Fetal heart rate variability is a biomarker of rapid but not progressive exacerbation of inflammation in preterm fetal sheep.

Perinatal infection/inflammation can trigger preterm birth and contribute to neurodevelopmental disability. There are currently no sensitive, specific methods to identify perinatal infection. We investigated the utility of time, frequency and non-linear measures of fetal heart rate (FHR) variability (FHRV) to identify either progressive or more rapid inflammation. Chronically instrumented preterm fetal sheep were randomly assigned to one of three different 5d continuous i.v. infusions: 1) control (saline infusions; n = 10), 2) progressive lipopolysaccharide (LPS; 200 ng/kg over 24 h, doubled every 24 h for 5d, n = 8), or 3) acute-on-chronic LPS (100 ng/kg over 24 h then 250 ng/kg/24 h for 4d plus 1 µg boluses at 48, 72, and 96 h, n = 9). Both LPS protocols triggered transient increases in multiple measures of FHRV at the onset of infusions. No FHRV or physiological changes occurred from 12 h after starting progressive LPS infusions. LPS boluses during the acute-on-chronic protocol triggered transient hypotension, tachycardia and an initial increase in multiple time and frequency domain measures of FHRV, with an asymmetric FHR pattern of predominant decelerations. Following resolution of hypotension after the second and third LPS boluses, all frequencies of FHRV became suppressed. These data suggest that FHRV may be a useful biomarker of rapid but not progressive preterm infection/inflammation.

A systematic review of maternal TORCH serology as a screen for suspected fetal infection.

BACKGROUND: The acronym 'TORCH' refers to well-recognised causes of perinatal infections: toxoplasmosis, rubella, cytomegalovirus (CMV) and herpes simplex virus (HSV). A TORCH serology panel is often used to test for maternal primary infection following detection of ultrasound abnormalities in pregnancy. AIM: This review aims to estimate the diagnostic yield of maternal TORCH serology in pregnancy following fetal ultrasound abnormalities. MATERIALS AND METHODS: Primary studies published since 2000 that assessed maternal TORCH serology for suspected fetal infection and included information on indications for testing, definition of positive TORCH serology results, and perinatal outcomes were included. RESULTS: Eight studies with a total of 2538 pregnancies were included. The main indications for testing were polyhydramnios, fetal growth restriction and hyperechogenic bowel. There were 26 confirmed cases of congenital CMV, of which 15 had multiple ultrasound abnormalities. There were no cases of congenital toxoplasmosis, rubella or HSV confirmed in any of the eight studies. CONCLUSIONS: The clinical utility of TORCH serology for non-specific ultrasound abnormalities such as isolated fetal growth restriction or isolated polyhydramnios is low. It is time to retire the TORCH acronym and the reflex ordering of 'TORCH' panels, as their continued use obscures, rather than illuminates, appropriate investigation for fetal ultrasound abnormalities.

Prenatal exome sequencing and chromosomal microarray analysis in fetal structural anomalies in a highly consanguineous population reveals a propensity of ciliopathy genes causing multisystem phenotypes.

Fetal abnormalities are detected in 3% of all pregnancies and are responsible for approximately 20% of all perinatal deaths. Chromosomal microarray analysis (CMA) and exome sequencing (ES) are widely used in prenatal settings for molecular genetic diagnostics with variable diagnostic yields. In this study, we aimed to determine the diagnostic yield of trio-ES in detecting the cause of fetal abnormalities within a highly consanguineous population. In families with a history of congenital anomalies, a total of 119 fetuses with structural anomalies were recruited and DNA from invasive samples were used together with parental DNA samples for trio-ES and CMA. Data were analysed to determine possible underlying genetic disorders associated with observed fetal phenotypes. The cohort had a known consanguinity of 81%. Trio-ES led to diagnostic molecular genetic findings in 59 fetuses (with pathogenic/likely pathogenic variants) most with multisystem or renal abnormalities. CMA detected chromosomal abnormalities compatible with the fetal phenotype in another 7 cases. Monogenic ciliopathy disorders with an autosomal recessive inheritance were the predominant cause of multisystem fetal anomalies (24/59 cases, 40.7%) with loss of function variants representing the vast majority of molecular genetic abnormalities. Heterozygous de novo pathogenic variants were found in four fetuses. A total of 23 novel variants predicted to be associated with the phenotype were detected. Prenatal trio-ES and CMA detected likely causative molecular genetic defects in a total of 55% of families with fetal anomalies confirming the diagnostic utility of trio-ES and CMA as first-line genetic test in the prenatal diagnosis of multisystem fetal anomalies including ciliopathy syndromes.

