHR patterns with more accelerations and decelerations, as well as higher baseline variability than was anticipated. Information from this study provides an important foundation for further, more detailed, studies of early FHR patterns. PMID:23991757

Advances in early fetal loss research: importance for risk assessment.

PubMed Central

Sweeney, A M; LaPorte, R E

1991-01-01

The assessment of early fetal losses (EFLs) in relationship to environmental agents offers unique advantages compared to other end points for hazard assessment. There is a high incidence (greater than 20% of all pregnancies end in an EFL), and the interval between exposure and end point is the short duration between conception and event, i.e., approximately 12 weeks. In contrast, cancer, which is the primary end point evaluated in risk assessment models, occurs with much lower frequency, and the latency period is measured in years or decades. EFLs have not been used effectively for risk assessment because most of the events are not detected. Prospective studies provide the only approach whereby it is possible to link exposure to EFLs. Recent methodologic advancements have demonstrated that it is now possible to conduct population-based studies of EFLs. It is likely that EFLs could serve as sentinels to monitor adverse health effects of many potential environmental hazards. The methodology will be demonstrated using lead exposure in utero as an example. PMID:2050056

Digital atlas of fetal brain MRI.

PubMed

Chapman, Teresa; Matesan, Manuela; Weinberger, Ed; Bulas, Dorothy I

2010-02-01

Fetal MRI can be performed in the second and third trimesters. During this time, the fetal brain undergoes profound structural changes. Interpretation of appropriate development might require comparison with normal age-based models. Consultation of a hard-copy atlas is limited by the inability to compare multiple ages simultaneously. To provide images of normal fetal brains from weeks 18 through 37 in a digital format that can be reviewed interactively. This will facilitate recognition of abnormal brain development. T2-W images for the atlas were obtained from fetal MR studies of normal brains scanned for other indications from 2005 to 2007. Images were oriented in standard axial, coronal and sagittal projections, with laterality established by situs. Gestational age was determined by last menstrual period, earliest US measurements and sonogram performed on the same day as the MR. The software program used for viewing the atlas, written in C#, permits linked scrolling and resizing the images. Simultaneous comparison of varying gestational ages is permissible. Fetal brain images across gestational ages 18 to 37 weeks are provided as an interactive digital atlas and are available for free download from http://radiology.seattlechildrens.org/teaching/fetal_brain . Improved interpretation of fetal brain abnormalities can be facilitated by the use of digital atlas cataloging of the normal changes throughout fetal development. Here we provide a description of the atlas and a discussion of normal fetal brain development.

Ultrasound studies of the effects of certain poisonous plants on uterine function and fetal development in livestock.

PubMed

Bunch, T D; Panter, K E; James, L F

1992-05-01

Ingestion of locoweed (Astragalus spp. and Oxytropis spp.) by pregnant livestock may result in fetal malformations, delayed placentation, reduced placental and uterine vascular development, hydrops amnii, hydrops allantois, abnormal cotyledonary development, interruption of fetal fluid balance, and abortion. Ultrasonography of pregnant sheep fed locoweed demonstrated that abortion was first preceded by changes in fetal heart rate and strength of contraction and structural changes of the cotyledons, followed by increased accumulation of fetal fluid within the placental membranes and death of the fetus. During pregnancy the toxic agent in locoweed (swainsonine) apparently passes through the placental barrier to the fetus and during lactation through the milk to the neonate. Poison-hemlock (Conium maculatum), wild tree tobacco (Nicotiana glauca), and lunara lupine (Lupinus formosus) all contain piperidine alkaloids and induce fetal malformations, including multiple congenital contractures and cleft palate in livestock. Ultrasonography studies of pregnant sheep and goats gavaged with these plants during 30 to 60 d of gestation suggests that the primary cause of multiple congenital contractures and cleft palate is the degree and the duration of the alkaloid-induced fetal immobilization.

High transduction efficiency of circulating first trimester fetal mesenchymal stem cells: potential targets for in utero ex vivo gene therapy.

PubMed

Campagnoli, Cesare; Bellantuono, Ilaria; Kumar, Sailesh; Fairbairn, Leslie J; Roberts, Irene; Fisk, Nicholas M

2002-08-01

We recently reported the existence of fetal mesenchymal stem cells in first trimester fetal blood. Here we demonstrate that fetal mesenchymal stem cells from as early as eight weeks of gestation can be retrovirally transduced with 99% efficiency without selection. Circulating fetal mesenchymal stem cells are known to readily expand and differentiate into multiple tissue types both in vitro and in vivo, and might be suitable vehicles for prenatal gene delivery. With advances in early fetal blood sampling techniques, we suggest that genetic disorders causing irreversible damage before birth could be treated in utero in the late first/early second trimester by genetically manipulated autologous fetal stem cells.

Premature Brain Aging in Baboons Resulting from Moderate Fetal Undernutrition.

PubMed

Franke, Katja; Clarke, Geoffrey D; Dahnke, Robert; Gaser, Christian; Kuo, Anderson H; Li, Cun; Schwab, Matthias; Nathanielsz, Peter W

2017-01-01

Contrary to the known benefits from a moderate dietary reduction during adulthood on life span and health, maternal nutrient reduction during pregnancy is supposed to affect the developing brain, probably resulting in impaired brain structure and function throughout life. Decreased fetal nutrition delivery is widespread in both developing and developed countries, caused by poverty and natural disasters, but also due to maternal dieting, teenage pregnancy, pregnancy in women over 35 years of age, placental insufficiency, or multiples. Compromised development of fetal cerebral structures was already shown in our baboon model of moderate maternal nutrient reduction. The present study was designed to follow-up and evaluate the effects of moderate maternal nutrient reduction on individual brain aging in the baboon during young adulthood (4-7 years; human equivalent 14-24 years), applying a novel, non-invasive neuroimaging aging biomarker. The study reveals premature brain aging of +2.7 years ( p < 0.01) in the female baboon exposed to fetal undernutrition. The effects of moderate maternal nutrient reduction on individual brain aging occurred in the absence of fetal growth restriction or marked maternal weight reduction at birth, which stresses the significance of early nutritional conditions in life-long developmental programming. This non-invasive MRI biomarker allows further longitudinal in vivo tracking of individual brain aging trajectories to assess the life-long effects of developmental and environmental influences in programming paradigms, aiding preventive and curative treatments on cerebral atrophy in experimental animal models and humans.

Premature Brain Aging in Baboons Resulting from Moderate Fetal Undernutrition

PubMed Central

Franke, Katja; Clarke, Geoffrey D.; Dahnke, Robert; Gaser, Christian; Kuo, Anderson H.; Li, Cun; Schwab, Matthias; Nathanielsz, Peter W.

2017-01-01

Contrary to the known benefits from a moderate dietary reduction during adulthood on life span and health, maternal nutrient reduction during pregnancy is supposed to affect the developing brain, probably resulting in impaired brain structure and function throughout life. Decreased fetal nutrition delivery is widespread in both developing and developed countries, caused by poverty and natural disasters, but also due to maternal dieting, teenage pregnancy, pregnancy in women over 35 years of age, placental insufficiency, or multiples. Compromised development of fetal cerebral structures was already shown in our baboon model of moderate maternal nutrient reduction. The present study was designed to follow-up and evaluate the effects of moderate maternal nutrient reduction on individual brain aging in the baboon during young adulthood (4–7 years; human equivalent 14–24 years), applying a novel, non-invasive neuroimaging aging biomarker. The study reveals premature brain aging of +2.7 years (p < 0.01) in the female baboon exposed to fetal undernutrition. The effects of moderate maternal nutrient reduction on individual brain aging occurred in the absence of fetal growth restriction or marked maternal weight reduction at birth, which stresses the significance of early nutritional conditions in life-long developmental programming. This non-invasive MRI biomarker allows further longitudinal in vivo tracking of individual brain aging trajectories to assess the life-long effects of developmental and environmental influences in programming paradigms, aiding preventive and curative treatments on cerebral atrophy in experimental animal models and humans. PMID:28443017

Study of a fetal brain affected by a severe form of tyrosine hydroxylase deficiency, a rare cause of early parkinsonism.

PubMed

Tristán-Noguero, Alba; Díez, Héctor; Jou, Cristina; Pineda, Mercè; Ormazábal, Aida; Sánchez, Aurora; Artuch, Rafael; Garcia-Cazorla, Àngels

2016-06-01

Tyrosine hydroxylase (TH) deficiency is an inborn error of dopamine synthesis. Two clinical phenotypes have been described. The THD "B" phenotype produces a severe encephalopathy of early-onset with sub-optimal L-Dopa response, whereas the "A" phenotype has a better L-Dopa response and outcome. The objective of the study is to describe the expression of key synaptic proteins and neurodevelopmental markers in a fetal brain of THD "B" phenotype. The brain of a 16-week-old miscarried human fetus was dissected in different brain areas and frozen until the analysis. TH gene study revealed the p.R328W/p.T399M mutations, the same mutations that produced a B phenotype in her sister. After protein extraction, western blot analyses were performed to assess protein expression. The results were compared to an age-matched control. We observed a decreased expression in TH and in other dopaminergic proteins, such as VMAT 1 and 2 and dopamine receptors, especially D2DR. GABAergic and glutamatergic proteins such as GABA VT, NMDAR1 and calbindin were also altered. Developmental markers for synapses, axons and dendrites were decreased whereas markers of neuronal volume were preserved. Although this is an isolated case, this brain sample is unique and corresponds to the first reported study of a THD brain. It provides interesting information about the influence of dopamine as a regulator of other neurotransmitter systems, brain development and movement disorders with origin at the embryological state. This study could also contribute to a better understanding of the pathophysiology of THD at early fetal stages.

[Current status and recommendations for intrapartum monitoring of fetal heart rate].

PubMed

Měchurová, A; Velebil, P; Hruban, L; Janků, P

2016-04-01

Monitoring of fetal heart rate is one of the basic components of obstetrical care, in which the cardiotocography remains the gold standard and screening method in early diagnosis of fetal hypoxia, even after introduction of other selective methods of intrauterine monitoring of fetal well-being. The review article is divided into several parts: pathophysiology of fetal oxygenation, fetal heart rate and changes of fetal hemodynamics, and rules for fetal heart rate auscultation. The main principles of cardiotocographic monitoring and evaluation of ante- and intrapartrum recordings according to the FIGO criteria from 1986 and evaluation of intrapartum recordings according to the 2015 FIGO recommendations are mentioned. At the end a comparative table of 1986 FIGO and 2015 FIGO criteria is presented. Review.

Cell-free fetal nucleic acid testing: a review of the technology and its applications.

PubMed

Sayres, Lauren C; Cho, Mildred K

2011-07-01

Cell-free fetal nucleic acids circulating in the blood of pregnant women afford the opportunity for early, noninvasive prenatal genetic testing. The predominance of admixed maternal genetic material in circulation demands innovative means for identification and analysis of cell-free fetal DNA and RNA. Techniques using polymerase chain reaction, mass spectrometry, and sequencing have been developed for the purposes of detecting fetal-specific sequences, such as paternally inherited or de novo mutations, or determining allelic balance or chromosome dosage. Clinical applications of these methods include fetal sex determination and blood group typing, which are currently available commercially although not offered routinely in the United States. Other uses of cell-free fetal DNA and RNA being explored are the detection of single-gene disorders, chromosomal abnormalities, and inheritance of parental polymorphisms across the whole fetal genome. The concentration of cell-free fetal DNA may also provide predictive capabilities for pregnancy-associated complications. The roles that cell-free fetal nucleic acid testing assume in the existing framework of prenatal screening and invasive diagnostic testing will depend on factors such as costs, clinical validity and utility, and perceived benefit-risk ratios for different applications. As cell-free fetal DNA and RNA testing continues to be developed and translated, significant ethical, legal, and social questions will arise that will need to be addressed by those with a stake in the use of this technology. Obstetricians & Gynecologists and Family Physicians Learning Objectives: After participating in this activity, physicians should be better able to evaluate techniques and tools for analyzing cell-free fetal nucleic acids, assess clinical applications of prenatal testing, using cell-free fetal nucleic acids and barriers to implementation, and distinguish between relevant clinical features of cell-free fetal nucleic acid

A uniform management approach to optimize outcome in fetal growth restriction.

PubMed

Seravalli, Viola; Baschat, Ahmet A

2015-06-01

A uniform approach to the diagnosis and management of fetal growth restriction (FGR) consistently produces better outcome, prevention of unanticipated stillbirth, and appropriate timing of delivery. Early-onset and late-onset FGR represent two distinct clinical phenotypes of placental dysfunction. Management challenges in early-onset FGR revolve around prematurity and coexisting maternal hypertensive disease, whereas in late-onset disease failure of diagnosis or surveillance leading to unanticipated stillbirth is the primary issue. Identifying the surveillance tests that have the highest predictive accuracy for fetal acidemia and establishing the appropriate monitoring interval to detect fetal deterioration is a high priority. Copyright © 2015 Elsevier Inc. All rights reserved.

Automatic Measurement of Fetal Brain Development from Magnetic Resonance Imaging: New Reference Data.

PubMed

Link, Daphna; Braginsky, Michael B; Joskowicz, Leo; Ben Sira, Liat; Harel, Shaul; Many, Ariel; Tarrasch, Ricardo; Malinger, Gustavo; Artzi, Moran; Kapoor, Cassandra; Miller, Elka; Ben Bashat, Dafna

2018-01-01

Accurate fetal brain volume estimation is of paramount importance in evaluating fetal development. The aim of this study was to develop an automatic method for fetal brain segmentation from magnetic resonance imaging (MRI) data, and to create for the first time a normal volumetric growth chart based on a large cohort. A semi-automatic segmentation method based on Seeded Region Growing algorithm was developed and applied to MRI data of 199 typically developed fetuses between 18 and 37 weeks' gestation. The accuracy of the algorithm was tested against a sub-cohort of ground truth manual segmentations. A quadratic regression analysis was used to create normal growth charts. The sensitivity of the method to identify developmental disorders was demonstrated on 9 fetuses with intrauterine growth restriction (IUGR). The developed method showed high correlation with manual segmentation (r2 = 0.9183, p < 0.001) as well as mean volume and volume overlap differences of 4.77 and 18.13%, respectively. New reference data on 199 normal fetuses were created, and all 9 IUGR fetuses were at or below the third percentile of the normal growth chart. The proposed method is fast, accurate, reproducible, user independent, applicable with retrospective data, and is suggested for use in routine clinical practice. © 2017 S. Karger AG, Basel.

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

Fetal electrocardiogram (ECG) for fetal monitoring during labour.

PubMed

Neilson, James P

2015-12-21

Hypoxaemia during labour can alter the shape of the fetal electrocardiogram (ECG) waveform, notably the relation of the PR to RR intervals, and elevation or depression of the ST segment. Technical systems have therefore been developed to monitor the fetal ECG during labour as an adjunct to continuous electronic fetal heart rate monitoring with the aim of improving fetal outcome and minimising unnecessary obstetric interference. To compare the effects of analysis of fetal ECG waveforms during labour with alternative methods of fetal monitoring. The Cochrane Pregnancy and Childbirth Group's Trials Register (latest search 23 September 2015) and reference lists of retrieved studies. Randomised trials comparing fetal ECG waveform analysis with alternative methods of fetal monitoring during labour. One review author independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. One review author assessed the quality of the evidence using the GRADE approach. Seven trials (27,403 women) were included: six trials of ST waveform analysis (26,446 women) and one trial of PR interval analysis (957 women). The trials were generally at low risk of bias for most domains and the quality of evidence for ST waveform analysis trials was graded moderate to high. In comparison to continuous electronic fetal heart rate monitoring alone, the use of adjunctive ST waveform analysis made no obvious difference to primary outcomes: births by caesarean section (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.96 to 1.08; six trials, 26,446 women; high quality evidence); the number of babies with severe metabolic acidosis at birth (cord arterial pH less than 7.05 and base deficit greater than 12 mmol/L) (average RR 0.72, 95% CI 0.43 to 1.20; six trials, 25,682 babies; moderate quality evidence); or babies with neonatal encephalopathy (RR 0.61, 95% CI 0.30 to 1.22; six trials, 26,410 babies; high quality evidence). There were, however, on average

Examiner's finger-mounted fetal tissue oximetry.

PubMed

Kanayama, Naohiro; Niwayama, Masatsugu

2014-06-01

The best way to assess fetal condition is to observe the oxygen status of the fetus (as well as to assess the condition of infants, children, and adults). Previously, several fetal oximeters have been developed; however, no instrument has been utilized in clinical practice because of the low-capturing rate of the fetal oxygen saturation. To overcome the problem, we developed a doctor's finger-mounted fetal tissue oximeter, whose sensor volume is one hundredth of the conventional one. Additionally, we prepared transparent gloves. The calculation algorithm of the hemoglobin concentration was derived from the light propagation analysis based on the transport theory. We measured neonatal and fetal oxygen saturation (StO₂) with the new tissue oximeter. Neonatal StO₂ was measured at any position of the head regardless of amount of hair. Neonatal StO₂ was found to be around 77%. Fetal StO₂ was detected in every position of the fetal head during labor regardless of the presence of labor pain. Fetal StO₂ without labor pain was around 70% in the first stage of labor and around 60% in the second stage of labor. We concluded that our new concept of fetal tissue oximetry would be useful for detecting fetal StO₂ in any condition of the fetus.

Examiner's finger-mounted fetal tissue oximetry

NASA Astrophysics Data System (ADS)

Kanayama, Naohiro; Niwayama, Masatsugu

2014-06-01

The best way to assess fetal condition is to observe the oxygen status of the fetus (as well as to assess the condition of infants, children, and adults). Previously, several fetal oximeters have been developed; however, no instrument has been utilized in clinical practice because of the low-capturing rate of the fetal oxygen saturation. To overcome the problem, we developed a doctor's finger-mounted fetal tissue oximeter, whose sensor volume is one hundredth of the conventional one. Additionally, we prepared transparent gloves. The calculation algorithm of the hemoglobin concentration was derived from the light propagation analysis based on the transport theory. We measured neonatal and fetal oxygen saturation (StO2) with the new tissue oximeter. Neonatal StO was measured at any position of the head regardless of amount of hair. Neonatal StO was found to be around 77%. Fetal StO was detected in every position of the fetal head during labor regardless of the presence of labor pain. Fetal StO without labor pain was around 70% in the first stage of labor and around 60% in the second stage of labor. We concluded that our new concept of fetal tissue oximetry would be useful for detecting fetal StO in any condition of the fetus.

The three-dimensional feto-maternal vascular interrelationship during early bovine placental development: a scanning electron microscopical study

PubMed Central

PFARRER, CHRISTIANE; EBERT, BRIGITTE; MIGLINO, MARIA ANGELICA; KLISCH, KARL; LEISER, RUDOLF

2001-01-01

Both the fetal and maternal microvasculature of bovine placentomes was examined by scanning electron microscopy of vascular casts. So far the development of the vascular architecture of the bovine placentome in early gestation has only been studied 2-dimensionally due to technical difficulties arising from the fragility of the early placental blood vessels. Repeated experiments led to the selection of the microvascular corrosion casts presented here. The vasculature of the maternal compartment is supplied by large caruncular stalk or spiral arteries, which release short maternal stem arteries. In the 3rd month of gestation, these arteries branch into several arterioles at their base, thus providing the vascular framework for the lower part of the septal walls of the primary crypts. In the 4th month, due to progressive longitudinal growth of the stem arteries, branching into arterioles occurs not only at the base, but over the whole length of the stem arteries. These arterioles supply the capillary complexes of the septa which resemble the major part of the septal vasculature and face the secondary crypts. Further indentation results in the formation of tertiary crypt capillary complexes, encircling the earlier secondary unit. From the 6th month of gestation the architecture resembles the fully developed maternal placenta with stem arteries running directly to the fetal side to branch into 4 to 6 arterioles, which turn back to enter secondary and tertiary septa. Maternal venules, collecting the blood from the capillary bed of secondary and tertiary septa, converge onto stem veins leaving the caruncle via branches of the uterine vein. The fetal part of the placentome is supplied by the cotyledonary arteries, which branch into fetal stem arteries that are the tributary to single villous trees. Over their whole course towards the maternal side, these give off arterioles entering secondary villi. The tertiary or terminal villous vasculature consists of capillaries

Quantitative and Qualitative Analysis of Transient Fetal Compartments during Prenatal Human Brain Development

PubMed Central

Vasung, Lana; Lepage, Claude; Radoš, Milan; Pletikos, Mihovil; Goldman, Jennifer S.; Richiardi, Jonas; Raguž, Marina; Fischi-Gómez, Elda; Karama, Sherif; Huppi, Petra S.; Evans, Alan C.; Kostovic, Ivica

2016-01-01

The cerebral wall of the human fetal brain is composed of transient cellular compartments, which show characteristic spatiotemporal relationships with intensity of major neurogenic events (cell proliferation, migration, axonal growth, dendritic differentiation, synaptogenesis, cell death, and myelination). The aim of the present study was to obtain new quantitative data describing volume, surface area, and thickness of transient compartments in the human fetal cerebrum. Forty-four postmortem fetal brains aged 13–40 postconceptional weeks (PCW) were included in this study. High-resolution T1 weighted MR images were acquired on 19 fetal brain hemispheres. MR images were processed using in-house software (MNI-ACE toolbox). Delineation of fetal compartments was performed semi-automatically by co-registration of MRI with histological sections of the same brains, or with the age-matched brains from Zagreb Neuroembryological Collection. Growth trajectories of transient fetal compartments were reconstructed. The composition of telencephalic wall was quantitatively assessed. Between 13 and 25 PCW, when the intensity of neuronal proliferation decreases drastically, the relative volume of proliferative (ventricular and subventricular) compartments showed pronounced decline. In contrast, synapse- and extracellular matrix-rich subplate compartment continued to grow during the first two trimesters, occupying up to 45% of telencephalon and reaching its maximum volume and thickness around 30 PCW. This developmental maximum coincides with a period of intensive growth of long cortico-cortical fibers, which enter and wait in subplate before approaching the cortical plate. Although we did not find significant age related changes in mean thickness of the cortical plate, the volume, gyrification index, and surface area of the cortical plate continued to exponentially grow during the last phases of prenatal development. This cortical expansion coincides developmentally with the

Pregnancy interruption after second trimester diagnosis of fetal structural anomalies: the New Jersey Fetal Abnormalities Registry.

PubMed

Rauch, Eden R; Smulian, John C; DePrince, Kristin; Ananth, Cande V; Marcella, Stephen W

2005-10-01

The purpose of this study was to identify factors that predict a decision to interrupt a pregnancy in which there are fetal anomalies in the second trimester. The New Jersey Fetal Abnormalities Registry prospectively recruits and collects information on pregnancies (> or = 15 weeks of gestation) from New Jersey residents in whom a fetal structural anomaly has been suspected by maternal-fetal medicine specialists. Enrolled pregnancies that have major fetal structural abnormalities identified from 15 to 23 weeks of gestation were included. Outcomes were classified as either elective interruption or a natural pregnancy course, which might include a spontaneous fetal death or live birth. Predictors of elective interruption of pregnancy were examined with univariable and multivariable logistic regression analyses. Of the 97 cases, 33% of the women (n = 32) interrupted the pregnancy. Significant variables in the regression model that were associated with a decision to interrupt a pregnancy were earlier identification of fetal anomalies (19.0 +/- 2 weeks of gestation vs 20.5 +/- 2 weeks of gestation; P = .003), the presence of multiple anomalies (78% [25/32] vs 52% [33/63]; P = .01], and a presumption of lethality (56% [18/32] vs 14% [9/65]; P = .0001). These variables corresponded to an odds ratio for pregnancy interruption of 4.2 (95% CI, 1.0, 17.0) for multiple anomalies, 0.8 (95% CI, 0.7, 1.0) for each week of advancing gestational age, and 36.1 (95% CI, 2.9, 450.7) for presumed lethal abnormalities. Early diagnosis, the identification of multiple abnormalities, and an assessment of likely lethality of fetal anomalies are important factors for the optimization of parental autonomy in deciding pregnancy management.

A Probability Analysis of Historical Pregnancy and Fetal Data from Dutch Belted and New Zealand White Rabbit Strains from Embryo-Fetal Development Studies.

PubMed

Posobiec, Lorraine M; Cox, Estella M; Solomon, Howard M; Lewis, Elise M; Wang, Kai-fen; Stanislaus, Dinesh

2016-04-01

Embryo-fetal development (EFD) studies, typically in pregnant rats and rabbits, are conducted prior to enrolling females of reproductive age in clinical trials. Common rabbit strains used are the New Zealand White (NZW) and Dutch Belted (DB). As fetal abnormalities can occur in all groups, including controls, Historical Control Data (HCD) is compiled using data from control groups of EFD studies, and is used along with each study's concurrent control group to help determine whether fetal abnormalities are caused by the test article or are part of background incidences. A probability analysis was conducted on 2014 HCD collected at Charles River Inc., Horsham PA on Covance NZW, Covance DB, and Charles River (CR) NZW rabbits. The analysis was designed to determine the probability of 2 or 3 out of a group of 22 does aborting their litter or of having a fetal abnormality by chance. Results demonstrate that pregnancy parameters and fetal observations differ not only between strains, but between sources of rabbits of the same strain. As a result the probability of these observations occurring by chance in two or three litters was drastically different. Although no one single strain is perfect, this analysis highlights the need to appreciate the inherent differences in pregnancy and fetal abnormalities between strains, and points out that an apparent isolated increased incidence of an observation in one strain will not necessarily be test-article related in another strain. A robust HCD is critical for interpretation of EFD rabbit studies, regardless of the rabbit strain used. © 2016 Wiley Periodicals, Inc.

Morphology, development, and evolution of fetal membranes and placentation in squamate reptiles.

PubMed

Blackburn, Daniel G; Flemming, Alexander F

2009-09-15

Current studies on fetal membranes of reptiles are providing insight into three major historical transformations: evolution of the amniote egg, evolution of viviparity, and evolution of placentotrophy. Squamates (lizards and snakes) are ideal for such studies because their fetal membranes sustain embryos in oviparous species and contribute to placentas in viviparous species. Ultrastructure of the fetal membranes in oviparous corn snakes (Pituophis guttatus) shows that the chorioallantois is specialized for gas exchange and the omphalopleure, for water absorption. Transmission and scanning electron microscopic studies of viviparous thamnophine snakes (Thamnophis, Storeria) have revealed morphological specializations for gas exchange and absorption in the intra-uterine environment that represent modifications of features found in oviparous species. Thus, fetal membranes in oviparous species show morphological differentiation for distinct functions that have been recruited and enhanced under viviparous conditions. The ultimate in specialization of fetal membranes is found in viviparous skinks of South America (Mabuya) and Africa (Trachylepis, Eumecia), in which placentotrophy accounts for nearly all of the nutrients for development. Ongoing research on these lizards has revealed morphological specializations of the chorioallantoic placenta through which nutrient transfer is accomplished. In addition, African Trachylepis show an invasive form of implantation, in which uterine epithelium is replaced by invading chorionic cells. Ongoing analysis of these lizards shows how integration of multiple lines of evidence can provide insight into the evolution of developmental and reproductive specializations once thought to be confined to eutherian mammals.

