Fetal Size Research Articles

The structure of the porcine uterine-conceptus interface is associated with gestational day, fetal size and sex

This study aimed to characterize histological changes of the maternal-conceptus interface in feto-placental units associated with fetal weight and sex throughout pregnancy. Pregnant Large-White X Landrace gilts(n=18) were euthanized and hysterectomized on gestational days[GDs] 30(n=3), 45(n=5), 60(n=5), and 90(n=5). Intact cross-sections of fetoplacental interface associated with the lightest[LW] and normally-grown[NW] littermates were collected on GD30(n=4 per size). On GDs 45, 60 and 90, interactions between fetal size and sex were investigated in light-weight males[LWM] and females[LWF]; normal-weight males[NWM] and females[NWF] (n=4/group/GD). Fetal weight did not affect the endometrium composition, including relative proportion of glandular epithelium, blood vessels, and connective tissue. Feto-placental units from LW embryos tended to have longer chorioallantoic fold length on GD30(P=0.06). On GD45, higher proportion of larger endometrial glands was observed in NWM, and taller trophoblastic epithelium in NW conceptuses, regardless of sex(P<0.05). NWF presented the greatest proportion of subluminal endometrial epithelial blood vessels(P<0.05). On GD60, more blood vessels were present at the folds’ base in males feto-placental units, whereas taller trophoblastic epithelium were present in NWF fetuses’ feto-placental units(P<0.05). Feto-placental units’ morphological composition throughout gestation in NW and LW conceptuses revealed that fold length was higher as early as GD30, with no further increase up to GD90 in LW conceptuses(P>0.05). Increased proportion of glandular epithelium was observed in LW conceptuses; the highest percentage present on GD90(P<0.05). Collectively, we demonstrated that fetal weight and sex influence the morphological structure of feto-placental units from as early as GD30, suggesting potential differences in the ability for nutrient transport.

Nomograms of fetal thoracic dimensions from 17 to 37 weeks of gestation

Abstract Introduction: We aimed to construct the nomograms for fetal thoracic parameters among Thai fetuses that were between 17 and 37 gestational weeks, as assessed by three distinct two‐dimensional (2D) measurement techniques (thoracic diameter, circumference and area) and compare our findings with those of previous publications. Methods: A cross-sectional study involving 511 low-risk singleton pregnancies with normal fetuses at Siriraj Hospital, Bangkok, Thailand, was conducted. Using the four-chamber view, fetal thoracic measurements were obtained through three 2D sonographic measurement methods. Reference intervals at 95% and Z-scores were established for all techniques based on gestational age (GA) and biparietal diameter (BPD). Intraclass correlation coefficients (ICCs) were computed to assess reproducibility of the measurement methods. Results: Measurements of fetal thorax size exhibited consistent, proportional increases with advancing GA and BPD across all techniques. Intraobserver and interobserver reliability coefficients for all methods indicated excellent agreement, with all ICCs being at least 0.991. Nomograms of fetal thoracic diameter, circumference and area across GA and BPD were constructed from the obtained values. Discrepancies in Z-score reference ranges for fetal thoracic circumference were noted between the present study and previous research in other populations, particularly among Caucasians. Conclusion: Our study established normal reference ranges for evaluating fetal chest size through three different methods from 17 to 37 weeks of gestation in the Thai population. Nomograms may vary due to population differences, emphasising the importance of using reference values from similar demographic groups. The findings could potentially be used to identify fetuses that are at risk of abnormal thoracic dimensions or thoracic dysplasia.

Vilazodone exposure during pregnancy: Effects on embryo-fetal development, pregnancy outcomes and fetal neurotoxicity by BDNF/Bax-Bcl2/5-HT mediated mechanisms