Detection of maternal and fetal stress from the electrocardiogram with self-supervised representation learning.

In the pregnant mother and her fetus, chronic prenatal stress results in entrainment of the fetal heartbeat by the maternal heartbeat, quantified by the fetal stress index (FSI). Deep learning (DL) is capable of pattern detection in complex medical data with high accuracy in noisy real-life environments, but little is known about DL's utility in non-invasive biometric monitoring during pregnancy. A recently established self-supervised learning (SSL) approach to DL provides emotional recognition from electrocardiogram (ECG). We hypothesized that SSL will identify chronically stressed mother-fetus dyads from the raw maternal abdominal electrocardiograms (aECG), containing fetal and maternal ECG. Chronically stressed mothers and controls matched at enrolment at 32 weeks of gestation were studied. We validated the chronic stress exposure by psychological inventory, maternal hair cortisol and FSI. We tested two variants of SSL architecture, one trained on the generic ECG features for emotional recognition obtained from public datasets and another transfer-learned on a subset of our data. Our DL models accurately detect the chronic stress exposure group (AUROC = 0.982 ± 0.002), the individual psychological stress score (R2 = 0.943 ± 0.009) and FSI at 34 weeks of gestation (R2 = 0.946 ± 0.013), as well as the maternal hair cortisol at birth reflecting chronic stress exposure (0.931 ± 0.006). The best performance was achieved with the DL model trained on the public dataset and using maternal ECG alone. The present DL approach provides a novel source of physiological insights into complex multi-modal relationships between different regulatory systems exposed to chronic stress. The final DL model can be deployed in low-cost regular ECG biosensors as a simple, ubiquitous early stress detection and monitoring tool during pregnancy. This discovery should enable early behavioral interventions.

Placental Endocrine Activity: Adaptation and Disruption of Maternal Glucose Metabolism in Pregnancy and the Influence of Fetal Sex.

The placenta is an endocrine fetal organ, which secretes a plethora of steroid- and proteo-hormones, metabolic proteins, growth factors, and cytokines in order to adapt maternal physiology to pregnancy. Central to the growth of the fetus is the supply with nutrients, foremost with glucose. Therefore, during pregnancy, maternal insulin resistance arises, which elevates maternal blood glucose levels, and consequently ensures an adequate glucose supply for the developing fetus. At the same time, maternal ß-cell mass and function increase to compensate for the higher insulin demand. These adaptations are also regulated by the endocrine function of the placenta. Excessive insulin resistance or the inability to increase insulin production accordingly disrupts physiological modulation of pregnancy mediated glucose metabolism and may cause maternal gestational diabetes (GDM). A growing body of evidence suggests that this adaptation of maternal glucose metabolism differs between pregnancies carrying a girl vs. pregnancies carrying a boy. Moreover, the risk of developing GDM differs depending on the sex of the fetus. Sex differences in placenta derived hormones and bioactive proteins, which adapt and modulate maternal glucose metabolism, are likely to contribute to this sexual dimorphism. This review provides an overview on the adaptation and maladaptation of maternal glucose metabolism by placenta-derived factors, and highlights sex differences in this regulatory network.

Novel metabolic marker Afamin: A predictive factor for Large-for-Gestational-Age (LGA) fetus estimation in pregnancies with gestational diabetes mellitus?

