Fetal Response Research Articles

Estrogen receptor 1 appears essential for fetal viability in a murine model of premature birth.

Protective effects for adult neurological disorders have been attributed to sex hormones. Using a murine model of prematurity, we evaluated the role of estrogen signaling in the process of perinatal brain injury following exposure to intrauterine inflammation. Intrauterine lipopolysaccharide (LPS) was used to invoke preterm labor and fetal neuroinflammation. Fetal brains were analyzed for changes in Esr1, Esr2 and Cyp19. Dams heterozygous for the Esr1 knockout allele were also given intrauterine LPS to compare delivery and offspring viability to wild type controls. The upregulation in inflammatory cytokines was accompanied by an increase in Esr1 and Esr2 transcripts, though protein levels declined. Cyp19 did not differ by mRNA or protein abundance. Offspring from Esr1 mutants were larger, had a longer gestation and significantly greater mortality. Estrogen signaling is altered in the fetal brains of preterm offspring exposed to neuroinflammatory injury. The reduction of Esr1 and Esr2 proteins with LPS suggests that these proteins are degraded. It is possible that transcriptional upregulation of Esr1 and Esr2 occurs to compensate for the loss of these proteins. Alternatively, the translation of Esr1 and Esr2 mRNAs may be disrupted with LPS while a feedback mechanism upregulates transcription. Intact Esr1 signaling is also associated with early preterm delivery following exposure to intrauterine LPS. A loss of one Esr1 allele delays this process, but appears to do so at the cost of fetal viability. These results suggest estrogen signaling plays opposing roles between maternal and fetal responses to preterm birth.

Ultrasonography on the labour ward

The role of fetal ultrasonography in the antepartum period is well established. Its utility on the labour ward - either intra-partum, just prior to labour or post-partum - is less clear however. Its current application on the labour ward ranges from simple determination of fetal position to the more complex assessment/prediction of labour progress to appraising fetal physiological responses to intrapartum stress. Unfortunately, established guidelines for the appropriate implementation of these techniques appear to be lacking. Here, we review the current evidence-base for the clinical application of ultrasound on the labour ward and suggest future research directions.

Color Doppler Ultrasonography in the Third Trimester of Pregnancy Significantly Reclassifies Fetal Growth Restriction in the Samrakshan Program of IRIA in India.

The failure of a fetus to achieve its optimal growth potential is classified as fetal growth restriction (FGR). Small fetuses are a major risk for adverse perinatal outcomes including perinatal mortality, perinatal brain injury, and fetal distress compared to fetuses with normal growth.[1] [2] [3] [4] [5] FGR is considered as a fetus with an estimated fetal weight (EFW) less than 10th percentile. However, FGR also shows Doppler signs of hemodynamic redistribution as a fetal adaptation response to undernutrition or hypoxia and histological and biochemical signs of placental disease.[1] Small for gestational age (SGA) fetuses, on the other hand, are defined as constitutionally small fetuses without evidence for fetal adaptation to abnormal fetal environment and have perinatal outcomes similar to fetuses with normal growth.[1] Samrakshan, a national program of Indian Radiological and Imaging Association (IRIA), integrated trimester-specific Doppler studies with routine antenatal ultrasound assessments.[6] We present the results pertaining to the prevalence of FGR and SGA identified through the Samrakshan program.

Severe maternal-fetal pathological damage and inflammatory responses contribute to miscarriage caused by hepatitis E viral infection during pregnancy.