Fetal bladder catheterization in severe obstructive uropathy before the 24th week of pregnancy.

PubMed

Szaflik, K; Kozarzewski, M; Adamczewski, D

1998-01-01

Fetal obstructive uropathy is simple to diagnose before the 24th week of life. Drainage of the pathologically enlarged fetal bladder avoids development of hydronephrosis and destruction of kidneys and, obviously, prevents development of secondary oligohydramnios and pulmonary hypoplasia. The aim of our study was to evaluate the usefulness of a fetal bladder shunt in cases of obstructive uropathy before the 24th week of gestation. From January 1997 we diagnosed 6 cases of fetal obstructive uropathy before the 24th week of gestation. In all cases oligohydramnios or ahydramnios was also observed. After evaluation of the renal function on the basis of fetal urine samples, we shunted 5 fetuses. After routine preparation of the operative field, a special puncture needle was inserted through the abdominal wall of mother and fetus into the fetal bladder. Through the needle a fetal bladder catheter was inserted between the fetal bladder and the amniotic sac. After shunt placement, fetal urine fills the amniotic sac and the fetal bladder is decompressed. After the procedure, the patients were hospitalized and serial sonographic examinations were performed to evaluate shunt function. Bladder size, presence and size of hydronephrosis, and volume of amniotic fluid were evaluated. The Rocket Medical catheters have an excellent 'shape memory'. All but 1 newborns had a good perinatal outcome. Mean Apgar score was 8 at 1 min, weight at delivery was between 1,700 and 3,100 g. No pulmonary hypoplasia was observed. All deliveries were after the 33rd week of gestation (range 33-38 weeks). The minimum drainage time was 11 weeks, maximum 18 weeks. In 2 cases premature delivery occurred because of premature rupture of the membranes. One newborn died of respiratory distress syndrome. Early bladder drainage (before the 24th week of gestation) enables delivery of newborns with a good perinatal outcome, without pulmonary hypoplasia. This method of therapy limits renal damage and allows time

Bovine maternal, fetal and neonatal responses to bovine viral diarrhea virus infections.

PubMed

Kelling, Clayton L; Topliff, Christina L

2013-01-01

Due to the affinity of BVDV for the fetus and for cells of lymphatic organs of infected cattle, reproductive failure or immunosuppression, respectively, are likely consequences of BVDV infections of susceptible cattle. Infection of susceptible pregnant cattle with noncytopathic (ncp) BVDV results in transplacental infection with induction of maternal and fetal innate and adaptive immune responses. Differences in maternal innate and adaptive immune responses are evident in late gestation between cows carrying fetuses persistently-infected (PI) with BVDV and cows with fetuses transiently-infected with BVDV. Fetal innate and adaptive immune responses to ncp BVDV infection are defined by fetal age and developmental stage of the fetal immune system. Since a functional fetal adaptive immune response does not occur in the early fetus, immunotolerance to ncp BVDV is established, virus replicates unrestricted in fetal tissues and calves are born immunotolerant and PI with the virus. In the last trimester of gestation, the fetal immune system is adequately developed to respond in an efficacious manner, most commonly resulting in the birth of a clinically normal calf with pre-colostral antibodies. Immunosuppression due to postnatal acute ncp BVDV infections of susceptible calves may contribute to the occurrence and severity of multi-factorial respiratory tract and enteric diseases. Copyright © 2012 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise.

PubMed

McQueen, Dana B; Bernardi, Lia A; Stephenson, Mary D

2014-04-01

To assess the prevalence of chronic endometritis in women with a history of recurrent early pregnancy loss (REPL) and/or fetal demise (FD). Observational cohort study using prospectively collected data. Recurrent pregnancy loss program in an academic medical center. Three hundred ninety-five women with a history of two or more pregnancy losses of less than 10 weeks' size or a fetal demise of 10 or more weeks' size. All women had an endometrial biopsy. Chronic endometritis was treated with antibiotics, and a second endometrial biopsy was recommended as a "test of cure." Subsequent live-birth rate (LBR). The overall prevalence of chronic endometritis was 9% (35/395) in this cohort; 7% (21/285) in the REPL group, 14% (8/57) in the FD group, and 11% (6/53) in the combined REPL/FD group. The cure rate was 100% after a course(s) of antibiotics. The subsequent cumulative LBR was 88% (21/24) for the treated chronic endometritis group versus 74% (180/244) for the group without chronic endometritis. The per-pregnancy LBR for the treated chronic endometritis group was 7% (7/98) before treatment versus 56% (28/50) after treatment. There was a high prevalence of chronic endometritis in this cohort. The test of cure was 100% with antibiotics. Subsequent LBRs after treatment were encouraging. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Electronic fetal monitoring: family medicine obstetrics.

PubMed

Rodney, John R M; Huntley, Benjamin J F; Rodney, Wm Macmillan

2012-03-01

Electronic fetal monitoring assesses fetal health during the prenatal and intrapartum process. Intermittent auscultation does not detect key elements of fetal risk, such as beat-to-beat variability. Family medicine obstetric fellowships have contributed new knowledge to this process by articulating a method of analysis that builds on evidence-based recommendations from the American College of Obstetrics and Gynecology as well as the National Institute of Child Health and Development. This article summarizes the development, interpretation, and management of electronic fetal heart rate patterns and tracings. Copyright © 2012 Elsevier Inc. All rights reserved.

Evolution and development of fetal membranes and placentation in amniote vertebrates.

PubMed

Ferner, Kirsten; Mess, Andrea

2011-08-31

We review aspects of fetal membrane evolution and patterns of placentation within amniotes, the most successful land vertebrates. Special reference is given to embryonic gas supply. The evolution of fetal membranes is a prerequisite for reproduction independent from aquatic environments. Starting from a basically similar repertoire of fetal membranes - the amnion, chorion, allantois and yolk sac, which form the cleidoic egg - different structural solutions for embryonic development have evolved. In oviparous amniotes the chorioallantoic membrane is the major site for the exchange of respiratory gases between fetus and outer environment. The richly vascularised yolk sac and allantois in concert with the chorion play an important role in the evolution of placentation in various viviparous amniotes. Highly complex placentas have evolved independently among squamate sauropsids and in marsupial and placental mammals. In conclusion, there seems to be a natural force to improve gas exchange processes in intrauterine environments by reducing the barrier between the blood systems and optimising the exchange areas. Copyright © 2011 Elsevier B.V. All rights reserved.

The Placental Interleukin-6 Signaling Controls Fetal Brain Development and Behavior

PubMed Central

Wu, Wei-Li; Hsiao, Elaine Y.; Yan, Zihao; Mazmanian, Sarkis K.; Patterson, Paul H.

2016-01-01

Epidemiological studies show that maternal immune activation (MIA) during pregnancy is a risk factor for autism. However, mechanisms for how MIA affects brain development and behaviors in offspring remain poorly described. To determine whether placental interleukin-6 (IL-6) signaling is required for mediating MIA on the offspring, we generated mice with restricted deletion of the receptor for IL-6 (IL-6Rα) in placental trophoblasts (Cyp19-Cre+;Il6rafl/fl), and tested offspring of Cyp19-Cre+;Il6rafl/fl mothers for immunological, pathological and behavioral abnormalities following induction of MIA. We reveal that MIA results in acute inflammatory responses in the fetal brain. Lack of IL-6 signaling in trophoblasts effectively blocks MIA-induced inflammatory responses in the placenta and the fetal brain. Furthermore, behavioral abnormalities and cerebellar neuropathologies observed in MIA control offspring are prevented in Cyp19-Cre+;Il6rafl/fl offspring. Our results demonstrate that IL-6 activation in placenta is required for relaying inflammatory signals to the fetal brain and impacting behaviors and neuropathologies relevant to neurodevelopmental disease. PMID:27838335

KDR (VEGFR2) identifies a conserved human and murine hepatic progenitor and instructs early liver development

PubMed Central

Goldman, Orit; Han, Songyan; Sourrisseau, Marion; Dziedzic, Noelle; Hamou, Wissam; Corneo, Barbara; D’Souza, Sunita; Sato, Thomas; Kotton, Darrell N.; Bissig, Karl-Dimiter; Kalir, Tamara; Jacobs, Adam; Evans, Todd; Evans, Matthew J.; Gouon-Evans, Valerie

2013-01-01

SUMMARY Understanding the fetal hepatic niche is essential for optimizing the generation of functional hepatocyte-like (hepatic) cells from human embryonic stem cells (hESCs). Here, we show that KDR (VEGFR2), previously assumed to be mostly restricted to mesodermal lineages, marks a hESC-derived hepatic progenitor. hESC-derived endoderm cells do not express KDR, but when cultured in media supporting hepatic differentiation, generate KDR+ hepatic progenitors and KDR- hepatic cells. KDR+ progenitors require active KDR signaling both to instruct their own differentiation into hepatic cells, and to support non-cell-autonomously the functional maturation of co-cultured KDR- hepatic cells. Analysis of human fetal livers suggests that similar progenitors are present in human livers. Lineage tracing in mice provides in vivo evidence of a KDR+ hepatic progenitor for fetal hepatoblasts and subsequently adult hepatocytes and cholangiocytes. Altogether, our findings reveal that KDR is a conserved marker for endoderm-derived hepatic progenitors, and a functional receptor instructing early liver development. PMID:23746980

IGF2 DNA methylation is a modulator of newborn's fetal growth and development.

PubMed

St-Pierre, Julie; Hivert, Marie-France; Perron, Patrice; Poirier, Paul; Guay, Simon-Pierre; Brisson, Diane; Bouchard, Luigi

2012-10-01

The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn's fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn's weight variance. No association was observed with maternal diabetic status, glucose concentrations or prenatal maternal body mass index. This is the first study showing that DNA methylation at the IGF2/H19 genes locus may act as a modulator of IGF2 newborn's fetal growth and development within normal range. IGF2/H19 DNA methylation could represent a cornerstone in linking birth weight and fetal metabolic programming of late onset obesity.

Early stress and human behavioral development: emerging evolutionary perspectives.

PubMed

Del Giudice, M

2014-08-01

Stress experienced early in life exerts a powerful, lasting influence on development. Converging empirical findings show that stressful experiences become deeply embedded in the child's neurobiology, with an astonishing range of long-term effects on cognition, emotion, and behavior. In contrast with the prevailing view that such effects are the maladaptive outcomes of 'toxic' stress, adaptive models regard them as manifestations of evolved developmental plasticity. In this paper, I offer a brief introduction to adaptive models of early stress and human behavioral development, with emphasis on recent theoretical contributions and emerging concepts in the field. I begin by contrasting dysregulation models of early stress with their adaptive counterparts; I then introduce life history theory as a unifying framework, and review recent work on predictive adaptive responses (PARs) in human life history development. In particular, I discuss the distinction between forecasting the future state of the environment (external prediction) and forecasting the future state of the organism (internal prediction). Next, I present the adaptive calibration model, an integrative model of individual differences in stress responsivity based on life history concepts. I conclude by examining how maternal-fetal conflict may shape the physiology of prenatal stress and its adaptive and maladaptive effects on postnatal development. In total, I aim to show how theoretical work from evolutionary biology is reshaping the way we think about the role of stress in human development, and provide researchers with an up-to-date conceptual map of this fascinating and rapidly evolving field.

Fetal Heart Rate and Variability: Stability and Prediction to Developmental Outcomes in Early Childhood

ERIC Educational Resources Information Center

DiPietro, Janet A.; Bornstein, Marc H.; Hahn, Chun-Shin; Costigan, Kathleen; Achy-Brou, Aristide

2007-01-01

Stability in cardiac indicators before birth and their utility in predicting variation in postnatal development were examined. Fetal heart rate and variability were measured longitudinally from 20 through 38 weeks gestation (n = 137) and again at age 2 (n = 79). Significant within-individual stability during the prenatal period and into childhood…

Development of the genital ducts and external genitalia in the early human embryo.

PubMed

Sajjad, Yasmin

2010-10-01

The course of development of the human genital tract is undifferentiated to the 9th week of development. At this time two symmetrical paired ducts known as the mesonephric (MD) and paramesonephric ducts (PMD) are present, which together with the urogenital sinus provide the tissue sources for internal and external genital development. Normal differentiation of the bipotential external genitalia and reproductive ducts are dependent upon the presence or absence of certain hormones. Masculinization of the internal and external genitalia during fetal development depends on the existence of two discrete testicular hormones. Testosterone secreted from Leydig cells induces the differentiation of the mesonephric ducts into the epididymis, vasa deferentia and seminal vesicles, whereas anti-Müllerian hormone (AMH) produced by Sertoli cells induces the regression of the paramesonephric ducts. The absence of AMH action in early fetal life results in the formation of the fallopian tubes, uterus and upper third of the vagina. In some target tissues, testosterone is converted to dihydrotestosterone, which is responsible for the masculinization of the urogenital sinus and external genitalia. © 2010 The Author. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology.

Development of a Smart Mobile Data Module for Fetal Monitoring in E-Healthcare.

PubMed

Houzé de l'Aulnoit, Agathe; Boudet, Samuel; Génin, Michaël; Gautier, Pierre-François; Schiro, Jessica; Houzé de l'Aulnoit, Denis; Beuscart, Régis

2018-03-23

The fetal heart rate (FHR) is a marker of fetal well-being in utero (when monitoring maternal and/or fetal pathologies) and during labor. Here, we developed a smart mobile data module for the remote acquisition and transmission (via a Wi-Fi or 4G connection) of FHR recordings, together with a web-based viewer for displaying the FHR datasets on a computer, smartphone or tablet. In order to define the features required by users, we modelled the fetal monitoring procedure (in home and hospital settings) via semi-structured interviews with midwives and obstetricians. Using this information, we developed a mobile data transfer module based on a Raspberry Pi. When connected to a standalone fetal monitor, the module acquires the FHR signal and sends it (via a Wi-Fi or a 3G/4G mobile internet connection) to a secure server within our hospital information system. The archived, digitized signal data are linked to the patient's electronic medical records. An HTML5/JavaScript web viewer converts the digitized FHR data into easily readable and interpretable graphs for viewing on a computer (running Windows, Linux or MacOS) or a mobile device (running Android, iOS or Windows Phone OS). The data can be viewed in real time or offline. The application includes tools required for correct interpretation of the data (signal loss calculation, scale adjustment, and precise measurements of the signal's characteristics). We performed a proof-of-concept case study of the transmission, reception and visualization of FHR data for a pregnant woman at 30 weeks of amenorrhea. She was hospitalized in the pregnancy assessment unit and FHR data were acquired three times a day with a Philips Avalon® FM30 fetal monitor. The prototype (Raspberry Pi) was connected to the fetal monitor's RS232 port. The emission and reception of prerecorded signals were tested and the web server correctly received the signals, and the FHR recording was visualized in real time on a computer, a tablet and smartphones

Fetal Fibroblasts and Keratinocytes with Immunosuppressive Properties for Allogeneic Cell-Based Wound Therapy

PubMed Central

Zuliani, Thomas; Saiagh, Soraya; Knol, Anne-Chantal; Esbelin, Julie; Dréno, Brigitte

2013-01-01

Fetal skin heals rapidly without scar formation early in gestation, conferring to fetal skin cells a high and unique potential for tissue regeneration and scar management. In this study, we investigated the possibility of using fetal fibroblasts and keratinocytes to stimulate wound repair and regeneration for further allogeneic cell-based therapy development. From a single fetal skin sample, two clinical batches of keratinocytes and fibroblasts were manufactured and characterized. Tolerogenic properties of the fetal cells were investigated by allogeneic PBMC proliferation tests. In addition, the potential advantage of fibroblasts/keratinocytes co-application for wound healing stimulation has been examined in co-culture experiments with in vitro scratch assays and a multiplex cytokines array system. Based on keratin 14 and prolyl-4-hydroxylase expression analyses, purity of both clinical batches was found to be above 98% and neither melanocytes nor Langerhans cells could be detected. Both cell types demonstrated strong immunosuppressive properties as shown by the dramatic decrease in allogeneic PBMC proliferation when co-cultured with fibroblasts and/or keratinocytes. We further showed that the indoleamine 2,3 dioxygenase (IDO) activity is required for the immunoregulatory activity of fetal skin cells. Co-cultures experiments have also revealed that fibroblasts-keratinocytes interactions strongly enhanced fetal cells secretion of HGF, GM-CSF, IL-8 and to a lesser extent VEGF-A. Accordingly, in the in vitro scratch assays the fetal fibroblasts and keratinocytes co-culture accelerated the scratch closure compared to fibroblast or keratinocyte mono-cultures. In conclusion, our data suggest that the combination of fetal keratinocytes and fibroblasts could be of particular interest for the development of a new allogeneic skin substitute with immunomodulatory activity, acting as a reservoir for wound healing growth factors. PMID:23894651

Fetal anemia as a signal of congenital syphilis.

PubMed

Macé, Guillaume; Castaigne, Vanina; Trabbia, Aurore; Guigue, Virginie; Cynober, Evelyne; Cortey, Anne; Lalande, Valérie; Carbonne, Bruno

2014-09-01

An upsurge in syphilis has been observed almost everywhere over the past decade. The mother's clinical presentation is often uninformative. The diagnosis of maternal syphilis infection is most often based on serologic tests that allow early Extencilline treatment. Syphilis ultrasound findings are non-specific, and delay before treatment can be decisive for prognosis. Fetal anemia is a physiological consequence of severe infection. We confirmed that syphilis can be suggested non-invasively by MCA-PSV measurements in a context of ascitis or atypical hydrops in the absence of usual causes. It is therefore important to perform maternal TPHA/VDRL serology if fetal anemia is suspected. In association with Extencilline treatment, intra uterine transfusion can limit consequences of infection. Reduced fetal movements and non-reactive fetal heart rate may prefigure acute perinatal complications or stillbirth.

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

Fetal kidney length as a useful adjunct parameter for better determination of gestational age.

PubMed

Ugur, Mete G; Mustafa, Aynur; Ozcan, Huseyin C; Tepe, Neslihan B; Kurt, Huseyin; Akcil, Emre; Gunduz, Reyhan

2016-05-01

To determine the validity of fetal kidney length and amniotic fluid index (AFI) in labor dating.  This prospective study included 180 pregnant women followed up in the outpatient clinic at the Department of Obstetrics and Gynecology, Gaziantep University, Turkey, between January 2014 and January 2015. The gestational age (GA) was estimated by early fetal ultrasound measures and last menstrual period. Routine fetal biometric parameters, fetal kidney length, and amniotic fluid index were measured. We studied the correlation between fetal kidney length, amniotic fluid index, and gestational age.  The mean gestational age depending on last menstrual period and early ultrasound was 31.98±4.29 (24-39 weeks). The mean kidney length was 35.66±6.61 (19-49 mm). There was a significant correlation between gestational age and fetal kidney length (r=0.947, p=0.001). However, there was a moderate negative correlation between GA and AFI. Adding fetal kidney length to the routine biometrics improved the effectiveness of the model used to estimate GA (R2=0.965 to R2=0.987).  Gestational age can be better predicted by adding fetal kidney length to other routine parameters.

Genetic and Environmental Influences on Fetal Growth Vary during Sensitive Periods in Pregnancy.

PubMed

Workalemahu, Tsegaselassie; Grantz, Katherine L; Grewal, Jagteshwar; Zhang, Cuilin; Louis, Germaine M Buck; Tekola-Ayele, Fasil

2018-05-08

Aberrant fetal growth is associated with morbidities and mortality during childhood and adult life. Although genetic and environmental factors are known to influence in utero growth, their relative contributions over pregnancy is unknown. We estimated, across gestation, the genetic heritability, contribution of shared environment, and genetic correlations of fetal growth measures (abdominal circumference (AC), humerus length (HL), femur length (FL), and estimated fetal weight (EFW)) in a prospective cohort of dichorionic twin gestations recruited through the NICHD Fetal Growth Studies. Structural equation models were fit at the end of first trimester, during mid-gestation, late second trimester, and third trimester of pregnancy. The contribution of fetal genetics on fetal size increased with gestational age, peaking in late second trimester (AC = 53%, HL = 57%, FL = 72%, EFW = 71%; p < 0.05). In contrast, shared environment explained most of phenotypic variations in fetal growth in the first trimester (AC = 50%, HL = 54%, FL = 47%, EFW = 54%; p < 0.05), suggesting that the first trimester presents an intervention opportunity for a more optimal early fetal growth. Genetic correlations between growth traits (range 0.34-1.00; p < 0.05) were strongest at the end of first trimester and declined with gestation, suggesting that different fetal growth measures are more likely to be influenced by the same genes in early pregnancy.

[Impact on environmental factors on the reproductive system and fetal development].

PubMed

Dulskiene, Virginija; Maroziene, Ligita

2002-01-01

A literature review discusses the effect of selected environmental factors on women reproductive system, fetal development and growth. According to recent reports, 2-3% of newborns have congenital malformations. These malformations are caused by interaction of genetic and environmental factors. Exposure of paternal or maternal organisms to environmental hazards may damage germ cells or interfere fetal development, resulting in malformation of various organ systems. Since environmental hazards exposures are complex, it is difficult to establish the primary effect of single factor. Factors, that are known to increase the risk of congenital malformations, preterm delivery or spontaneous abortion, are classified into five groups--psychological, social, biological, physical and chemical factors. The governments of most counties recognize the effect of hazardous environmental factors on public health as global problem. World Health Organization encourages researches, aimed at evaluation of various environmental factors impact on health of pregnant women and their offsprings.

In utero exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep

PubMed Central

Fowler, Paul A.; Dorà, Natalie J.; McFerran, Helen; Amezaga, Maria R.; Miller, David W.; Lea, Richard G.; Cash, Phillip; McNeilly, Alan S.; Evans, Neil P.; Cotinot, Corinne; Sharpe, Richard M.; Rhind, Stewart M.

2008-01-01

Epidemiological studies of the impact of environmental chemicals on reproductive health demonstrate consequences of exposure but establishing causative links requires animal models using ‘real life’ in utero exposures. We aimed to determine whether prolonged, low-dose, exposure of pregnant sheep to a mixture of environmental chemicals affects fetal ovarian development. Exposure of treated ewes (n = 7) to pollutants was maximized by surface application of processed sewage sludge to pasture. Control ewes (n = 10) were reared on pasture treated with inorganic fertilizer. Ovaries and blood were collected from fetuses (n = 15 control and n = 8 treated) on Day 110 of gestation for investigation of fetal endocrinology, ovarian follicle/oocyte numbers and ovarian proteome. Treated fetuses were 14% lighter than controls but fetal ovary weights were unchanged. Prolactin (48% lower) was the only measured hormone significantly affected by treatment. Treatment reduced numbers of growth differentiation factor (GDF9) and induced myeloid leukaemia cell differentiation protein (MCL1) positive oocytes by 25–26% and increased pro-apoptotic BAX by 65% and 42% of protein spots in the treated ovarian proteome were differently expressed compared with controls. Nineteen spots were identified and included proteins involved in gene expression/transcription, protein synthesis, phosphorylation and receptor activity. Fetal exposure to environmental chemicals, via the mother, significantly perturbs fetal ovarian development. If such effects are replicated in humans, premature menopause could be an outcome. PMID:18436539

Screening for fetal growth restriction using fetal biometry combined with maternal biomarkers.

PubMed

Gaccioli, Francesca; Aye, Irving L M H; Sovio, Ulla; Charnock-Jones, D Stephen; Smith, Gordon C S

2018-02-01

Fetal growth restriction is a major determinant of perinatal morbidity and mortality. Screening for fetal growth restriction is a key element of prenatal care but it is recognized to be problematic. Screening using clinical risk assessment and targeting ultrasound to high-risk women is the standard of care in the United States and United Kingdom, but the approach is known to have low sensitivity. Systematic reviews of randomized controlled trials do not demonstrate any benefit from universal ultrasound screening for fetal growth restriction in the third trimester, but the evidence base is not strong. Implementation of universal ultrasound screening in low-risk women in France failed to reduce the risk of complications among small-for-gestational-age infants but did appear to cause iatrogenic harm to false positives. One strategy to making progress is to improve screening by developing more sensitive and specific tests with the key goal of differentiating between healthy small fetuses and those that are small through fetal growth restriction. As abnormal placentation is thought to be the major cause of fetal growth restriction, one approach is to combine fetal biometry with an indicator of placental dysfunction. In the past, these indicators were generally ultrasonic measurements, such as Doppler flow velocimetry of the uteroplacental circulation. However, another promising approach is to combine ultrasonic suspicion of small-for-gestational-age infant with a blood test indicating placental dysfunction. Thus far, much of the research on maternal serum biomarkers for fetal growth restriction has involved the secondary analysis of tests performed for other indications, such as fetal aneuploidies. An exemplar of this is pregnancy-associated plasma protein A. This blood test is performed primarily to assess the risk of Down syndrome, but women with low first-trimester levels are now serially scanned in later pregnancy due to associations with placental causes of

Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome

PubMed Central

Hatzirodos, Nicholas; Bayne, Rosemary A.; Irving-Rodgers, Helen F.; Hummitzsch, Katja; Sabatier, Laetitia; Lee, Sam; Bonner, Wendy; Gibson, Mark A.; Rainey, William E.; Carr, Bruce R.; Mason, Helen D.; Reinhardt, Dieter P.; Anderson, Richard A.; Rodgers, Raymond J.

