Fetal Differences Research Articles

Brain Metabolite Differences in Fetuses With Cytomegalovirus Infection: A Magnetic Resonance Spectroscopy Study.

Cytomegalovirus (CMV) is the most common intrauterine infection and may be associated with unfavorable outcomes. While some CMV-infected fetuses may show gross or subtle brain abnormalities on MRI, their clinical significance may be unclear. Conversely, normal development cannot be guaranteed in CMV-infected fetuses with normal MRI. To assess brain metabolite differences in CMV-infected fetuses using magnetic resonance spectroscopy (MRS). Retrospective. Out of a cohort of 149 cases, 44 with maternal CMV infection, amniocentesis results, and good-quality MRS were included. CMV-infected fetuses with positive polymerase chain reaction (PCR) (N = 35) were divided based on MRI results as follows: typical brain abnormalities (gross findings, N = 8), exclusive white matter hyperintense signal (WMHS) on T2-weighted images (subtle findings, N = 7), and normal MRI (N = 20). Uninfected fetuses (negative PCR) with normal MRI were included as controls (N = 9). 3 T, T2-weighted half Fourier single-shot turbo spin-echo (HASTE), T2-weighted true fast imaging with steady-state free precession (TrueFISP), T1- and T2*-weighted fast low angle shot (FLASH), and 1H-MRS single-voxel point resolved spectroscopy (PRESS) sequences. MRI findings were assessed by three radiologists, and metabolic ratios within the basal ganglia were calculated using LCModel. Analysis of covariance test with Bonferroni correction for multiple comparisons was used to compare metabolic ratios between groups while accounting for gestational age. A P-value <0.05 was deemed significant. MRS was successfully acquired in 63% of fetuses. Substantial agreement was observed between radiologists (Fleiss' kappa [k] = 0.8). Infected fetuses with gross MRI findings exhibited significantly reduced tNAA/tCr ratios (0.64 ± 0.08) compared with infected fetuses with subtle MRI findings (0.85 ± 0.19), infected fetuses with normal MRI (0.8 ± 0.14) and controls (0.81 ± 0.15). No other significant differences were detected (P ≥ 0.261). Reduced tNAA/tCr within the apparently normal brain tissue was detected in CMV-infected fetuses with gross brain abnormalities, suggesting extensive brain damage. In CMV-infected fetuses with isolated WMHS, no damage was detected by MRS. 3 TECHNICAL EFFICACY: Stage 3.

22 Feeding the early gestating gilt during heat stress: Implications towards fetal viability, growth, and development

Abstract Gestational heat stress (GHS) directly impacts litter development and viability and has long term negative postnatal effects on offspring. However, current data on the interactions between GHS, maternal feed energy partitioning, and fetal development measures in pigs are limited. Therefore, the study objective was to gain a greater understanding of how early GHS influences fetal development and viability and whether maternal feed energy partitioning has a role. Gestating gilts (n = 23) were exposed to thermoneutral (TN; n = 11; 18.5 ± 1.2°C) or heat stress (HS; n = 12; cyclic 26 to 38°C) conditions beginning on d 6.0 ± 0.9 of gestation to 33.0 ± 1.7. The HS treatments resulted in greater (P &amp;lt; 0.05) respiration rates and body temperature and HS gilts grew faster (P &amp;lt; 0.05; 0.5 ± 0.1 kg/d) than TN gilts (0.3 ± 0.1 kg/d) as previously reported. Pregnant gilts were individually housed and limit-fed a standard gestating gilt diet (1.82 kg/d; 4.39 Mcal NE intake/d). On gestation d 33 ± 1.7, gilts were harvested and reproductive tract weight, corpus luteum (CL) counts, and fetal weights and counts were recorded. Additionally, fetal images were taken with a digital camera to assess fetal length, width, crown rump length (CRL), and viability using Image J. Fetuses were considered nonviable if CRL was more than 2 standard deviations less than the mean litter CRL or had irregular anatomical traits. All data were analyzed using PROC GLIMMIX with either pregnant gilt as the experimental unit for litter-based measures or individual fetus as the experimental unit for fetal based measures. Gilt NE intake efficiency [average daily gain (ADG); NE intake) was greater for HS (P = 0.04; 0.11 ± 0.01) when compared with TN gilts (0.07 ± 0.01). No fetal ADG (P = 0.26; 0.12 ± 0.04 g/d) or fetal ADG; gilt NE intake differences (P = 0.26; 0.03 ± 0.01) were detected between treatments. Total fetuses per CL were decreased for HS gilts (P = 0.01; 0.72 ± 0.03 fetuses) when compared with TN gilts (0.85 ± 0.04 fetuses). Viable fetuses per CL were reduced for HS gilts (P = 0.05; 0.69 ± 0.01 fetuses) when compared with TN gilts (0.80 ± 0.04 fetuses). The difference between total CL count and total fetuses per gilt tended to be increased for HS (P = 0.08; 6 ± 1 fetus) versus TN gilts (4 ± 1 fetus). No other fetal differences were observed (P &amp;gt; 0.10). In conclusion, early GHS improved gilt growth performance and NE efficiency, but resulted in decreased fertilization rates and reduced fetal viability and had no impact on fetal growth and development.