The high prevalence of major depressive disorder (MDD) among women of childbearing age necessitates careful consideration of antidepressant use during pregnancy. Although newer antidepressants, such as Vilazodone (VLZ), are preferred for their enhanced therapeutic profiles; however, their safety during pregnancy and long-term effects on offspring brains remain inadequately addressed. Therefore, this study aimed to investigate the reproductive and developmental neurotoxicity of VLZ given at equivalent therapeutic doses during gestation in a rat model. Pregnant Wistar dams were orally administered either with 1 mg/day or 2 mg/day of VLZ from gestation day (GD) 6–21. The dams were sacrificed at GD 21, and the placentas and fetuses were collected. Fetal brains were then subjected to neurohistopathological, neurochemical, and biochemical analysis. Prenatal exposure to VLZ at 2 mg/day resulted in significant maternal, reproductive, and embryo-fetal toxicity, characterized by reduced food intake, diminished weight gain in pregnant dams, and smaller litter sizes, along with decreased fetal and placental weights. These effects were associated with developmental neurotoxicity, which manifested as decreased fetal brain size and weight, a substantial reduction in neocortical layer thickness, brain-derived neurotrophic factor (BDNF) expression, serotonin, dopamine, and norepinephrine neurotransmitter levels (5-HT, DA, and NE), and increased apoptotic activity (Bax and Bcl-2 ratio) and acetylcholinesterase levels in the developing brain. Our findings indicate that prenatal VLZ exposure interfere with crucial brain development processes involving the BDNF/Bax-Bcl2/5-HT signalling pathways, leading to long-lasting neurodevelopmental impairments. This study is the first to document the adverse effects of VLZ on fetal brain development, highlighting the need for further research to assess the safety of VLZ use during pregnancy.

Lysosomal enzyme binding to the cation-independent mannose 6-phosphate receptor is regulated allosterically by insulin-like growth factor 2.

The cation-independent mannose 6-phosphate receptor (CI-MPR) is clinically significant in the treatment of patients with lysosomal storage diseases because it functions in the biogenesis of lysosomes by transporting mannose 6-phosphate (M6P)-containing lysosomal enzymes to endosomal compartments. CI-MPR is multifunctional and modulates embryonic growth and fetal size by downregulating circulating levels of the peptide hormone insulin-like growth factor 2 (IGF2). The extracellular region of CI-MPR comprises 15 homologous domains with binding sites for M6P-containing ligands located in domains 3, 5, 9, and 15, whereas IGF2 interacts with residues in domain 11. How a particular ligand affects the receptor's conformation or its ability to bind other ligands remains poorly understood. To address these questions, we purified a soluble form of the receptor from newborn calf serum, carried out glycoproteomics to define the N-glycans at its 19 potential glycosylation sites, probed its ability to bind lysosomal enzymes in the presence and absence of IGF2 using surface plasmon resonance, and assessed its conformation in the presence and absence of IGF2 by negative-staining electron microscopy and hydroxyl radical protein footprinting studies. Together, our findings support the hypothesis that IGF2 acts as an allosteric inhibitor of lysosomal enzyme binding by inducing global conformational changes of CI-MPR.

COMPARISON OF PLGF LEVELS, AMONG SMALL FOR GESTATIONAL AGE AND APPROPRIATE FOR GESTATIONAL AGE MOTHERS

Objective. Early detection of small for gestational age fetuses can prevent infant morbidity and mortality. The objective of this study was to compare the levels of Placental Growth Factor among small for gestational age with appropriate for gestational age mothers and to identify the predictive value of PlGF in detecting pregnancies with Intra uterine growth retardation in local population. Design. Quasi experimental (comparative cross-sectional) study. Place &amp; duration of study. Gynecological department of Ayub Medical complex, Abbottabad from August 2021 to January 2022. Methodology. The studied population included total 68 mothers in last trimester with 34 in each group, i.e. appropriate for gestational age and small for gestational age. Fetal size was estimated either by clinical examination (symphysis fundal height) or estimated fetal weight by ultrasound examination. Sociodemographic along with reproductive history were recorded and blood samples analyzed for PlGF difference in both groups. Results. The median age of mothers was 32.5 years. The PlGF in small for gestational age was observed in the below normal concentration (mean value = 126.7 pg/mL) while it was observed in normal ranges in appropriate for gestational age mothers (mean value = 24.2 pg/ml) with P-value (&lt;0.001). Conclusion. Mothers with small for gestational age were having significantly lower placental growth factor levels compared to mothers with appropriate for gestational age.