2011-01-01

Although not often discussed, the ovaries of women with polycystic ovary syndrome (PCOS) show all the hallmarks of increased TGF-β activity, with increased amounts of fibrous tissue and collagen in the ovarian capsule or tunica albuginea and ovarian stroma. Recent studies suggest that PCOS could have fetal origins. Genetic studies of PCOS have also found linkage with a microsatellite located in intron 55 of the extracellular matrix protein fibrillin 3. Fibrillins regulate TGF-β bioactivity in tissues by binding latent TGF-β binding proteins. We therefore examined expression of fibrillins 1–3, latent TGF-β binding proteins 1–4, and TGF-β 1–3 in bovine and human fetal ovaries at different stages of gestation and in adult ovaries. We also immunolocalized fibrillins 1 and 3. The results indicate that TGF-β pathways operate during ovarian fetal development, but most important, we show fibrillin 3 is present in the stromal compartments of fetal ovaries and is highly expressed at a critical stage early in developing human and bovine fetal ovaries when stroma is expanding and follicles are forming. These changes in expression of fibrillin 3 in the fetal ovary could lead to a predisposition to develop PCOS in later life.—Hatzirodos, N., Bayne, R. A., Irving-Rodgers, H. F., Hummitzsch, K., Sabatier, L., Lee, S., Bonner, W., Gibson, M. A., Rainey, W. E., Carr, B. R., Mason, H. D., Reinhardt, D. P., Anderson, R. A., Rodgers, R. J. Linkage of regulators of TGF-β activity in the fetal ovary to polycystic ovary syndrome. PMID:21411746

[Fetal programming and the etiology of osteoporosis].

PubMed

Pieńkowski, Wojciech; Wolski, Hubert; Drews, Krzysztof; Seremak-Mrozikiewicz, Agnieszka

2015-08-01

Osteoporosis is a multifactorial skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased risk of fracture. Peak bone mass is an important predictor of later risk of osteoporosis. Epidemiological studies revealed that the risk of osteoporosis might be modified by exposure to environmental factors during intrauterine life and early postnatal period. This review summarizes the influence of fetal programming on the development of osteoporosis based on the epidemiological studies and potential mechanisms of epigenetic regulation of gene expression.

Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development.

PubMed

Conover, Cheryl A; Bale, Laurie K; Overgaard, Michael T; Johnstone, Edward W; Laursen, Ulla H; Füchtbauer, Ernst-Martin; Oxvig, Claus; van Deursen, Jan

2004-03-01

Pregnancy-associated plasma protein A (PAPPA) is a metzincin superfamily metalloproteinase in the insulin-like growth factor (IGF) system. PAPPA increases IGF bioavailability and mitogenic effectiveness in vitro through regulated cleavage of IGF-binding protein 4 (IGFBP4). To determine its function in vivo, we generated PAPPA-null mice by gene targeting. Mice homozygous for targeted disruption of the PAPPA gene were viable but 60% the size of wild-type littermates at birth. The impact of the mutation was exerted during the early embryonic period prior to organogenesis, resulting in proportional dwarfism. PAPPA, IGF2 and IGFBP4 transcripts co-localized in wild-type embryos, and expression of IGF2 and IGFBP4 mRNA was not altered in PAPPA-deficient embryos. However, IGFBP4 proteolytic activity was completely lacking in fibroblasts derived from PAPPA-deficient embryos, and IGFBP4 effectively inhibited IGF-stimulated mitogenesis in these cells. These results provide the first direct evidence that PAPPA is an essential growth regulatory factor in vivo, and suggest a novel mechanism for regulated IGF bioavailability during early fetal development.

Effects of Fetal Exposure to Asian Sand Dust on Development and Reproduction in Male Offspring.

PubMed

Yoshida, Seiichi; Ichinose, Takamichi; Arashidani, Keiichi; He, Miao; Takano, Hirohisa; Shibamoto, Takayuki

2016-11-23

In recent experimental studies, we reported the aggravating effects of Asian sand dust (ASD) on male reproduction in mice. However, the effects of fetal ASD exposure on male reproduction have not been investigated. The present study investigated the effects of fetal ASD exposure on reproduction in male offspring. Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14 of gestation, and the reproduction of male offspring was determined at 5, 10, and 15 weeks after birth. The secondary sex ratio was significantly lower in the fetal ASD-exposed mice than in the controls. Histologic examination showed partial vacuolation of seminiferous tubules in immature mice. Moreover, daily sperm production (DSP) was significantly less in the fetal ASD-exposed mice than in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less than the controls at both 5 and 10 weeks. However, both the histologic changes and the DSP decrease were reversed as the mice matured. These findings suggest that ASD exposure affects both the fetal development and the reproduction of male offspring. In the future, it will be necessary to clarify the onset mechanisms of ASD-induced male fetus death and male reproductive disorders.

Guilty as charged: all available evidence implicates complement's role in fetal demise.

PubMed

Girardi, Guillermina

2008-03-01

Appropriate complement inhibition is an absolute requirement for normal pregancy. Uncontrolled complement activation in the maternal-fetal interface leads to fetal death. Here we show that complement activation is a crucial and early mediator of pregnancy loss in two different mouse models of pregnancy loss. Using a mouse model of fetal loss and growth restriction (IUGR) induced by antiphospholipid antibodies (aPL), we examined the role of complement activation in fetal loss and IUGR. We found that C5a-C5aR interaction and neutrophils are key mediators of fetal injury. Treatment with heparin, the standard therapy for pregnant patients with aPL, prevents complement activation and protects mice from pregnancy complications induced by aPL, and anticoagulants that do not inhibit complement do not protect pregnancies. In an antibody-independent mouse model of spontaneous miscarriage and IUGR (CBA/JxDBA/2) we also identified C5a as an essential mediator. Complement activation caused dysregulation of the angiogenic factors required for normal placental development. In CBA/JxDBA/2 mice, we observed inflammatory infiltrates in placentas, functional deficiency of free vascular endothelial growth factor (VEGF), elevated levels of soluble VEGF receptor-1 (sVEGFR-1, also known as sFlt-1; a potent anti-angiogenic molecule), and defective placental development. Inhibition of complement activation blocked the increase in sVEGFR-1 and rescued pregnancies. Our studies in antibody-dependent and antibody-independent models of pregnancy complications identified complement activation as the key mediator of damage and will allow development of new interventions to prevent pregnancy loss and IUGR.

Male germline transmits fetal alcohol epigenetic marks for multiple generations: a review.

PubMed

Sarkar, Dipak K

2016-01-01

Alcohol exposure during fetal and early postnatal development can lead to an increased incidence of later life adult-onset diseases. Examples include central nervous system dysfunction, depression, anxiety, hyperactivity, and an inability to deal with stressful situations, increased infection and cancer. Direct effects of alcohol leading to developmental abnormalities often involve epigenetic modifications of genes that regulate cellular functions. Epigenetic marks carried over from the parents are known to undergo molecular programming events that happen early in embryonic development by a wave of DNA demethylation, which leaves the embryo with a fresh genomic composition. The proopiomelanocortin (Pomc) gene controls neuroendocrine-immune functions and is imprinted by fetal alcohol exposure. Recently, this gene has been shown to be hypermethylated through three generations. Additionally, the alcohol epigenetic marks on the Pomc gene are maintained in the male but not in the female germline during this transgenerational transmission. These data suggest that the male-specific chromosome might be involved in transmitting alcohol epigenetic marks through multiple generations. © 2015 Society for the Study of Addiction.

Diagnosis of fetal syndromes by three- and four-dimensional ultrasound: is there any improvement?

PubMed

Barišić, Lara Spalldi; Stanojević, Milan; Kurjak, Asim; Porović, Selma; Gaber, Ghalia

2017-08-28

With all of our present knowledge, high technology diagnostic equipment, electronic databases and other available supporting resources, detection of fetal syndromes is still a challenge for healthcare providers in prenatal as well as in the postnatal period. Prenatal diagnosis of fetal syndromes is not straightforward, and it is a difficult puzzle that needs to be assembled and solved. Detection of one anomaly should always raise a suspicion of the existence of more anomalies, and can be a trigger to investigate further and raise awareness of possible syndromes. Highly specialized software systems for three- and four-dimensional ultrasound (3D/4D US) enabled detailed depiction of fetal anatomy and assessment of the dynamics of fetal structural and functional development in real time. With recent advances in 3D/4D US technology, antenatal diagnosis of fetal anomalies and syndromes shifted from the 2nd to the 1st trimester of pregnancy. It is questionable what can and should be done after the prenatal diagnosis of fetal syndrome. The 3D and 4D US techniques improved detection accuracy of fetal abnormalities and syndromes from early pregnancy onwards. It is not easy to make prenatal diagnosis of fetal syndromes, so tools which help like online integrated databases are needed to increase diagnostic precision. The aim of this paper is to present the possibilities of different US techniques in the detection of some fetal syndromes prenatally.

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.

Choriodecidual Group B Streptococcal Inoculation Induces Fetal Lung Injury without Intra-Amniotic Infection and Preterm Labor in Macaca nemestrina

PubMed Central

Adams Waldorf, Kristina M.; Gravett, Michael G.; McAdams, Ryan M.; Paolella, Louis J.; Gough, G. Michael; Carl, David J.; Bansal, Aasthaa; Liggitt, H. Denny; Kapur, Raj P.; Reitz, Frederick B.; Rubens, Craig E.

2011-01-01

Background Early events leading to intrauterine infection and fetal lung injury remain poorly defined, but may hold the key to preventing neonatal and adult chronic lung disease. Our objective was to establish a nonhuman primate model of an early stage of chorioamnionitis in order to determine the time course and mechanisms of fetal lung injury in utero. Methodology/Principal Findings Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received one of two treatments: 1) choriodecidual and intra-amniotic saline (n = 5), or 2) choriodecidual inoculation of Group B Streptococcus (GBS) 1×106 colony forming units (n = 5). Cesarean section was performed regardless of labor 4 days after GBS or 7 days after saline infusion to collect fetal and placental tissues. Only two GBS animals developed early labor with no cervical change in the remaining animals. Despite uterine quiescence in most cases, blinded review found histopathological evidence of fetal lung injury in four GBS animals characterized by intra-alveolar neutrophils and interstitial thickening, which was absent in controls. Significant elevations of cytokines in amniotic fluid (TNF-α, IL-8, IL-1β, IL-6) and fetal plasma (IL-8) were detected in GBS animals and correlated with lung injury (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable in amniotic fluid (∼10 samples tested/animal), maternal and fetal blood by culture and polymerase chain reaction. In only two cases was GBS cultured from the inoculation site in low numbers. Chorioamnionitis occurred in two GBS animals with lung injury, but two others with lung injury had normal placental histology. Conclusions/Significance A transient choriodecidual infection can induce cytokine production, which is associated with fetal lung injury without overt infection of amniotic fluid, chorioamnionitis or preterm labor. Fetal lung injury may, thus, occur silently

Fetal Eye Movements on Magnetic Resonance Imaging

PubMed Central

Woitek, Ramona; Kasprian, Gregor; Lindner, Christian; Stuhr, Fritz; Weber, Michael; Schöpf, Veronika; Brugger, Peter C.; Asenbaum, Ulrika; Furtner, Julia; Bettelheim, Dieter; Seidl, Rainer; Prayer, Daniela

2013-01-01

Objectives Eye movements are the physical expression of upper fetal brainstem function. Our aim was to identify and differentiate specific types of fetal eye movement patterns using dynamic MRI sequences. Their occurrence as well as the presence of conjugated eyeball motion and consistently parallel eyeball position was systematically analyzed. Methods Dynamic SSFP sequences were acquired in 72 singleton fetuses (17–40 GW, three age groups [17–23 GW, 24–32 GW, 33–40 GW]). Fetal eye movements were evaluated according to a modified classification originally published by Birnholz (1981): Type 0: no eye movements; Type I: single transient deviations; Type Ia: fast deviation, slower reposition; Type Ib: fast deviation, fast reposition; Type II: single prolonged eye movements; Type III: complex sequences; and Type IV: nystagmoid. Results In 95.8% of fetuses, the evaluation of eye movements was possible using MRI, with a mean acquisition time of 70 seconds. Due to head motion, 4.2% of the fetuses and 20.1% of all dynamic SSFP sequences were excluded. Eye movements were observed in 45 fetuses (65.2%). Significant differences between the age groups were found for Type I (p = 0.03), Type Ia (p = 0.031), and Type IV eye movements (p = 0.033). Consistently parallel bulbs were found in 27.3–45%. Conclusions In human fetuses, different eye movement patterns can be identified and described by MRI in utero. In addition to the originally classified eye movement patterns, a novel subtype has been observed, which apparently characterizes an important step in fetal brainstem development. We evaluated, for the first time, eyeball position in fetuses. Ultimately, the assessment of fetal eye movements by MRI yields the potential to identify early signs of brainstem dysfunction, as encountered in brain malformations such as Chiari II or molar tooth malformations. PMID:24194885

Fetal eye movements on magnetic resonance imaging.

PubMed

Woitek, Ramona; Kasprian, Gregor; Lindner, Christian; Stuhr, Fritz; Weber, Michael; Schöpf, Veronika; Brugger, Peter C; Asenbaum, Ulrika; Furtner, Julia; Bettelheim, Dieter; Seidl, Rainer; Prayer, Daniela

2013-01-01

Eye movements are the physical expression of upper fetal brainstem function. Our aim was to identify and differentiate specific types of fetal eye movement patterns using dynamic MRI sequences. Their occurrence as well as the presence of conjugated eyeball motion and consistently parallel eyeball position was systematically analyzed. Dynamic SSFP sequences were acquired in 72 singleton fetuses (17-40 GW, three age groups [17-23 GW, 24-32 GW, 33-40 GW]). Fetal eye movements were evaluated according to a modified classification originally published by Birnholz (1981): Type 0: no eye movements; Type I: single transient deviations; Type Ia: fast deviation, slower reposition; Type Ib: fast deviation, fast reposition; Type II: single prolonged eye movements; Type III: complex sequences; and Type IV: nystagmoid. In 95.8% of fetuses, the evaluation of eye movements was possible using MRI, with a mean acquisition time of 70 seconds. Due to head motion, 4.2% of the fetuses and 20.1% of all dynamic SSFP sequences were excluded. Eye movements were observed in 45 fetuses (65.2%). Significant differences between the age groups were found for Type I (p = 0.03), Type Ia (p = 0.031), and Type IV eye movements (p = 0.033). Consistently parallel bulbs were found in 27.3-45%. In human fetuses, different eye movement patterns can be identified and described by MRI in utero. In addition to the originally classified eye movement patterns, a novel subtype has been observed, which apparently characterizes an important step in fetal brainstem development. We evaluated, for the first time, eyeball position in fetuses. Ultimately, the assessment of fetal eye movements by MRI yields the potential to identify early signs of brainstem dysfunction, as encountered in brain malformations such as Chiari II or molar tooth malformations.

A Survey of English Sixth Formers' Knowledge of Early Brain Development.

PubMed

Nolan, Mary

2017-10-01

Objectives To ascertain the knowledge of young people aged 16 to 19 of early brain development and their attitudes towards the care of babies and preschool children. Design Cross-sectional, school- and college-based survey including all sixth form students present on the days of data collection. The survey instrument comprised forced-choice questions in four sections: Demographics, Perceptions and Understanding of Early Childhood Development, Parental Behaviors to Support Early Brain development, and Resource Needs and Usage. Setting Two sixth form schools and one sixth form college in three towns of varying affluence in the West Midlands of the United Kingdom. Method The survey was mounted online and completed by 905 students who returned it directly to the researcher. Results Most students knew that tobacco, alcohol, and drugs are hazardous in pregnancy, and many recognized the impact of maternal stress on fetal brain development. Many believed that babies can be "spoiled" and did not appreciate the importance of reading to babies and of the relationship between play and early brain development. A significant minority thought that physical activity and a healthy diet have little impact on young children's development. Respondents said they would turn firstly to their parents for advice on baby care rather than professionals. Conclusion Young people need educating about parenting activities that support the all-round healthy development of infants. The importance of a healthy diet, physical activity, reading, and play should be included in sixth form curricula and antenatal classes. Consideration should be given to educating grandparents because of their influence on new parents.

Fetal liver contains committed NK progenitors, but is not a site for development of CD34+ cells into T cells.

PubMed

Jaleco, A C; Blom, B; Res, P; Weijer, K; Lanier, L L; Phillips, J H; Spits, H

1997-07-15

The presence of T and NK cells in the human fetal liver and the fact that fetal liver hemopoietic progenitor cells develop into T and NK cells suggest a role for the fetal liver compartment in T and NK cell development. In this work, we show that the capacity of fetal liver progenitors to develop into T cells, in a human/mouse fetal thymic organ culture system, is restricted to an immature subset of CD34+ CD38- cells. No T cell-committed precursors are contained within the more differentiated CD34+ CD38+ population. This conclusion is supported by the observations that no TCR-delta gene rearrangements and no pre-TCR-alpha expression can be detected in this population. However, NK cells were derived from CD34+ CD38- and CD34+ CD38+ fetal liver cells cultured in the presence of IL-15, IL-7, and Flt-3 ligand. Eighty to ninety percent of cells arising from the CD34+ CD38+ population expressed the NK cell-associated markers CD56, CD16, CD94, and NKR-P1A. Several subpopulations of NK cell precursors were identified by differential expression of these receptors. Based on the detection of populations with a similar antigenic profile in freshly isolated fetal liver cells, we propose a model of NK cell differentiation. Collectively, our findings suggest that CD34+ cells differentiate into NK cells, but not into mature T cells, in the human fetal liver.

Prediction of fetal compromise in labor.

PubMed

Prior, Tomas; Mullins, Edward; Bennett, Phillip; Kumar, Sailesh

2014-06-01

The majority of intrapartum fetal hypoxia occurs in uncomplicated pregnancies. Current intrapartum monitoring techniques have not resulted in a reduction in the incidence of cerebral palsy in term neonates. We report the development of a composite risk score to allow risk stratification of normal pregnancies before labor. Six hundred one women were recruited to this prospective observational study. All women underwent an ultrasound examination before active labor, during which fetal biometry and fetal Doppler flow resistance indices were measured. A composite risk score, amalgamating data from the umbilical artery, middle cerebral artery, and umbilical vein, was then developed and correlated with intrapartum outcomes. In cases with the highest composite risk scores, the incidence of fetal compromise (the primary outcome) was 80.0% compared with just 15.3% in cases with the lowest risk scores (relative risk 5.2, 95% confidence interval 2.7-10.1). These cases were also at increased risk of cesarean delivery (53.3% compared with 3.4%, P<.001) and of developing a fetal heart rate pattern considered pathologic by National Institute for Health and Clinical Excellence criteria (P=.003). No significant variation in Apgar scores or umbilical artery pH was observed. Intrapartum fetal compromise remains a significant global health issue. The composite risk score reported here can identify fetuses at both high risk and low risk of a subsequent diagnosis of intrapartum fetal compromise. This may enable more judicious use of current intrapartum fetal monitoring techniques, which are hampered by low specificity. II.

IGF2 DNA methylation is a modulator of newborn’s fetal growth and development

PubMed Central

St-Pierre, Julie; Hivert, Marie-France; Perron, Patrice; Poirier, Paul; Guay, Simon-Pierre; Brisson, Diane; Bouchard, Luigi

2012-01-01

The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn’s fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn’s weight variance. No association was observed with maternal diabetic status, glucose concentrations or prenatal maternal body mass index. This is the first study showing that DNA methylation at the IGF2/H19 genes locus may act as a modulator of IGF2 newborn’s fetal growth and development within normal range. IGF2/H19 DNA methylation could represent a cornerstone in linking birth weight and fetal metabolic programming of late onset obesity. PMID:22907587

Fetal exposure to lead during pregnancy and the risk of preterm and early-term deliveries.

PubMed

Cheng, Lu; Zhang, Bin; Huo, Wenqian; Cao, Zhongqiang; Liu, Wenyu; Liao, Jiaqiang; Xia, Wei; Xu, Shunqing; Li, Yuanyuan

2017-08-01

Studies have reported the association between lead exposure during pregnancy and preterm birth. However, findings are still inconsistent. This prospective birth cohort study evaluated the risks of preterm and early-term births and its association with prenatal lead exposure in Hubei, China. A total of 7299 pregnant women were selected from the Healthy Baby Cohort. Maternal urinary lead levels were measured by the Inductively Coupled Plasma Mass Spectrometry. The associations between tertiles of urinary lead levels and the risks of preterm and early-term deliveries were assessed using multiple logistic regression models. The geometric mean of creatinine-adjusted urinary lead concentrations among all participating mothers, preterm birth, and early-term birth were 3.19, 3.68, and 3.17μg/g creatinine, respectively. A significant increase in the risk of preterm births was associated with the highest urinary lead tertile after adjusting for confounders with odds ratio (OR) of 1.96. The association was more pronounced among 25-36 years old mothers with OR of 2.03. Though significant p trends were observed between lead exposure (medium and high tertiles) and the risk of early-term births, their ORs were not significant. Our findings indicate that the risk of preterm birth might increase with higher fetal lead exposure, particularly among women between the age of 25 and 36 years. Copyright © 2017 Elsevier GmbH. All rights reserved.

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.

Allogenic fetal liver cells have a distinct competitive engraftment advantage over adult bone marrow cells when infused into fetal as compared with adult severe combined immunodeficient recipients.

PubMed

Taylor, Patricia A; McElmurry, Ronald T; Lees, Christopher J; Harrison, David E; Blazar, Bruce R

2002-03-01

In utero transplantation (IUT) is becoming a viable option for the treatment of various immune and metabolic disorders diagnosed early in gestation. In this study, donor fetal liver cells had a 10-fold competitive engraftment advantage relative to adult bone marrow in allogeneic fetal severe combined immunodeficient (SCID) recipients compared with adult recipients. In contrast, adult bone marrow cells engrafted slightly better than fetal liver cells in allogeneic adult SCID transplant recipients. By using different ratios of fetal and adult cell mixtures, fetal liver cells repopulated 8.2 times better than adult bone marrow cells in fetal recipients, but only 0.8 times as well in adult recipients. Fetal SCID recipients were more permissive to an allogeneic donor graft than adult recipients. These data indicate that the recipient microenvironment may regulate the engraftment efficiency of a given stem cell source and suggest that the use of cord blood should be tested in clinical IUT.

Periconceptional Folic Acid Supplementation Benefit to Development of Early Sensory-Motor Function through Increase DNA Methylation in Rat Offspring

PubMed Central

Li, Wen; Li, Zhenshu; Li, Shou; Wang, Xinyan; Wilson, John X.; Huang, Guowei

2018-01-01

Periconceptional maternal folate levels may alter DNA methylation patterns and health outcomes in offspring. We hypothesized that maternal folic acid supplementation alters fetal neural development through DNA methylation in the fetal brain. Twenty-eight rats were randomly assigned to four groups: three groups of the female rats were fed folate-normal, folate-deficient or folate-supplemented diets from seven days before mating to delivery. In another group, folic acid supplementation diet short-period group was fed a folate-normal diet, except for 10 days (begin mating) when this group was fed a folate-supplemented diet. After delivery, the diets were changed to folate-normal diet for all four groups. The cliff avoidance and forelimb grip tests were used to assess sensory motor function of rat offspring. The results indicate that maternal folic acid supplementation improved the early development of sensory-motor function in offspring. Maternal folic acid supplementation increased the methylation potential, global DNA methylation (5-mC) and DNA methyltransferase expression and activity in the brains of the offspring. In conclusion, maternal folic acid supplementation increases DNA methylation pattern in offspring brain and improves the early development of sensory-motor function. PMID:29494536

Teaching Students with Developmental Disabilities: Tips from Teens and Young Adults with Fetal Alcohol Spectrum Disorder

ERIC Educational Resources Information Center

Duquette, Cheryll; Stodel, Emma; Fullarton, Stephanie; Hagglund, Karras

2006-01-01

Fetal Alcohol Spectrum Disorder (FASD) is a term that encompasses the various neurodevelopmental disorders experienced by individuals with prenatal alcohol exposure. FASD incorporates the terms Fetal Alcohol Syndrome (FAS), Fetal Alcohol Effects (FAE), and Alcohol-Related Neurodevelopmental Disorder (ARND). Early studies showed that students with…

The Relationship between Autism Spectrum Disorder and Melatonin during Fetal Development.

PubMed

Jin, Yunho; Choi, Jeonghyun; Won, Jinyoung; Hong, Yonggeun

2018-01-18

The aim of this review is to clarify the interrelationship between melatonin and autism spectrum disorder (ASD) during fetal development. ASD refers to a diverse range of neurodevelopmental disorders characterized by social deficits, impaired communication, and stereotyped or repetitive behaviors. Melatonin, which is secreted by the pineal gland, has well-established neuroprotective and circadian entraining effects. During pregnancy, the hormone crosses the placenta into the fetal circulation and transmits photoperiodic information to the fetus allowing the establishment of normal sleep patterns and circadian rhythms that are essential for normal neurodevelopment. Melatonin synthesis is frequently impaired in patients with ASD. The hormone reduces oxidative stress, which is harmful to the central nervous system. Therefore, the neuroprotective and circadian entraining roles of melatonin may reduce the risk of neurodevelopmental disorders such as ASD.

Accelerated fetal growth in early pregnancy and risk of severe large-for-gestational-age and macrosomic infant: a cohort study in a low-risk population.

PubMed

Simic, Marija; Wikström, Anna-Karin; Stephansson, Olof

2017-10-01

Our objective was to examine the association between fetal growth in early pregnancy and risk of severe large-for-gestational-age (LGA) and macrosomia at birth in a low-risk population. Cohort study that included 68 771 women with non-anomalous singleton pregnancies, without history of diabetes or hypertension, based on an electronic database on pregnancies and deliveries in Stockholm-Gotland Region, Sweden, 2008-2014. We performed multivariable logistic regression to estimate the association between accelerated fetal growth occurring in the first through early second trimester as measured by ultrasound and LGA and macrosomia at birth. Restricted analyses were performed in the groups without gestational diabetes and with normal body mass index (18.5-24.9 kg/m 2 ). When adjusting for confounders, the odds of having a severely LGA or macrosomic infant were elevated in mothers with fetuses that were at least 7 days larger than expected as compared with mothers without age discrepancy at the second-trimester scan (adjusted odds ratio 1.80; 95% CI 1.23-2.64 and adjusted odds ratio 2.15; 95% CI 1.55-2.98, respectively). Additionally, mothers without gestational diabetes and mothers with normal weight had an elevated risk of having a severely LGA or macrosomic infant when the age discrepancy by second-trimester ultrasound was at least 7 days. In a low-risk population, ultrasound-estimated accelerated fetal growth in early pregnancy was associated with an increased risk of having a severely LGA or macrosomic infant. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Fetal Growth Restriction Is Associated With Malaria in Pregnancy: A Prospective Longitudinal Study in Benin.