Automatic Quantification of Normal Brain Gyrification Patterns and Changes in Fetuses with Polymicrogyria and Lissencephaly Based on MRI.

The current imaging assessment of fetal brain gyrification is performed qualitatively and subjectively using sonography and MR imaging. A few previous studies have suggested methods for quantification of fetal gyrification based on 3D reconstructed MR imaging, which requires unique data and is time-consuming. In this study, we aimed to develop an automatic pipeline for gyrification assessment based on routinely acquired fetal 2D MR imaging data, to quantify normal changes with gestation, and to measure differences in fetuses with lissencephaly and polymicrogyria compared with controls. We included coronal T2-weighted MR imaging data of 162 fetuses retrospectively collected from 2 clinical sites: 134 controls, 12 with lissencephaly, 13 with polymicrogyria, and 3 with suspected lissencephaly based on sonography, yet with normal MR imaging diagnoses. Following brain segmentation, 5 gyrification parameters were calculated separately for each hemisphere on the basis of the area and ratio between the contours of the cerebrum and its convex hull. Seven machine learning classifiers were evaluated to differentiate control fetuses and fetuses with lissencephaly or polymicrogyria. In control fetuses, all parameters changed significantly with gestational age (P < .05). Compared with controls, fetuses with lissencephaly showed significant reductions in all gyrification parameters (P ≤ .02). Similarly, significant reductions were detected for fetuses with polymicrogyria in several parameters (P ≤ .001). The 3 suspected fetuses showed normal gyrification values, supporting the MR imaging diagnosis. An XGBoost-linear algorithm achieved the best results for classification between fetuses with lissencephaly and control fetuses (n = 32), with an area under the curve of 0.90 and a recall of 0.83. Similarly, a random forest classifier showed the best performance for classification of fetuses with polymicrogyria and control fetuses (n = 33), with an area under the curve of 0.84 and a recall of 0.62. This study presents a pipeline for automatic quantification of fetal brain gyrification and provides normal developmental curves from a large cohort. Our method significantly differentiated fetuses with lissencephaly and polymicrogyria, demonstrating lower gyrification values. The method can aid radiologic assessment, highlight fetuses at risk, and may improve early identification of fetuses with cortical malformations.

Male fetuses negatively affect the vitality of the litter and the dam's metabolic and physiological state in multifetal pregnant ewe.

In sheep, ~30% of fetuses do not survive till parturition, and 17.7% of the multifetal pregnancies experience partial litter loss (PLL). In humans, multifetal pregnancies are associated with a higher risk of perinatal mortality. Therefore, the objectives were to examine the association between partial litter loss, fetal sex, dam's metabolic and physiological state, and pregnancy outcome in multifetal pregnant ewes. The study includes two parts. The first was a retrospective study, in which we analyzed data of 675 lambings and examined the PLL incidence according to male ratio (MR) for all litter sizes (range 2-6). Lambings were categorized as having a low male ratio (LMR; <50% males) or a high male ratio (LMR; >50% males). In the second part, we monitored 24 ewes from 80 to 138 days in pregnancy every 10 days, and then daily until lambing, by ultrasound scanning for maternal heart rate (HR), and Doppler ultrasound for litter vitality. Blood samples were taken from dams on the days of scanning. Male ratio strongly affected PLL, where the general survival rate (for all lambings) was reduced from 90% in LMR lambings to 85% in HMR lambings. The odds ratio for PLL in HMR vs. LMR litters was 1.82. Birth body weight and the survival rate of female was higher in LMR than HMR lambings, with no differences for male lambs in both parameters. In the second part, dams' HR during the last trimester was 9.4% higher in LMR than in HMR pregnancies, with no differences in fetuses' HR. The plasma glucose and insulin concentrations were not significantly different between groups, but plasma β-hydroxybutyrate and nonesterified fatty acid concentrations were, respectively, 31% and 20% lower in HMR vs. LMR ewes. In conclusion, male fetuses negatively affect pregnancy outcomes and influence dams' metabolic and physiological state in sheep.

