Estimated fetal weight accuracy in pregnancies with preterm prelabor rupture of membranes by the Hadlock method.

OBJECTIVE: We aimed to assess the accuracy of the estimated fetal weight (EFW) to predict the birthweigth (BW) in pregnancies complicated by PPROM. STUDY DESIGN: This study was a secondary analysis of a prospective cohort of pregnancies with PPROM. We included singleton pregnancies from 23 to 36 + 6 weeks, mothers from 13 to 46 years of age, and those with an EFW within two weeks of delivery. We excluded pregnancies with complex fetal anomalies and fetal demise. The accuracy of the EFW was determined by the absolute percent difference between BW and EFW ([BW-EFW]/BW*100%). T tests and linear regression were performed for statistical analysis. RESULTS: The mean percent difference of BW vs. EFW was 8.72 ± 6.94%. The EFW was more accurate (8.24 ± 6.81 vs. 13.31 ± 6.88%, p = .027) and had more measurements with a absolute difference < 10% (70% vs. 30%; p = .034) when performed within seven days of delivery. The EFW accuracy decreased with anhydramnios (11.37 ± 7.06 vs. 7.69 ± 6.77%, p = .020), but the measurements with an absolute difference <10% was not significantly different (p = .27) with anhydramnios. CONCLUSION: In PPROM, the EFW within seven days to delivery by Hadlock accurately predicts the birthweight with a mean absolute difference of 8.2%. BRIEF RATIONALE: There are a limited number of studies evaluating the accuracy of the EFW in pregnancies with PPROM in the last four decades.

Lack of Fetal Insulin Resistance in Maternal Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) affects 8-10% of women. NIH criteria for diagnosis include chronic anovulation and evidence of clinical or biochemical hyperandrogenism. PCOS is associated with adverse neonatal outcomes. Our hypothesis is that insulin resistance is increased in fetuses born to women with PCOS. This is a prospective cohort of women who delivered at our institution. Subjects with a body mass index < 20 or ≥ 50 kg/m2, multiple gestation, and major fetal malformations were excluded. Maternal blood was collected at admission, and umbilical cord blood was collected after delivery. Serum concentrations of insulin and glucose were measured from each sample. The homeostasis model assessment index of insulin resistance (HOMA-IR) was calculated (plasma glucose (mmol/L) × insulin (µU/mL)/22.5). The HOMA-IR from mothers and fetuses with PCOS was compared with mothers and fetuses without PCOS (controls). Mann-Whitney U test was utilized for statistical analysis. Forty-six women and fetal pairs were included; 28 with PCOS and 18 controls. Maternal insulin (20 [7.7-26.5] vs. 6.6 µU/ml [5.1-7.2]; p = 0.005) and HOMA-IR (3.9 [1.6-4.5] vs. 1.1 [0.9-1.3]; p = 0.01) were increased in the PCOS group. There was no statistical difference in fetal insulin, glucose, or HOMA-IR (p = 0.31) in the umbilical artery (p = 0.10; p = 0.34; p = 0.45, respectively) or the umbilical vein (p = 0.13; p = > 0.99; p = 0.31, respectively). Insulin resistance is present in non-diabetic pregnant women with PCOS, however not in their fetuses. This might explain variations in the occurrence of the adverse neonatal and maternal outcomes reported in PCOS.

Fetal pulmonary artery acceleration/ejection time prognostic accuracy for respiratory complications in preterm prelabor rupture of membranes.