Hepatitis E virus (HEV) infection causes serious adverse pregnancy outcomes during pregnancy. However, the maternal and fetal damage induced by HEV infection is rarely reported. A BALB/c pregnant mouse model was established to explore the maternal and fetal pathological damage and inflammatory responses caused by HEV infection. Notably, miscarriages and stillbirths were observed in HEV-infected pregnant mice. HEV infections were identified by qRT-PCR, immunohistochemical analysis and immunofluorescence assay in the uterus, placenta, umbilical cords and livers and brains of fetuses. Serious inflammatory responses and pathological damage were triggered in the uterus and placenta of HEV-infected pregnant mice. Vertical transmission of HEV resulted in severe pathological damage and inflammatory responses in the livers and brains of fetuses, as well as emerging apoptosis cells in the brains of fetuses. Most of the cytokines/chemokines in the sera were significantly increased in the HEV-infected pregnant mice. Remarkably, cytokines/chemokines were significantly different between HEV-infected pregnant and miscarriage mice; IL9, GM-CSF and IL1α were the most important three cytokines/chemokines in determining the pregnancy outcomes. HEV infections cause serious maternal/fetal pathological damage, inflammatory responses and apoptosis, which may be responsible for adverse pregnancy outcomes.

Neuropathology Evaluation of in Utero Correction of Myelomeningocele and Complications of Late-Onset GBS Infection

Background: Myelomeningocele (MMC) causes significant morbidity and mortality. Efforts have been directed to correct this defect in utero. The neuropathology literature on antenatally repaired MMC and associated complications in humans is limited. Case report: A 12-day-old female, who underwent prenatal MMC repair via a two-layer closure (dural replacement patch, primary skin closure), was born at 34 weeks’ gestation. Her group B streptococcus positive mother received appropriate antepartum prophylactic antibiotics. She remained stable until day 11 of life when she underwent rapid clinical deterioration. Despite aggressive intervention, she expired on day 12. Review of placental pathology showed maternal and fetal inflammatory response. Autopsy revealed Gram-positive cocci and inflammation within the basilar leptomeninges and lumbosacral region. Neural and dermal elements were present within the MMC repair. Conclusion: This case documents integration of the dermal matrix patch to neural elements, adhering the spinal cord to scar tissue, the clinical implications of which remain unclear.

Hydroxyurea Pharmacokinetics and Fetal Hemoglobin Response in Ugandan Children with Sickle Cell Anemia

Introduction Over 300,000 infants are born with sickle cell anemia (SCA) in Africa every year, and the under-5 mortality of this population is estimated to be 50-90% without treatment. Hydroxyurea is a safe, oral medication that decreases morbidity and mortality in SCA by increasing protective fetal hemoglobin (HbF) production and reducing inflammation. Hydroxyurea dosing to maximum tolerated dose (MTD) offers the optimal treatment with greatest laboratory responses and clinical benefits. Patients have variable hydroxyurea absorption and elimination rates, so the traditional approach to determining MTD is through incremental dose escalation to achieve mild myelosuppression and reduction in absolute neutrophil count (ANC). In the United States, pharmacokinetic (PK)-guided dosing of hydroxyurea for children with SCA has been shown to decrease time to MTD and to augment treatment responses, with most patients achieving over 30% HbF. Maximizing clinical benefits and minimizing logistical burdens of dosing hydroxyurea would be advantageous for areas with high SCA prevalence, but PK parameters of African children with SCA who might have higher rates of malnutrition, infections, and organ damage that affect drug absorption, distribution, and clearance are yet to be determined. Here we describe hydroxyurea PK exposure-response in Ugandan children with SCA from the Optimizing Hydroxyurea Therapy in Children with Sickle Cell Anemia In Malaria Endemic Areas: The NOHARM MTD Study (NOHARM MTD, NCT03128515). Methods NOHARM MTD was a randomized controlled trial that compared dosing strategies between hydroxyurea at fixed, weight-based dosing (~20 mg/kg/day) and dose escalation to MTD in children with SCA living in Uganda. NOHARM MTD participants underwent PK testing after 18 months of treatment. Children were administered their prescribed hydroxyurea dose in the morning at clinic, and blood was obtained by fingerstick using Mitra® microsampler devices after 20, 60, and 180 minutes. The microsampler devices were frozen at -80C in Uganda and then transported to Cincinnati Children's Hospital for analysis of hydroxyurea concentration via liquid chromatography with tandem mass spectrometry. Using our previously published population PK model, individual hydroxyurea exposures expressed as area-under-the-curve (AUC) were generated by Bayesian estimation using the PK modeling software NONMEM (Version 7.5, ICON Development Solutions, Ellicott City, USA). A hydroxyurea exposure-response analysis was completed with HbF% as the primary pharmacodynamic outcome. Results A total of 90 NOHARM MTD participants completed PK testing; samples from 12 were excluded from full analysis due to an elevated baseline concentration suggesting the participant already received the daily hydroxyurea dose before PK testing (9), supraphysiologic concentration (1), or mislabeling (2). PK profiles were analyzed for the remaining 78 participants (mean age 6.5 years, SD 0.9); of these, 41 were on fixed dose hydroxyurea and 37 were at MTD with mean doses of 18.7 mg/kg/day (SD 1.6) and 28.3 mg/kg/day (SD 4.3), respectively (Table). Those at MTD had a higher AUC with a significantly higher %HbF (mean 19% HbF on fixed dose vs 29% at MTD, p=0.0002) and lower ANC (mean 4.7 x109/L at fixed dose vs 3.2 at MTD, p=0.0045). Eighteen participants (23%) had malnutrition with a body mass index Z-score less than -1.0, and 12 (15%) participants had renal hyperfiltration with an estimated glomerular filtration rate over 150 mL/min/1.73m2; neither condition was associated with differences in AUC. Conclusion This study demonstrates the feasibility of collecting hydroxyurea PK data with timed, sparse sampling in Uganda, and the exposure-response analysis confirms that higher hydroxyurea exposure in Ugandan children with SCA is associated with greater induction of protective HbF and reduction in ANC. Malnutrition and glomerular hyperfiltration did not affect hydroxyurea exposure in this cohort. Further studies of PK-guided dosing to optimize response and time to response in this population are needed. Future directions include building capacity for local analysis of hydroxyurea concentrations using HPLC technology, real-time dose calculation via a PK model-informed algorithm, and prospective evaluation of PK-guided dosing. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Why We should Recommend Exercise in Pregnancy?