Correlation between Intrapartum Cardiotocogram Findings and Cord Blood pH in Term and Preterm Labors

Background: The purpose of intrapartum fetal monitoring by cardiotocograph (CTG) is to identify early signs of developing hypoxia so that appropriate action can be taken to improve the perinatal outcome. Although CTG findings are well known to monitor the progress of the labor due to the paucity of recommendations, there has always been a clinical dilemma as the term fetuses respond differently than a preterm fetus. However, umbilical cord blood pH can distinguish the infant at high risk for asphyxia and related sequel. Therefore, because of differences in fetal physiology in term and preterm fetuses, CTG findings vary, and hence the validity of CTG to determine fetal acidosis should be different. Aims and Objectives: This study aimed to correlate abnormal intrapartum CTG findings with umbilical cord blood pH in term and preterm labor and thus evaluate the success of CTG in predicting fetal acidosis during labor. Methods: The present study included 210 women in labor (70 preterm and 140 term) with abnormal intrapartum CTG that was classified as per 2015 revised International Federation of Gynecologists and Obstetrician (FIGO) guidelines. Immediately after delivery, 2 ml Umbilical artery cord blood sample was taken in a pre-heparinized syringe for analysis, pH &lt;=7.2 was taken as acidosis and pH &gt;7.2 was taken as normal. The measured data were general maternal characteristics which included gravida status, associated comorbidities, method of induction and character of liquor, the intrapartum CTG tracings recorded, the cord arterial blood pH and the neonatal characteristics such as APGAR score and neonatal outcome. Results: Data from 70 preterm labor was compared with 140 term labor. In this study, 20.9% of the babies had acidosis. Suspicious CTG due to decreased variability were more common in the preterm group than in the term group (21.4% vs. 8.6% p&lt;0.05). Positive predictive value (PPV) of abnormal CTG for fetal acidosis in the preterm group was found to be higher than that in the term group, PPV of pathological CTG being even higher than suspicious CTG. Women with suspicious CTG had 82% less risk of fetal acidosis as compared to pathological CTG. Women with Bradycardia had 5.9 times the risk of fetal acidosis as compared with normal and tachycardia. Conclusion: Abnormal CTG should be managed appropriately without any delay to prevent acidosis and cord blood pH should be done in all labors with abnormal CTG. However, our findings of a higher incidence of lower cord blood pH and suspicious CTG due to decreased variability alone highlight the limitation of criteria currently used for interpretation of CTG in preterm labors.

Expectant Versus Interventionist Care in the Management of Severe Preeclampsia Remote from Term: A Systematic Review.

To compare the effects of expectant versus interventionist care in the management of pregnant women with severe preeclampsia remote from term. An electronic search was conducted in the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature (LILACS, for its Spanish acronym), World Health Organization's International Clinical Trials Registry Platform (WHO-ICTRP), and OpenGrey databases. The International Federation of Gynecology and Obstetrics (FIGO, for its French acronym), Royal College of Obstetricians and Gynaecologists (RCOG), American College of Obstetricians and Gynecologists (ACOG), and Colombian Journal of Obstetrics and Gynecology (CJOG) websites were searched for conference proceedings, without language restrictions, up to March 25, 2020. Randomized clinical trials (RCTs), and non-randomized controlled studies (NRSs) were included. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to evaluate the quality of the evidence. Studies were independently assessed for inclusion criteria, data extraction, and risk of bias. Disagreements were resolved by consensus. Four RCTs and six NRS were included. Low-quality evidence from the RCTs showed that expectant care may result in a lower incidence of appearance, pulse, grimace, activity, and respiration (Apgar) scores < 7 at 5 minutes (risk ratio [RR]: 0.48; 95% confidence interval [95%CI]: 0.23%to 0.99) and a higher average birth weight (mean difference [MD]: 254.7 g; 95%CI: 98.5 g to 410.9 g). Very low quality evidence from the NRSs suggested that expectant care might decrease the rates of neonatal death (RR: 0.42; 95%CI 0.22 to 0.80), hyaline membrane disease (RR: 0.59; 95%CI: 0.40 to 0.87), and admission to neonatal care (RR: 0.73; 95%CI: 0.54 to 0.99). No maternal or fetal differences were found for other perinatal outcomes. Compared with interventionist management, expectant care may improve neonatal outcomes without increasing maternal morbidity and mortality.