PubMed

Briand, Valérie; Saal, Jessica; Ghafari, Caline; Huynh, Bich-Tram; Fievet, Nadine; Schmiegelow, Christentze; Massougbodji, Achille; Deloron, Philippe; Zeitlin, Jennifer; Cot, Michel

2016-08-01

Few studies have evaluated the effect of malaria on intrauterine growth restriction on the basis of the fetal growth rate, rather than just the small-for-gestational age z score. Here, we assessed the impact of malaria on IUGR, using data from a longitudinal, ultrasonography-based follow-up study of Beninese women. A total of 1016 women were followed up from gestational week 17 to delivery. Malaria was detected every month. Women underwent ultrasonography 4 times for gestational age determination and fetal biometry. We assessed the effect of malaria on birth weight-for-gestational age z score (n = 735 women) and fetal growth velocity (n = 664), defined as a change in fetal weight z score over time. Malaria was detected in 43% of women. Fetal growth velocity was negative overall, decreasing further at the end of the third trimester. Women with ≥2 malarial parasite infections tended to have lower z scores than uninfected women. Malaria both in early and late pregnancy was associated with a reduction in fetal growth velocity, which occurred either immediately or with a delay after infection. We confirmed the deleterious effect of malaria during both early and late pregnancy on fetal growth. This stresses the importance of starting preventive measures against malaria as early as possible during pregnancy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Evaluation of early fetal loss induced by gavage with eastern tent caterpillars in pregnant mares.

PubMed

Bernard, William V; LeBlanc, Michelle M; Webb, Bruce A; Stromberg, Arnold J

2004-09-01

To determine whether gavage of pregnant mares (housed without access to pasture) with starved eastern tent caterpillars (ETCs) or their excreta is associated with early fetal loss (EFL), panophthalmitis, or pericarditis. Randomized clinical trial. 15 mares. 15 mares with fetuses from 40 to 80 days of gestation (dGa) were randomly assigned to 1 of 3 groups and received 2.5 g of ETC excreta, 50 g of starved ETCs, or 500 mL of water, respectively, once daily for 10 days. Mares were housed in box stalls, walked twice daily, and not allowed access to pasture for 12 days before or during the 21-day trial. 4 of 5 mares gavaged with starved ETCs (group 2) aborted on trial days 8 (2 mares), 10, and 13. No control mares or mares that received excreta aborted. Differences between the ETC group and other groups were significant. Abortion occurred on 49, 64, 70, and 96 dGa. Allantoic fluids became hyperechoic the day before or the day of fetal death. Alpha streptococci were recovered from 1 fetus and Serratia marcescens from 3 fetuses. Neither panophthalmitis nor pericarditis was seen. The abortifacient component of the ETCs was not elucidated. These findings suggest that mares with fetuses from 40 to 120 days of gestation should not be exposed to ETCs because they may induce abortion.

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

Development of multiscale complexity and multifractality of fetal heart rate variability.

PubMed

Gierałtowski, Jan; Hoyer, Dirk; Tetschke, Florian; Nowack, Samuel; Schneider, Uwe; Zebrowski, Jan

2013-11-01

During fetal development a complex system grows and coordination over multiple time scales is formed towards an integrated behavior of the organism. Since essential cardiovascular and associated coordination is mediated by the autonomic nervous system (ANS) and the ANS activity is reflected in recordable heart rate patterns, multiscale heart rate analysis is a tool predestined for the diagnosis of prenatal maturation. The analyses over multiple time scales requires sufficiently long data sets while the recordings of fetal heart rate as well as the behavioral states studied are themselves short. Care must be taken that the analysis methods used are appropriate for short data lengths. We investigated multiscale entropy and multifractal scaling exponents from 30 minute recordings of 27 normal fetuses, aged between 23 and 38 weeks of gestational age (WGA) during the quiet state. In multiscale entropy, we found complexity lower than that of non-correlated white noise over all 20 coarse graining time scales investigated. Significant maturation age related complexity increase was strongest expressed at scale 2, both using sample entropy and generalized mutual information as complexity estimates. Multiscale multifractal analysis (MMA) in which the Hurst surface h(q,s) is calculated, where q is the multifractal parameter and s is the scale, was applied to the fetal heart rate data. MMA is a method derived from detrended fluctuation analysis (DFA). We modified the base algorithm of MMA to be applicable for short time series analysis using overlapping data windows and a reduction of the scale range. We looked for such q and s for which the Hurst exponent h(q,s) is most correlated with gestational age. We used this value of the Hurst exponent to predict the gestational age based only on fetal heart rate variability properties. Comparison with the true age of the fetus gave satisfying results (error 2.17±3.29 weeks; p<0.001; R(2)=0.52). In addition, we found that the normally

Injurious effects of curcumin on maturation of mouse oocytes, fertilization and fetal development via apoptosis.

PubMed

Chen, Chia-Chi; Chan, Wen-Hsiung

2012-01-01

Curcumin, a common dietary pigment and spice, is a hydrophobic polyphenol derived from the rhizome of the herb Curcuma longa. Previously, we reported a cytotoxic effect of curcumin on mouse embryonic stem cells and blastocysts and its association with defects in subsequent development. In the present study, we further investigated the effects of curcumin on oocyte maturation and subsequent pre- and post-implantation development, both in vitro and in vivo. Notably, curcumin induced a significant reduction in the rate of oocyte maturation, fertilization, and in vitro embryonic development. Treatment of oocytes with curcumin during in vitro maturation (IVM) led to increased resorption of postimplantation embryos and decreased fetal weight. Experiments with an in vivo mouse model disclosed that consumption of drinking water containing 40 μM curcumin led to decreased oocyte maturation and in vitro fertilization as well as early embryonic developmental injury. Finally, pretreatment with a caspase-3-specific inhibitor effectively prevented curcumin-triggered injury effects, suggesting that embryo impairment by curcumin occurs mainly via a caspase-dependent apoptotic process.

Development of a piezopolymer pressure sensor for a portable fetal heart rate monitor

NASA Technical Reports Server (NTRS)

Zuckerwar, A. J.; Pretlow, R. A.; Stoughton, J. W.; Baker, D. A.

1993-01-01

A piezopolymer pressure sensor has been developed for service in a portable fetal heart rate monitor, which will permit an expectant mother to perform the fetal nonstress test, a standard predelivery test, in her home. Several sensors are mounted in an array on a belt worn by the mother. The sensor design conforms to the distinctive features of the fetal heart tone, namely, the acoustic signature, frequency spectrum, signal amplitude, and localization. The components of a sensor serve to fulfill five functions: signal detection, acceleration cancellation, acoustical isolation, electrical shielding, and electrical isolation of the mother. A theoretical analysis of the sensor response yields a numerical value for the sensor sensitivity, which is compared to experiment in an in vitro sensor calibration. Finally, an in vivo test on patients within the last six weeks of term reveals that nonstress test recordings from the acoustic monitor compare well with those obtained from conventional ultrasound.

Periconceptional intake of vitamins and fetal death: a cohort study on multivitamins and folate.

PubMed

Nohr, Ellen A; Olsen, Jorn; Bech, Bodil H; Bodnar, Lisa M; Olsen, Sjurdur F; Catov, Janet M

2014-02-01

Women planning to conceive are often advised to take multivitamins. Whether this affects the survival of the fetus is not known. We used data from 35 914 women in the Danish National Birth Cohort who at recruitment had reported the number of weeks of supplement use during a 12-week periconceptional period. A telephone interview provided information about maternal characteristics and data on fetal death came from registers. The associations between periconceptional multivitamin or folate-only use and early (<20 weeks) and late (≥20 weeks) fetal death were estimated by hazard ratios (HR) with 95% confidence intervals (CI). Follow-up started at 8 completed weeks of gestation, and comparisons were made with no supplement use at any time during the periconceptional period. Any multivitamin use was associated with a small increased crude risk of fetal death [HR 1.12 (1.01-1.25)], which was restricted to early losses [HR 1.18 (1.05-1.33)] compared with late losses [HR 0.82 (0.62-1.10)]. Adjustment for maternal factors increased this excess risk further. Whereas regular users of multivitamins (4-6 weeks of 6) before conception had more early losses [HR 1.29 (1.12-1.48)], a decreased risk of late losses was indicated when use started after conception [HR 0.65 (0.39-1.09)]. Folate-only use was not associated with fetal death. Multivitamin use was associated with a modest increased risk of early fetal death. For late fetal death, regular supplement use after conception may decrease risk, but numbers were small. Further studies on preconceptional multivitamin use are needed to guide public health recommendations.

Impact of Fetal-Neonatal Iron Deficiency on Recognition Memory at 2 Months of Age.

PubMed

Geng, Fengji; Mai, Xiaoqin; Zhan, Jianying; Xu, Lin; Zhao, Zhengyan; Georgieff, Michael; Shao, Jie; Lozoff, Betsy

2015-12-01

To assess the effects of fetal-neonatal iron deficiency on recognition memory in early infancy. Perinatal iron deficiency delays or disrupts hippocampal development in animal models and thus may impair related neural functions in human infants, such as recognition memory. Event-related potentials were used in an auditory recognition memory task to compare 2-month-old Chinese infants with iron sufficiency or deficiency at birth. Fetal-neonatal iron deficiency was defined 2 ways: high zinc protoporphyrin/heme ratio (ZPP/H > 118 μmol/mol) or low serum ferritin (<75 μg/L) in cord blood. Late slow wave was used to measure infant recognition of mother's voice. Event related potentials patterns differed significantly for fetal-neonatal iron deficiency as defined by high cord ZPP/H but not low ferritin. Comparing 35 infants with iron deficiency (ZPP/H > 118 μmol/mol) to 92 with lower ZPP/H (iron-sufficient), only infants with iron sufficiency showed larger late slow wave amplitude for stranger's voice than mother's voice in frontal-central and parietal-occipital locations, indicating the recognition of mother's voice. Infants with iron sufficiency showed electrophysiological evidence of recognizing their mother's voice, whereas infants with fetal-neonatal iron deficiency did not. Their poorer auditory recognition memory at 2 months of age is consistent with effects of fetal-neonatal iron deficiency on the developing hippocampus. Copyright © 2015 Elsevier Inc. All rights reserved.

Expression of intracellular interferon-alpha confers antiviral properties in transfected bovine fetal fibroblasts and does not affect the full development of SCNT embryos.

PubMed

Yu, Dawei; Zhang, Shoufeng; Du, Weihua; Zhang, Jinxia; Fan, Zongxing; Hao, Haisheng; Liu, Yan; Zhao, Xueming; Qin, Tong; Zhu, Huabin

2014-01-01

Foot-and-mouth disease, one of the most significant diseases of dairy herds, has substantial effects on farm economics, and currently, disease control measures are limited. In this study, we constructed a vector with a human interferon-α (hIFN-α) (without secretory signal sequence) gene cassette containing the immediate early promoter of human cytomegalovirus. Stably transfected bovine fetal fibroblasts were obtained by G418 selection, and hIFN-α transgenic embryos were produced by somatic cell nuclear transfer (SCNT). Forty-six transgenic embryos were transplanted into surrogate cows, and five cows (10.9%) became pregnant. Two male cloned calves were born. Expression of hIFN-α was detected in transfected bovine fetal fibroblasts, transgenic SCNT embryos, and different tissues from a transgenic SCNT calf at two days old. In transfected bovine fetal fibroblasts, expression of intracellular IFN-α induced resistance to vesicular stomatitis virus infection, increased apoptosis, and induced the expression of double-stranded RNA-activated protein kinase gene (PKR) and the 2'-5'-oligoadenylate synthetase gene (2'-5' OAS), which are IFN-inducible genes with antiviral activity. Analysis by qRT-PCR showed that the mRNA expression levels of PKR, 2'-5' OAS, and P53 were significantly increased in wild-type bovine fetal fibroblasts stimulated with extracellular recombinant human IFN-α-2b, showing that intracellular IFN-α induces biological functions similar to extracellular IFN-α. In conclusion, expression of intracellular hIFN-α conferred antiviral properties in transfected bovine fetal fibroblasts and did not significantly affect the full development of SCNT embryos. Thus, IFN-α transgenic technology may provide a revolutionary way to achieve elite breeding of livestock.

Fetal heart rate monitoring.

PubMed

Nageotte, Michael P

2015-06-01

Electronic fetal heart rate monitoring is a widely utilized means of assessment of fetal status during labor. Whereas little evidence exists regarding efficacy, this modality continues to be used extensively in every modern labor and delivery unit in developed countries. It is of importance that all providers of health care to the woman in labor and her newborn have a clear understanding of the basic pathophysiology of fetal heart rate monitoring and an appreciation for labor course and concerns as they arise in order to optimize outcomes and patient safety. Copyright © 2015 Elsevier Ltd. All rights reserved.

Injurious effects of emodin on maturation of mouse oocytes, fertilization and fetal development via apoptosis.

PubMed

Chang, Mei-Hui; Chang, Shao-Chung; Chan, Wen-Hsiung

2012-10-29

Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a major constituent of rhubarb, has a wide range of therapeutic applications. Previous studies have established that emodin induces apoptosis in the inner cell mass and trophectoderm of mouse blastocysts and leads to decreased embryonic development and viability, indicating a role as an injury risk factor for normal embryonic development. However, the mechanisms underlying its hazardous effects have yet to be characterized. In the current study, we further investigated the effects of emodin on oocyte maturation and subsequent pre- and post-implantation development, both in vitro and in vivo. Notably, emodin induced a significant reduction in the rates of oocyte maturation, fertilization, and in vitro embryonic development. Treatment of oocytes with emodin during in vitro maturation (IVM) led to increased resorption of postimplantation embryos and decreased fetal weight. Experiments using an in vivo mouse model disclosed that consumption of drinking water containing 20-40 μM emodin led to decreased oocyte maturation and in vitro fertilization, as well as early embryonic developmental injury. Notably, pretreatment with a caspase-3-specific inhibitor effectively prevented emodin-triggered injury effects, suggesting that impairment of embryo development occurs via a caspase-dependent apoptotic process.

Association between the high soluble fms-like tyrosine kinase-1 to placental growth factor ratio and adverse outcomes in asymptomatic women with early-onset fetal growth restriction.

PubMed

Shinohara, Satoshi; Uchida, Yuzo; Kasai, Mayuko; Sunami, Rei

2017-08-01

To assess whether the high soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is associated with adverse outcomes (e.g., HELLP syndrome [hemolysis, elevated liver enzymes, and low platelets], severe hypertension uncontrolled by medication, non-reassuring fetal status, placental abruption, pulmonary edema, growth arrest, maternal death, or fetal death) and a shorter duration to delivery in early-onset fetal growth restriction (FGR). Thirty-four women with FGR diagnosed at <34.0 weeks were recruited. Serum angiogenic marker levels were estimated within 6 hours of a diagnosis of FGR. A receiver operating characteristic curve was used to determine the threshold of the sFlt-1/PlGF ratio to predict adverse outcomes. We used multivariable logistic regression analysis to examine the association between the sFlt-1/PlGF ratio and adverse outcomes. Finally, we used Kaplan-Meier analysis and the log-rank test to assess the probability of delay in delivery. Women who developed adverse outcomes within a week had a significantly higher sFlt-1/PlGF ratio than did those who did not develop complications. A cutoff value of 86.2 for the sFlt-1/PlGF ratio predicted adverse outcomes, with a sensitivity and specificity of 77.8% and 80.0%, respectively. Moreover, 58.4% of women with an sFlt-1/PlGF ratio ≥86.2 versus 9.1% of those with an sFlt-1/PlGF ratio <86.2 delivered within a week of presentation (p < 0.001). In multivariate analyses, an sFlt-1/PlGF ratio ≥86.2 (adjusted odds ratio 9.52; 95% confidence interval, 1.25-72.8) was associated with adverse maternal and neonatal outcomes. A high sFlt-1/PlGF ratio was associated with adverse outcomes and a shorter duration to delivery in early-onset FGR.

Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders

DTIC Science & Technology

2014-07-01

Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders PRINCIPAL INVESTIGATOR: Alexandre Bonnin, PhD CONTRACTING...Fetal Programming of Neurodevelopmental Disorders 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Alexandre Bonnin, PhD; Betty...metabolism by maternal inflammation during early gestation constitutes a new molecular pathway for the fetal programming of neurodevelopmental

Type I interferons instigate fetal demise after Zika virus infection.

PubMed

Yockey, Laura J; Jurado, Kellie A; Arora, Nitin; Millet, Alon; Rakib, Tasfia; Milano, Kristin M; Hastings, Andrew K; Fikrig, Erol; Kong, Yong; Horvath, Tamas L; Weatherbee, Scott; Kliman, Harvey J; Coyne, Carolyn B; Iwasaki, Akiko

2018-01-05

Zika virus (ZIKV) infection during pregnancy is associated with adverse fetal outcomes, including microcephaly, growth restriction, and fetal demise. Type I interferons (IFNs) are essential for host resistance against ZIKV, and IFN-α/β receptor (IFNAR)-deficient mice are highly susceptible to ZIKV infection. Severe fetal growth restriction with placental damage and fetal resorption is observed after ZIKV infection of type I IFN receptor knockout ( Ifnar1 -/- ) dams mated with wild-type sires, resulting in fetuses with functional type I IFN signaling. The role of type I IFNs in limiting or mediating ZIKV disease within this congenital infection model remains unknown. In this study, we challenged Ifnar1 -/- dams mated with Ifnar1 +/- sires with ZIKV. This breeding scheme enabled us to examine pregnant dams that carry a mixture of fetuses that express ( Ifnar1 +/- ) or do not express IFNAR ( Ifnar1 -/- ) within the same uterus. Virus replicated to a higher titer in the placenta of Ifnar1 -/- than within the Ifnar1 +/- concepti. Yet, rather unexpectedly, we found that only Ifnar1 +/- fetuses were resorbed after ZIKV infection during early pregnancy, whereas their Ifnar1 -/- littermates continue to develop. Analyses of the fetus and placenta revealed that, after ZIKV infection, IFNAR signaling in the conceptus inhibits development of the placental labyrinth, resulting in abnormal architecture of the maternal-fetal barrier. Exposure of midgestation human chorionic villous explants to type I IFN, but not type III IFNs, altered placental morphology and induced cytoskeletal rearrangements within the villous core. Our results implicate type I IFNs as a possible mediator of pregnancy complications, including spontaneous abortions and growth restriction, in the context of congenital viral infections. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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

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

Fetal Nicotine Exposure Increases Preference for Nicotine Odor in Early Postnatal and Adolescent, but Not Adult, Rats

PubMed Central

Mantella, Nicole M.; Kent, Paul F.; Youngentob, Steven L.

2013-01-01

Human studies demonstrate a four-fold increased possibility of smoking in the children of mothers who smoked during pregnancy. Nicotine is the active addictive component in tobacco-related products, crossing the placenta and contaminating the amniotic fluid. It is known that chemosensory experience in the womb can influence postnatal odor-guided preference behaviors for an exposure stimulus. By means of behavioral and neurophysiologic approaches, we examined whether fetal nicotine exposure, using mini-osmotic pumps, altered the response to nicotine odor in early postnatal (P17), adolescent (P35) and adult (P90) progeny. Compared with controls, fetal exposed rats displayed an altered innate response to nicotine odor that was evident at P17, declined in magnitude by P35 and was absent at P90 - these effects were specific to nicotine odor. The behavioral effect in P17 rats occurred in conjunction with a tuned olfactory mucosal response to nicotine odor along with an untoward consequence on the epithelial response to other stimuli – these P17 neural effects were absent in P35 and P90 animals. The absence of an altered neural effect at P35 suggests that central mechanisms, such as nicotine-induced modifications of the olfactory bulb, bring about the altered behavioral response to nicotine odor. Together, these findings provide insights into how fetal nicotine exposure influences the behavioral preference and responsiveness to the drug later in life. Moreover, they add to a growing literature demonstrating chemosensory mechanisms by which patterns of maternal drug use can be conveyed to offspring, thereby enhancing postnatal vulnerability for subsequent use and abuse. PMID:24358374

Development of an implantable synthetic membrane for the treatment of preterm premature rupture of fetal membranes.

PubMed

Roman, Sabiniano; Bullock, Anthony J; Anumba, Dilly O; MacNeil, Sheila

2016-02-01

Preterm premature rupture of fetal membranes is a very common condition leading to premature labour of a non viable fetus. Significant morbidities may occur when preterm premature rupture of fetal membranes management is attempted to prolong the pregnancy for fetal maturation. Reducing the rate of loss of amniotic fluid and providing a barrier to bacterial entry may allow the pregnancy to continue to term, avoiding complications. Our aim is to develop a synthetic biocompatible membrane to form a distensible barrier for cervical closure which acts to reduce fluid loss and provide a surface for epithelial ingrowth to help repair the damaged membranes. Therefore, a bilayer membrane was developed using an electrospinning technique of combining two FDA-approved polymers, poly-L-lactic acid (PLA) and polyurethane (Z3) polymer. This was compared to a plain electrospun Z3 membrane. The physical and mechanical properties were assessed using scanning electron microscope images and a BOSE tensiometer, respectively, and compared to native fetal membranes. The performance of the membranes in preventing fluid loss was assessed by measuring their ability to support a column of water. Finally the ability of the membranes to support cell ingrowth was assessed by culturing adipose-derived stem cells on the membranes for two weeks and assessing metabolic activity after 7 and 14 days. The physical properties of the bilayer were similar to that of the native fetal membranes and it was resistant to fluid penetration. This bilayer membrane presented mechanical properties close to those for fetal membranes and showed elastic distention, which may be crucial for progress of the pregnancy. The membrane was also able to retain surgical sutures. In addition, it also supported the attachment and growth of adipose-derived stem cells for two weeks. In conclusion, this membrane may prove a useful approach in the treatment of preterm premature rupture of fetal membranes and now merits further

The Gini coefficient: a methodological pilot study to assess fetal brain development employing postmortem diffusion MRI.

PubMed

Viehweger, Adrian; Riffert, Till; Dhital, Bibek; Knösche, Thomas R; Anwander, Alfred; Stepan, Holger; Sorge, Ina; Hirsch, Wolfgang

2014-10-01

Diffusion-weighted imaging (DWI) is important in the assessment of fetal brain development. However, it is clinically challenging and time-consuming to prepare neuromorphological examinations to assess real brain age and to detect abnormalities. To demonstrate that the Gini coefficient can be a simple, intuitive parameter for modelling fetal brain development. Postmortem fetal specimens(n = 28) were evaluated by diffusion-weighted imaging (DWI) on a 3-T MRI scanner using 60 directions, 0.7-mm isotropic voxels and b-values of 0, 150, 1,600 s/mm(2). Constrained spherical deconvolution (CSD) was used as the local diffusion model. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and complexity (CX) maps were generated. CX was defined as a novel diffusion metric. On the basis of those three parameters, the Gini coefficient was calculated. Study of fetal brain development in postmortem specimens was feasible using DWI. The Gini coefficient could be calculated for the combination of the three diffusion parameters. This multidimensional Gini coefficient correlated well with age (Adjusted R(2) = 0.59) between the ages of 17 and 26 gestational weeks. We propose a new method that uses an economics concept, the Gini coefficient, to describe the whole brain with one simple and intuitive measure, which can be used to assess the brain's developmental state.

Human Fetal Behavior: 100 Years of Study.

ERIC Educational Resources Information Center

Kisilevsky, B. S.; Low, J. A.

1998-01-01

Reviews literature on human fetal behavior. Includes descriptions of coupling of body movements and fetal heart rate and behavior maturation from conception to term. Discusses use of stimulus-induced behavior to examine sensory and cognitive development, and spontaneous and stimulus-induced behavior to assess fetal well-being. Notes research focus…

The effect of fetal sex on customized fetal growth charts.

PubMed

Rizzo, Giuseppe; Prefumo, Federico; Ferrazzi, Enrico; Zanardini, Cristina; Di Martino, Daniela; Boito, Simona; Aiello, Elisa; Ghi, Tullio

2016-12-01

To evaluate the effect of fetal sex on singleton pregnancy growth charts customized for parental characteristics, race, and parity Methods: In a multicentric cross-sectional study, 8070 ultrasonographic examinations from low-risk singleton pregnancies between 16 and 40 weeks of gestation were considered. The fetal measurements obtained were biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). Quantile regression was used to examine the impact of fetal sex across the biometric percentiles of the fetal measurements considered together with parents' height, weight, parity, and race. Fetal gender resulted to be a significant covariate for BDP, HC, and AC with higher values for male fetuses (p ≤ 0.0009). Minimal differences were found among sexes for FL. Parity, maternal race, paternal height and maternal height, and weight resulted significantly related to the fetal biometric parameters considered independently from fetal gender. In this study, we constructed customized biometric growth charts for fetal sex, parental, and obstetrical characteristics using quantile regression. The use of gender-specific charts offers the advantage to define individualized normal ranges of fetal biometric parameters at each specific centile. This approach may improve the antenatal identification of abnormal fetal growth.

Periconceptional intake of vitamins and fetal death: a cohort study on multivitamins and folate

PubMed Central

Nohr, Ellen A; Olsen, Jorn; Bech, Bodil H; Bodnar, Lisa M; Olsen, Sjurdur F; Catov, Janet M

2014-01-01

Background Women planning to conceive are often advised to take multivitamins. Whether this affects the survival of the fetus is not known. Methods We used data from 35 914 women in the Danish National Birth Cohort who at recruitment had reported the number of weeks of supplement use during a 12-week periconceptional period. A telephone interview provided information about maternal characteristics and data on fetal death came from registers. The associations between periconceptional multivitamin or folate-only use and early (<20 weeks) and late (≥20 weeks) fetal death were estimated by hazard ratios (HR) with 95% confidence intervals (CI). Follow-up started at 8 completed weeks of gestation, and comparisons were made with no supplement use at any time during the periconceptional period. Results Any multivitamin use was associated with a small increased crude risk of fetal death [HR 1.12 (1.01–1.25)], which was restricted to early losses [HR 1.18 (1.05–1.33)] compared with late losses [HR 0.82 (0.62–1.10)]. Adjustment for maternal factors increased this excess risk further. Whereas regular users of multivitamins (4–6 weeks of 6) before conception had more early losses [HR 1.29 (1.12–1.48)], a decreased risk of late losses was indicated when use started after conception [HR 0.65 (0.39–1.09)]. Folate-only use was not associated with fetal death. Conclusions Multivitamin use was associated with a modest increased risk of early fetal death. For late fetal death, regular supplement use after conception may decrease risk, but numbers were small. Further studies on preconceptional multivitamin use are needed to guide public health recommendations. PMID:24453235

Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

PubMed

Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

2016-03-15

Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. Copyright © 2016 by The American Association of Immunologists, Inc.

Pleiotrophin regulates lung epithelial cell proliferation and differentiation during fetal lung development via beta-catenin and Dlk1.