Objective: This narrative review is presenting the impact of exercise on pregnant women and fetus and provides current recommendations for exercise in pregnancy. Mechanism: Exercise during pregnancy has a numerous effects on both pregnant woman and her fetus. When recommending exercise during pregnancy, it is necessary to keep in mind the physiological responses of the body’s systems during exercise, changes occuring in pregnancy and the influence of this changes on pregnant woman’s body as well as on the fetus and fetal responses to exercise during pregnancy. The type, intensity, duration, and frequency of exercise should be adjusted to the level of physical activity of pregnant women and period of pregnancy in order to achieve clinically significant health benefits. Findings in Brief: Exercise in pregnancy is beneficial for both the mother and her fetus and contributes to the prevention of pregnancy-related disorders. It is recommend to exercise 30 minutes daily five days a week with a tendency to increase the exercise each day in order to accumulate 150 to 300 minutes of exercise per week with moderate intensity. Conclusions: Regular exercise leads to specific adaptation processes of the body systems improving the physical and mental health of pregnant women with positive effect on her fetus.

Abstract 10875: Metabolic Reprogramming of the Failing Fetal Heart in Twin-Twin Transfusion Syndrome

Adult heart failure is associated with reactivation of the fetal metabolic program, including impaired mitochondrial oxidative phosphorylation and a shift toward glycolysis. In the fetus, the metabolic response to cardiac stress is less clear. We used twin-twin transfusion syndrome (TTTS) as a model to uncover metabolic adaptations of the fetus to cardiovascular stress. TTTS is a unique complication that occurs in monochorionic-diamniotic twins (one placenta, two amniotic sacs) when unequal blood flow between twins within the shared placenta is the set up for donor-recipient physiology (Fig 1a). This circulatory imbalance is detected by sonographic signs of donor hypovolemia and recipient hypervolemia. We analyzed second trimester amniotic fluid to identify alterations in metabolism of TTTS recipient twins (n=22) vs. singleton controls (n=10) using untargeted metabolomics (LC/MS). All TTTS cases were severe (stage III; abnormal Dopplers indicating increased afterload and/or right heart failure). Due to dilution of amniotic fluid molecules in TTTS, data for each sample was normalized to protein concentration. Evaluation of differential metabolites in TTTS cases revealed two distinct clusters of disease (Fig. 1b). Compared with TTTS cluster 1 and controls, cluster 2 showed significantly increased lactate and alanine production, and evidence of redox stress (Fig. 1c). No differences in clinical characteristics or outcomes were observed between TTTS cluster 1 vs. 2 (maternal age, gestational age, fetal sex, disease severity, preterm birth, and perinatal death). Our findings reveal subclinical heterogeneity of stage III TTTS and suggest that some fetuses undergo metabolic reprogramming under conditions of cardiac stress, shifting even further toward energy-efficient glucose utilization. These differences in fetal response may represent different points along the same spectrum vs. inherent differences in the ability of fetuses to adapt to stress.