Prenatal exposure to neonicotinoid insecticides, fetal endocrine hormones and birth size: Findings from SMBCS

BackgroundNeonicotinoid insecticides (NNIs) were reported to be endocrine disruptors and cause adverse health effects in human. However, epidemiological evidence about the effect of prenatal NNIs exposure on birth outcome and hormones remains limited. ObjectivesThis study aimed to explore the effects of prenatal NNIs exposure on neonatal birth size and endocrine hormones, and assess the potential mediating role of hormones. MethodsThe study included 860 mother–child pairs from the Sheyang Mini Birth Cohort Study. 12 parent NNIs (p-NNIs) and 6 metabolites of NNIs (m-NNIs) were measured in maternal urine samples collected on their delivery days, and 5 thyroid hormones and 2 sex hormones were analyzed in cord serum. The concentrations of p-NNIs and its specific metabolite(s) were summed to characterize the role of each class of NNIs. Generalized linear model and weighted quantile sum regression were used to examine the impact of prenatal NNIs exposure on birth size and endocrine hormones, and potential mediating roles of hormones were further explored using mediation analysis. ResultsHigher detection frequencies of m-NNIs were observed than those in p-NNIs. A decrease in neonatal head circumference for gestation age z-score was associated with a 10-fold increase in 5-OH-IMI (β = -0.15, 95 %CI: −0.26, −0.03), ∑DIN (β = -0.22, 95 %CI: −0.40, −0.03), ∑IMI (β = -0.20, 95 %CI: −0.35, −0.06) and ∑NNIs (β = -0.23, 95 %CI: −0.42, −0.04). ∑IMI and ∑DIN were the major contributors to the significantly negative mixture effect and no sex-specific effect was observed. Negative associations were observed between ∑DIN and TT3 (β = -0.013, 95 %CI: −0.025, −0.002), ∑IMI and T (β = -0.035, 95 %CI: −0.065, −0.004), respectively. Furthermore, TT3 and T demonstrated 6.7 % and 6.1 % mediating effects on the negative association of prenatal ∑DIN and ∑IMI exposure with head circumference. ConclusionsOur findings suggested the potential endocrine disruptive properties of NNIs and their impacts on head circumference. Endocrine hormones may partly mediate these associations.

Isolated Fetal Liver Calcifications: Case Report and Literature Review

ABSTRACTFetal liver calcifications (FLCs) are isolated or multiple areas of increased echogenicity in the fetal liver, with an estimated prevalence of 5–10 per 10 000 births. However, their clinical importance remains still unclear. Although they are often linked to infections, chromosomal disorders, thrombotic events, or tumors, isolated FLCs generally have a favorable outcome. This article aims to present a case of a 29‐year‐old pregnant woman with a low‐risk cfDNA test, who presented for the first trimester screening scan at our hospital at 12 weeks of pregnancy. The morphology scan at 20 weeks and 5 days revealed a normal fetal size with areas of increased echogenicity in the liver. No other fetal issues were identified. The patient was monitored throughout her pregnancy at our center, receiving genetic counseling and tests for detecting cystic fibrosis, STORCH (syphilis, cytomegalovirus, herpes virus 1;2, rubella, and toxoplasma), fetal echocardiography, and MRI, all of which were normal. At 35 weeks and 6 days, the patient gave birth to a healthy male, and all subsequent postnatal examinations confirmed the baby's health. This article aims to offer comprehensive insights into the management and postnatal outcomes of isolated FLCs, based on a review of the literature.

Study protocol for an observational cohort study of heat stress impacts in pregnancy in The Gambia, West Africa

Climate change has resulted in an increase in heat exposure globally. There is strong evidence that this increased heat stress is associated with poor maternal and fetal outcomes, especially in vulnerable populations. However, there remains poor understanding of the biological pathways and mechanisms involved in the impact of heat in pregnancy. This observational cohort study of 764 pregnant participants based in sub-Saharan Africa, a geographical region at risk of extreme heat events, aims to evaluate the physiological and biochemical changes that occur in pregnancy due to heat stress. The key objectives of the study are to 1) map exposure to heat stress in the cohort and understand what environmental, social and community factors increase the risk of extreme heat exposure; 2) assess the impact of heat stress on maternal health, e.g. heat strain, subjective psychological well-being, sleep and activity level; 3) evaluate how heat stress impacts placenta structure and function; 4) determine how chronic heat exposure impacts birth outcomes; and 5) explore the epigenetic changes in the placenta and infant by heat stress exposure per trimester. Pregnant women will be recruited from two distinct regions in The Gambia to exploit the naturally occurring heat gradient across the country. Microclimate mapping of the area of recruitment will give detailed exposure measurements. Participants will be asked to wear a watch-style device at 28- and 35-weeks gestational age to evaluate maternal heart rate, activity and sleep. At the end of the week, an ultrasound scan will be performed to evaluate fetal size and placental blood flow. At delivery, birth outcomes will be recorded and maternal, placental and cord samples taken for epigenetic, biochemical and histological evaluation. Evaluation of neuro-behaviour and final infant samples will be taken at 1 month following birth.