PubMed

Weng, Tingting; Gao, Li; Bhaskaran, Manoj; Guo, Yujie; Gou, Deming; Narayanaperumal, Jeyaparthasarathy; Chintagari, Narendranath Reddy; Zhang, Kexiong; Liu, Lin

2009-10-09

The role of pleiotrophin in fetal lung development was investigated. We found that pleiotrophin and its receptor, protein-tyrosine phosphatase receptor beta/zeta, were highly expressed in mesenchymal and epithelial cells of the fetal lungs, respectively. Using isolated fetal alveolar epithelial type II cells, we demonstrated that pleiotrophin promoted fetal type II cell proliferation and arrested type II cell trans-differentiation into alveolar epithelial type I cells. Pleiotrophin also increased wound healing of injured type II cell monolayer. Knockdown of pleiotrophin influenced lung branching morphogenesis in a fetal lung organ culture model. Pleiotrophin increased the tyrosine phosphorylation of beta-catenin, promoted beta-catenin translocation into the nucleus, and activated T cell factor/lymphoid enhancer factor transcription factors. Dlk1, a membrane ligand that initiates the Notch signaling pathway, was identified as a downstream target of the pleiotrophin/beta-catenin pathway by endogenous dlk1 expression, promoter assay, and chromatin immunoprecipitation. These results provide evidence that pleiotrophin regulates fetal type II cell proliferation and differentiation via integration of multiple signaling pathways including pleiotrophin, beta-catenin, and Notch pathways.

Fetal, neonatal, infant, and child international growth standards: an unprecedented opportunity for an integrated approach to assess growth and development.

PubMed

Garza, Cutberto

2015-07-01

The recent publication of fetal growth and gestational age-specific growth standards by the International Fetal and Newborn Growth Consortium for the 21st Century Project and the previous publication by the WHO of infant and young child growth standards based on the WHO Multicentre Growth Reference Study enable evaluations of growth from ∼9 wk gestation to 5 y. The most important features of these projects are the prescriptive approach used for subject selection and the rigorous testing of the assertion that growth is very similar among geographically and ethnically diverse nonisolated populations when health, nutrition, and other care needs are met and the environment imposes minimal constraints on growth. Both studies documented that with adequate controls, the principal source of variability in growth during gestation and early childhood resides among individuals. Study sites contributed much less to observed variability. The agreement between anthropometric measurements common to both studies also is noteworthy. Jointly, these studies provide for the first time, to my knowledge, a conceptually consistent basis for worldwide and localized assessments and comparisons of growth performance in early life. This is an important contribution to improving the health care of children across key periods of growth and development, especially given the appropriate interest in pursuing "optimal" health in the "first 1000 d," i.e., the period covering fertilization/implantation, gestation, and postnatal life to 2 y of age. © 2015 American Society for Nutrition.

Angiogenin Expression during Early Human Placental Development; Association with Blood Vessel Formation

PubMed Central

Pavlov, Nadine; Guibourdenche, Jean; Degrelle, Séverine A.; Evain-Brion, Danièle

2014-01-01

The placenta is a transient organ essential for fetal development. During human placental development, chorionic villi grow in coordination with a large capillary network resulting from both vasculogenesis and angiogenesis. Angiogenin is one of the most potent inducers of neovascularisation in experimental models in vivo. We and others have previously mapped angiogenin expression in the human term placenta. Here, we explored angiogenin involvement in early human placental development. We studied, angiogenin expression by in situ hybridisation and/or by RT-PCR in tissues and primary cultured trophoblastic cells and angiogenin cellular distribution by coimmunolabelling with cell markers: CD31 (PECAM-1), vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGF-R2), Tie-2, von Willebrand factor, CD34, erythropoeitin receptor (Epo-R), alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Extravillous and villous cytotrophoblasts, isolated and differentiated in vitro, expressed and secreted angiogenin. Angiogenin was detected in villous trophoblastic layers, and structured and nascent fetal vessels. In decidua, it was expressed by glandular epithelial cells, vascular cells and macrophages. The observed pattern of angiogenin expression is compatible with a role in blood vessel formation and in cross-talk between trophoblasts and endothelial cells. In view of angiogenin properties, we suggest that angiogenin may participate in placental vasculogenesis and organogenesis. PMID:25093183

[Fetal neurosonography using 3-dimensional multiplanar sonography].

PubMed

Chaoui, R; Heling, K S; Kainer, F; Karl, K

2012-04-01

This review focuses on the examination of the fetal brain, using three-dimensional (3D) ultrasound and the multiplanar rendering mode (MPR). The routine examination of the brain is achieved with axial planes but a dedicated fetal neurosonogram requires additional coronal and sagittal views, in order to provide a complete view of the different brain structures. Because these planes are difficult to obtain under many conditions, the present paper shows how 3D MPR allows one to obtain 1 or multiple reconstructed images from a digital volume. The display can be either as orthogonal planes, tomographic planes with parallel slices or as one single plane of the region of interest, which can be selected by the examiner. This approach allows easily the demonstration of the corpus callosum, the cerebellar vermis, the three-horn view, the foetal hippocampus and other regions. In addition, early neurosonography of the developing brain from the 7th week of pregnancy onwards can be achieved. © Georg Thieme Verlag KG Stuttgart · New York.

Autoradiographic localization of specific (/sup 3/H)dexamethasone binding in fetal lung

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

Beer, D.G.; Butley, M.S.; Cunha, G.R.

1984-10-01

The cellular and subcellular localization of specific (/sup 3/H)dexamethasone binding was examined in fetal mouse lung at various stages of development and in human fetal lung at 8 weeks of gestation using a rapid in vitro steroid incubation technique followed by thaw-mount autoradiography. Competition studies with unlabeled steroids demonstrate the specificity of (/sup 3/H)dexamethasone labeling, and indicate that fetal lung mesenchyme is a primary glucocorticoid target during lung development. Autoradiographs of (/sup 3/H)dexamethasone binding in lung tissue at early stages of development demonstrate that the mesenchyme directly adjacent to the more proximal portions of the bronchiolar network is heavily labeled.more » In contrast, the epithelium which will later differentiate into bronchi and bronchioles, is relatively unlabeled. Distal portions of the growing epithelium, destined to become alveolar ducts and alveoli, do show nuclear localization of (/sup 3/H)dexamethasone. In addition, by utilizing a technique which allows the simultaneous examination of extracellular matrix components and (/sup 3/H)dexamethasone binding, a relationship is observed between extensive mesenchymal (/sup 3/H)dexamethasone binding and extensive extracellular matrix accumulation. Since glucocorticoids stimulate the synthesis of many extracellular matrix components, these results suggest a role for these hormones in affecting mesenchymal-epithelial interactions during lung morphogenesis.« less

Morphologic analysis of artifacts in human fetal eyes confounding histopathologic investigations.

PubMed

Herwig, Martina C; Müller, Annette M; Holz, Frank G; Loeffler, Karin U

2011-04-25

Human fetal eyes are an excellent source for studies of the normal ocular development and for examining early ocular changes associated with various syndromes in the context of a pediatric pathologic or prenatal sonographic diagnosis. However, artifacts caused by different factors often render an exact interpretation difficult. In this study, the frequency and extent of artifacts in human fetal eyes were investigated with the aim of distinguishing more precisely these artifacts from real findings, allowing also for a more diligent forensic interpretation. The cohort included 341 fetal eyes, ranging in age from 8 to 38 weeks of gestation, that were investigated macroscopically and by light microscopy. In most specimens, artifacts such as pigment spillage and autolytic changes of the retina were noted. Nearly all specimens showed changes of the lens with remarkable similarities to cataractous lenses in adult eyes. Structural ocular changes associated with systemic syndromes were also observed and in most instances could be distinguished from artifacts. Morphologic changes in fetal eyes should be classified in artifacts caused by way of abortion, mechanical effects from the removal of the eyes, delayed fixation with autolysis, and the fixative itself and should be distinguished from genuine structural abnormalities associated with ocular or systemic disease. This classification can be fairly difficult and requires experience. In addition, lens artifacts are often misleading, and the diagnosis of a fetal cataract should not be made based on histopathologic examination alone.

Epigenetic regulation of fetal bone development and placental transfer of nutrients: progress for osteoporosis.

PubMed

Bocheva, Georgeta; Boyadjieva, Nadka

2011-12-01

Osteoporosis is a common age-related disorder and causes acute and long-term disability and economic cost. Many factors influence the accumulation of bone minerals, including heredity, diet, physical activity, gender, endocrine functions, and risk factors such as alcohol, drug abuse, some pharmacological drugs or cigarette smoking. The pathology of bone development during intrauterine life is a factor for osteoporosis. Moreover, the placental transfer of nutrients plays an important role in the building of bones of fetuses. The importance of maternal calcium intake and vitamin D status are highlighted in this review. Various environmental factors including nutrition state or maternal stress may affect the epigenetic state of a number of genes during fetal development of bones. Histone modifications as histone hypomethylation, histone hypermethylation, hypoacetylation, etc. are involved in chromatin remodeling, known to contribute to the epigenetic landscape of chromosomes, and play roles in both fetal bone development and osteoporosis. This review will give an overview of epigenetic modulation of bone development and placental transfer of nutrients. In addition, the data from animal and human studies support the role of epigenetic modulation of calcium and vitamin D in the pathogenesis of osteoporosis. We review the evidence suggesting that various genes are involved in regulation of osteoclast formation and differentiation by osteoblasts and stem cells. Epigenetic changes in growth factors as well as cytokines play a rol in fetal bone development. On balance, the data suggest that there is a link between epigenetic changes in placental transfer of nutrients, including calcium and vitamin D, abnormal intrauterine bone development and pathogenesis of osteoporosis.

Third trimester fetal heart rate predicts phenotype and mutation burden in the type 1 long QT syndrome.

PubMed

Winbo, Annika; Fosdal, Inger; Lindh, Maria; Diamant, Ulla-Britt; Persson, Johan; Wettrell, Göran; Rydberg, Annika

2015-08-01

Early diagnosis and risk stratification is of clinical importance in the long QT syndrome (LQTS), however, little genotype-specific data are available regarding fetal LQTS. We investigate third trimester fetal heart rate, routinely recorded within public maternal health care, as a possible marker for LQT1 genotype and phenotype. This retrospective study includes 184 fetuses from 2 LQT1 founder populations segregating p.Y111C and p.R518X (74 noncarriers and 110 KCNQ1 mutation carriers, whereof 13 double mutation carriers). Pedigree-based measured genotype analysis revealed significant associations between fetal heart rate, genotype, and phenotype; mean third trimester prelabor fetal heart rates obtained from obstetric records (gestational week 29-41) were lower per added mutation (no mutation, 143±5 beats per minute; single mutation, 134±8 beats per minute; double mutations, 111±6 beats per minute; P<0.0001), and lower in symptomatic versus asymptomatic mutation carriers (122±10 versus 137±9 beats per minute; P<0.0001). Strong correlations between fetal heart rate and neonatal heart rate (r=0.700; P<0.001), and postnatal QTc (r=-0.762; P<0.001) were found. In a multivariable model, fetal genotype explained the majority of variance in fetal heart rate (-10 beats per minute per added mutation; P<1.0×10(-23)). Arrhythmia symptoms and intrauterine β-blocker exposure each predicted -7 beats per minute, P<0.0001. In this study including 184 fetuses from 2 LQT1 founder populations, third trimester fetal heart rate discriminated between fetal genotypes and correlated with severity of postnatal cardiac phenotype. This finding strengthens the role of fetal heart rate in the early detection and risk stratification of LQTS, particularly for fetuses with double mutations, at high risk of early life-threatening arrhythmias. © 2015 American Heart Association, Inc.

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.

Regulation of fibrillins and modulators of TGFβ in fetal bovine and human ovaries.

PubMed

Bastian, Nicole A; Bayne, Rosemary A; Hummitzsch, Katja; Hatzirodos, Nicholas; Bonner, Wendy M; Hartanti, Monica D; Irving-Rodgers, Helen F; Anderson, Richard A; Rodgers, Raymond J

2016-08-01

Fibrillins 1-3 are stromal extracellular matrix proteins that play important roles in regulating TGFβ activity, which stimulates fibroblasts to proliferate and synthesize collagen. In the developing ovary, the action of stroma is initially necessary for the formation of ovigerous cords and subsequently for the formation of follicles and the surface epithelium of the ovary. FBN3 is highly expressed only in early ovarian development and then it declines. In contrast, FBN1 and 2 are upregulated in later ovarian development. We examined the expression of FBN1-3 in bovine and human fetal ovaries. We used cell dispersion and monolayer culture, cell passaging and tissue culture. Cells were treated with growth factors, hormones or inhibitors to assess the regulation of expression of FBN1-3 When bovine fetal ovarian tissue was cultured, FBN3 expression declined significantly. Treatment with TGFβ-1 increased FBN1 and FBN2 expression in bovine fibroblasts, but did not affect FBN3 expression. Additionally, in cultures of human fetal ovarian fibroblasts (9-17weeks gestational age), the expression of FBN1 and FBN2 increased with passage, whereas FBN3 dramatically decreased. Treatment with activin A and a TGFβ family signaling inhibitor, SB431542, differentially regulated the expression of a range of modulators of TGFβ signaling and of other growth factors in cultured human fetal ovarian fibroblasts suggesting that TGFβ signaling is differentially involved in the regulation of ovarian fibroblasts. Additionally, since the changes in FBN1-3 expression that occur in vitro are those that occur with increasing gestational age in vivo, we suggest that the fetal ovarian fibroblasts mature in vitro. © 2016 Society for Reproduction and Fertility.

Mathematical Model of Cardiovascular and Metabolic Responses to Umbilical Cord Occlusions in Fetal Sheep.

PubMed

Wang, Qiming; Gold, Nathan; Frasch, Martin G; Huang, Huaxiong; Thiriet, Marc; Wang, Xiaogang

2015-12-01

Fetal acidemia during labor is associated with an increased risk of brain injury and lasting neurological deficits. This is in part due to the repetitive occlusions of the umbilical cord (UCO) induced by uterine contractions. Whereas fetal heart rate (FHR) monitoring is widely used clinically, it fails to detect fetal acidemia. Hence, new approaches are needed for early detection of fetal acidemia during labor. We built a mathematical model of the UCO effects on FHR, mean arterial blood pressure (MABP), oxygenation and metabolism. Mimicking fetal experiments, our in silico model reproduces salient features of experimentally observed fetal cardiovascular and metabolic behavior including FHR overshoot, gradual MABP decrease and mixed metabolic and respiratory acidemia during UCO. Combined with statistical analysis, our model provides valuable insight into the labor-like fetal distress and guidance for refining FHR monitoring algorithms to improve detection of fetal acidemia and cardiovascular decompensation.

Biomimetics of fetal alveolar flow phenomena using microfluidics.

PubMed

Tenenbaum-Katan, Janna; Fishler, Rami; Rothen-Rutishauser, Barbara; Sznitman, Josué

2015-01-01

At the onset of life in utero, the respiratory system begins as a liquid-filled tubular organ and undergoes significant morphological changes during fetal development towards establishing a respiratory organ optimized for gas exchange. As airspace morphology evolves, respiratory alveolar flows have been hypothesized to exhibit evolving flow patterns. In the present study, we have investigated flow topologies during increasing phases of embryonic life within an anatomically inspired microfluidic device, reproducing real-scale features of fetal airways representative of three distinct phases of in utero gestation. Micro-particle image velocimetry measurements, supported by computational fluid dynamics simulations, reveal distinct respiratory alveolar flow patterns throughout different stages of fetal life. While attached, streamlined flows characterize the shallow structures of premature alveoli indicative of the onset of saccular stage, separated recirculating vortex flows become the signature of developed and extruded alveoli characteristic of the advanced stages of fetal development. To further mimic physiological aspects of the cellular environment of developing airways, our biomimetic devices integrate an alveolar epithelium using the A549 cell line, recreating a confluent monolayer that produces pulmonary surfactant. Overall, our in vitro biomimetic fetal airways model delivers a robust and reliable platform combining key features of alveolar morphology, flow patterns, and physiological aspects of fetal lungs developing in utero.

Fetal tissue Doppler imaging in pregnancies complicated with preeclampsia with or without intrauterine growth restriction.

PubMed

Zhou, Qiongjie; Ren, Yunyun; Yan, Yingliu; Chu, Chen; Gui, Yonghao; Li, Xiaotian

2012-11-01

This study's aim was to evaluate the effect of preeclampsia and intrauterine growth restriction (IUGR) on fetal cardiac function, and the relationship of the latter with adverse pregnancy outcomes. We did a cross-sectional study of 132 women with uncomplicated singleton pregnancies, 34 with preeclampsia without IUGR, and 12 with preeclampsia and IUGR. Fetal cardiac structure and function were evaluated using fetal two-dimension ultrasound, pulsed wave Doppler and tissue Doppler imaging (TDI). Data were analyzed by t-tests, ANOVA, Chi-square tests, or Wilcoxon rank-sum test. Compared with the normal pregnancy group, mitral/tricuspid early systolic peak velocity of annulus/late diastolic peak velocity of annulus (Sa) and left ventricular (LV)/right ventricular (RV) early diastolic peak velocity at the annulus (Ea) in TDI decreased in preeclampsia with or without IUGR (P < 0.05). LV/RV Ea underwent a gestational decrease in preeclampsia with or without IUGR (P < 0.05). The changes in mitral/tricuspid Sa and LV Sa associated with preeclampsia were even more pronounced with preterm delivery at less than 34 gestational weeks and stillbirth (P < 0.05). Intrauterine growth restriction influences fetal cardiac function in the presence of preeclampsia, and TDI may be a sensitive and preferable method to detect such changes. Fetal LV/RV Ea is a potential marker for early fetal cardiac diastolic impairment, and mitral/tricuspid Sa and LV Sa may be predictors for adverse pregnancy outcomes. © 2012 John Wiley & Sons, Ltd.

Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

PubMed

Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

2016-08-01

Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

CHARACTERIZATION OF THE PERIOD OF SENSITIVITY OF FETAL MALE SEXUAL DEVELOPMENT TO VINCLOZOLIN

EPA Science Inventory

Characterization of the period of sensitivity of fetal male sexual development to vinclozolin.

Wolf CJ, LeBlanc GA, Ostby JS, Gray LE Jr.

Endocrinology Branch, MD 72, Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U....

Correlation of fetal oxygen saturation to fetal heart rate patterns. Evaluation of fetal pulse oximetry with two different oxisensors.

PubMed

Luttkus, A K; Friedmann, W; Homm-Luttkus, C; Dudenhausen, J W

1998-03-01

The purpose of this study was the correlation of fetal oxygen saturation values to various fetal heart rate patterns, as well as to oxygen saturation values obtained by fetal blood analysis. These objectives need to be evaluated from the perspective that two generations of fetal oxisensors have been used. Two different oxisensor systems (FS10: 660+890 nm and FS14: 735+890 nm) and a blinded pulse oximeter (type N400, Nellcor Puritan Bennett) were utilized to monitor 112 fetuses. All data, including oxygen saturation, fetal heart rate patterns, signal and contact quality were stored on a personal computer and evaluated after delivery. The following median fetal oxygen saturation values were obtained: during reassuring fetal heart rate sequences 54% with the oxisensor FS10 and 48% with the newer FS14 oxisensor, during intervals of variable decelerations 43% with the FS10 oxisensor and 40% with the FS14 oxisensor. These differences between values obtained during normal and abnormal fetal heart rate patterns are significant. Due to non-reassuring fetal heart rate patterns 81 fetal blood analyses were performed. The values of pulse oximetry were 9% higher (6% for the FS14) than those of spectrophotometry. Correlation of both methods was r=0.66 (0.74 for the FS14). In combination with fetal heart rate monitoring, fetal pulse oximetry promises a better differentiation between low and high risk heart rate patterns. Oxygen saturation values from intermittent fetal blood sampling reassure the clinician concerning the accuracy of this new method of intrapartum fetal surveillance and underline the increased quality of the new generation of oxisensor using light of a wavelength of 735 and 890 nm.

Effect of zinc oxide nanoparticles on dams and embryo–fetal development in rats

PubMed Central

Hong, Jeong-Sup; Park, Myeong-Kyu; Kim, Min-Seok; Lim, Jeong-Hyeon; Park, Gil-Jong; Maeng, Eun-Ho; Shin, Jae-Ho; Kim, Yu-Ri; Kim, Meyoung-Kon; Lee, Jong-Kwon; Park, Jin-A; Kim, Jong-Choon; Shin, Ho-Chul

2014-01-01

This study investigated the potential adverse effects of zinc oxide nanoparticles (ZnOSM20[−] NPs; negatively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague Dawley rats. ZnOSM20(−) NPs were administered to pregnant rats by gavage at 0 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day. All dams were subjected to caesarean section on gestational day 20, and all the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight at 400 mg/kg/day and decreased liver weight, and increased adrenal glands weight at 200 mg/kg/day and 400 mg/kg/day. However, no treatment-related difference in the number of corpora lutea, the number of implantation sites, the implantation rate (%), resorption, dead fetuses, litter size, fetal deaths, fetal and placental weights, and sex ratio were observed between the groups. Morphological examinations of the fetuses demonstrated no significant difference in the incidences of abnormalities between the groups. No significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that a 15-day repeated oral dose of ZnOSM20(−) was minimally maternotoxic at dose of 200 mg/kg/day and 400 mg/kg/day. PMID:25565833

Fetal monitoring indications for delivery and 2-year outcome in 310 infants with fetal growth restriction delivered before 32 weeks' gestation in the TRUFFLE study.

PubMed

Visser, G H A; Bilardo, C M; Derks, J B; Ferrazzi, E; Fratelli, N; Frusca, T; Ganzevoort, W; Lees, C C; Napolitano, R; Todros, T; Wolf, H; Hecher, K

2017-09-01

In the TRUFFLE (Trial of Randomized Umbilical and Fetal Flow in Europe) study on the outcome of early fetal growth restriction, women were allocated to one of three groups of indication for delivery according to the following monitoring strategies: (1) reduced fetal heart rate (FHR) short-term variation (STV) on cardiotocography (CTG); (2) early changes in fetal ductus venosus (DV) waveform (DV-p95); and (3) late changes in fetal DV waveform (DV-no-A). However, many infants per monitoring protocol were delivered because of safety-net criteria, for maternal or other fetal indications, or after 32 weeks of gestation when the protocol was no longer applied. The objective of the present posthoc subanalysis was to investigate the indications for delivery in relation to 2-year outcome in infants delivered before 32 weeks to further refine management proposals. We included all 310 cases of the TRUFFLE study with known outcome at 2 years' corrected age and seven fetal deaths, excluding seven cases with inevitable perinatal death. Data were analyzed according to the allocated fetal monitoring strategy in combination with the indication for delivery. Overall, only 32% of liveborn infants were delivered according to the specified monitoring parameter for indication for delivery; 38% were delivered because of safety-net criteria, 15% for other fetal reasons and 15% for maternal reasons. In the CTG-STV group, 51% of infants were delivered because of reduced STV. In the DV-p95 group, 34% of infants were delivered because of abnormal DV and, in the DV-no-A group, only 10% of infants were delivered accordingly. The majority of infants in the DV groups were delivered for the safety-net criterion of spontaneous decelerations in FHR. Two-year intact survival was highest in the DV groups combined compared with the CTG-STV group (P = 0.05 for live births only, P = 0.21 including fetal death), with no difference between DV groups. A poorer outcome in the CTG-STV group was restricted to

Fetal thrombocytopenia in pregnancies with fetal human parvovirus-B19 infection.

PubMed

Melamed, Nir; Whittle, Wendy; Kelly, Edmond N; Windrim, Rory; Seaward, P Gareth R; Keunen, Johannes; Keating, Sarah; Ryan, Greg

2015-06-01

Fetal infection with human parvovirus B19 (hParvo-B19) has been associated mainly with fetal anemia, although data regarding other fetal hematologic effects are limited. Our aim was to assess the rate and consequences of severe fetal thrombocytopenia after fetal hParvo-B19 infection. We conducted a retrospective study of pregnancies that were complicated by fetal hParvo-B19 infection that underwent fetal blood sampling (FBS). The characteristics and outcomes of fetuses with severe thrombocytopenia (<50 × 10(9)/L) were compared with those of fetuses with a platelet concentration of ≥50 × 10(9)/L (control fetuses). Fetuses in whom 3 FBSs were performed (n = 4) were analyzed to assess the natural history of platelet levels after fetal hParvo-B19 infection. A total of 37 pregnancies that were affected by fetal hParvo-B19 infection were identified. Of the 29 cases that underwent FBS and had information regarding fetal platelets, 11 cases (38%) were complicated by severe fetal thrombocytopenia. Severely thrombocytopenic fetuses were characterized by a lower hemoglobin concentration (2.6 ± 0.9 g/dL vs 5.5 ± 3.6 g/dL; P = .01), lower reticulocyte count (9.1% ± 2.8% vs 17.3% ± 10.6%; P = .02), and lower gestational age at the time of diagnosis (21.4 ± 3.1 wk vs 23.6 ± 2.2 wk; P = .03). Both the fetal death rate within 48 hours of FBS (27.3% vs 0%; P = .02) and the risk of prematurity (100.0% vs 13.3%; P < .001) were higher in fetuses with severe thrombocytopenia. Fetal thrombocytopenia was more common during the second trimester but, in some cases, persisted into the third trimester. Intrauterine transfusion (IUT) of red blood cells resulted in a further mean decrease of 40.1% ± 31.0% in fetal platelet concentration. Severe fetal thrombocytopenia is relatively common after fetal hParvo-B19 infection, can be further worsened by IUT, and may be associated with an increased risk of procedure-related fetal loss after either FBS or IUT. Copyright © 2015. Published by

Development of a media campaign on fetal alcohol spectrum disorders for Northern Plains American Indian communities.

PubMed

Hanson, Jessica D; Winberg, Austin; Elliott, Amy

2012-11-01

Alcohol-exposed pregnancies are especially of concern for American Indians. The Indian Health Service reported that 47% to 56% of pregnant patients admitted to drinking alcohol during their pregnancy. In addition, rates of Fetal Alcohol Syndrome are estimated to be as high as 3.9 to 9.0 per 1,000 live births among American Indians in the Northern Plains, making prevention of alcohol-exposed pregnancies an important public health effort for this population. The goal of this article is to add to the literature on universal prevention of Fetal Alcohol Spectrum disorders by describing the development, dissemination, and evaluation of a media campaign on Fetal Alcohol Spectrum Disorders that was created by and for American Indian communities in the Northern Plains.

High Fat Diet Induced Developmental Defects in the Mouse: Oocyte Meiotic Aneuploidy and Fetal Growth Retardation/Brain Defects

PubMed Central

Purcell, Scott H.; Chi, Maggie; Jimenez, Patricia T.; Grindler, Natalia; Schedl, Tim; Moley, Kelle H.