Impact of elevated body mass index on cumulative live birth rate and obstetric safety in women undergoing assisted reproductive technology

This study evaluated the impact of elevated body mass index (BMI) on short- and long-term outcomes of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments. A total of 7229 patients undergoing IVF/ICSI fresh cycles and subsequent frozen embryo transfer cycles from 2014 to 2020 were divided into normal (18.5–24.9 kg/m2) and high BMI (≥ 25 kg/m2) groups. Ovarian response, pregnancy outcomes, and safety of both mother and fetus were the main outcome measures. Furthermore, multivariate analysis was used to determine whether BMI was associated with cumulative live birth rate (CLBR). Results showed that for younger women (< 38 year), CLBR was significantly reduced in the high BMI group compared with the normal BMI control and was accompanied by fewer retrieved oocytes and available embryos. Additionally, the incidence of hypertensive disorders of pregnancy, fetal macrosomia, and cleft lip and palate birth defects resulting from cumulative live births was significantly higher compared with the normal BMI group. No differences were observed among older women (≥ 38 year). Multivariate analysis revealed that high BMI was a risk factor for CLBR. Our study suggested that elevated BMI has a greater adverse impact on younger women.

The neutrophil-to-lymphocyte ratio: A low-cost antenatal indicator of placental chorioamnionitis in women who deliver preterm without clinical signs and symptoms of infection

Chorioamnionitis is present in up to 70% of spontaneous preterm births and is associated with poor maternal, fetal and neonatal outcomes. ObjectiveTo explore the relationship between the neutrophil-to-lymphocyte ratio and histological chorioamnionitis in women who delivered preterm with no clinical signs or symptoms of infection. Study designThis was a retrospective analysis of a cohort of women who delivered spontaneously between 16 and 36+6 weeks at a tertiary UK hospital. Only women with placental histology and no signs of clinical infection were included. The neutrophil-to-lymphocyte ratio was calculated from a full blood count sample taken routinely within 24 h of delivery. The neutrophil-to-lymphocyte ratio was also calculated from first trimester booking bloods (<13 + 6 weeks) in a subgroup. Placental histopathology was categorised as either inflammatory (i.e. histologic chorioamnionitis, with or without evidence of fetal inflammatory response) or non-inflammatory (vascular pathology or a normal placenta). Results169 women had available placental pathology and were included in the analysis. 70 % (118/169) had confirmed placental inflammation. The mean neutrophil-to-lymphocyte ratio was significantly raised in this group compared to those with normal (n = 24) or vascular (n = 27) pathology (inflammatory neutrophil-to-lymphocyte ratio 9.81 vs non-inflammatory neutrophil-to-lymphocyte ratio 6.53, p = 0.002.The delivery neutrophil-to-lymphocyte ratio had an area under the receiver operating characteristic curve of 0.69 (0.60 to 0.78) for predicting placental inflammation. A raised neutrophil-to-lymphocyte ratio (>6) was associated with an odds ratio of 5.2 (95 % CI 2.55 to 10.56) for histological chorioamnionitis, with a sensitivity of 80 % and negative predictive value of 86 %. A higher cut-off of 9 had a negative predictive value of 79 % for fetal inflammatory response. ConclusionsA raised neutrophil-to-lymphocyte ratio is associated with a 5-fold increased risk of histological chorioamnionitis in women who delivered early without signs or symptoms of infection. It was also raised at the time of preterm labour compared to the first trimester. A full blood count is an almost universal investigation in women admitted in preterm labour, often repeated, making this inexpensive and non-invasive ratio a useful additional antenatal biomarker in women admitted in spontaneous preterm labour at risk of subclinical chorioamnionitis and its associated poor outcomes.