1052: Brain composition differences in fetuses after laser surgery for twin-twin transfusion syndrome (TTTS)

We describe the maturational pattern differences of various brain tissues between donor versus recipient twins treated with in utero laser surgery for TTTS using 3D MRI reconstruction. This was a prospective study of 20 patients with TTTS and dual survivors 4 weeks postoperatively. Fetal MRI scans were performed with a 1.5-T scanner. Multiple stacks of singleshot fast spin-echo T2-weighted slices of the fetal brain were obtained in the axial, sagittal, and coronal planes for each fetus. The images were reconstructed into 3D MRI volumes after motion correction. Total brain volume (TBV), cortical plate region (CR), developing white matter region (WMR), cerebellum, and ventricles were delineated using a semi-automated, atlas based segmentation method (Figure 1(a)). CR, WMR, cerebellum, and ventricular volumes were normalized by TBV for each subject. The CR and WMR were additionally normalized to the supratentorial structures only, called total parenchymal volume (TPV). Relationship between gestational age (GA), twin status (donor/recipient) and normalized tissue volumes were modeled using robust, multiple linear regression and tested for significance (defined as p<0.05). Eighteen of 20 twin pairs had sufficient image quality for analysis. The median gestational age (GA) at laser surgery was 19.8 (16.4-26.4) weeks, and 25.1 (22.1-30.7) weeks at MRI examination. Figure 1 (b-f) shows the comparative relationship between normalized tissue volumes and gestational age between the donor and recipient twin pairs. TBV was significantly lower in the donor twins (Figure 1b), although TPV were not different between the twin pairs (Figure 1c). Recipients showed significantly lower proportions of CR and cerebellar volumes normalized to TBV compared to donors (Figure 1d,e). Ventricular volumes normalized to TBV were significantly higher in the donor twins (Figure 1f). No significant differences were detected in WMR volumes between the two groups. Recipients showed significantly lower proportions of CR normalized to TPV compared to donors. Although the total brain volume of the donor twin was smaller than that of the recipient twin, the proportional brain tissue volumes of the donor were preserved. Rather, it was the recipient twin that had relatively reduced proportions of cortical plate region and cerebellar volumes.

A novel method for determining sex in late term gestational mice based on the external genitalia.

In many experiments using fetal mice, it is necessary to determine the sex of the individual fetus. However, other than genotyping for sex-specific genes, there is no convenient, reliable method of sexing mice between gestational day (GD) 16.5 and GD 18.0. We designed a rapid, relatively simple visual method to determine the sex of mouse fetuses in the GD 16.5—GD 18.0 range that can be performed as part of a routine morphological assessment. By examining the genitalia for the presence or absence of key features, raters with minimal experience with the method were able to correctly identify the sex of embryos with 99% accuracy, while raters with no experience were 95% accurate. The critical genital features include: the presence or absence of urethral seam or proximal urethral meatus; the shape of the genitalia, and the presence or absence of an area related to the urethral plate. By comparing these morphological features of the external genitalia, we show a simple, accurate, and fast way to determine the sex of late stage mouse fetuses. Integrating this method into regular morphological assessments will facilitate the determination of sex differences in fetuses between GD 16.5 and GD 18.0.

Micrognathia and Oropharyngeal Space in Patients With Robin Sequence: Prenatal MRI Measurements