Objective: To determine the prognostic accuracy of the fetal pulmonary artery acceleration time/ejection time (PATET) for the prediction of neonatal respiratory complications (NRCs) in pregnancies with preterm premature rupture of membranes (PPROM).Methods: This is a prospective cohort of singleton pregnancies complicated by PPROM managed in our institution from October 2015 to April 2018. Inclusion criteria included mothers from 13 to 46 years of age and singleton pregnancies with PATET measurements <7 days prior to delivery. PATET was obtained by placing the Doppler caliper in the main pulmonary artery proximal to the bifurcation of this vessel. NRC was defined as: need for ventilatory support, respiratory distress syndrome (RDS), or lung hypoplasia. Logistic regression models and area under the receiver operating characteristic curves (ROC) were utilized to determine the prognostic accuracy of PATET and gestational age for NRC and RDS.Results: Of 95 patients included, 46 had NRC (RDS = 33). PATET was a significant predictor of NRC (AUC 0.74; 95%CI: 0.61-0.83; p < .001) and RDS (AUC 0.69; 95%CI: 0.57-0.80; p = .021) in PPROM. Gestational age at delivery and gestational age at PPROM were also significantly associated with NRC and RDS. Their predictive accuracy for NRC was 0.87 and 0.84, and for RDS 0.85 and 0.86, respectively.Conclusions: PATET is a statistically significant predictor for NRC in pregnancies with PPROM; however, its clinical use may be limited as gestational age is a better predictor of these outcomes.Rationale: NRCs are common in pregnancies complicated by preterm prelabor rupture of membranes (PPROM). We aim to determine the prognostic accuracy of the fetal PATET for the prediction of neonatal NRC in these pregnancies. Our results indicate that PATET is a statistically significant predictor for NRC in pregnancies with PPROM; however, its clinical use may be limited, as gestational age is a better predictor of these outcomes.

Gestational Age-Dependent Interplay between Endocannabinoid Receptors and Alcohol in Fetal Cerebral Arteries.

Alcohol (ethanol) is one of the most widely consumed drugs. Alcohol consumption by pregnant women may result in a range of fetal abnormalities termed fetal alcohol spectrum disorders (FASDs). The cerebrovascular system is emerging as a critical target of alcohol in the developing brain. We recently showed that three episodes of prenatal alcohol exposure resulting in 80 mg/dL alcohol in maternal blood during mid-pregnancy up-regulated anandamide-induced dilation of fetal cerebral arteries. Moreover, ethanol dilated fetal cerebral arteries via cannabinoid (CB) receptors. Whether a critical role of fetal cerebral artery CB system in responses to alcohol was maintained throughout the gestation, remains unknow. MAIN METHODS: Pregnant baboons (second trimester equivalent) were subjected to three episodes of either alcohol or control drink infusion via gavage. Cerebral arteries from mothers and near-term female fetuses were in vitro pressurized for diameter monitoring. KEY FINDINGS: Near-term fetal and maternal arteries exhibited similar ability to develop myogenic tone, to constrict in presence of 60 mM KCl, and to respond to 10 µM anandamide. Fetal and maternal arteries largely failed to dilate in presence of 63 mM ethanol. No differences were detected between arteries from control and alcohol-exposed baboon donors. Therefore, previously observed ethanol-induced dilation of fetal cerebral arteries and up-regulation of CB components in response to fetal alcohol exposure during mid-pregnancy was transient and disappeared by near-term.

Serum Anti-Müllerian hormone (AMH) in mothers with polycystic ovary syndrome (PCOS) and their term fetuses.

We sought to determine serum AMH levels in the maternal circulation, and the umbilical artery and vein, in normal women and women with PCOS, and their neonates at time of delivery. This represents a cross-sectional study of 57 pregnant patients who presented to the labor and delivery suite and subsequently delivered. We obtained maternal, as well as fetal blood from both, umbilical artery and vein. We measured serum concentrations of estradiol, AMH, testosterone and FSH. A total of 30 patients delivered a female and 27 a male neonate. Of them, 18/30 and 18/27 had a diagnosis of PCOS by NIH criteria. Mean age, BMI, weight gain in pregnancy, and gestational age did not differ between the two groups of mothers. AMH serum levels were statistically higher in women with PCOS (p < 0.005) and in their fetuses, independently of gender. Testosterone was higher in women with PCOS (p < 0.001), but there was no PCOS-related difference in their fetuses. FSH levels were significantly lower in PCOS than non-PCOS mothers carrying a male (p = 0.022), but not a female, fetus. AMH was positively correlated with maternal serum testosterone (p = 0.001) and negatively with fetal serum FSH (p < 0.026). In PCOS pregnancies, AMH was negatively correlated with maternal BMI (p = 0.019), menstrual cycle length (p = 0.035), and fetal uterine vein FSH (p = 0.021). In conclusion, at time of delivery, fetuses of women with PCOS had higher AMH levels and similar testosterone levels compared to fetuses from non-PCOS mothers, irrespective of gender. Our results may help explaining developmental differences in offspring of PCOS women.