Prenatal inflammation perturbs murine fetal hematopoietic development and causes persistent changes to postnatal immunity.

Adult hematopoietic stem and progenitor cells (HSPCs) respond directly to inflammation and infection, causing both acute and persistent changes to quiescence, mobilization, and differentiation. Here we show that murine fetal HSPCs respond to prenatal inflammation in utero and that the fetal response shapes postnatal hematopoiesis and immune cell function. Heterogeneous fetal HSPCs show divergent responses to maternal immune activation (MIA), including changes in quiescence, expansion, and lineage-biased output. Single-cell transcriptomic analysis of fetal HSPCs in response to MIA reveals specific upregulation of inflammatory gene profiles in discrete, transient hematopoietic stem cell (HSC) populations that propagate expansion of lymphoid-biased progenitors. Beyond fetal development, MIA causes the inappropriate expansion and persistence of fetal lymphoid-biased progenitors postnatally, concomitant with increased cellularity and hyperresponsiveness of fetal-derived innate-like lymphocytes. Our investigation demonstrates how inflammation in utero can direct the output and function of fetal-derived immune cells by reshaping fetal HSC establishment.

Maternal Serum α-Fetoprotein Levels during Pregnancy and Testicular Cancer in Male Offspring: A Cohort Study within a Danish Pregnancy Screening Registry.

Testicular cancer is believed to originate from disruptions of normal androgen-estrogen balance in-utero. α-fetoprotein (AFP) may modify fetal response to estrogens via estrogen interaction. In a cohort study, we investigated the association between circulating maternal pregnancy AFP and testicular cancer risk in offspring. Of the 56,709 live-born males from a pregnancy screening registry in 1980-1995, our study included 50,519 singleton males with available second trimester blood samples from their mothers and complete covariate ascertainment. Testicular cancer diagnoses and covariate data were obtained from nationwide Danish health registries. Cox regression and Kaplan-Meier analyses estimated the prospective risk of testicular cancer (all, seminoma, nonseminoma) by AFP multiples of the median. During follow-up, 163 (0.3%) of the included males developed testicular cancer, of which 89 (54.6%) were nonseminomas. Maternal serum AFP levels greater than/equal to the median were associated with a relative risk of testicular cancer close to unity (RR 1.04, 95% CI 0.76; 1.41) compared to AFP below the median. Associations differed by type of testicular cancer (RRseminoma 0.81, 95% CI 0.51; 1.29, RRnonseminoma 1.31, 95% CI 0.85; 2.02). On balance, our findings do not support that serum AFP in pregnancy can be used as a predictor of testicular cancer in offspring.

Immune Responses to SARS-CoV-2 in Pregnancy: Implications for the Health of the Next Generation.

Widespread SARS-CoV-2 infection among pregnant individuals has led to a generation of fetuses exposed in utero, but the long-term impact of such exposure remains unknown. Although fetal infection is rare, children born to mothers with SARS-CoV-2 infection may be at increased risk for adverse neurodevelopmental and cardiometabolic outcomes. Fetal programming effects are likely to be mediated at least in part by maternal immune activation. In this review, we discuss recent evidence regarding the effects of prenatal SARS-CoV-2 infection on the maternal, placental, and fetal immune response, as well as the implications for the long-term health of offspring. Extrapolating from what is known about the impact of maternal immune activation in other contexts (e.g., obesity, HIV, influenza), we review the potential for neurodevelopmental and cardiometabolic morbidity in offspring. Based on available data suggesting potential increased neurodevelopmental risk, we highlight the importance of establishing large cohorts to monitor offspring born to SARS-CoV-2-positive mothers for neurodevelopmental and cardiometabolic sequelae.