OBJECTIVE: Gestational diabetes mellitus (GDM) affects both maternal and fetal/infant outcomes during and after pregnancy. The reason for the high incidence of large-for-gestational-age (LGA) infants in GDM patients despite close monitorization of glucose levels with early detection of the disease remains unclear to date. Our study aims to investigate the levels of the third-trimester novel marker afamin in GDM versus non-GDM pregnancies in terms of glycemic control status and their utility in the prediction of LGA fetuses. MATERIAL AND METHODS: This prospective case-control study analysis involved 49 pregnant women with GDM diagnosed using the 75-g oral glucose tolerance test (75-g OGTT) and 40 randomly selected women with a similar body mass index (BMI) and gestational age (GA). Blood samples were collected in the third trimester of pregnancy. The afamin level was determined using a human afamin ELISA kit according to the manufacturer's procedure. RESULTS: There was no significant difference found in BMI or GA of patients. Third-trimester afamin levels were 93.91 mg/L and 83.87 mg/L in the GDM and non-GDM groups, respectively (p=0.625). Afamin values of patients were not correlated with age, BMI, GA, HgA1c, 75-g OGTT fasting and 75-g OGTT 1-hour, or 75-g OGTT 2-hour values (p>0.05). GDM patients with LGA fetuses had significantly higher afamin values than patients with appropriate-for-gestational-age (AGA) fetuses (120.8 mg/L versus 91.26 mg/L, respectively). Between GDM patients with either LGA or AGA fetuses, there was no statistically significant difference found for age, BMI, GAs, insulin dose, 75-g OGTT results, or HgA1c values. CONCLUSION: Our findings conclude that novel marker afamin levels could predict the risk of LGA infants independently of glycemic control status and provide insight into the pathogenesis of LGA fetuses, thus helping to reduce the risk of associated complications.

Alterations of brain metrics in fetuses of women with polycystic ovary syndrome : a retrospective study based on fetal magnetic resonance imaging.

BACKGROUND: Maternal polycystic ovary syndrome (PCOS) has potential detrimental effects on the neurodevelopment of offspring. This study aimed to evaluate the brain metrics in fetuses of women with PCOS based on fetal magnetic resonance imaging (MRI). METHODS: This retrospective study included 60 pregnant women with PCOS (PCOS group) and 120 pregnant non-PCOS women (control group). Fetal MRI was performed followed an ultrasound and for numerous clinical indications including known or suspected fetal pathology, history of fetal abnormality in previous pregnancy or in a family member. Fetal brain biometry and apparent diffusion coefficient (ADC) value were analysed. RESULTS: After adjusting for potential confounders, fetuses in the PCOS group showed the following characteristics compared to fetuses in the control group: (1) smaller cerebral fronto-occipital diameter (FOD), vermian height (VH) and anteroposterior diameter of the pons (APDP) (evident before 32 weeks; P = 0.042, P = 0.002 and P = 0.016, respectively); (2) larger left and right biparietal index (evident before 32 weeks; P = 0.048 and P = 0.025, respectively); (3) smaller left lateral ventricle (LV) (evident after 32 weeks; P = 0.005); (4) larger anteroposterior diameter of the vermis (APDV) and hippocampal infolding angle (HIA) (evident after 32 weeks; P = 0.003 and P < 0.001, respectively); (5) higher ADC value in frontal white matter (FWM) and in basal ganglia (BG) (evident before and after 32 weeks; all P < 0.05). CONCLUSIONS: There exist a different pattern of brain metrics in PCOS offspring in utero.

Placental hypoxia: What have we learnt from small animal models?