Uterine artery flow velocity waveforms before and after delivery in hypertensive disorders of pregnancy near term.

OBJECTIVE: To compare the uterine artery pulsatility index (UtAPI-AP) before labor and immediate postpartum (UtAPI-PP) in hypertensive disorders of pregnancy (HTNP) and normotensives near term. METHODS: Pregnancies ≥36 weeks admitted for labor induction in our institution from October 2015 to October 2017 were included. We excluded active labor, multiple gestations, fetal demise, and those with inadequate uterine artery sampling. Our primary outcome was to compare the UtAPI-AP and UtAPI-PP between subjects with HTNP (gestational hypertension, preeclampsia with and without severe features) and normotensive participants. Our secondary outcomes were to compare the UtAPI-AP and UtAPI-PP by subgroups (severe HNTP, non-severe HTNP, and controls) and the UtAPI-PP in participants while on MgSO4 and after its discontinuation. A linear regression model was applied to test the above associations. A P < .05 was considered significant. RESULTS: We included 108 women (HTNP = 71; controls = 37). The UtAPI-AP was higher in the HTNP group (.85 ± .3 vs. .71 ± .2; P < .001); however, the UtAPI-PP was not different between groups (1.11 ± .3 vs. 1.16 ± .4; P = .46). The UtAPI-AP was higher in the severe HTNP group than controls (P = .004), but there was no significant difference in the UtAPI-PP between subgroups. Our results remained unchanged after adjusting for confounders. The UtAPI while on MgSO4 and after its discontinuation was similar (P =  >.99). CONCLUSION: The increased UtAPI in patients with HTNP resolves soon after delivery. MgSO4 does not seem to have an effect on the UtAPI postpartum.

Prenatal Alcohol Exposure, Anesthesia, and Fetal Loss in Baboon Model of Pregnancy.

Approximately half of pregnant women engage in alcohol consumption some time during pregnancy. On the other hand, a small percentage of pregnant women undergo surgery and anesthesia at some time during pregnancy. In emergencies, anesthesia has to be administered to patients who are under alcohol intoxication. Anesthetic management during pregnancy while patients are intoxicated with alcohol is challenging. Here, we utilized a retrospective analysis of data available from 17 pregnant baboons that underwent anesthesia with alcohol exposure during mid-pregnancy. The analysis was designed to answer three questions: whether maternal vital signs remained stable under anesthesia combined with alcohol, whether maternal vital signs that were routinely monitored under anesthesia could serve as predictor(s) of fetal loss, and what the impact of the combined application of anesthesia and alcohol was on fetal loss. For the purpose of this retrospective analysis, we utilized vital sign (heart and respiratory rates, temperature, oxygen, carbon dioxide, systolic and diastolic blood pressure) and pregnancy outcome (miscarriage versus fetal survival through second trimester-equivalent of human pregnancy) records from 17 pregnant baboons that underwent gastric infusion of either control or alcohol-containing drink under isoflurane anesthesia during the second trimester-equivalent of human pregnancy. Half of the dams underwent a brief prior anesthetic episode for the purpose of gestational age confirmation. Thus, in our analysis, baboons were divided into four groups: "Control" without prior anesthesia, "Control" with prior anesthesia, "Alcohol" without prior anesthesia, and "Alcohol" with prior anesthesia. We did not detect any maternal vital sign in any of the groups that would be predictive of a fetal loss. However, prior anesthesia predisposed dams to the risk of lowering maternal systolic blood pressure and to a significant decrease in maternal oxygen level during the combined application of anesthesia and alcohol. Conceivably, our data showed the largest fetal loss in this group. The disruptive nature of anesthesia and alcohol on maternal vital parameters warns against the use of anesthesia in combination with alcohol during pregnancy.