Harmful Effects on the Hippocampal Morpho-Histology and on Learning and Memory in the Offspring of Rats with Streptozotocin-Induced Diabetes.

Learning alterations in the child population may be linked to gestational diabetes as a causal factor, though this remains an open and highly controversial question. In that sense, it has been reported that maternal hyperglycemia generates a threatening condition that affects hippocampal development in offspring. The pyramidal cells of the CA3 subfield, a key structure in learning and memory processes, are particularly important in cognitive deficiencies. We evaluate the effect of the hyperglycemic intrauterine environment on hippocampal histomorphometry in offspring, correlating it with spatial learning and memory, as well as the morphology of dendrites and spines in 30-day-old pups (P30). The maternal hyperglycemia affected the body weight, height, and brain size of fetuses at 21 days of gestation (F21), newborn pups (P0) and P30 pups from diabetic rats, which were smaller compared to the control group. Consequently, this resulted in a decrease in hippocampal size, lower neuronal density and cytoarchitectural disorganization in the CA3 region of the hippocampus in the offspring at the three ages studied. The behavioral tests performed showed a direct relationship between morpho-histological alterations and deficiencies in learning and memory, as well as alterations in the morphology of the dendrites and spines. Therefore, knowing the harmful effects caused by gestational diabetes can be of great help to establish therapeutic and educational strategies that can help to improve learning and memory in children.

Lung volumes are increased in fetuses with transposition of the great arteries on intrauterine MRI.

Fetal brain size is decreased in some children with complex CHDs, and the distribution of blood and accompanying oxygen and nutrients is regionally skewed from early fetal life dependent on the CHD. In transposition of the great arteries, deoxygenated blood preferentially runs to the brain, whereas the more oxygenated blood is directed towards the lungs and the abdomen. Knowledge of whether this impactsintrauterine organ development is limited. We investigated lung, liver, and total intracranial volume in fetuses with transposition of the great arteries using MRI.Eight fetuses with dextro-transposition and without concomitant disease or chromosomal abnormalities and 42 fetuses without CHD or other known diseases were scanned once or twice at gestational age 30 through 39 weeks. The MRI scans were conducted on a 1.5T system, using a 2D balanced steady-state free precession sequence. Slices acquired covered the entire fetus, slice thickness was 10 mm, pixel size 1.5 × 1.5 mm, and scan duration was 30 sec.The mean lung z score was significantly larger in fetuses with transposition compared with those without a CHD; mean difference is 1.24, 95% CI:(0.59;1.89), p < 0.001. The lung size, corrected for estimated fetal weight, was larger than in the fetuses without transposition; mean difference is 8.1 cm3/kg, 95% CI:(2.5;13.7 cm3/kg), p = 0.004.In summary, fetuses with dextro-transposition of the great arteries had both absolute and relatively larger lung volumes than those without CHD. No differences were seen in liver and total intracranial volume. Despite the small number of cases, the results are interesting and warrant further investigation.

Crista Galli Morphology in Fetuses.

To determine alterations in the crista galli (CG) size in fetuses with advancing weeks. Skull bases of 32 fetuses (11 males/21 females) aged 17 to 32 weeks in utero were included in the study. The width (width of CG), height (height of CG), and length (length of CG) of CG were measured, and also olfactory fossa depth (OFD) was measured to determine the relation of CG with OFD. Width of CG, height of CG, length of CG, and OFD were measured as 1.77 ± 0.59mm, 5.10 ± 1.70mm, 12.32 ± 2.25mm, and 1.56 ± 0.56mm, respectively. No significant difference was observed between the measurements in terms of sex and side (P> 0.05). Apart from OFD, the parameters were greater in the third-trimester fetuses than in the second-trimester fetuses (P< 0.001). Olfactory fossa depth was similar in both trimester fetuses (P= 0.798). Olfactory fossa depth did not alter with advancing gestational weeks (P= 0.077), but the others increased (P< 0.01). Only one configuration regarding Keros types was observed. Type 1 was detected in all fetuses (100%). A linear function was calculated as y=1.442+0.455×age for the length of CG, y=-2.566+0.321×age for the height of CG, y=0.641+0.039×age for OFD, and y=-1.088+0.119×age for the width of CG. Crista galli size increased with advancing fetal weeks. The authors detected Keros type 1 in all fetuses. The authors' linear functions representing the growth pattern of CG and OFD in fetuses may be useful in estimating their dimensions.