Intrauterine hypoxia is a feature of pregnancy complications, both at high altitude and sea level. To understand the placental response to reduced oxygen availability, small animal models of maternal inhalation hypoxia (MIH) or reduced uterine perfusion pressure (RUPP) may be utilised. The aim of this review was to compare the findings of those studies to identify the role of oxygen availability in adapting placental structural and functional phenotypes in relation to fetal outcome. It also sought to explore the evidence for the involvement of particular genes and protein signalling pathways in the placenta in mediating hypoxia driven alterations. The data available demonstrate that both MIH and RUPP can induce placental hypoxia, which affects placental structure and vascularity, as well as glucose, amino acid, calcium and possibly lipid transport capacity. In addition, changes have been observed in HIF, VEGF, insulin/IGF2, AMPK, mTOR, PI3K and PPARγ signalling, which may be key in linking together observed phenotypes under conditions of placental hypoxia. Many different manipulations have been examined, with varied outcomes depending on the intensity, timing and duration of the insult. Some manipulations have detrimental effects on placental phenotype, viability and fetal growth, whereas in others, the placenta appears to adapt to uphold fetal growth despite the challenge of low oxygen. Together these data suggest a complex response of the placenta to reduced oxygen availability, which links to changes in fetal outcomes. However, further work is required to explore the role of fetal sex, altered maternal physiology and placental molecular mechanisms to fully understand placental responses to hypoxia and their relevance for pregnancy outcome.

Impact of the cystic neural tube defects on fetal motor function in prenatal myelomeningocele repairs: A retrospective cohort study.

OBJECTIVE: To determine the impact of the lesion type (cystic [myelomeningocele] or flat [myeloschisis]) on the fetal motor function (MF) in cases candidates for prenatal open neural tube defect (ONTD) repair. METHODS: Retrospective cohort study of patients with ONTD who underwent prenatal repair at a single institution between 2011 and 2019. The lesion type and the measurements of the length and width of the lesions to calculate the surface of the ellipsoid lesion were performed using MR scans. Prenatal MF of the lower extremities was evaluated by ultrasound following a metameric distribution at the time of referral. Intact MF was defined as the observation of plantar flexion of the ankle. Logistic regression was performed to determine the predictive value of the type of lesion for having an intact MF at the time of referral. RESULTS: 103 patients were included at 22.9 (19-25.4) weeks; 65% had cystic and 35% had flat lesions. At the time of referral, there was a higher proportion of cases with an intact MF in the presence of flat lesions (34/36; 94.4%) as compared to cystic lesion (48/67; 71.6%, p < 0.01). When adjusting for gestational age and anatomical level of the lesion, flat ONTD were 3.1 times more likely to be associated by intact motor function (CI%95 [2.1-4.6], p < 0.01) at the time of referral. CONCLUSION: Cystic ONTD are more likely to be associated with impaired MF at mid-gestation in candidates for prenatal ONTD repair.

New genetic and clinical evidence associated with fetal Beckwith-Wiedemann syndrome.

Early detection of Beckwith-Wiedemann syndrome (BWS) is very important since it is very useful regarding counseling of parents concerning the risk of developing embryonic tumors, selection of the mode of delivery due to potential adrenal cysts that might bleed during labor, prevention of neonatal hypoglycemia and even options of pregnancy termination in non-viable fetuses. This report describes the prenatal classic sonographic triad of fetal BWS (omphalocele, macrosomia, macroglossia) and other supporting findings (hepatomegaly, adrenal enlargement) as well as additional postnatal evidence. Also, it demonstrates new molecular genetic evidence potentially associated with the disease (the presence of a novel heterozygous c.358G>T variant of the CDKN1C gene). Importantly, we provide new evidence indicating that elevated levels of the four serum biomarkers (alpha-fetoprotein, beta-human gonadotropin, unconjugated estriol, and inhibin-A) in late first or early second trimester might be strongly suggestive of BWS which may facilitate early detection especially in cases of no obvious anomaly. In conclusion, this study emphasizes on early detection of BWS as early as at 14 weeks of gestation, based on the abnormal rise of the four serum biomarkers together with omphalocele. To the best of our knowledge, this is the earliest prenatal detection of BWS ever reported. Finally, we provide new molecular genetic evidence that is, potentially associated with BWS.