The significance of TNF-α and MMP-8 concentrations in non-invasively obtained amniotic fluid predicting fetal inflammatory response syndrome.

To determine the significance of tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-8 (MMP-8) in vaginally obtained amniotic fluid predicting fetal inflammatory response syndrome (FIRS) after preterm premature rupture of membranes (PPROM). In this prospective case-control study, TNF-α and MMP-8 concentrations were evaluated in vaginally obtained amniotic fluid from women with PPROM at 22-34 weeks of pregnancy. Biomarkers' concentrations were determined using an enzyme-linked immunosorbent assay. Patients were divided into two groups: the FIRS group (cord blood interleukin-6> 11 pg/ml or histological funisitis) and the non-FIRS group (without these findings). The data were analyzed using R package (R-4.0.5). The median TNF-α and MMP-8 concentrations in amniotic fluid from the 145 women included in the study were higher in the FIRS group than in the non-FIRS group. The area under the curve of TNF-α and MMP-8 was 0.77 and 0.75, respectively. The TNF-α concentration cut-off predicting FIRS was 89.20 pg/ml and was 170.76 pg/ml for MMP-8. In regression analysis, MMP-8 concentration was an independent predictor for FIRS. An MMP-8 concentration greater than 170 ng/ml and a TNF-α concentration greater than 89 pg/ml increased the odds of FIRS 7.62 and 14.92 times, respectively. MMP-8 and TNF-α concentrations in vaginally obtained amniotic fluid may be good predictors for FIRS after PPROM before 34 weeks of pregnancy. The non-invasive amniotic fluid analysis could be an alternative method to invasive amniocentesis.

Fetal Cardiac Inflow Characteristics in Response to Fetal Anemia: Based on Fetal Hemoglobin Bart's Disease at Mid-Pregnancy.

To identify the inflow (filling time fraction [FTF] and E/A ratio) characteristics of fetuses with anemia, and to evaluate the performance of the inflow markers in predicting the affected fetuses. Fetuses at risk of hemoglobin (Hb) Bart's disease at 17-22 weeks were prospectively recruited to undergo echocardiography before diagnostic cordocentesis. Cardiac Doppler images were digitally stored for off-line blinded measurements of FTF and E/A ratio. A total of 428 fetuses at risk of Hb Bart's disease were analyzed, including 88 affected fetuses (20.6%). The mean gestational age at the time of diagnosis was 19.43 ± 1.5 weeks. The FTFs in both sides were significantly lower in the affected fetuses, whereas the E/A ratios of both sides were significantly higher in the affected group. According to the receiver operating characteristic curves, the performance of the FTF of the right side in predicting affected fetuses was slightly better than that of the left side (area under curve: 0.707 versus 0.680, P < .001). Likewise, the performance of the E/A ratio of the tricuspid valve was slightly better than that of the mitral valve. Also, FTF was superior to E/A ratio in predicting the affected fetuses. New insights leading to a better understanding of the fetal cardiac response to anemia are: 1) the FTFs in both sides were significantly decreased, suggesting some degree of diastolic ventricular dysfunction; 2) the E/A ratios of both sides were significantly increased, indicating volume load; and 3) The inflow parameters may be useful as a new predictor of fetal anemia, especially among pregnancies at risk.

Altered Cord Blood Lipid Concentrations Correlate with Birth Weight and Doppler Velocimetry of Fetal Vessels in Human Fetal Growth Restriction Pregnancies.