Comparative Study between the Accuracy of Transcerebellar Diameter versus Femur Length and Biparietal Diameter Measurements in Estimation of Gestational Age during Third Trimester

Abstract Background Knowledge of accurate gestational age is of great importance in obstetric practice. Pregnancy complications as low birth weight, preterm labor are very common in pregnancies with unknown and inaccurate estimated gestational age, gestational age estimation is essential for proper prenatal care and determining whether the fetal size is appropriate-for- gestational age. Moreover, it is essential for many prenatal interventions, such as fetal lung maturation, use of magnesium for neuroprophylaxis in preterm infants, induction of delivery and neonatal resuscitation. Optimal assessment requires good judgment by the obstetrician caring for the patient. Objective To compare the accuracy of transcerebellar diameter versus the current fetal biometrics including (femur length and biparietal diameter) in estimation of the gestational age during the third trimester according to last menstrual period. Patients and Methods The study was conducted in clinic of Obstetrics and Gynaecology Department- MUST University Hospital. This study included 120 pregnant females. They were divided equally into three equal groups each contained 40 patients; Group I: Biparietal diameter measured group, Group II: Femur Length measured group, and Group III: Transcerebellar measured group. Results The comparison in 1 week proved that the TCD gave correct assessment of gestational age in 107 patients (89.17%), the BPD gave correct assessment of gestational age in 73 patients (60.83%) and the FL gave correct assessment of gestational age in 97 patients (80.83%). Conclusion Transcerebellar diameter is the most accurate and reliable method for assessment of gestational age in third trimester followed by FL and the least accurate is the BPD.

50 Awardee Talk: The role of non-traditional inheritance patterns among Bos indicus-Bos taurus crosses for global beef value chain considerations

Abstract Bos indicus-Bos taurus crosses have been effectively used in many production environments globally. Substantially higher amounts of hybrid vigor have been reported in these F1 crosses as compared with those involving only Bos taurus or only Bos indicus breeds. However, for many years, and in many environments, “unusual” aspects of calf growth have been documented among these crosses. Among F1 crosses, Bos indicus-sired calves (Bos indicus x Bos taurus) have birth weight 8 to 12 kg heavier than contemporary Bos taurus-sired calves (Bos taurus x Bos indicus); additionally, pronounced sexual dimorphism occurs where males may weigh 5 to 10 kg more than females from Bos indicus sires (Bos taurus dams) but 1 kg or less from Bos taurus sires (Bos indicus dams) in both natural service and embryo transfer calves. These reciprocal differences have been reported for fetal and placentome size mid gestation. Reciprocal differences in birth weight have also been reported among backcrosses and F2 calves, and also exist for longer gestation length from Bos indicus sires (Bos taurus dams). Increased birth weight and gestation length occur when more Bos indicus is present in the sire vs. the dam, and when Bos indicus influence is inherited through the sire vs. the dam. There is speculation that sex-specific genomic imprinting may be involved for reciprocal birth weight differences that are analogous to mouse interspecific crosses for litter weight. Reports of hybrid vigor retention among inter se matings after the F1 have been variable historically, and this variation may relate to how the foundational F1 parents were produced (Bos indicus- vs. Bos taurus-sired). Breed-of-origin haplotype on BTA5 has been shown to affect heifer pregnancy and rebreeding among F2 Nellore-Angus cows where Nellore-derived haplotypes had much lower performance compared with Angus-derived and hybrid haplotypes. Disproportionate calf sex has been reported among reciprocal F2 Nellore (Bos indicus)-Angus (Bos taurus) with 66.6% male calves from Nellore x Angus F1 sires. When retrospectively evaluating historical literature for reciprocal crosses, it appears that several instances occur with disproportionate calf sex percentage, and this phenomenon warrants further study. The extent that potential reciprocal differences may affect post-weaning growth and carcass traits has not been widely evaluated. Recent investigations have shown reciprocal F1 differences for some cell-mediated immune responses regarding T-lymphocyte proliferation, but no differences for humoral response. There needs to be additional research that completely characterizes the X chromosome of Bos indicus and Bos taurus origins and their roles for multiple production traits. There also needs to be more investigation of non-additive and parent-of-origin effects in genetic evaluations of Bos indicus-Bos taurus composites, particularly with desired first-generation breed percentage. Improved utilization of Bos indicus cattle and crosses will be instrumental in meeting global dietary protein demands.