Central role of the placenta during viral infection: Immuno-competences and miRNA defensive responses.

Pregnancy is a unique immunological condition in which an "immune-diplomatic" dialogue between trophoblasts and maternal immune cells is established to protect the fetus from rejection, to create a privileged environment in the uterus and to simultaneously be alert to any infectious challenge. The maternal-placental-fetal interface (MPFI) performs an essential role in this immunological defense. In this review, we will address the MPFI as an active immuno-mechanical barrier that protects against viral infections. We will describe the main viral infections affecting the placenta and trophoblasts and present their structure, mechanisms of immunocompetence and defensive responses to viral infections in pregnancy. In particular, we will analyze infection routes in the placenta and trophoblasts and the maternal-fetal outcomes in both. Finally, we will focus on the cellular targets of the antiviral microRNAs from the C19MC cluster, and their effects at both the intra- and extracellular level.

Hourly fetal urine production rate in isolated oligohydramnios at term.

OBJECTIVE: The aim of this study was to evaluate the hourly fetal urine production rate (HFUPR) via three-dimensional ultrasonography in women with isolated oligohydramnios and compare with normal pregnant women at term. MATERIALS AND METHODS: This was a prospective observational cohort study of 112 women from 34 to 40 6/7 weeks' gestation. They were classified into three groups according to the amniotic fluid index (AFI) and ultrasonographic estimated fetal weight (EFW) as isolated oligohydramnios (defined as AFI below 5% and appropriate EFW corresponding to gestational age) (n = 34) and IUGR (defined as EFW below 5% corresponding to gestational age irrespective amniotic fluid) (n = 17), and normal pregnancy (n = 61). HFUPR was measured using three-dimensional virtual organ computer-aided analysis. Adverse perinatal outcomes in all participants were examined. RESULTS: There was no significant difference in HFUPR between patients with isolated oligohydramnios and women with normal pregnancies (median, 40.0 mL/h [interquartile range [IQR] 31.0-66.5] vs. 48.6 [31.5-81.2], p = 0.224). HFUPR was significantly decreased in the IUGR group (13.8 mL/h [IQR 10.1-24.8]), compared to the normal pregnancy group (p<0.001) and the isolated oligohydramnios group (p<0.001). HFUPR was significantly decreased in neonates with adverse perinatal outcomes compared to the control (24.7 mL/h [IQR 13.4-47.4] vs. 43.6 [29.8-79.0], p = 0.016). CONCLUSION: HFUPR was not decreased in patients with isolated oligohydramnios but was decreased in patients with IUGR when compared to normal controls at term.

Hyporegenerative anemia in anti-M-associated hemolytic disease of the fetus.

BACKGROUND: The anti-M antibody can lead to hemolytic disease of the fetus and newborn (HDFN) and adverse fetal outcomes, especially in the Asian population. However, fetal erythropoiesis resulting from M alloimmunization needs further investigation. STUDY DESIGN AND METHODS: We analyzed erythropoiesis in eight fetuses with M alloimmunization and compared them with the fetuses affected by anti-D. They were matched as pairs according to the gestational age of diagnosis and the hematocrit before treatment. Paired t-tests or paired Wilcoxon rank-sum tests were conducted to compare the difference in the cord blood indexes. Pearson correlation analysis was used to evaluate the correlativity between hematocrit and the reticulocyte percentage in the two groups. RESULTS: The fetuses in the MN group had lower reticulocyte count and percentage than those in the RhD group (p < .05). All of the fetal reticulocyte production indexes (RPIs) in the MN group were less than 2, indicating an inadequate hemopoietic response to anemia, while the majority of the RPIs in the RhD group (85.7%) were significantly higher (p = .003), with 6 cases greater than 2.5. Hematocrit was negatively correlated with reticulocyte percentage (y = 54.7-171.7x, r2  = 0.825, p = .005) in the RhD group, while no significant correlation was found in the MN group. No difference in the number of IUT, interval, or the fetal outcome was found between the two groups. CONCLUSION: Fetal reticulocytopenia provided direct evidence of an inadequate hemopoietic response in HDFN due to anti-M, leading to hyporegenerative anemia. Once the IgG component of anti-M is detected, close monitoring should be considered.