Micrognathia is the initiating feature of Robin sequence (RS) and leads to airway obstruction. Prenatal identification of micrognathia is currently qualitative and has not correlated with postnatal findings in previous studies. Oropharyngeal airway space has not been evaluated prenatally. The purposes of this study were to 1) quantitate mandibular characteristics and oropharyngeal size at prenatal magnetic resonance imaging (MRI) and 2) identify differences in fetuses with postnatal RS compared with those with micrognathia (without RS) and normal controls. This is a retrospective case-control study of fetuses with prenatal MRIs performed from 2002 through 2017 who were live born and evaluated postnatally for craniofacial findings. Postnatal findings were used to divide patients into 3 groups: 1) RS (micrognathia, glossoptosis, and airway obstruction), 2) micrognathia without RS ("micrognathia"), and 3) a gestational-age matched control group with normal craniofacial morphology ("control"). Inferior facial angle (IFA), jaw index, and oropharyngeal space (OPS) were calculated and compared among groups. Of 116 patients in this study, 27 had RS (23%), 35 had micrognathia (30%), and 54 were control subjects (47%). IFA, jaw index, and OPS were statistically significantly smaller in the RS group compared with the comparison groups (P<.0001). Prenatal MRI measurements of micrognathia and OPS are considerably different in patients with RS compared with other groups, including those with micrognathia alone. These measurements might serve as reliable prenatal predictors of RS.

INFLUENCE OF MATERNAL FACTORS ON GROWTH PARAMETERS IN LOW-BIRTH-WEIGHT BABIES WITH KANGAROO MOTHER CARE

Background: Kangaroo mother care (KMC) in low birth weight newborns has been found to be beneficial, but studies have shown that maternal factors might be of concern in the successful application of KMC. Aim: To study the influence of maternal factors on growth parameters in low-birth-weight babies with KMC. Methods: This is a prospective cohort study of 40 low birth weight newborns in our institutions. We randomly assigned the newborns to the group which received KMC and to the group which received conventional care. Maternal factors were recorded. We measured weight, length, and head circumferences of newborns daily for thirty days. Data was processed by SPSS x22.0. Results: A total of 40 newborns were recruited into the study. Weight parameters were significantly higher in the KMC group than in the conventional group except for the Z scores. Regarding maternal characteristics, only gestational age was found to influence the initial and the last head circumference (p=0.035). There were no differences in maternal age, parity, maternal education, mode of delivery, fetal sex, and initial Apgar score with any of the growth parameters. Conclusion: There were no maternal and fetal differences in the growth parameters of the groups, except in the delayed growth of head circumferences in preterm infants.

Development of the central nervous system in guinea pig (Cavia porcellus, Rodentia, Caviidae)

Abstract: This study describes the development of the central nervous system in guinea pigs from 12th day post conception (dpc) until birth. Totally, 41 embryos and fetuses were analyzed macroscopically and by means of light and electron microscopy. The neural tube closure was observed at day 14 and the development of the spinal cord and differentiation of the primitive central nervous system vesicles was on 20th dpc. Histologically, undifferentiated brain tissue was observed as a mass of mesenchymal tissue between 18th and 20th dpc, and at 25th dpc the tissue within the medullary canal had higher density. On day 30 the brain tissue was differentiated on day 30 and the spinal cord filling throughout the spinal canal, period from which it was possible to observe cerebral and cerebellar stratums. At day 45 intumescences were visualized and cerebral hemispheres were divided, with a clear division between white and gray matter in brain and cerebellum. Median sulcus of the dorsal spinal cord and the cauda equina were only evident on day 50. There were no significant structural differences in fetuses of 50 and 60 dpc, and animals at term were all lissencephalic. In conclusion, morphological studies of the nervous system in guinea pig can provide important information for clinical studies in humans, due to its high degree of neurological maturity in relation to its short gestation period, what can provide a good tool for neurological studies.

Does corticosteroid therapy impact fetal pulmonary artery blood flow in women at risk for preterm birth?

Maternal corticosteroid administration in pregnancy is known to enhance fetal lung maturity in at risk fetuses. The aim of this study was to test the hypothesis that corticosteroid therapy alters fetal pulmonary blood flow in pregnancies at risk for preterm birth (PTB). We prospectively evaluated main fetal pulmonary artery (MPA) blood flow in pregnant women at risk for PTB and treated with corticosteroids (betamethasone), compared to an uncomplicated cohort without steroid therapy. The Doppler indices of interest included Peak Systolic Velocity (PSV), Resistive Index (RI), Pulsatility Index (PI), Systolic/Diastolic ratio (S/D ratio), Acceleration Time (AT), and Acceleration Time/Ejection Time Ratio (AT/ET ratio), with the latter serving as the primary outcomes due to its stability irrespective of gestational age. When compared with controls, fetuses treated with corticosteroids demonstrated significantly decreased pulmonary artery acceleration time (median: 28.89 (22.22-51.11) vs. 33.33 (22.20-57.00), p=0.006), while all other indices remained similar. We found no difference in pulmonary blood flow between fetuses who developed respiratory distress syndrome (RDS) and those that did not (31.56 +/- 6.842 vs. 32.36 +/- 7.265, p= 0.76). Our data demonstrate altered fetal pulmonary blood flow with corticosteroid therapy, possibly due to increased arterial elastance brought on by medication effect, which leads to the decreased acceleration time or possible gestational age affect. Contrary to a recent report, we did not observe any Doppler differences in fetuses with RDS, which underscores the need for further examination of this proposed association.