Fetal Growth Following Electronic Cigarette Use in Pregnancy.

Electronic cigarette (e-cig) use in pregnancy is common, but potential effects on fetal development are largely unknown. This study's goal was to examine the association between e-cig exposure and fetal growth. Data were extracted from medical charts in this single-site retrospective study. The sample, excluding those with known tobacco, alcohol, illicit drug, opioid, and benzodiazepine use, contained women who used e-cigs throughout pregnancy and non-e-cig user controls. Fetal size measurements from second- and third-trimester ultrasounds and at birth were expressed as percentiles for gestational age. Following adjustment for confounding factors, in the second trimester, only femur length was significant, with an adjusted deficit of 11.5 percentile points for e-cig exposure compared to controls. By the third trimester, the femur length difference was 28.5 points, with the fetal weight difference also significant (17.2 points). At birth, all three size parameter differences between groups were significant. Significant size deficits were predicted by prenatal e-cig exposure, becoming larger and impacting more parameters with increasing gestation. While additional studies are warranted to confirm and expand upon these findings, this study adds to emerging data pointing to specific harms following e-cig exposure in pregnancy and suggests that e-cigs may not be a "safer" alternative to combustible cigarette smoking in pregnancy.

Measuring Atrial Size, Shape, and Contractility of the Fetal Heart Using FetalHQ: A New Technique Using Speckle Tracking Analysis.

Measurements of fetal atrial size, shape, and contractility have been previously reported using the TomTec fetal heart speckle tracking analysis software, which currently is no longer available in the marketplace. At the present time, the only software available for speckle-tracking analysis of the fetal heart is fetalHQ, which analyzes the fetal heart ventricles using the same algorithms as the TomTec software used for speckle-tracking analysis. This communication will review how to use the fetalHQ software to measure the size, shape, and contractility of the atrial chambers.

Study of Ultrasonographic Changes of the Adrenal Gland in Growth Restricted Fetus

Background: Fetuses with Fetal Growth Restriction (FGR) are at increased risk of chronic intra-uterine hypoxia, due to increased secretion of corticosterone from the fetal adrenal glands. This plays a major role in the cardiovascular and circulatory adaptation of FGR fetuses. These modifications are untimely identified by sonographic imaging. Objective: To study the association between ultrasound features of the adrenal gland and growth restriction in the fetus. Methods: A total of 104 pregnant women (52 FGR pregnancies and 52 controls) were evaluated between 28 and 36 weeks of gestation. All the study participants underwent transabdominal ultrasonography to measure bilateral fetal adrenal gland volume and fetal zone volume, corrected for gestational age. They were followed up until delivery. The two groups were compared to analyze the perinatal outcome in relation to ultrasonographic changes in the adrenal gland. Results: The adrenal gland measurements were significantly larger in fetuses with FGR as compared to the control group. FGR group had a larger corrected adrenal gland volume(cAGV) and fetal zone and adrenal gland (FZ/AG)ratio A statistically significant correlation was found between the two groups regarding gestational age at delivery, birth weight, APGAR score, and NICU admissions. Perinatal morbidity was found to be higher among women diagnosed with FGR, i.e., 14 (53.84%). Conclusion: Fetal adrenal gland size measurement is important to identify FGR fetuses that are vulnerable to hypoxia. It helps the obstetrician prepare for effective in-utero management to reduce perinatal morbidity and mortality.

Treatment of Diabetes in Pregnancy With Metformin.

Metformin is a commonly used drug in the treatment of type 2 diabetes and has been used to treat gestational diabetes since the 1970s. In pregnancy, its proven benefits include reduced gestational weight gain and reduced fetal size; some studies have shown reduced risk of cesarean delivery and lower rates of hypertension. Metformin can reduce the need for insulin therapy but does not eliminate such need in many patients. Despite these benefits, metformin crosses the placenta and has been associated with increases in the risk of giving birth to small-for-gestational-age neonates in some studies of individuals with type 2 diabetes in pregnancy. In addition, higher body mass index (BMI) z-scores have been observed among exposed offspring in some of the long-term follow-up studies. Nevertheless, metformin's low cost, ease of administration, and global reach make it a reasonable intervention in a population affected by rising rates of obesity and diabetes in pregnancy. Further follow-up studies are required to monitor the long-term health of exposed offspring.