2012-01-01

Background Maternal obesity is associated with poor outcomes across the reproductive spectrum including infertility, increased time to pregnancy, early pregnancy loss, fetal loss, congenital abnormalities and neonatal conditions. Furthermore, the proportion of reproductive-aged woman that are obese in the population is increasing sharply. From current studies it is not clear if the origin of the reproductive complications is attributable to problems that arise in the oocyte or the uterine environment. Methodology/Principal Findings We examined the developmental basis of the reproductive phenotypes in obese animals by employing a high fat diet mouse model of obesity. We analyzed very early embryonic and fetal phenotypes, which can be parsed into three abnormal developmental processes that occur in obese mothers. The first is oocyte meiotic aneuploidy that then leads to early embryonic loss. The second is an abnormal process distinct from meiotic aneuploidy that also leads to early embryonic loss. The third is fetal growth retardation and brain developmental abnormalities, which based on embryo transfer experiments are not due to the obese uterine environment but instead must be from a defect that arises prior to the blastocyst stage. Conclusions/Significance Our results suggest that reproductive complications in obese females are, at least in part, from oocyte maternal effects. This conclusion is consistent with IVF studies where the increased pregnancy failure rate in obese women returns to the normal rate if donor oocytes are used instead of autologous oocytes. We postulate that preconceptional weight gain adversely affects pregnancy outcomes and fetal development. In light of our findings, preconceptional counseling may be indicated as the preferable, earlier target for intervention in obese women desiring pregnancy and healthy outcomes. PMID:23152876

Development of fetal yawn compared with non-yawn mouth openings from 24-36 weeks gestation.

PubMed

Reissland, Nadja; Francis, Brian; Mason, James

2012-01-01

Although some research suggests that fetuses yawn, others disagree arguing that is it simple mouth opening. Furthermore there is no developmental account of fetal yawning compared with simple mouth opening. The aim of the present study was to establish in a repeated measures design the development of fetal yawning compared with simple mouth opening. Video recordings were made of the fetal face and upper torso visualized by means of 4D full frontal or facial profile ultrasound recordings. Fifteen healthy fetuses were scanned four times at 24, 28, 32 and 36 weeks gestation. Yawning was distinguished from non-yawning in terms of the length of time it took to reach the apex of the mouth stretch, with yawns being defined as more than 50% of the total time observed. To assess changes in frequency, a Poisson mixed effects model was fitted to the count of number of yawn and simple mouth opening events with age and gender as fixed effects, and person as a random effect. For both yawns and simple mouth openings a smooth varying age effect was significant. The number of yawns observed declined with age from 28 weeks gestation, whereas simple mouth openings were less frequent and the decline was observed from 24 weeks. Gender was not significant either for yawn and simple mouth openings. Yawning can be reliably distinguished from other forms of mouth opening with the potential of using yawning as an index of fetal healthy development.

Injurious Effects of Emodin on Maturation of Mouse Oocytes, Fertilization and Fetal Development via Apoptosis

PubMed Central

Chang, Mei-Hui; Chang, Shao-Chung; Chan, Wen-Hsiung

2012-01-01

Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a major constituent of rhubarb, has a wide range of therapeutic applications. Previous studies have established that emodin induces apoptosis in the inner cell mass and trophectoderm of mouse blastocysts and leads to decreased embryonic development and viability, indicating a role as an injury risk factor for normal embryonic development. However, the mechanisms underlying its hazardous effects have yet to be characterized. In the current study, we further investigated the effects of emodin on oocyte maturation and subsequent pre- and post-implantation development, both in vitro and in vivo. Notably, emodin induced a significant reduction in the rates of oocyte maturation, fertilization, and in vitro embryonic development. Treatment of oocytes with emodin during in vitro maturation (IVM) led to increased resorption of postimplantation embryos and decreased fetal weight. Experiments using an in vivo mouse model disclosed that consumption of drinking water containing 20–40 μM emodin led to decreased oocyte maturation and in vitro fertilization, as well as early embryonic developmental injury. Notably, pretreatment with a caspase-3-specific inhibitor effectively prevented emodin-triggered injury effects, suggesting that impairment of embryo development occurs via a caspase-dependent apoptotic process. PMID:23203041

Fetal growth in muskoxen determined by transabdominal ultrasonography.

PubMed Central

Pharr, J W; Rowell, J E; Flood, P F

1994-01-01

A 5 MHz commercial sector scanner was used to monitor 13 muskox pregnancies and establish normal fetal growth curves. Examinations were carried out between 40 and 197 days of gestation and pregnancy could be detected throughout the period. Early pregnancies were found by scanning lateral to the udder but as pregnancy progressed the fetus was found closer to the dam's umbilicus. Measurements of cranial and abdominal diameters taken at about two week intervals in seven uncomplicated pregnancies in four cows were used to construct fetal growth curves. These can be reliably used in the reproductive management of muskoxen. In addition a series of regressions based on measurements of the fetuses of muskoxen killed in the Arctic are provided. These allow cranial and abdominal diameters to be related to fetal weight and crown-rump length. Images Fig. 1. Fig. 2. PMID:7954117

Prepregnancy and early adulthood body mass index and adult weight change in relation to fetal loss.

PubMed

Gaskins, Audrey J; Rich-Edwards, Janet W; Colaci, Daniela S; Afeiche, Myriam C; Toth, Thomas L; Gillman, Matthew W; Missmer, Stacey A; Chavarro, Jorge E

2014-10-01

To examine prospectively the relationships of prepregnancy body mass index (BMI), BMI at age 18 years, and weight change since age 18 years with risk of fetal loss. Our prospective cohort study included 25,719 pregnancies reported by 17,027 women in the Nurses' Health Study II between 1990 and 2009. In 1989, height, current weight, and weight at age 18 years were self-reported. Current weight was updated every 2 years thereafter. Pregnancies were self-reported, with case pregnancies lost spontaneously and comparison pregnancies ending in ectopic pregnancy, induced abortion, or live birth. Incident fetal loss was reported in 4,494 (17.5%) pregnancies. Compared with those of normal BMI, the multivariate relative risks of fetal loss were 1.07 (95% CI [confidence interval] 1.00-1.15) for overweight women, 1.10 (95% CI 0.98-1.23) for class I obese women, and 1.27 (95% CI 1.11-1.45) for class II and class III obese women (P trend ≤ .001). Body mass index at age 18 years was not associated with fetal loss (P trend=.59). Compared with women who maintained a stable weight (± 4 kg) between age 18 years and before pregnancy, women who lost weight had a 20% (95% CI 9-29%) lower risk of fetal loss. This association was stronger among women who were overweight at age 18 years. Being overweight or obese before pregnancy was associated with higher risk of fetal loss. In women overweight or obese at age 18 years, losing 4 kg or more was associated with a lower risk of fetal loss. : II.

Prenatal caffeine intake differently affects synaptic proteins during fetal brain development.

PubMed

Mioranzza, Sabrina; Nunes, Fernanda; Marques, Daniela M; Fioreze, Gabriela T; Rocha, Andréia S; Botton, Paulo Henrique S; Costa, Marcelo S; Porciúncula, Lisiane O

2014-08-01

Caffeine is the psychostimulant most consumed worldwide. However, little is known about its effects during fetal brain development. In this study, adult female Wistar rats received caffeine in drinking water (0.1, 0.3 and 1.0 g/L) during the active cycle in weekdays, two weeks before mating and throughout pregnancy. Cerebral cortex and hippocampus from embryonic stages 18 or 20 (E18 or E20, respectively) were collected for immunodetection of the following synaptic proteins: brain-derived neurotrophic factor (BDNF), TrkB receptor, Sonic Hedgehog (Shh), Growth Associated Protein 43 (GAP-43) and Synaptosomal-associated Protein 25 (SNAP-25). Besides, the estimation of NeuN-stained nuclei (mature neurons) and non-neuronal nuclei was verified in both brain regions and embryonic periods. Caffeine (1.0 g/L) decreased the body weight of embryos at E20. Cortical BDNF at E18 was decreased by caffeine (1.0 g/L), while it increased at E20, with no major effects on TrkB receptors. In the hippocampus, caffeine decreased TrkB receptor only at E18, with no effects on BDNF. Moderate and high doses of caffeine promoted an increase in Shh in both brain regions at E18, and in the hippocampus at E20. Caffeine (0.3g/L) decreased GAP-43 only in the hippocampus at E18. The NeuN-stained nuclei increased in the cortex at E20 by lower dose and in the hippocampus at E18 by moderate dose. Our data revealed that caffeine transitorily affect synaptic proteins during fetal brain development. The increased number of NeuN-stained nuclei by prenatal caffeine suggests a possible acceleration of the telencephalon maturation. Although some modifications in the synaptic proteins were transient, our data suggest that caffeine even in lower doses may alter the fetal brain development. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

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.

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

Fetal programming of appetite and obesity.

PubMed

Breier, B H; Vickers, M H; Ikenasio, B A; Chan, K Y; Wong, W P

2001-12-20

Obesity and related metabolic disorders are prevalent health issues in modern society and are commonly attributed to lifestyle and dietary factors. However, the mechanisms by which environmental factors modulate the physiological systems that control weight regulation and the aetiology of metabolic disorders, which manifest in adult life, may have their roots before birth. The 'fetal origins' or 'fetal programming' paradigm is based on the observation that environmental changes can reset the developmental path during intrauterine development leading to obesity and cardiovascular and metabolic disorders later in life. The pathogenesis is not based on genetic defects but on altered genetic expression as a consequence of an adaptation to environmental changes during fetal development. While many endocrine systems can be affected by fetal programming recent experimental studies suggest that leptin and insulin resistance are critical endocrine defects in the pathogenesis of programming-induced obesity and metabolic disorders. However, it remains to be determined whether postnatal obesity is a consequence of programming of appetite regulation and whether hyperphagia is the main underlying cause of the increased adiposity and the development of metabolic disorders.

Electronic fetal heart rate monitoring and its relationship to neonatal and infant mortality in the United States.

PubMed

Chen, Han-Yang; Chauhan, Suneet P; Ananth, Cande V; Vintzileos, Anthony M; Abuhamad, Alfred Z

2011-06-01

To examine the association between electronic fetal heart rate monitoring and neonatal and infant mortality, as well as neonatal morbidity. We used the United States 2004 linked birth and infant death data. Multivariable log-binomial regression models were fitted to estimate risk ratio for association between electronic fetal heart rate monitoring and mortality, while adjusting for potential confounders. In 2004, 89% of singleton pregnancies had electronic fetal heart rate monitoring. Electronic fetal heart rate monitoring was associated with significantly lower infant mortality (adjusted relative risk, 0.75); this was mainly driven by the lower risk of early neonatal mortality (adjusted relative risk, 0.50). In low-risk pregnancies, electronic fetal heart rate monitoring was associated with decreased risk for Apgar scores <4 at 5 minutes (relative risk, 0.54); in high-risk pregnancies, with decreased risk of neonatal seizures (relative risk, 0.65). In the United States, the use of electronic fetal heart rate monitoring was associated with a substantial decrease in early neonatal mortality and morbidity that lowered infant mortality. Copyright © 2011 Mosby, Inc. All rights reserved.

Antibody repertoire development in fetal and neonatal piglets. VI. B cell lymphogenesis occurs at multiple sites with differences in the frequency of in-frame rearrangements.

PubMed

Sinkora, Marek; Sun, Jishan; Sinkorová, Jana; Christenson, Ronald K; Ford, Steven P; Butler, John E

2003-02-15

B cell lymphogenesis in mammals occurs in various tissues during development but it is generally accepted that it operates by the same mechanism in all tissues. We show that in swine, the frequency of in-frame (IF) VDJ rearrangements differs among yolk sac, fetal liver, spleen, early thymus, bone marrow, and late thymus. All VDJ rearrangements recovered and analyzed on the 20th day of gestation (DG20) from the yolk sac were 100% IF. Those recovered at DG30 in the fetal liver were >90% IF, and this predominance of cells with apparently a single IF rearrangement continued in all organs until approximately DG45, which corresponds to the time when lymphopoiesis begins in the bone marrow. Thereafter, the proportion of IF rearrangements drops to approximately 71%, i.e., the value predicted whether VDJ rearrangement is random and both chromosomes were involved. Unlike other tissues, VDJs recovered from thymus after DG50 display a pattern suggesting no selection for IF rearrangements. Regardless of differences in the proportion of IF rearrangements, we observed no significant age- or tissue-dependent changes in CDR3 diversity, N region additions, or other characteristics of fetal VDJs during ontogeny. These findings indicate there are multiple sites of B cell lymphogenesis in fetal piglets and differences in the frequency of productive VDJ rearrangements at various sites. We propose the latter to result from differential selection or a developmentally dependent change in the intrinsic mechanism of VDJ rearrangement.

Fetal wound healing using a genetically modified murine model: the contribution of P-selectin

USDA-ARS?s Scientific Manuscript database

During early gestation, fetal wounds heal with paucity of inflammation and absent scar formation. P-selectin is an adhesion molecule that is important for leukocyte recruitment to injury sites. We used a murine fetal wound healing model to study the specific contribution of P-selectin to scarless wo...

Fetal programming and environmental exposures ...

EPA Pesticide Factsheets

Fetal programming is an enormously complex process that relies on numerous environmental inputs from uterine tissue, the placenta, the maternal blood supply, and other sources. Recent evidence has made clear that the process is not based entirely on genetics, but rather on a delicate series of interactions between genes and the environment. It is likely that epigenctic (“above the genome”) changes are responsible for modifying gene expression in the developing fetus, and these modifications can have long-lasting health impacts. Determining which epigenetic regulators are most vital in embryonic development will improve pregnancy outcomes and our ability to treat and prevent disorders that emerge later in life. “Fetal Programming and Environmental Exposures: Implications for Prenatal Care and Preterm Birth’ began with a keynote address by Frederick vom Saal, who explained that low-level exposure to endocrine disrupting chemicals (EDCs) perturbs hormone systems in utero and can have negative effects on fetal development. vom Saal presented data on the LOC bisphenol A (BPA), an estrogen-mimicking compound found in many plastics. He suggested that low-dose exposure to LOCs can alter the development process and enhance chances of acquiring adult diseases, such as breastcancer, diabetes, and even developmental disorders such as attention deficit disorder (ADHD).’ Fetal programming is an enormously complex process that relies on numerous environmental inputs

Non-invasive fetal sex determination by maternal plasma sequencing and application in X-linked disorder counseling.

PubMed

Pan, Xiaoyu; Zhang, Chunlei; Li, Xuchao; Chen, Shengpei; Ge, Huijuan; Zhang, Yanyan; Chen, Fang; Jiang, Hui; Jiang, Fuman; Zhang, Hongyun; Wang, Wei; Zhang, Xiuqing

2014-12-01

To develop a fetal sex determination method based on maternal plasma sequencing (MPS), assess its performance and potential use in X-linked disorder counseling. 900 cases of MPS data from a previous study were reviewed, in which 100 and 800 cases were used as training and validation set, respectively. The percentage of uniquely mapped sequencing reads on Y chromosome was calculated and used to classify male and female cases. Eight pregnant women who are carriers of Duchenne muscular dystrophy (DMD) mutations were recruited, whose plasma were subjected to multiplex sequencing and fetal sex determination analysis. In the training set, a sensitivity of 96% and false positive rate of 0% for male cases detection were reached in our method. The blinded validation results showed 421 in 423 male cases and 374 in 377 female cases were successfully identified, revealing sensitivity and specificity of 99.53% and 99.20% for fetal sex determination, at as early as 12 gestational weeks. Fetal sex for all eight DMD genetic counseling cases were correctly identified, which were confirmed by amniocentesis. Based on MPS, high accuracy of non-invasive fetal sex determination can be achieved. This method can potentially be used for prenatal genetic counseling.

Expression of growth differentiation factor 6 in the human developing fetal spine retreats from vertebral ossifying regions and is restricted to cartilaginous tissues.

PubMed

Wei, Aiqun; Shen, Bojiang; Williams, Lisa A; Bhargav, Divya; Gulati, Twishi; Fang, Zhimin; Pathmanandavel, Sarennya; Diwan, Ashish D

2016-02-01

During embryogenesis vertebral segmentation is initiated by sclerotomal cell migration and condensation around the notochord, forming anlagen of vertebral bodies and intervertebral discs. The factors that govern the segmentation are not clear. Previous research demonstrated that mutations in growth differentiation factor 6 resulted in congenital vertebral fusion, suggesting this factor plays a role in development of vertebral column. In this study, we detected expression and localization of growth differentiation factor 6 in human fetal spinal column, especially in the period of early ossification of vertebrae and the developing intervertebral discs. The extracellular matrix proteins were also examined. Results showed that high levels of growth differentiation factor 6 were expressed in the nucleus pulposus of intervertebral discs and the hypertrophic chondrocytes adjacent to the ossification centre in vertebral bodies, where strong expression of proteoglycan and collagens was also detected. As fetal age increased, the expression of growth differentiation factor 6 was decreased correspondingly with the progress of ossification in vertebral bodies and restricted to cartilaginous regions. This expression pattern and the genetic link to vertebral fusion suggest that growth differentiation factor 6 may play an important role in suppression of ossification to ensure proper vertebral segmentation during spinal development. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Uromodulin: a new biomarker of fetal renal function?

PubMed

Botelho, Thais Emanuelle Faria; Pereira, Alamanda Kfoury; Teixeira, Patrícia Gonçalves; Lage, Eura Martins; Osanan, Gabriel Costa; Silva, Ana Cristina Simões E

2016-12-01

Obstructive uropathies are main diseases affecting the fetus. Early diagnosis allows to establish the appropriate therapy to minimize the risk of damage to kidney function at birth. Biochemical markers have been used to predict the prognosis of renal function in fetuses. Uromodulin, also known by Tamm-Horsfall protein (THP) is exclusively produced in the kidneys and in normal conditions is the protein excreted in larger amounts in human urine. It plays important roles in kidneys and urinary tract. Also it participates in ion transport processes, interact with various components of the immune system and has a role in defense against urinary tract infections. Moreover, this protein was proved to be a good marker of renal function in adult patients with several renal diseases. To evaluate if uromodulin is produced and eliminated by the kidneys during fetal life by analyzing fetal urine and amniotic fluid and to establish correlation with biochemical parameter of renal function already used in Fetal Medicine Center at the Clinic Hospital of UFMG (CEMEFE/HC). Between 2013 and 2015, were selected 29 fetuses with indication of invasive tests for fetal diagnosis in monitoring at the CEMEFE/HC. The determination of uromodulin was possible and measurable in all samples and showed statistically significant correlation with the osmolarity. There was a tendency of lower levels of Uromodulin values in fetuses with severe renal impairment prenatally. Thus, high levels of this protein in fetal amniotic fluid or fetal urine dosages possibly mean kidney function preserved.

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

CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation.

PubMed

Sunday, M E; Hua, J; Torday, J S; Reyes, B; Shipp, M A

1992-12-01

The cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) functions in multiple organ systems to downregulate responses to peptide hormones. Recently, CD10/NEP was found to hydrolyze bombesin-like peptides (BLP), which are mitogens for normal bronchial epithelial cells and small cell lung carcinomas. Growth of BLP-responsive small cell lung carcinomas was potentiated by CD10/NEP inhibition, implicating CD10/NEP in regulation of BLP-mediated tumor growth. BLP are also likely to participate in normal lung development because high BLP levels are found in fetal lung, and bombesin induces proliferation and maturation of human fetal lung in organ cultures and murine fetal lung in utero. To explore potential roles for CD10/NEP in regulating peptide-mediated human fetal lung development, we have characterized temporal and cellular patterns of CD10/NEP expression and effects of CD10/NEP inhibition in organ cultures. Peak CD10/NEP transcript levels are identified at 11-13 wk gestation by Northern blots and localized to epithelial cells and mesenchyme of developing airways by in situ hybridization. CD10/NEP immunostaining is most intense in undifferentiated airway epithelium. In human fetal lung organ cultures, inhibition of CD10/NEP with either phosphoramidon or SCH32615 increases thymidine incorporation by 166-182% (P < 0.025). The specific BLP receptor antagonist, [Leu13-psi(CH2NH)Leu14]bombesin abolishes these effects on fetal lung growth, suggesting that CD10/NEP modulates BLP-mediated proliferation. CD10/NEP expression in the growing front of airway epithelium and the effects of CD10/NEP inhibitors in lung explants implicate the enzyme in the regulation of peptide-mediated fetal lung growth.

Legionnaire's disease complicating pregnancy: a case report with intrauterine fetal demise.

PubMed

Vimercati, A; Greco, P; Bettocchi, S; Resta, L; Selvaggi, L

2000-01-01

Legionnaire's disease complicating pregnancy is an unusual event that can seriously compromise both the mother and the fetus. We describe one case of such association, with an unfavourable intrauterine fetal outcome, secondary to acute placental insufficiency, related to infection. It is important in these high risk pregnancies complicated by acute pneumonia to take into consideration the diagnosis, as early as possible, and the appropriate treatment or the careful monitoring of fetal wellbeing.

Development of a guinea pig model of chorioamnionitis and fetal brain injury.

PubMed

Patrick, Lindsay A; Gaudet, Laura M; Farley, Anne E; Rossiter, John P; Tomalty, Lewis L; Smith, Graeme N

2004-10-01

The purpose of this study was to develop a guinea pig model of chorioamnionitis to study the mechanisms that lead to fetal brain injury. Study design Pregnant guinea pigs at 70% gestation were inoculated intracervically with 1000 to 2500 colony-forming units of Escherichia coli. Guinea pigs were killed 2 to 3 days after bacterial inoculation. Maternal blood and fetal amniotic fluid samples were analyzed for proinflammatory cytokine tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 levels with the use of enzyme-linked immunosorbent assay kits. Fetal brains were stained for evidence of cell death with NeuroTacs stain. Of 34 maternal guinea pigs that were given an intracervical inoculation of E coli, 8 guinea pigs showed microbiologic evidence of chorioamnionitis in the amniotic fluid. Tumor necrosis factor-alpha and interleukin-6 were significantly higher (P<.05) in amniotic fluid samples that were obtained from sows that were subjected to intracervical inoculation with bacteria as compared with control animals (n=6 control maternal animals). These results were observed even if no bacteria were found subsequently on culture of the amniotic fluid from inoculated animals, which indicated that indirect exposure to infectious agents was sufficient to cause an elevated inflammatory response in the fetus. Levels of white matter injury were greater in fetuses that were exposed to bacterial infection in utero, as compared with control animals (P<.05). This result was found in the staining of periventricular and cortical white matter for the immunolabeling of activated caspase 3 and NeuroTacs staining for cells that exhibited evidence of apoptotic cell death (positive stain with evidence of karyorrhexis). Intracervical inoculation with E coli results in chorioamnionitis in guinea pigs that is associated with fetal brain injury.

Cross-hemispheric functional connectivity in the human fetal brain.

PubMed

Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

2013-02-20

Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

Photon migration through fetal head in utero using continuous wave, near infrared spectroscopy: development and evaluation of experimental and numerical models

NASA Astrophysics Data System (ADS)

Vishnoi, Gargi; Hielscher, Andreas H.; Ramanujam, Nirmala; Chance, Britton

2000-04-01

In this work experimental tissue phantoms and numerical models were developed to estimate photon migration through the fetal head in utero. The tissue phantoms incorporate a fetal head within an amniotic fluid sac surrounded by a maternal tissue layer. A continuous wave, dual-wavelength ((lambda) equals 760 and 850 nm) spectrometer was employed to make near-infrared measurements on the tissue phantoms for various source-detector separations, fetal-head positions, and fetal-head optical properties. In addition, numerical simulations of photon propagation were performed with finite-difference algorithms that provide solutions to the equation of radiative transfer as well as the diffusion equation. The simulations were compared with measurements on tissue phantoms to determine the best numerical model to describe photon migration through the fetal head in utero. Evaluation of the results indicates that tissue phantoms in which the contact between fetal head and uterine wall is uniform best simulates the fetal head in utero for near-term pregnancies. Furthermore, we found that maximum sensitivity to the head can be achieved if the source of the probe is positioned directly above the fetal head. By optimizing the source-detector separation, this signal originating from photons that have traveled through the fetal head can drastically be increased.

Adverse fetal outcome in road accidents: Injury mechanism study and injury criteria development in a pregnant woman finite element model.

PubMed

Auriault, F; Thollon, L; Pérès, J; Behr, M

2016-12-01

This study documents the development of adverse fetal outcome predictors dedicated to the analysis of road accidents involving pregnant women. To do so, a pre-existing whole body finite element model representative of a 50th percentile 26 weeks pregnant woman was used. A total of 8 accident scenarios were simulated with the model positioned on a sled. Each of these scenarios was associated to a risk of adverse fetal outcome based on results from real car crash investigations involving pregnant women from the literature. The use of airbags and accidents involving unbelted occupants were not considered in this study. Several adverse fetal outcome potential predictors were then evaluated with regard to their correlation to this risk of fetal injuries. Three predictors appeared strongly correlated to the risk of adverse fetal outcome: (1) the intra uterine pressure at the placenta fetal side area (r=0.92), (2) the fetal head acceleration (HIC) (r=0.99) and (3) area of utero-placental interface over a strain threshold (r=0.90). Finally, sensitivity analysis against slight variations of the simulation parameters was performed and assess robustness of these criteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

New Predictive Model at 11+0 to 13+6 Gestational Weeks for Early-Onset Preeclampsia With Fetal Growth Restriction.

PubMed

Chang, Ying; Chen, Xu; Cui, Hong-Yan; Li, Xing; Xu, Ya-Ling

2017-05-01

The aim of the present study was to determine a predictive model for early-onset preeclampsia with fetal growth restriction (FGR) to be used at 11 +0 to 13 +6 gestational weeks, by combining the maternal serum level of pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF), placental protein 13 (PP13), soluble endoglin (sEng), mean arterial pressure (MAP), and uterine artery Doppler. This was a retrospective cohort study of 4453 pregnant women. Uterine artery Doppler examination was conducted in the first trimester. Maternal serum PAPP-A, PLGF, PP13, and sEng were measured. Mean arterial pressure was obtained. Women were classified as with/without early-onset preeclampsia, and women with preeclampsia were classified as with/without FGR. Receiver operating characteristic analysis was performed to determine the value of the model. There were 30 and 32 pregnant women with early-onset preeclampsia with and without FGR. The diagnosis rate of early-onset preeclampsia with FGR was 67.4% using the predictive model when the false positive rate was set at 5% and 73.2% when the false positive rate was 10%. The predictive model (MAP, uterine artery Doppler measurements, and serum biomarkers) had some predictive value for the early diagnosis (11 +0 to 13 +6 gestational weeks) of early-onset preeclampsia with FGR.