Transient effects of forebrain ischemia on fetal heart rate variability in fetal sheep.

Fetal heart rate variability (FHRV) is a key index of antenatal and intrapartum fetal well-being. FHRV is well established to be mediated by both arms of the autonomic nervous system, but it remains unknown whether higher centers in the forebrain contribute to FHRV. We tested the hypothesis that selective forebrain ischemia would impair the generation of FHRV. Sixteen chronically instrumented near-term fetal sheep were subjected to either forebrain ischemia induced by bilateral carotid occlusion or sham-ischemia for 30 min. Time, frequency, and nonlinear measures of FHRV were assessed during and for seven days after ischemia. Ischemia was associated with profound suppression of electroencephalographic (EEG) power, which remained suppressed throughout the recovery period (P < 0.001). During the first 5 min of ischemia, multiple time and frequency domain measures were increased (all P < 0.05) before returning back to sham levels. A delayed increase in sample entropy was observed during ischemia (P < 0.05). For the first 3 h after ischemia, there was moderate suppression of two measures of FHRV (very-low frequency power and the standard deviation of RR-intervals, both P < 0.05) and increased sample entropy (P < 0.05). Thereafter, all measures of FHRV returned to control levels. In conclusion, profound forebrain ischemia sufficient to lead to severe neural injury had only transient effect on multiple measures of FHRV. These findings suggest that the forebrain makes a limited contribution to FHRV. FHRV therefore primarily originates in the hindbrain and is unlikely to provide meaningful information on forebrain neurodevelopment or metabolism.

Breech progression angle: new feasible and reliable transperineal ultrasound parameter for assessment of fetal breech descent in birth canal.

OBJECTIVE: To assess the feasibility and reliability of transperineal ultrasound in the assessment of fetal breech descent in the birth canal, by measuring the breech progression angle (BPA). METHODS: Women with a singleton pregnancy with the fetus in breech presentation between 34 and 41 weeks' gestation were recruited. Transperineal ultrasound images were acquired in the midsagittal view for each woman, twice by one operator and once by another. Each operator measured the BPA after anonymization of the transperineal ultrasound images. BPA was defined as the angle between a line running along the long axis of the pubic symphysis and another line extending from the most inferior portion of the pubic symphysis tangentially to the lowest recognizable fetal part in the maternal pelvis. Each operator was blinded to all other measurements performed for each woman. Intra- and interobserver reproducibility of BPA measurement was evaluated using the intraclass correlation coefficient (ICC). To investigate the presence of any bias, intra- and interobserver agreement was also analyzed using Bland-Altman analysis. Student's t-test and Levene's W0 test were used to investigate whether a number of different clinical factors had an effect on systematic differences and homogeneity, respectively, between BPA measurements. RESULTS: Overall, 44 women were included in the analysis. BPA was measured successfully by both operators on all images. Both intra- and interobserver agreement analyses showed excellent reproducibility in BPA measurement, with ICCs of 0.88 (95% CI, 0.80-0.93) and 0.83 (95% CI, 0.71-0.90), respectively. The mean difference between measurements was 0.4° (95% CI, -1.4 to 2.2°) for intraobserver repeatability and -0.4° (95% CI, -2.6 to 1.8°) for interobserver repeatability. The upper limits of agreement were 12.0° (95% CI, 8.9-15.1°) and 13.6° (95% CI, 9.9-17.3°) for intra- and interobserver repeatability, respectively. The lower limits of agreement were -11.2° (95% CI, -14.3 to -8.1°) and -14.4° (95% CI, -18.2 to -10.7°) for intra- and interobserver repeatability, respectively. No systematic difference between BPA measurements was found on either intra- or interobserver agreement analysis. None of the clinical factors examined (maternal body mass index, maternal age, gestational age at the ultrasound scan and parity) showed a statistically significant effect on intra- or interobserver reliability. CONCLUSIONS: BPA represents a new feasible and highly reproducible measurement for the evaluation of fetal breech descent in the birth canal. Future studies assessing its usefulness in the prediction of successful external cephalic version and breech vaginal delivery are needed. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction.