Assessment of Fetal Ventricular Size and Shape in Women With Intrahepatic Cholestasis of Pregnancy Using Speckle Tracking.

To examine the effect of intrahepatic cholestasis of pregnancy (ICP) on fetal heart morphology. This case-control study was conducted with 40 women with ICP and 54 pregnant controls. Fetal heart quantification based on speckle tracking technology was used to assess the morphology of the fetal right and left ventricles. Routine ventricular size parameters, global and 24-segment spherical indices (SIs) were measured and compared between groups. The routine fetal cardiac parameters, global and right-ventricular SIs did not differ between the ICP and control groups. The left-ventricular apical (segments 16-24) SIs were lower in the ICP group than in the control group (P < .05), with no significant difference in the other left-ventricular segments. Subclinical morphological changes were observed in the left ventricular apical segments of the fetal hearts in women with ICP, which indicates an intrauterine environment with high bile acid concentrations. Twenty-four-segment SIs can be used to effectively evaluate these changes.

Sex-dependent effects of Setd1a haploinsufficiency on development and adult behaviour.

Loss of function (LoF) mutations affecting the histone methyl transferase SETD1A are implicated in the aetiology of a range of neurodevelopmental disorders including schizophrenia. We examined indices of development and adult behaviour in a mouse model of Setd1a haploinsufficiency, revealing a complex pattern of sex-related differences spanning the pre- and post-natal period. Specifically, male Setd1a+/- mice had smaller placentae at E11.5 and females at E18.5 without any apparent changes in foetal size. In contrast, young male Setd1a+/- mice had lower body weight and showed enhanced growth, leading to equivalent weights by adulthood. Embryonic whole brain RNA-seq analysis revealed expression changes that were significantly enriched for mitochondria-related genes in Setd1a+/ samples. In adulthood, we found enhanced acoustic startle responding in male Setd1a+/- mice which was insentitive to the effects of risperidone, but not haloperidol, both commonly used antipsychotic drugs. We also observed reduced pre-pulse inhibition of acoustic startle, a schizophrenia-relevant phenotype, in both male and female Setd1a+/- mice which could not be rescued by either drug. In the open field and elevated plus maze tests of anxiety, Setd1a haplosufficiency led to more anxiogenic behaviour in both sexes, whereas there were no differences in general motoric ability and memory. Thus, we find evidence for changes in a number of phenotypes which strengthen the support for the use of Setd1a haploinsufficient mice as a model for the biological basis of schizophrenia. Furthermore, our data point towards possible underpinning neural and developmental mechanisms that may be subtly different between the sexes.

Prenatal organophosphate pesticide exposure and sex-specific estimated Fetal size.

Prenatal organophosphate (OP) pesticide exposure may be associated with reduced fetal growth, although studies are limited and have mixed results. We investigated associations between prenatal OP pesticide exposure and fetal size and modification by fetal sex. Maternal urinary concentrations of dialkyl phosphate (DAP) metabolites were measured at three time points. Fetal biometrics were obtained from ultrasounds in the second (n=773) and third (n=535) trimesters. Associations between pregnancy-averaged ΣDAP and fetal biometry z-scores were determined through multiple linear regression. Modification by sex was investigated through stratification and interaction. In the second trimester, one ln-unit increase in ΣDAP was associated with lower estimated fetal weight (-0.15 SD; 95% CI: -0.29, -0.01), head circumference (-0.11 SD; CI: -0.22, 0.01), biparietal diameter (-0.14 SD; CI: -0.27, -0.01), and abdominal circumference (-0.12 SD; CI: -0.26, 0.01) in females. In the third trimester, one ln-unit increase in ΣDAP was associated with lower head circumference (-0.14 SD; CI: -0.28, 0.00) and biparietal diameter (-0.12 SD; CI: -0.26, 0.03) in males. Our results suggest that prenatal OP pesticide exposure is negatively associated with fetal growth in a sex-specific manner, with associations present for females in mid-gestation and males in late gestation.