Fetal growth restriction (FGR) is associated with short- and long-term morbidity, often with fetal compromise in utero, evidenced by abnormal Doppler velocimetry of fetal vessels. Lipids are vital for growth and development, but metabolism in FGR pregnancy, where fetuses do not grow to full genetic potential, is poorly understood. We hypothesize that triglyceride concentrations are increased in placentas and that important complex lipids are reduced in cord plasma from pregnancies producing the smallest babies (birth weight < 5%) and correlate with ultrasound Dopplers. Dopplers (umbilical artery, UA; middle cerebral artery, MCA) were assessed longitudinally in pregnancies diagnosed with estimated fetal weight (EFW) < 10% at ≥29 weeks gestation. For a subset of enrolled women, placentas and cord blood were collected at delivery, fatty acids were extracted and targeted lipid class analysis (triglyceride, TG; phosphatidylcholine, PC; lysophosphatidylcholine, LPC; eicosanoid) performed by LCMS. For this sub-analysis, participants were categorized as FGR (Fenton birth weight, BW ≤ 5%) or SGA “controls” (Fenton BW > 5%). FGRs (n = 8) delivered 1 week earlier (p = 0.04), were 29% smaller (p = 0.002), and had 133% higher UA pulsatility index (PI, p = 0.02) than SGAs (n = 12). FGR plasma TG, free arachidonic acid (AA), and several eicosanoids were increased (p < 0.05); docosahexaenoic acid (DHA)-LPC was decreased (p < 0.01). Plasma TG correlated inversely with BW (p < 0.05). Plasma EET, non-esterified AA, and DHA correlated inversely with BW and directly with UA PI (p < 0.05). Placental DHA-PC and AA-PC correlated directly with MCA PI (p < 0.05). In fetuses initially referred for inadequate fetal growth (EFW < 10%), those with BW ≤ 5% demonstrated distinctly different cord plasma lipid profiles than those with BW > 5%, which correlated with Doppler PIs. This provides new insights into fetal lipidomic response to the FGR in utero environment. The impact of these changes on specific processes of growth and development (particularly fetal brain) have not been elucidated, but the relationship with Doppler PI may provide additional context for FGR surveillance, and a more targeted approach to nutritional management of these infants.

Multi System Inflammatory Syndrome In Neonates (MIS-N): A Case Report

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy may increase the risk of stillbirth, neonatal death, preterm birth, low birth weight, fetal distress, and neonatal asphyxia (1). Vertical transmission of SARS-CoV-2 is under investigation. A few reports suggest the possibility of SARS-CoV-2 transmission from mothers to their neonates. The SARS-CoV-2 virus was reported as one of the rare causes of fetal inflammatory response syndrome (FIRS) (5) and is associated with multisystem inflammatory syndrome in children (MIS-C) (6).Most neonates have mild symptoms, but some develop multisystem involvement including respiratory distress, feeding intolerance, lethargy. Most of the infants have elevated biomarkers, positive septic screen, and elevated inflammatory markers. Infants diagnosed with MIS-N gradually improve after 2 doses of IVIG and IV Steroid ( Methylprednisolone).