Fetal growth restriction (FGR) is defined as the failure of the fetus to meet its growth potential due to a pathological factor, most commonly placental dysfunction. Worldwide, FGR is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Ongoing advances in clinical care, especially in definitions, diagnosis, and management of FGR, require efforts to effectively translate these changes to the wide range of obstetric care providers. This article highlights agreements based on current research in the diagnosis and management of FGR, and the areas that need more research to provide further clarification of recommendations. The purpose of this article is to provide a comprehensive summary of available evidence along with practical recommendations concerning the care of pregnancies at risk of or complicated by FGR, with the overall goal to decrease the risk of stillbirth and neonatal mortality and morbidity associated with this condition. To achieve these goals, FIGO (the International Federation of Gynecology and Obstetrics) brought together international experts to review and summarize current knowledge of FGR. This summary is directed at multiple stakeholders, including healthcare providers, healthcare delivery organizations and providers, FIGO member societies, and professional organizations. Recognizing the variation in the resources and expertise available for the management of FGR in different countries or regions, this article attempts to take into consideration the unique aspects of antenatal care in low-resource settings (labelled "LRS" in the recommendations). This was achieved by collaboration with authors and FIGO member societies from low-resource settings such as India, Sub-Saharan Africa, the Middle East, and Latin America.

Effect of Bone Marrow Transplantation on the Fetal Skeleton of Maternally Irradiated Pregnant Rats.

BACKGROUND AND OBJECTIVE: Prenatal exposure to ionizing radiation can interfere with embryonic and fetal growth depending on the dose and gestational age. The present study was completed to evaluate the effect of transplanted bone marrow on the fetal skeleton of pregnant rats exposed to gamma radiation. MATERIALS AND METHODS: Experimental animals were separated into 5 groups: C group, R7 group, R7+BM group, R14 group and R14+BM group. All pregnant rats were sacrificed on day 20 days of gestation and the skeletal systems of the fetuses were examined and photographed. This study focused on skull, upper and lower jaw, occipital region, sacral and caudal region, fore and hind limbs. RESULTS: Gamma rays caused any disturbance in the ossification process of the skull bones, upper and lower jaws, occipital bones, it caused the loss of some ossification centers in metacarpal bones, metatarsal bones but bone marrow transplantation greatly reduced the injury that happened because of γ-radiation. CONCLUSION: This study showed that transplantation of bone marrow post-irradiation in pregnant rats could reduce the hazards of gamma-irradiation in the different regions of the fetal skeleton.

Gestational long-term hypoxia induces metabolomic reprogramming and phenotypic transformations in fetal sheep pulmonary arteries.