The Effect of Prenatal Alcohol Exposure on Fetal Growth and Cardiovascular Parameters in a Baboon Model of Pregnancy.

Prenatal alcohol exposure often results in an array of fetal developmental abnormalities termed fetal alcohol spectrum disorders (FASDs). Despite the high prevalence of FASDs, the pathophysiology of fetal damage by alcohol remains poorly understood. One of the major obstacles in studying fetal development in response to alcohol exposure is the inability to standardize the amount, pattern of alcohol consumption, and peak blood alcohol levels in pregnant mothers. In the present study, we used Doppler ultrasonography to assess fetal growth and cardiovascular parameters in response to alcohol exposure in pregnant baboons. Baboons were subjected to gastric alcohol infusion 3 times during the second trimester equivalent to human pregnancy, with maternal blood alcohol levels reaching 80 mg/dL within 30 to 60 minutes following alcohol infusion. The control group received a drink that was isocaloric to the alcohol-containing one. Doppler ultrasonography was used for longitudinal assessment of fetal biometric parameters and fetal cardiovascular indices. Fetal abdominal and head circumferences, but not femur length, were significantly decreased in alcohol-exposed fetuses near term. Peak systolic velocity of anterior and middle cerebral arteries decreased during episodes of alcohol intoxication, but there was no difference in Doppler indices between groups near term. Acute alcohol intoxication affected fetal cerebral blood flow independent of changes in the fetal cardiac output. Unlike fetal growth parameters, changes in vascular indices did not persist over gestation. In summary, alcohol effects on fetal growth and on fetal vascular function have different time courses.

Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors.

Prenatal alcohol exposure often results in fetal alcohol syndrome and fetal alcohol spectrum disorders. Mechanisms of fetal brain damage by alcohol remain unclear. We used baboons (Papio spp.) to study alcohol-driven changes in the fetal cerebral artery endocannabinoid system. Pregnant baboons were subjected to binge alcohol exposure via gastric infusion three times during a period equivalent to the second trimester of human pregnancy. A control group was infused with orange-flavored drink that was isocaloric to the alcohol-containing solution. Cesarean sections were performed at a time equivalent to the end of the second trimester of human pregnancy. Fetal cerebral arteries were harvested and subjected to in vitro pressurization followed by pharmacological profiling. During each alcohol-infusion episode, maternal blood alcohol concentrations (BAC) reached 80 mg/dL, that is, equivalent to the BAC considered legal intoxication in humans. Circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) remained unchanged. Ultrasound studies on pregnant mothers revealed that fetal alcohol exposure decreased peak systolic blood velocity in middle cerebral arteries when compared to pre-alcohol levels. Moreover, ethanol-induced dilation was observed in fetal cerebral arteries pressurized in vitro. This dilation was abolished by the mixture of AM251 and AM630, which block cannabinoid receptors 1 and 2, respectively. In the presence of AM251, the cannabinoid receptor agonist AEA evoked a higher, concentration-dependent dilation of cerebral arteries from alcohol-exposed fetuses. The difference in AEA-induced cerebral artery dilation vanished in the presence of AM630. CB1 and CB2 receptor mRNA and protein levels were similar in cerebral arteries from alcohol-exposed and control-exposed fetuses. In summary, alcohol exposure dilates fetal cerebral arteries via endocannabinoid receptors and results in an increased function of CB2.

Maternal vitamin K deficient embryopathy: association with hyperemesis gravidarum and Crohn disease.

Chondrodysplasia punctata (CDP) is an etiologically heterogeneous disorder characterized by the radiographic finding of stippled epiphyses (punctate calcifications). It is often accompanied by a characteristic facial appearance, known as the Binder phenotype, which is attributed to hypoplasia of the nasal cartilages; abnormal distal phalanges (brachytelephalangy) are a common component manifestation as well. We report eight patients with a Binder phenotype with or without CDP who all shared a known or suspected maternal deficiency of vitamin K. We suspect that this phenotype is probably under recognized, and we hope to increase awareness about the maternal risk factors, especially hyperemesis gravidarum, which lead to nutritional deficiency.