IX. SEX DIFFERENCES IN FETAL DEVELOPMENT

Monographs of the Society for Research in Child DevelopmentVolume 80, Issue 3 p. 59-65 STUDIES IN FETAL BEHAVIOR: REVISITED, RENEWED, AND REIMAGINED IX. SEX DIFFERENCES IN FETAL DEVELOPMENT First published: 01 July 2015 https://doi.org/10.1111/mono.12179Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume80, Issue3September 2015Pages 59-65 RelatedInformation

Influence of maternal metabolism and parental genetics on fetal maldevelopment in diabetic rat pregnancy

The purpose of this study was to investigate the influence of parental transgenerational genetics and maternal metabolic state on fetal maldevelopment in diabetic rat pregnancy. Rats from an inbred malformation-resistant (W) strain, and an inbred malformation-prone (L) strain, were cross-mated to produce two different F(1) hybrids, WL and LW. Normal (N) and manifestly diabetic (MD) WL and LW females were mated with normal males of the same F(1) generation to obtain WLWL and LWLW F(2) hybrids. Maternal diabetes increased malformation and resorption rates in both F(2) generations. MD-WLWL offspring had higher resorption rate but similar malformation rate compared with the MD-LWLW offspring. Malformed MD-WLWL offspring presented with 100% agnathia/micrognathia, whereas malformed MD-LWL offspring had 60% agnathia/micrognathia and 40% cleft lip and palate. The MD-WL dams showed increased β-hydroxybutyrate levels and alterations in concentrations of several amino acids (taurine, asparagine, citrulline, cystine, glutamic acid, leucine, tyrosine, and tryptophan) compared with MD-LW dams. Fetal glyceraldehyde-3-phosphate dehydrogenase (Gapdh) activity and gene expression were more altered in MD-WLWL than MD-LWLW. Fetal gene expression of reactive oxygen species (ROS) scavenger enzymes was diminished in MD-WLWL compared with MD-LWLW. Glial cell line-derived neurotrophic factor and Ret proto-oncogene gene expression was decreased in both MD-WLWL and MD-LWLW fetuses, whereas increased bone morphogenetic protein 4 and decreased Sonic hedgehog homolog expression was found only in MD-LWLW fetuses. Despite identical autosomal genotypes, the WL and LW dams gave birth to offspring with markedly different malformation patterns. Together with fetal differences in enzymatic activity and expression of Gapdh, ROS scavengers, and developmental genes, these results may suggest a teratological mechanism in diabetic pregnancy influenced by maternal metabolism and parental strain epigenetics.

Transcriptomic analysis of cell-free fetal RNA suggests a specific molecular phenotype in trisomy 18.

Trisomy 18 is a common human aneuploidy that is associated with significant perinatal mortality. Unlike the well-characterized "critical region" in trisomy 21 (21q22), there is no corresponding region on chromosome 18 associated with its pathogenesis. The high morbidity and mortality of affected individuals has limited extensive investigations. In order to better understand the molecular mechanisms underlying the congenital anomalies observed in this condition, we investigated the in utero gene expression profile of second trimester fetuses affected with trisomy 18. Total RNA was extracted from cell-free amniotic fluid supernatant from aneuploid fetuses and euploid controls matched for gestational age and hybridized to Affymetrix U133 Plus 2.0 arrays. Individual differentially expressed transcripts were obtained by two-tailed t tests. Over-represented functional pathways among these genes were identified with DAVID and Ingenuity(®) Pathways Analysis. Results show that three hundred and fifty-two probe sets representing 251 annotated genes were statistically significantly differentially expressed between trisomy 18 and controls. Only 7 genes (2.8% of the annotated total) were located on chromosome 18, including ROCK1, an up-regulated gene involved in valvuloseptal and endocardial cushion formation. Pathway analysis indicated disrupted function in ion transport, MHCII/T cell mediated immunity, DNA repair, G-protein mediated signaling, kinases, and glycosylation. Significant down-regulation of genes involved in adrenal development was identified, which may explain both the abnormal maternal serum estriols and the pre and postnatal growth restriction in trisomy 18. Comparison of this gene set to one previously generated for trisomy 21 fetuses revealed only six overlapping differentially regulated genes. This study contributes novel information regarding functional developmental gene expression differences in fetuses with trisomy 18.