The Normal Fetal Pancreas.

PubMed

Kivilevitch, Zvi; Achiron, Reuven; Perlman, Sharon; Gilboa, Yinon

2017-10-01

The aim of the study was to assess the sonographic feasibility of measuring the fetal pancreas and its normal development throughout pregnancy. We conducted a cross-sectional prospective study between 19 and 36 weeks' gestation. The study included singleton pregnancies with normal pregnancy follow-up. The pancreas circumference was measured. The first 90 cases were tested to assess feasibility. Two hundred ninety-seven fetuses of nondiabetic mothers were recruited during a 3-year period. The overall satisfactory visualization rate was 61.6%. The intraobserver and interobserver variability had high interclass correlation coefficients of of 0.964 and 0.967, respectively. A cubic polynomial regression described best the correlation of pancreas circumference with gestational age (r = 0.744; P < .001) and significant correlations also with abdominal circumference and estimated fetal weight (Pearson r = 0.829 and 0.812, respectively; P < .001). Modeled pancreas circumference percentiles for each week of gestation were calculated. During the study period, we detected 2 cases with overgrowth syndrome and 1 case with an annular pancreas. In this study, we assessed the feasibility of sonography for measuring the fetal pancreas and established a normal reference range for the fetal pancreas circumference throughout pregnancy. This database can be helpful when investigating fetomaternal disorders that can involve its normal development. © 2017 by the American Institute of Ultrasound in Medicine.

Passive fetal heart rate monitoring apparatus and method with enhanced fetal heart beat discrimination

NASA Technical Reports Server (NTRS)

Zahorian, Stephen A. (Inventor); Livingston, David L. (Inventor); Pretlow, III, Robert A. (Inventor)

1996-01-01

An apparatus for acquiring signals emitted by a fetus, identifying fetal heart beats and determining a fetal heart rate. Multiple sensor signals are outputted by a passive fetal heart rate monitoring sensor. Multiple parallel nonlinear filters filter these multiple sensor signals to identify fetal heart beats in the signal data. A processor determines a fetal heart rate based on these identified fetal heart beats. The processor includes the use of a figure of merit weighting of heart rate estimates based on the identified heart beats from each filter for each signal. The fetal heart rate thus determined is outputted to a display, storage, or communications channel. A method for enhanced fetal heart beat discrimination includes acquiring signals from a fetus, identifying fetal heart beats from the signals by multiple parallel nonlinear filtering, and determining a fetal heart rate based on the identified fetal heart beats. A figure of merit operation in this method provides for weighting a plurality of fetal heart rate estimates based on the identified fetal heart beats and selecting the highest ranking fetal heart rate estimate.

Passive fetal heart rate monitoring apparatus and method with enhanced fetal heart beat discrimination

NASA Technical Reports Server (NTRS)

Zahorian, Stephen A. (Inventor); Livingston, David L. (Inventor); Pretlow, Robert A., III (Inventor)

1994-01-01

An apparatus for acquiring signals emitted by a fetus, identifying fetal heart beats and determining a fetal heart rate is presented. Multiple sensor signals are outputted by a passive fetal heart rate monitoring sensor. Multiple parallel nonlinear filters filter these multiple sensor signals to identify fetal heart beats in the signal data. A processor determines a fetal heart rate based on these identified fetal heart beats. The processor includes the use of a figure of merit weighting of heart rate estimates based on the identified heart beats from each filter for each signal. The fetal heart rate thus determined is outputted to a display, storage, or communications channel. A method for enhanced fetal heart beat discrimination includes acquiring signals from a fetus, identifying fetal heart beats from the signals by multiple parallel nonlinear filtering, and determining a fetal heart rate based on the identified fetal heart beats. A figure of merit operation in this method provides for weighting a plurality of fetal heart rate estimates based on the identified fetal heart beats and selecting the highest ranking fetal heart rate estimate.

Embryo-fetal development toxicity of honokiol microemulsion intravenously administered to pregnant rats.

PubMed

Zhang, Qianqian; Ye, Xiangfeng; Wang, Lingzhi; Peng, Bangjie; Zhang, Yingxue; Bao, Jie; Li, Wanfang; Wei, Jinfeng; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

2016-02-01

The aim of this study was to evaluate the embryo-fetal development toxicity of honokiol microemulsion. The drug was intravenously injected to pregnant SD rats at dose levels of 0, 200, 600 and 2000 μg/kg/day from day 6-15 of gestation. All the pregnant animals were observed for body weights and any abnormal changes and subjected to caesarean-section on gestation day (GD) 20; all fetuses obtained from caesarean-section were assessed by external inspection, visceral and skeletal examinations. No treatment-related external alterations as well as visceral and skeletal malformations were observed in honokiol microemulsion groups. There was no significant difference in the body weight gain of the pregnant rats, average number of corpora lutea, and the gravid uterus weight in the honokiol microemulsion groups compared with the vehicle control group. However, at a dose level of 2000 μg/kg/day, there was embryo-fetal developmental toxicity observed, including a decrease in the body length and tail length of fetuses. In conclusion, the no-observed-adverse-effect level (NOAEL) of honokiol microemulsion is 600 μg/kg/day, 75 times above the therapeutic dosage and it has embryo-fetal toxicity at a dose level of 2000 μg/kg/day, which is approximately 250 times above the therapeutic dosage. Copyright © 2015 Elsevier Inc. All rights reserved.

Increased fetal epicardial fat thickness: A novel ultrasound marker for altered fetal metabolism in diabetic pregnancies.

PubMed

Akkurt, Mehmet O; Turan, Ozhan M; Crimmins, Sarah; Harman, Christopher R; Turan, Sifa

2018-05-08

To evaluate whether fetal epicardial fat thickness (EFT) differs in diabetic and nondiabetic pregnant women. Retrospective case-control study of pregnancies between 24 and 36 weeks complicated by preexisting (PDM) or gestational (GDM) diabetes mellitus, matched one to one with controls for body mass index and gestational age (GA). Epicardial fat was identified as the hypoechogenic area between myocardium and visceral pericardium over the right ventricle and its thickness was measured by a single observer blinded to clinical condition and outcomes. A linear regression analysis was performed to assess the relationship between GA and EFT, and regression lines were compared between diabetics and controls. 53 PDM and 53 GDM pregnant women were matched with controls. With the exception of maternal age, the demographics were similar among groups. EFT increased significantly with advancing gestation in both diabetics and controls (P < 0.0001) and was significantly greater in diabetics than in controls (P < 0.0001). The best fit lines were different between diabetics (EFT = 0.05 × GA + 0.07 mm; R 2  = 0.70) and controls (EFT = 0.07 × GA + 0.04 mm; R 2  = 0.93) (P < 0.0001). Fetal EFT was greater in diabetics than in nondiabetics, and even greater in pregestational diabetics. EFT maybe an additional and/or earlier marker to identify early changes in fetal metabolism before accelerated fetal growth and polyhydramnios is apparent. © 2018 Wiley Periodicals, Inc.

The entotympanic in late fetal Artiodactyla (Mammalia).

PubMed

Maier, Wolfgang

2013-08-01

The entotympanic is a neomorphic component of the bulla tympanica of placental mammals. Ontogenetically, its rostral component seems to be derived from the tubal cartilage, whereas its caudal component is normally connected with the sheath of the tympanohyal; the present study indicates additional sources of the caudal entotympanic. The entotympanics develop in late fetal or early postnatal life as cartilaginous structures, but in most taxa they ossifiy endochondrally as "os bullae". This skeletal element is absent only in a few placental orders, among them the Artiodactyla. Because it is present in their sister taxa within the Scrotifera, it is likely to be reduced secondarily in the even-toed mammals. The study of histological serial sections of late fetal stages of several artiodactyl species shows that vestigial cartilaginous homologues of the entotympanics are invariably present, contrary to statements in the literature. In a few perinatal stages even secondary ossifications or calcifications of the entotympanic cartilages can be observed. The tubal cartilage of artiodactyls also continues into an anterior tegmen tympani (new term) that forms the floor of the fossa muscularis major. Copyright © 2013 Wiley Periodicals, Inc.

Ultrasonographic fetal growth charts: an informatic approach by quantitative analysis of the impact of ethnicity on diagnoses based on a preliminary report on Salentinian population.

PubMed

Tinelli, Andrea; Bochicchio, Mario Alessandro; Vaira, Lucia; Malvasi, Antonio

2014-01-01

Clear guidance on fetal growth assessment is important because of the strong links between growth restriction or macrosomia and adverse perinatal outcome in order to reduce associated morbidity and mortality. Fetal growth curves are extensively adopted to track fetal sizes from the early phases of pregnancy up to delivery. In the literature, a large variety of reference charts are reported but they are mostly up to five decades old. Furthermore, they do not address several variables and factors (e.g., ethnicity, foods, lifestyle, smoke, and physiological and pathological variables), which are very important for a correct evaluation of the fetal well-being. Therefore, currently adopted fetal growth charts are inadequate to support the melting pot of ethnic groups and lifestyles of our society. Customized fetal growth charts are needed to provide an accurate fetal assessment and to avoid unnecessary obstetric interventions at the time of delivery. Starting from the development of a growth chart purposely built for a specific population, in the paper, authors quantify and analyse the impact of the adoption of wrong growth charts on fetal diagnoses. These results come from a preliminary evaluation of a new open service developed to produce personalized growth charts for specific ethnicity, lifestyle, and other parameters.

Clinical characteristics of mirror syndrome: a comparison of 10 cases of mirror syndrome with non-mirror syndrome fetal hydrops cases.

PubMed

Hirata, Go; Aoki, Shigeru; Sakamaki, Kentaro; Takahashi, Tsuneo; Hirahara, Fumiki; Ishikawa, Hiroshi

2016-01-01

To investigate clinical features of mirror syndrome. We retrospectively reviewed 71 cases of fetal hydrops with or without mirror syndrome, and compared with respect to maternal age, the body mass index, the primipara rate, the gestational age at delivery, the timing of fetal hydrops onset, the severity of fetal edema, placental swelling, the laboratory data and the fetal mortality. The data are expressed as the medians. Mirror syndrome developed in 29% (10/35) of the cases with fetal hydrops. In mirror group, the onset time of fetal hydrops was significantly earlier (29 weeks versus 31 weeks, p = 0.011), and the severity of fetal hydrops (fetal edema/biparietal diameter) was significantly higher than non-mirror group (0.23 versus 0.16, p < 0.001). There was significantly higher serum human chorionic gonadotropin (hCG) (453,000 IU/L versus 80,000 IU/L, p < 0.001) and lower hemoglobin (8.9 g/dL versus 10.1 g/dL, p =0.002), hypoalbuminemia (2.3 mg/dL versus 2.7 mg/dL, p = 0.007), hyperuricemia (6.4 mg/dL versus 5.0 mg/dL, p = 0.043) in mirror group. Mirror syndrome is occurred frequently in early and severe fetal hydrops and cause hemodilution and elevation of serum hCG.

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

Contribution of fetal brain MRI in management of severe fetal anemia.

PubMed

Ghesquière, L; Houfflin-Debarge, V; Verpillat, P; Fourquet, T; Joriot, S; Coulon, C; Vaast, P; Garabedian, C

2018-06-06

Intrauterine transfusion (IUT) has changed fetal anemia prognosis. However, long-term neurodevelopmental outcome is altered in 5% of children. Our objective was to study the contribution of fetal MRI to diagnosis brain lesions in case of fetal anemia. Retrospective monocentric descriptive study from 2005 to 2016, including all patients followed for fetal anemia requiring IUT. The indications for MRI were: hydrops fetalis and / or hemoglobin <5 g / dL and / or more than 3 IUTs and / or acute severe anemia and / or ultrasound abnormality. Fetal and neonatal outcome and pediatric neurological monitoring were studied. 89 patients were followed for fetal anemia with IUT and 28 (29.1%) had fetal MRI, 12 of which were abnormal. Two out of twelve had abnormal ultrasound. Seven out of twelve had poor neurological prognosis: 2 medical terminations of pregnancy were performed; 2 children had severe developmental delay and 3 children had schooling difficulties. Five out of twelve children had favorable neurological prognosis. MRI of the fetal brain makes it possible to better detect brain lesions than ultrasound does in the management of severe fetal anemia and seems particularly appropriate in cases of acute anemia. Copyright © 2018 Elsevier B.V. All rights reserved.

[Optimistic perspectives in communicating difficult news on fetal development].

PubMed

Ostermann, Ana Cristina; Frezza, Minéia; Rosa, Rafael Machado

2017-08-21

Communicating diagnostic news in health contexts is a potentially difficult event for all parties involved. However, despite this task's presence in the physician-patient context, it is rarely addressed during clinical training. The current study thus aimed to describe and evaluate how difficult news can be toned down during genetic counseling sessions involving cases of fetal syndromes and/or malformations. The study analyzed 33 naturalistic interactions (i.e. real situations), taped and transcribed, according to the theoretical and methodological perspective of Conversation Analysis, with an ethnomethodological basis. These interactions consisted of sessions in clinical genetics with pregnant women seen at the fetal medicine service of a reference hospital for maternal and child health in the Brazilian Unified National Health System (SUS). The analysis showed that communicating difficult news can be accompanied by optimistic perspectives that are scaled-up according to each situation's severity. In the absence of a positive diagnosis, the appointments can conclude with positive aspects such as recommendations for palliative care, so that the patient always leaves the appointment with some kind of recommendation. This study proposes to innovate and expand the scope of studies on communicating difficult news in the physician-patient relationship in Brazil, precisely by developing an analysis of real interactions in genetic counseling and thus providing interactional backing for training health professionals that deal with this challenge in their routine work.

Adjustable fetal phantom for pulse oximetry

NASA Astrophysics Data System (ADS)

Stubán, Norbert; Niwayama, Masatsugu

2009-05-01

As the measuring head of a fetal pulse oximeter must be attached to the head of the fetus inside the mother's uterus during labor, testing, and developing of fetal pulse oximeters in real environment have several difficulties. A fetal phantom could enable evaluation of pulse oximeters in a simulated environment without the restrictions and difficultness of medical experiments in the labor room. Based on anatomic data we developed an adjustable fetal head phantom with three different tissue layers and artificial arteries. The phantom consisted of two arteries with an inner diameter of 0.2 and 0.4 mm. An electronically controlled pump produced pulse waves in the arteries. With the phantom we investigated the sensitivity of a custom-designed wireless pulse oximeter at different pulsation intensity and artery diameters. The results showed that the oximeter was capable of identifying 4% and 2% changes in diameter between the diastolic and systolic point in arteries of over 0.2 and 0.4 mm inner diameter, respectively. As the structure of the phantom is based on reported anatomic values, the results predict that the investigated custom-designed wireless pulse oximeter has sufficient sensitivity to detect the pulse waves and to calculate the R rate on the fetal head.

Fetal MRI lung volumes are predictive of perinatal outcomes in fetuses with congenital lung masses.

PubMed

Zamora, Irving J; Sheikh, Fariha; Cassady, Christopher I; Olutoye, Oluyinka O; Mehollin-Ray, Amy R; Ruano, Rodrigo; Lee, Timothy C; Welty, Stephen E; Belfort, Michael A; Ethun, Cecilia G; Kim, Michael E; Cass, Darrell L

2014-06-01

The purpose of this study was to evaluate fetal magnetic resonance imaging (MRI) as a modality for predicting perinatal outcomes and lung-related morbidity in fetuses with congenital lung masses (CLM). The records of all patients treated for CLM from 2002 to 2012 were reviewed retrospectively. Fetal MRI-derived lung mass volume ratio (LMVR), observed/expected normal fetal lung volume (O/E-NFLV), and lesion-to-lung volume ratio (LLV) were calculated. Multivariate regression and receiver operating characteristic analyses were applied to determine the predictive accuracy of prenatal imaging. Of 128 fetuses with CLM, 93% (n=118) survived. MRI data were available for 113 fetuses. In early gestation (<26weeks), MRI measurements of LMVR and LLV correlated with risk of fetal hydrops, mortality, and/or need for fetal intervention. In later gestation (>26weeks), LMVR, LLV, and O/E-NFLV correlated with neonatal respiratory distress, intubation, NICU admission and need for neonatal surgery. On multivariate regression, LMVR was the strongest predictor for development of fetal hydrops (OR: 6.97, 1.58-30.84; p=0.01) and neonatal respiratory distress (OR: 12.38, 3.52-43.61; p≤0.001). An LMVR >2.0 predicted worse perinatal outcome with 83% sensitivity and 99% specificity (AUC=0.94; p<0.001). Fetal MRI volumetric measurements of lung masses and residual normal lung are predictive of perinatal outcomes in fetuses with CLM. These data may assist in perinatal risk stratification, counseling, and resource utilization. Copyright © 2014 Elsevier Inc. All rights reserved.

The effects of prenatal cannabis exposure on fetal development and pregnancy outcomes: a protocol.

PubMed

Gunn, Jayleen K L; Rosales, Cecilia B; Center, Katherine E; Nuñez, Annabelle V; Gibson, Steven J; Ehiri, John E

2015-03-13

The effects of exposure to marijuana in utero on fetal development are not clear. Given that the recent legislation on cannabis in the US is likely to result in increased use, there is a need to assess the effects of prenatal cannabis exposure on fetal development and pregnancy outcomes. The objective of this review is to assess the effects of prenatal exposure to cannabis on pregnancy outcomes (including maternal and child outcomes). Major databases will be searched from inception to the latest issue, with the aim of identifying studies that reported the effects of prenatal exposure to cannabis on fetal development and pregnancy outcomes. Two investigators will independently review all titles and abstracts to identify potential articles. Discrepancies will be resolved by repeated review, discussion and consensus. Study quality assessment will be undertaken, using standard protocols. To qualify for inclusion, studies must report at least one maternal or neonatal outcome post partum. Cross-sectional, case-control, cohort and randomised controlled trials published in English will be included. In order to rule out the effects of other drugs that may affect fetal development and pregnancy outcomes, studies will only be included if they report outcomes of prenatal exposure to cannabis while excluding other illicit substances. Data from eligible studies will be extracted, and data analysis will include a systematic review and critical appraisal of evidence, and meta-analysis if data permit. Meta-analysis will be conducted if three or more studies report comparable statistics on the same outcome. The review which will result from this protocol has not already been conducted. Preparation of the review will follow the procedures stated in this protocol, and will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ethical approval of data will not be required since the review will use data that are already available in the

Sonography in Fetal Birth Weight Estimation

ERIC Educational Resources Information Center

Akinola, R. A.; Akinola, O. I.; Oyekan, O. O.

2009-01-01

The estimation of fetal birth weight is an important factor in the management of high risk pregnancies. The information and knowledge gained through this study, comparing a combination of various fetal parameters using computer assisted analysis, will help the obstetrician to screen the high risk pregnancies, monitor the growth and development,…

Agonist mediated fetal muscle-type nicotinic acetylcholine receptor desensitization

USDA-ARS?s Scientific Manuscript database

The exposure of a developing embryo or fetus to teratogenic alkaloids from plants has the potential to cause developmental defects in livestock due to the inhibition of fetal movement by alkaloids. The mechanism behind the inhibition of fetal movement is the desensitization of fetal muscle-type nico...

Comparative assessments of the effects of alcohol exposure on fetal brain development using optical coherence tomography and ultrasound imaging

NASA Astrophysics Data System (ADS)

Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

2013-02-01

The developing fetal brain is vulnerable to a variety of environmental agents including maternal ethanol consumption. Preclinical studies on the development and amelioration of fetal teratology would be significantly facilitated by the application of high resolution imaging technologies like optical coherence tomography (OCT) and high-frequency ultrasound (US). This study investigates the ability of these imaging technologies to measure the effects of maternal ethanol exposure on brain development, ex vivo, in fetal mice. Pregnant mice at gestational day 12.5 were administered ethanol (3 g/Kg b.wt.) or water by intragastric gavage, twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and imaged. Three-dimensional images of the mice fetus brains were obtained by OCT and high-resolution US, and the volumes of the left and right ventricles of the brain were measured. Ethanol-exposed fetuses exhibited a statistically significant, 2-fold increase in average left and right ventricular volumes compared with the ventricular volume of control fetuses, with OCT-derived measures of 0.38 and 0.18 mm3, respectively, whereas the boundaries of the fetal mouse lateral ventricles were not clearly definable with US imaging. Our results indicate that OCT is a useful technology for assessing ventriculomegaly accompanying alcohol-induced developmental delay. This study clearly demonstrated advantages of using OCT for quantitative assessment of embryonic development compared with US imaging.

The human homeobox genes MSX-1, MSX-2, and MOX-1 are differentially expressed in the dermis and epidermis in fetal and adult skin.

PubMed

Stelnicki, E J; Kömüves, L G; Holmes, D; Clavin, W; Harrison, M R; Adzick, N S; Largman, C

1997-10-01

In order to identify homeobox genes which may regulate skin development and possibly mediate scarless fetal wound healing we have screened amplified human fetal skin cDNAs by polymerase chain reaction (PCR) using degenerate oligonucleotide primers designed against highly conserved regions within the homeobox. We identified three non-HOX homeobox genes, MSX-1, MSX-2, and MOX-1, which were differentially expressed in fetal and adult human skin. MSX-1 and MSX-2 were detected in the epidermis, hair follicles, and fibroblasts of the developing fetal skin by in situ hybridization. In contrast, MSX-1 and MSX-2 expression in adult skin was confined to epithelially derived structures. Immunohistochemical analysis of these two genes suggested that their respective homeoproteins may be differentially regulated. While Msx-1 was detected in the cell nucleus of both fetal and adult skin; Msx-2 was detected as a diffuse cytoplasmic signal in fetal epidermis and portions of the hair follicle and dermis, but was localized to the nucleus in adult epidermis. MOX-1 was expressed in a pattern similar to MSX early in gestation but then was restricted exclusively to follicular cells in the innermost layer of the outer root sheath by 21 weeks of development. Furthermore, MOX-1 expression was completely absent in adult cutaneous tissue. These data imply that each of these homeobox genes plays a specific role in skin development.

Histochemical properties of bovine and ovine mammary glands during fetal development.

PubMed

Hara, Asuka; Abe, Tomoyuki; Hirao, Atsushi; Sanbe, Kazuhiro; Ayakawa, Hiromichi; Sarantonglaga, Borjigin; Yamaguchi, Mio; Sato, Akane; Khurchabilig, Atchalalt; Ogata, Kazuko; Fukumori, Rika; Sugita, Shoei; Nagao, Yoshikazu

2018-02-20

In order to obtain more information on the development of bovine and ovine fetal mammary glands, a series of mammary glands from fetuses of different ages were analyzed. A total of 16 bovine fetuses with curved crown rump lengths ranging from 12 cm (80 days) to 75 cm (240 days) and 15 ovine fetuses ranging from 55 days to 131 days were examined. We used hematoxylin and eosin stain and Oil-Red-O stain to analyze the developmental and morphogenetic processes of mammary glands. In addition, we used immunohistochemical staining to determine the pattern of expression of cytokeratin 18 (CK18) during luminal epithelial differentiation, α-smooth-muscle actin (α-SMA) for myoepithelial differentiation, Ki-67 for cell proliferation, and estrogen receptor α (ERα). Our analyzes showed: (a) The primary mammary duct begin to proliferate in a lengthwise within the teat at 90 days in bovine fetuses and 63 days in ovine fetus; (b) luminal epithelial cells and myoepithelial cells appeared from 90 days in bovine fetuses and 63 days in ovine fetus; (c) proliferation of epithelial cells appeared to coincide with the development of the primary and secondary ducts; and (d) ERα was not found in the fetal mammary gland, but adipocytes showed the presence of ERα. Overall, these results indicate that the sequence of events in the prenatal development of the mammary gland of sheep is similar to that of cattle.

Histochemical properties of bovine and ovine mammary glands during fetal development

PubMed Central

HARA, Asuka; ABE, Tomoyuki; HIRAO, Atsushi; SANBE, Kazuhiro; AYAKAWA, Hiromichi; SARANTONGLAGA, Borjigin; YAMAGUCHI, Mio; SATO, Akane; KHURCHABILIG, Atchalalt; OGATA, Kazuko; FUKUMORI, Rika; SUGITA, Shoei; NAGAO, Yoshikazu

2017-01-01

In order to obtain more information on the development of bovine and ovine fetal mammary glands, a series of mammary glands from fetuses of different ages were analyzed. A total of 16 bovine fetuses with curved crown rump lengths ranging from 12 cm (80 days) to 75 cm (240 days) and 15 ovine fetuses ranging from 55 days to 131 days were examined. We used hematoxylin and eosin stain and Oil-Red-O stain to analyze the developmental and morphogenetic processes of mammary glands. In addition, we used immunohistochemical staining to determine the pattern of expression of cytokeratin 18 (CK18) during luminal epithelial differentiation, α-smooth-muscle actin (α-SMA) for myoepithelial differentiation, Ki-67 for cell proliferation, and estrogen receptor α (ERα). Our analyzes showed: (a) The primary mammary duct begin to proliferate in a lengthwise within the teat at 90 days in bovine fetuses and 63 days in ovine fetus; (b) luminal epithelial cells and myoepithelial cells appeared from 90 days in bovine fetuses and 63 days in ovine fetus; (c) proliferation of epithelial cells appeared to coincide with the development of the primary and secondary ducts; and (d) ERα was not found in the fetal mammary gland, but adipocytes showed the presence of ERα. Overall, these results indicate that the sequence of events in the prenatal development of the mammary gland of sheep is similar to that of cattle. PMID:29249731

From research to practice: an integrative framework for the development of interventions for children with fetal alcohol spectrum disorders.

PubMed

Kodituwakku, Piyadasa W; Kodituwakku, E Louise

2011-06-01

Since fetal alcohol syndrome was first described over 35 years ago, considerable progress has been made in the delineation of the neurocognitive profile in children with prenatal alcohol exposure. Preclinical investigators have made impressive strides in elucidating the mechanisms of alcohol teratogenesis and in testing the effectiveness of pharmacological agents and dietary supplementation in the amelioration of alcohol-induced deficits. Despite these advances, only limited progress has been made in the development of evidence-based comprehensive interventions for functional impairment in alcohol-exposed children. Having performed a search in PubMed and PsycINFO using key words, interventions, treatment, fetal alcohol syndrome, prenatal alcohol exposure, and fetal alcohol spectrum disorders, we found only 12 papers on empirically-based interventions. Only two of these interventions had been replicated and none met the criteria of "well-established," as defined by Chambless and Hollon (Journal of Consulting and Clinical Psychology 66(1):7-18, 1998). There has been only limited cross-fertilization of ideas between preclinical and clinical research with regard to the development of interventions. Therefore, we propose a framework that allows integrating data from preclinical and clinical investigations to develop comprehensive intervention programs for children with fetal alcohol spectrum disorders. This framework underscores the importance of multi-level evaluations and interventions.