Gestational long-term hypoxia increases the risk of myriad diseases in infants including persistent pulmonary hypertension. Similar to humans, fetal lamb lung development is susceptible to long-term intrauterine hypoxia, with structural and functional changes associated with the development of pulmonary hypertension including pulmonary arterial medial wall thickening and dysregulation of arterial reactivity, which culminates in decreased right ventricular output. To further explore the mechanisms associated with hypoxia-induced aberrations in the fetal sheep lung, we examined the premise that metabolomic changes and functional phenotypic transformations occur due to intrauterine, long-term hypoxia. To address this, we performed electron microscopy, Western immunoblotting, calcium imaging, and metabolomic analyses on pulmonary arteries isolated from near-term fetal lambs that had been exposed to low- or high-altitude (3,801 m) hypoxia for the latter 110+ days of gestation. Our results demonstrate that the sarcoplasmic reticulum was swollen with high luminal width and distances to the plasma membrane in the hypoxic group. Hypoxic animals were presented with higher endoplasmic reticulum stress and suppressed calcium storage. Metabolically, hypoxia was associated with lower levels of multiple omega-3 polyunsaturated fatty acids and derived lipid mediators (e.g., eicosapentaenoic acid, docosahexaenoic acid, α-linolenic acid, 5-hydroxyeicosapentaenoic acid (5-HEPE), 12-HEPE, 15-HEPE, prostaglandin E3, and 19(20)-epoxy docosapentaenoic acid) and higher levels of some omega-6 metabolites (P < 0.02) including 15-keto prostaglandin E2 and linoleoylglycerol. Collectively, the results reveal broad evidence for long-term hypoxia-induced metabolic reprogramming and phenotypic transformations in the pulmonary arteries of fetal sheep, conditions that likely contribute to the development of persistent pulmonary hypertension.

No Effect of Lifestyle Intervention during Third Trimester on Brain Programming in Fetuses of Mothers with Gestational Diabetes.

Maternal metabolism and intrauterine conditions influence development of health and disease in offspring, leading to metabolic, physiologic, and/or epigenetic adaptation of the fetus. Maternal gestational diabetes (GDM) leads to higher incidence of obesity and type 2 diabetes in offspring. We have previously shown that fetuses of insulin-resistant mothers with GDM have a delayed reaction to auditory stimuli in the postprandial state, indicating a fetal central insulin resistance. We tested whether this effect could be influenced by a lifestyle intervention in mothers with GDM, including diet counselling and regular blood glucose measurements. We measured fetal brain activity over the course of a maternal glucose challenge, at two measurement time points (baseline at an average of 29 weeks of gestation and follow-up after 4 weeks) in mothers with GDM and mothers with normal glucose tolerance (NGT). Data from eight mothers were able to be included. Fetuses of GDM mothers showed longer latencies than those of NGT mothers postprandially at both measurement time points during the third trimester and did not show a difference in response patterns between baseline and after 4 weeks. Maternal postprandial blood glucose and insulin values did not change from baseline to follow-up either. While the overall intervention seems to have been effective, it does not appear to have influenced the fetal postprandial brain responses. This might have been because interventions for GDM take place relatively late in pregnancy. Future research should focus on maternal lifestyle interventions as early as possible during gestation, or even prenatally.

A randomized controlled trial investigating the impact of maternal dietary supplementation with pomegranate juice on brain injury in infants with IUGR.

Animal studies have demonstrated the therapeutic potential of polyphenol-rich pomegranate juice. We recently reported altered white matter microstructure and functional connectivity in the infant brain following in utero pomegranate juice exposure in pregnancies with intrauterine growth restriction (IUGR). This double-blind exploratory randomized controlled trial further investigates the impact of maternal pomegranate juice intake on brain structure and injury in a second cohort of IUGR pregnancies diagnosed at 24-34 weeks' gestation. Ninety-nine mothers and their eligible fetuses (n = 103) were recruited from Brigham and Women's Hospital and randomly assigned to 8 oz pomegranate (n = 56) or placebo (n = 47) juice to be consumed daily from enrollment to delivery. A subset of participants underwent fetal echocardiogram after 2 weeks on juice with no evidence of ductal constriction. 57 infants (n = 26 pomegranate, n = 31 placebo) underwent term-equivalent MRI for assessment of brain injury, volumes and white matter diffusion. No significant group differences were found in brain volumes or white matter microstructure; however, infants whose mothers consumed pomegranate juice demonstrated lower risk for brain injury, including any white or cortical grey matter injury compared to placebo. These preliminary findings suggest pomegranate juice may be a safe in utero neuroprotectant in pregnancies with known IUGR warranting continued investigation.Clinical trial registration: NCT04394910, https://clinicaltrials.gov/ct2/show/NCT04394910 , Registered May 20, 2020, initial participant enrollment January 16, 2016.