Fetal heart rate responses to maternal sleep-disordered breathing

Maternal sleep-disordered breathing is associated with adverse pregnancy outcomes and is considered to be deleterious to the developing fetus. Maternal obesity potentiates sleep-disordered breathing, which, in turn, may contribute to the effect of maternal obesity on adverse fetal outcomes. However, only a few empirical studies have evaluated the contemporaneous effects of maternal sleep-disordered breathing events on fetal well-being. These events include apnea and hypopnea with accompanying desaturations in oxyhemoglobin. This study aimed to reconcile contradictory findings on the associations between maternal apnea or hypopnea events and clinical indicators of fetal compromise. It also sought to broaden the knowledge base by examining the fetal heart rate and heart rate variability before, during, and after episodes of maternal apnea or hypopnea. To accomplish this, we employed overnight polysomnography, the gold standard for ascertaining maternal sleep-disordered breathing, and synchronized it with continuous fetal electrocardiography. A total of 84 pregnant women with obesity (body mass index >30 kg/m2) participated in laboratory-based polysomnography with digitized fetal electrocardiography recordings during or near 36 weeks of gestation. Sleep was recorded, on average, for 7 hours. Decelerations in fetal heart rate were identified. Fetal heart rate and heart rate variability were quantified before, during, and after each apnea or hypopnea event. Event-level intensity (desaturation magnitude, duration, and nadir O2 saturation level) and person-level characteristics based on the full overnight recording (apnea-hypopnea index, mean O2 saturation, and O2 saturation variability) were analyzed as potential moderators using linear mixed effects models. A total of 2936 sleep-disordered breathing events were identified, distributed among all but 2 participants. On average, participants exhibited 8.7 episodes of apnea or hypopnea per hour (mean desaturation duration, 19.1 seconds; mean O2 saturation nadir, 86.6% per episode); nearly half (n=39) of the participants met the criteria for obstructive sleep apnea. Only 45 of 2936 apnea or hypopnea events were followed by decelerations (1.5%). Conversely, most (n=333, 88%) of the 378 observed decelerations, including the prolonged ones, did not follow an apnea or a hypopnea event. Maternal sleep-disordered breathing burden, body mass index, and fetal sex were unrelated to the number of decelerations. Fetal heart rate variability increased during events of maternal apnea or hypopnea but returned to initial levels soon thereafter. There was a dose-response association between the size of the increase in fetal heart rate variability and the maternal apnea-hypopnea index, event duration, and desaturation depth. Longer desaturations were associated with a decreased likelihood of the variability returning to baseline levels after the event. The mean fetal heart rate did not change during episodes of maternal apnea or hypopnea. Episodes of maternal sleep apnea and hypopnea did not evoke decelerations in the fetal heart rate despite the predisposing risk factors that accompany maternal obesity. The significance of the modest transitory increase in fetal heart rate variability in response to apnea and hypopnea episodes is not clear but may reflect compensatory, delimited autonomic responses to momentarily adverse conditions. This study found no evidence that episodes of maternal sleep-disordered breathing pose an immediate threat, as reflected in fetal heart rate responses, to the near-term fetus.

Dystocia and its management in a captured wild Monkey

A stray wild female monkey, aged 5-6 years were presented to the Referral Veterinary Polyclinics, ICAR- Indian Veterinary Research Institute, with a history of straining and discharge from the vulva since morning. A close physical examination of the external genitalia of the monkey revealed it as prominent, red and swollen implying pregnancy. The vulva was open due to the internal pressure revealing foetal part visible with reduced fetal fluid. Per-vaginal examination revealed a foetal head in the birth canal, but absence of foetal responses. Per vaginal examination revealed foetal presentation to be anterior longitudinal, dorso-sacral position, but it was difficult to palpate postural condition. To relieve the condition female monkey was positioned in a left lateral recumbent position followed by ample lubrication of the birth canal with CMC (Carboxymethyl cellulose) gel using an intrauterine catheter and syringe. The traction approach was used to extract the dead foetus. Following successful delivery bleeding was prevented by administering ethamsylate injections at a dose rate of 15 mg/Kg (1 ml), and other supportive medications were administered. The macaque monkeys can postpone labour making it difficult for an observer to determine the indicators of dystocia until the condition has worsened. This makes dystocia in nonhuman primates a grave condition requiring prompt medical attention.

Flavor Sensing in Utero and Emerging Discriminative Behaviors in the Human Fetus

The diet of pregnant women exposes fetuses to a variety of flavors consisting of compound sensations involving smell, taste, and chemesthesis. The effects of such prenatal flavor exposure on chemosensory development have so far been measured only postnatally in human infants. Here, we report the first direct evidence of human fetal responsiveness to flavors transferred via maternal consumption of a single-dose capsule by measuring frame-by-frame fetal facial movements. Pregnant women and their fetuses based in the northeast of England were involved in this study from 32 to 36 weeks’ gestation. Fetuses exposed to carrot flavor (n = 35) showed “lip-corner puller” and “laughter-face gestalt” more frequently, whereas fetuses exposed to kale flavor (n = 34) showed more “upper-lip raiser,” “lower-lip depressor,” “lip stretch,” “lip presser,” and “cry-face gestalt” in comparison with the carrot group and a control group not exposed to any flavors (n = 30). The complexity of facial gestalts increased from 32 to 36 weeks in the kale condition, but not in the carrot condition. Findings of this study have important implications for understanding the earliest evidence for fetal abilities to sense and discriminate different flavors.