“Tell Them It's Not so Bad”: Prenatal Screening for Down Syndrome and the Bias Toward Abortion

“Tell Them It's Not so Bad”: Prenatal Screening for Down Syndrome and the Bias Toward Abortion

Differences in Fetal Growth, Discordancy, and Placental Pathology in Reduced versus Nonreduced Twins

This study evaluated the effect of multifetal pregnancy reduction on the incidence of small for gestational age (SGA) and discordance in reduced versus nonreduced twins and differences in placental pathology. A computerized ultrasound database was used to identify diamniotic-dichorionic twins who delivered at our institution. Reduced (n = 36) versus nonreduced twins (n = 243) were compared for differences in rates of SGA and discordancy (>or= 20%.) The groups were compared for differences in maternal and neonatal characteristics, as well as differences in placental pathology. Chi-square tests were used to compare differences in means. Stepwise logistic regression was used to adjust for potential confounders including placental pathology. The rate of SGA in either twin A or B remained nonsignificant after adjustment for the use of assisted reproductive technology and gestational age at delivery in the stepwise logistic model (odds ratio, 1.7 95%; confidence interval, 0.5, 5.2). The average discordance at delivery was 12.4% in reduced versus 11.4% in the nonreduced twins ( P = 0.54). We found no overall differences in placental pathology between the two groups. Reduced and nonreduced twins have no significant differences in SGA fetuses, growth discordancy, or placental pathology.

Differences in fetal growth, discordancy and placental pathology in reduced vs. non-reduced twins

To evaluate the effect of multifetal pregnancy reduction on the incidence of small-for-gestational age (SGA) and discordance in reduced vs non-reduced twins and to examine differences in placental pathology. A computerized ultrasound database was used to identify diamniotic-dichorionic twins who delivered at our institution. Reduced (n=36) vs non-reduced twins(n=243) were compared for differences in rates of SGA and discordancy (>20%). The groups were compared for differences in maternal and neonatal characteristics, as well as differences in placental pathology. Chi-square and stepwise logistic regression were used as appropriate. A comparison of maternal and neonatal characteristics are presented in Table 1. Reduced twins were not found to have a greater incidence of growth discordancy than non-reduced twins. However, there was a trend towards a higher incidence of SGA in reduced vs. non-reduced twins. We found no differences placental path between the 2 groups, p=0.49. Reduced and non-reduced twins have no significant differences in SGA fetuses, growth discordancy, placental pathology or other selected characteristics.Tabled 1MPR vs non MPRMPR twins (%) n=36Non-MPR twins (%) n=243p-valueAge (avg+/-SD)36.7 (4.7)33.2 (6.3)<0.01Parity≥9 (25)71 (29)0.47SGA A610.06SGA B850.33Discordacne20%≥19140.43Preeclampsia19130.31IVF8656<0.01 Open table in a new tab Tabled 1Path MPR vs non MPRPath A+BMPR twins (%) n=34Non-MPR twins (%) n=192Velamentous610Ischemia3850Abruption03Inflammation911 Open table in a new tab

Sex differences in fetal gonadotropins and androgens

We investigated the hypothalamo-hypophyseo-gonadal system in human fetuses and neonates by serially sampling fetuses obtained either during spontaneous abortions, premature deliveries or under the conditions of the Eugenics Protection Law. Maternal specimens were obtained serially throughout pregnancy, at parturition and in the puerperium. The purpose of our study was to determine the presence or absence of sex differences in fetuses and neonates by determining plasma constituents. The subjects for determination were FSH, LH, hCG and its β-subunit, and androgens. We also attempted to determine the effects of LH-RH priming on the anterior hypophysics. We found fetal sex differences in FSH and testosterone levels, but were unable to detect any differences in the other materials determined. Furthermore we were able to detect an anterior pituitary response to LH-RH priming from the second trimester of pregnancy.