Sex-related differences in the development of fetal heart rate dynamics.

PubMed

Kim, Kyu Nam; Park, Young-Sun; Hoh, Jeong-Kyu

2016-02-01

Despite previous efforts to explain the general advantages of female fetuses over males regarding health, sex-related differences in the dynamics or complexity of fetal heart rate (FHR) variability and FHR maturation patterns have not yet been identified. To make linear and nonlinear comparisons of antepartum FHR indices, dynamics, complexity, and reactivity to the non-stress test (NST) and vibroacoustic-stimulation test (VAST) in male and female fetuses. A total of 3835 singleton term deliveries without maternal and fetal complications were divided into female (n=1849) and male (n=1986) groups, and subjected to comparison and analyses. Linear FHR indices, approximate entropy (ApEn), sample entropy (SampEn), short-term/long-term exponents (α1/α2), correlation dimension (CD), NST and VAST criteria, and modified nonlinear reactive criteria (MNRC) were used to evaluate outcomes. ApEn was consistently higher in female fetuses than in male ones. ApEn in female fetuses was maximal at 29-30 gestational weeks, while the increase in ApEn was delayed in male fetuses but more rapid, reaching its peak at 31-32 gestational weeks. In both sexes, CD increased up to term, and α2 rapidly decreased up to 31-32weeks in an analogous manner. The two sexes differed significantly in response to VAST at <31 gestational weeks and there was a structural difference in reactive patterns under MNRC. Female fetuses exhibit greater heart rate dynamics in early gestational periods, suggesting that their cardiovascular system matures earlier than that of males. Male fetuses undergo a compensatory period of rapid change to catch up with females at term. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Prominent periventricular fiber system related to ganglionic eminence and striatum in the human fetal cerebrum.

PubMed

Vasung, L; Jovanov-Milošević, N; Pletikos, M; Mori, S; Judaš, M; Kostović, Ivica

2011-01-01

Periventricular pathway (PVP) system of the developing human cerebrum is situated medial to the intermediate zone in the close proximity to proliferative cell compartments. In order to elucidate chemical properties and developing trajectories of the PVP we used DTI in combination with acetylcholinesterase histochemistry, SNAP-25 immunocytochemistry and axonal cytoskeletal markers (SMI312, MAP1b) immunocytochemistry on postmortem paraformaldehyde-fixed brains of 30 human fetuses ranging in age from 10 to 38 postconceptional weeks (PCW), 2 infants (age 1-3 months) and 1 adult brain. The PVP appears in the early fetal period (10-13 PCW) as two defined fibre bundles: the corpus callosum (CC) and the fetal fronto-occipital fascicle (FOF). In the midfetal period (15-18 PCW), all four components of the PVP can be identified: (1) the CC, which at rostral levels forms a voluminous callosal plate; (2) the FOF, with SNAP-25-positive fibers; (3) the fronto-pontine pathway (FPP) which for a short distance runs within the PVP; and (4) the subcallosal fascicle of Muratoff (SFM) which contains cortico-caudate projections. The PVPs are situated medial to the internal capsule at the level of the cortico-striatal junction; they remain prominent during the late fetal and early preterm period (19-28 PCW) and represent a portion of the wider periventricular crossroad of growing associative, callosal and projection pathways. In the perinatal period, the PVPs change their topographical relationships, decrease in size and the FOF looses its SNAP-25-reactivity. In conclusion, the hitherto undescribed PVP of the human fetal cerebrum contains forerunners of adult associative and projection pathways. Its transient chemical properties and relative exuberance suggest that the PVP may exert influence on the development of cortical connectivity (intermediate targeting) and other neurogenetic events such as neuronal proliferation. The PVP's topographical position also indicates that it is a major

Fetal and neonatal deaths of children of patients classified as near miss.

PubMed

Nardello, Daniele Marin; Guimarães, Alzira Maria D Avila Nery; Barreto, Ikaro Daniel de Carvalho; Gurgel, Ricardo Queiroz; Ribeiro, Eleonora Ramos de Oliveira; Gois, Cristiane Franca Lisboa

2017-01-01

identify the epidemiological aspects of early fetal and neonatal deaths in children of patients classified with near miss and the factors associated with this outcome. a cross-sectional study of 79 women identified with near miss and their newborns. The variables were analyzed using Fisher's exact test. Risk factors were estimated based on unadjusted and adjusted odds ratios, and by means of multiple correspondence analysis, with significance for p <0.05. hypertensive disorders totaled 40.5%; Of these, 58.3% had adverse fetal and neonatal outcome. The newborns admitted to the Neonatal Intensive Care Unit proved to be significant for the outcome (70.8%), gestational age <32 weeks (41.6%), birth weight <2500 (66.7%), neonatal asphyxia (50%) and early respiratory discomfort (72.2%). prematurity, neonatal asphyxia, and early respiratory distress were significant characteristics for the outcome among newborns.

Ethics of fetal tissue transplantation.

PubMed Central

Sanders, L M; Giudice, L; Raffin, T A

1993-01-01

Now that the Clinton Administration has overturned the ban on federal funding for fetal tissue transplantation, old ethical issues renew their relevance and new ethical issues arise. Is fetal tissue transplantation necessary and beneficial? Are fetal rights violated by the use of fetal tissue in research? Is there a moral danger that the potential of fetal tissue donation will encourage elective abortions? Should pregnant women be allowed to designate specific fetal transplant recipients? What criteria should be used to select fetal tissue transplants? Whose consent should be required for the use of fetal tissue for transplantation? We review the current state of clinical research with fetal tissue transplantation, the legal history of fetal tissue research, the major arguments against the use of fetal tissue for transplantation, and the new postmoratorium ethical dilemmas. We include recommendations for guidelines to govern the medical treatment of fetal tissue in transplantation. Images PMID:8236984

Fetal Urinary Tract Anomalies: Review of Pathophysiology, Imaging, and Management.

PubMed

Mileto, Achille; Itani, Malak; Katz, Douglas S; Siebert, Joseph R; Dighe, Manjiri K; Dubinsky, Theodore J; Moshiri, Mariam

2018-05-01

Common fetal anomalies of the kidneys and urinary tract encompass a complex spectrum of abnormalities that can be detected prenatally by ultrasound. Common fetal anomalies of the kidneys and urinary tract can affect amniotic fluid volume production with the development of oligohydramnios or anhydramnios, resulting in fetal pulmonary hypoplasia and, potentially, abnormal development of other fetal structures. We provide an overview of common fetal anomalies of the kidneys and urinary tract with an emphasis on sonographic patterns as well as pathologic and postnatal correlation, along with brief recommendations for postnatal management. Of note, we render an updated classification of fetal abnormalities of the kidneys and urinary tract based on the presence or absence of associated urinary tract dilation. In addition, we review the 2014 classification of urinary tract dilation based on the Linthicum multidisciplinary consensus panel.

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.

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

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

Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset

PubMed Central

McKinnell, Chris; Mitchell, Rod T.; Walker, Marion; Morris, Keith; Kelnar, Chris J.H.; Wallace, W. Hamish; Sharpe, Richard M.

2009-01-01

BACKGROUND Fetal exposure of male rats to some phthalates induces reproductive abnormalities, raising concerns for similar effects in humans. In order to address this in a more appropriate animal model, the aim of the present studies was to investigate the effect of fetal/neonatal exposure to monobutyl phthalate (MBP) in a non-human primate, the marmoset. In particular, to determine if exposure resulted in effects at birth, or in adulthood, similar to those in male rats, and whether there was evidence for induction of carcinoma-in-situ (CIS) or testicular germ cell tumours (TGCT). METHODS Pregnant female marmosets were dosed from ∼7–15 weeks gestation with 500 mg/kg/day MBP and male offspring studied at birth (1–5 days; n = 6) or in adulthood (n = 5). In another study, newborn males (n = 5 co-twins) were dosed with 500 mg/kg/day MBP for 14 days, commencing at ∼4 days of age. RESULTS Fetal exposure of marmosets to MBP did not affect gross testicular morphology, reproductive tract development or testosterone levels at birth, nor were germ cell number and proliferation, Sertoli cell number or germ:Sertoli cell ratio affected. In two of six MBP-exposed animals, unusual clusters of undifferentiated germ cells were found, but their significance is unclear. Neonatal MBP treatment did not affect germ cell numbers or differentiation. Fetal exposure to MBP did not affect testis size/morphology, germ cell numbers or fertility in adulthood. There was no evidence for CIS or TGCT. CONCLUSIONS Fetal exposure of marmosets to MBP does not measurably affect testis development/function or cause testicular dysgenesis, and no effects emerge by adulthood. Some effects on germ cell development were found, but these were inconsistent and of uncertain significance. PMID:19491204

Thyroid hormone is required for growth adaptation to pressure load in the ovine fetal heart.

PubMed

Segar, Jeffrey L; Volk, Ken A; Lipman, Michael H B; Scholz, Thomas D

2013-03-01

Thyroid hormone exerts broad effects on the adult heart, but little is known regarding the role of thyroid hormone in the regulation of cardiac growth early in development and in response to pathophysiological conditions. To address this issue, we determined the effects of fetal thyroidectomy on cardiac growth and growth-related gene expression in control and pulmonary-artery-banded fetal sheep. Fetal thyroidectomy (THX) and/or placement of a restrictive pulmonary artery band (PAB) were performed at 126 ± 1 days of gestation (term, 145 days). Four groups of animals [n = 5-6 in each group; (i) control; (ii) fetal THX; (iii) fetal PAB; and (iv) fetal PAB + THX] were monitored for 1 week prior to being killed. Fetal heart rate was significantly lower in the two THX groups compared with the non-THX groups, while mean arterial blood pressure was similar among groups. Combined left and right ventricle free wall + septum weight, expressed per kilogram of fetal weight, was significantly increased in PAB (6.27 ± 0.85 g kg(-1)) compared with control animals (4.72 ± 0.12 g kg(-1)). Thyroidectomy significantly attenuated the increase in cardiac mass associated with PAB (4.94 ± 0.13 g kg(-1)), while THX alone had no detectable effect on heart mass (4.95 ± 0.27 g kg(-1)). The percentage of binucleated cardiomyocytes was significantly decreased in THX and PAB +THX groups (∼16%) compared with the non-THX groups (∼27%). No differences in levels of activated Akt, extracellular signal-regulated kinase or c-Jun N-terminal kinase were detected among the groups. Markers of cellular proliferation but not apoptosis or expression of growth-related genes were lower in the THX and THX+ PAB groups relative to thyroid-intact animals. These findings suggest that in the late-gestation fetal heart, thyroid hormone has important cellular growth functions in both physiological and pathophysiological states. Specifically, thyroid hormone is required for adaptive fetal cardiac growth in

Subclinical decelerations during developing hypotension in preterm fetal sheep after acute on chronic lipopolysaccharide exposure

PubMed Central

Lear, Christopher A.; Davidson, Joanne O.; Galinsky, Robert; Yuill, Caroline A.; Wassink, Guido; Booth, Lindsea C.; Drury, Paul P.; Bennet, Laura; Gunn, Alistair J.

2015-01-01

Subclinical (shallow) heart rate decelerations occur during neonatal sepsis, but there is limited information on their relationship with hypotension or whether they occur before birth. We examined whether subclinical decelerations, a fall in fetal heart rate (FHR) that remained above 100 bpm, were associated with hypotension in preterm fetal sheep exposed to lipopolysaccharide (LPS). Chronically-instrumented fetal sheep at 0.7 gestation received continuous low-dose LPS infusions (n = 15, 100 ng/kg over 24 h, followed by 250 ng/kg/24 h for 96 h) or saline (n = 8). Boluses of 1 μg LPS or saline were given at 48 and 72 h. FHR variability (FHRV) was calculated, and sample asymmetry was used to assess the severity and frequency of decelerations. Low-dose LPS infusion did not affect FHR. After the first LPS bolus, 7 fetuses remained normotensive, while 8 developed hypotension (a fall in mean arterial blood pressure of ≥5 mmHg). Developing hypotension was associated with subclinical decelerations, with a corresponding increase in sample asymmetry and FHRV (p < 0.05). The second LPS bolus was associated with similar but attenuated changes in FHR and blood pressure (p < 0.05). In conclusion, subclinical decelerations are not consistently seen during prenatal exposure to LPS, but may be a useful marker of developing inflammation-related hypotension before birth. PMID:26537688

Congenital oculomotor nerve synkinesis associated with fetal retinoid syndrome.

PubMed

Morrison, David G; Elsas, Frederick J; Descartes, Maria

2005-04-01

Isotretinoin (RA), used for the treatment of cystic acne, is a powerful teratogen, causing craniofacial dysmorphisms and neural tube defects. We present two patients with RA embryopathy and oculomotor nerve synkinesis. Retrospective review of patient records. Two patients presented with third nerve synkinesis and fetal RA exposure. Both had marked elevation of the upper eyelids on adduction such that the lid fissures alternately opened and closed on gaze from side to side. Both patients showed typical dysmorphisms of RA embryopathy. The first patient had complete agenesis of the cerebellar vermix and died at 2 years. The second patient had restricted extraocular muscles in one eye and was exotropic and hypotropic. Both patients demonstrated simultaneous innervation of the medial rectus and levator palpebrae muscles causing coincident lid elevation in adduction. This evidence of oculomotor nerve synkinesis is consistent with animal studies showing abnormalities in the formation of cranial nerve ganglia following fetal RA exposure. RA is a powerful teratogen. These patients provide additional clinical evidence of its influence on neural migration during early development.

Intrapartum fetal heart rate classification from trajectory in Sparse SVM feature space.

PubMed

Spilka, J; Frecon, J; Leonarduzzi, R; Pustelnik, N; Abry, P; Doret, M

2015-01-01

Intrapartum fetal heart rate (FHR) constitutes a prominent source of information for the assessment of fetal reactions to stress events during delivery. Yet, early detection of fetal acidosis remains a challenging signal processing task. The originality of the present contribution are three-fold: multiscale representations and wavelet leader based multifractal analysis are used to quantify FHR variability ; Supervised classification is achieved by means of Sparse-SVM that aim jointly to achieve optimal detection performance and to select relevant features in a multivariate setting ; Trajectories in the feature space accounting for the evolution along time of features while labor progresses are involved in the construction of indices quantifying fetal health. The classification performance permitted by this combination of tools are quantified on a intrapartum FHR large database (≃ 1250 subjects) collected at a French academic public hospital.

Development of Fetal Yawn Compared with Non-Yawn Mouth Openings from 24–36 Weeks Gestation

PubMed Central

Reissland, Nadja; Francis, Brian; Mason, James

2012-01-01

Background Although some research suggests that fetuses yawn, others disagree arguing that is it simple mouth opening. Furthermore there is no developmental account of fetal yawning compared with simple mouth opening. The aim of the present study was to establish in a repeated measures design the development of fetal yawning compared with simple mouth opening. Methodology/Findings Video recordings were made of the fetal face and upper torso visualized by means of 4D full frontal or facial profile ultrasound recordings. Fifteen healthy fetuses were scanned four times at 24, 28, 32 and 36 weeks gestation. Yawning was distinguished from non-yawning in terms of the length of time it took to reach the apex of the mouth stretch, with yawns being defined as more than 50% of the total time observed. To assess changes in frequency, a Poisson mixed effects model was fitted to the count of number of yawn and simple mouth opening events with age and gender as fixed effects, and person as a random effect. For both yawns and simple mouth openings a smooth varying age effect was significant. The number of yawns observed declined with age from 28 weeks gestation, whereas simple mouth openings were less frequent and the decline was observed from 24 weeks. Gender was not significant either for yawn and simple mouth openings. Conclusions/Significance Yawning can be reliably distinguished from other forms of mouth opening with the potential of using yawning as an index of fetal healthy development. PMID:23185638

Fetal motion estimation from noninvasive cardiac signal recordings.

PubMed

Biglari, Hadis; Sameni, Reza

2016-11-01

Fetal motility is a widely accepted indicator of the well-being of a fetus. In previous research, it has be shown that fetal motion (FM) is coherent with fetal heart rate accelerations and an indicator for active/rest cycles of the fetus. The most common approach for FM and fetal heart rate (FHR) assessment is by Doppler ultrasound (DUS). While DUS is the most common approach for studying the mechanical activities of the heart, noninvasive fetal electrocardiogram (ECG) and magnetocardiogram (MCG) recording and processing techniques have been considered as a possible competitor (or complement) for the DUS. In this study, a fully automatic and robust framework is proposed for the extraction, ranking and alignment of fetal QRS-complexes from noninvasive fetal ECG/MCG. Using notions from subspace tracking, two measures, namely the actogram and rotatogram, are defined for fetal motion tracking. The method is applied to four fetal ECG/MCG databases, including twin MCG recordings. By defining a novel measure of causality, it is shown that there is significant coherency and causal relationship between the actogram/rotatogram and FHR accelerations/decelerations. Using this measure, it is shown that in many cases, the actogram and rotatogram precede the FHR variations, which supports the idea of motion-induced FHR accelerations/decelerations for these cases and raises attention for the non-motion-induced FHR variations, which can be associated to the fetal central nervous system developments. The results of this study can lead to novel perspectives of the fetal sympathetic and parasympathetic brain systems and future requirements of fetal cardiac monitoring.

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.

ACR Appropriateness Criteria Assessment of Fetal Well-Being.

PubMed

Simpson, Lynn; Khati, Nadia J; Deshmukh, Sandeep P; Dudiak, Kika M; Harisinghani, Mukesh G; Henrichsen, Tara L; Meyer, Benjamin J; Nyberg, David A; Poder, Liina; Shipp, Thomas D; Zelop, Carolyn M; Glanc, Phyllis

2016-12-01

Although there is limited evidence that antepartum testing decreases the risk for fetal death in low-risk pregnancies, women with high-risk factors for stillbirth should undergo antenatal fetal surveillance. The strongest evidence supporting antepartum testing pertains to pregnancies complicated by intrauterine fetal growth restriction secondary to uteroplacental insufficiency. The main ultrasound-based modalities to determine fetal health are the biophysical profile, modified biophysical profile, and duplex Doppler velocimetry. In patients at risk for cardiovascular compromise, fetal echocardiography may also be indicated to ensure fetal well-being. Although no single antenatal test has been shown to be superior, all have high negative predictive values. Weekly or twice-weekly fetal testing has become the standard practice in high-risk pregnancies. The timing for the initiation of assessments of fetal well-being should be tailored on the basis of the risk for stillbirth and the likelihood of survival with intervention. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (the RAND/UCLA Appropriateness Method and the Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Biomedical Instruments for Fetal and Neonatal Surveillance

NASA Astrophysics Data System (ADS)

Rolfe, P.; Scopesi, F.; Serra, G.

2006-10-01

Specialised instruments have been developed to aid the care of the fetus and the newborn baby. Miniature sensors using optical, electrical, chemical, mechanical and magnetic principles have been produced for capturing key measurands. These include temperature, pressure, flow and dimension, as well as several specific molecules such as glucose, oxygen and carbon dioxide. During pregnancy ultrasound imaging and blood flow techniques provide valuable information concerning fetal abnormalities, fetal growth, fetal breathing and fetal heart rate. Signal processing and pattern recognition can be useful for deriving indicators of fetal distress and clinical status, based on biopotentials as well as ultrasound signals. Fetal pH measurement is a critical requirement during labour and delivery. The intensive care of ill preterm babies involves provision of an optimal thermal environment and respiratory support. Monitoring of blood gas and acid-base status is essential, and this involves both blood sampling for in vitro analysis as well as the use of invasive or non-invasive sensors. For the future it will be vital that the technologies used are subjected to controlled trials to establish benefit or otherwise.

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.

Simvastatin reduces fetal testosterone production and permanently alters reproductive tract development in the male rat

EPA Science Inventory

Androgen signaling by fetal Leydig cells is critical in the proper development of the male reproductive tract. As cholesterol is a precursor for hormone biosynthesis,inhibition of the cholesterol pathway during sex differentiation may reduce testosterone {T). We hypothesized tha...

Mast cells contribute to scar formation during fetal wound healing.

PubMed

Wulff, Brian C; Parent, Allison E; Meleski, Melissa A; DiPietro, Luisa A; Schrementi, Megan E; Wilgus, Traci A

2012-02-01

Scar formation is a potentially detrimental process of tissue restoration in adults, affecting organ form and function. During fetal development, cutaneous wounds heal without inflammation or scarring at early stages of development; however, they begin to heal with significant inflammation and scarring as the skin becomes more mature. One possible cell type that could regulate the change from scarless to fibrotic healing is the mast cell. We show here that dermal mast cells in scarless wounds generated at embryonic day 15 (E15) are fewer in number, less mature, and do not degranulate in response to wounding as effectively as mast cells of fibrotic wounds made at embryonic day 18 (E18). Differences were also observed between cultured mast cells from E15 and E18 skin, with regard to degranulation and preformed cytokine levels. Injection of mast cell lysates into E15 wounds disrupted scarless healing, suggesting that mast cells interfere with scarless repair. Finally, wounds produced at E18, which normally heal with a scar, healed with significantly smaller scars in mast cell-deficient Kit(W/W-v) mice compared with Kit(+/+) littermates. Together, these data suggest that mast cells enhance scar formation, and that these cells may mediate the transition from scarless to fibrotic healing during fetal development.

Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome.

PubMed

Spong, C Y; Abebe, D T; Gozes, I; Brenneman, D E; Hill, J M

2001-05-01

Two peptides [NAPVSIPQ (NAP) and SALLRSIPA (ADNF-9)], that are associated with novel glial proteins regulated by vasoactive intestinal peptide, are shown now to provide protective intervention in a model of fetal alcohol syndrome. Fetal demise and growth restrictions were produced after intraperitoneal injection of ethanol to pregnant mice during midgestation (E8). Death and growth abnormalities elicited by alcohol treatment during development are believed to be associated, in part, with severe oxidative damage. NAP and ADNF-9 have been shown to exhibit antioxidative and antiapoptotic actions in vitro. Pretreatment with an equimolar combination of the peptides prevented the alcohol-induced fetal death and growth abnormalities. Pretreatment with NAP alone resulted in a significant decrease in alcohol-associated fetal death; whereas ADNF-9 alone had no detectable effect on fetal survival after alcohol exposure, indicating a pharmacological distinction between the peptides. Biochemical assessment of the fetuses indicated that the combination peptide treatment prevented the alcohol-induced decreases in reduced glutathione. Peptide efficacy was evident with either 30-min pretreatment or with 1-h post-alcohol administration. Bioavailability studies with [(3)H]NAPVSIPQ indicated that 39% of the total radioactivity comigrated with intact peptide in the fetus 60 min after administration. These studies demonstrate that fetal death and growth restriction associated with prenatal alcohol exposure were prevented by combinatorial peptide treatment and suggest that this therapeutic strategy be explored in other models/diseases associated with oxidative stress.

[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.

The use of non-invasive fetal electrocardiography in diagnosing second-degree fetal atrioventricular block.

PubMed

Lakhno, Igor; Behar, Joachim A; Oster, Julien; Shulgin, Vyacheslav; Ostras, Oleksii; Andreotti, Fernando

2017-01-01

Complete atrioventricular block in fetuses is known to be mostly associated with autoimmune disease and can be irreversible if no steroids treatment is provided. Conventional methods used in clinical practice for diagnosing fetal arrhythmia are limited since they do not reflect the primary electrophysiological conduction processes that take place in the myocardium. The non-invasive fetal electrocardiogram has the potential to better support fetal arrhythmias diagnosis through the continuous analysis of the beat to beat variation of the fetal heart rate and morphological analysis of the PQRST complex. We present two retrospective case reports on which atrioventricular block diagnosis could have been supported by the non-invasive fetal electrocardiogram. The two cases comprised a 22-year-old pregnant woman with the gestational age of 31 weeks and a 25-year-old pregnant woman with the gestational age of 41 weeks. Both women were admitted to the Department of Maternal and Fetal Medicine at the Kyiv and Kharkiv municipal perinatal clinics. Patients were observed using standard fetal monitoring methods as well as the non-invasive fetal electrocardiogram. The non-invasive fetal electrocardiographic recordings were analyzed retrospectively, where it is possible to identify the presence of the atrioventricular block. This study demonstrates, for the first time, the feasibility of the non-invasive fetal electrocardiogram as a supplementary method to diagnose of the fetal atrioventricular block. Combined with current fetal monitoring techniques, non-invasive fetal electrocardiography could support clinical decisions.

Maternal Stress and Affect Influence Fetal Neurobehavioral Development.

ERIC Educational Resources Information Center

DiPietro, Janet A.; Hilton, Sterling C.; Hawkins, Melissa; Costigan, Kathleen A.; Pressman, Eva K.

2002-01-01

Investigated associations between maternal psychological and fetal neurobehavioral functioning with data provided at 24, 30, and 36 weeks gestation. Found that fetuses of women who were more affectively intense, appraised their lives as more stressful, and reported more pregnancy-specific hassles were more active across gestation. Fetuses of women…

Registration of 3D fetal neurosonography and MRI☆

PubMed Central

Kuklisova-Murgasova, Maria; Cifor, Amalia; Napolitano, Raffaele; Papageorghiou, Aris; Quaghebeur, Gerardine; Rutherford, Mary A.; Hajnal, Joseph V.; Noble, J. Alison; Schnabel, Julia A.

2013-01-01

We propose a method for registration of 3D fetal brain ultrasound with a reconstructed magnetic resonance fetal brain volume. This method, for the first time, allows the alignment of models of the fetal brain built from magnetic resonance images with 3D fetal brain ultrasound, opening possibilities to develop new, prior information based image analysis methods for 3D fetal neurosonography. The reconstructed magnetic resonance volume is first segmented using a probabilistic atlas and a pseudo ultrasound image volume is simulated from the segmentation. This pseudo ultrasound image is then affinely aligned with clinical ultrasound fetal brain volumes using a robust block-matching approach that can deal with intensity artefacts and missing features in the ultrasound images. A qualitative and quantitative evaluation demonstrates good performance of the method for our application, in comparison with other tested approaches. The intensity average of 27 ultrasound images co-aligned with the pseudo ultrasound template shows good correlation with anatomy of the fetal brain as seen in the reconstructed magnetic resonance image. PMID:23969169