Duration of biophysical profile in periviable and very preterm low-risk pregnancies.

BACKGROUND: In recent years, perinatal viability has shifted from 24 to 22 weeks of gestation at many institutions after improvements in survival in neonates delivered at the limit of viability. Monitoring these fetuses is essential because antenatal interventions with resuscitation efforts are available for patients at risk of delivery at the limit of viability. However, fetal monitoring using biophysical profiles has not been extensively studied in very preterm pregnancies, particularly in the periviable period (20 weeks 0 days to 23 weeks 6 days). OBJECTIVE: This study aimed to (1) investigate whether the completion of biophysical profiles within 30 minutes is feasible in very preterm pregnancies, and (2) determine the average observation time required to achieve a score of 8 out of 8 in very preterm pregnancies from 20 weeks 0 days to 31 weeks 6 days. STUDY DESIGN: This study prospectively evaluated biophysical scores in singleton pregnancies undergoing routine ultrasonography at or near viability from 20 weeks 0 days to 23 weeks 6 days (periviable or group I), 24 weeks 0 days to 27 weeks 6 days (group II), and 28 weeks 0 days to 31 weeks 6 days (group III). The results and duration of biophysical profiles were compared with those of a control group (32 weeks 0 days to 35 weeks 6 days) undergoing indicated fetal surveillance. Biophysical profiles were performed for all studied pregnancies until a score of 8 out of 8 was obtained. When >1 biophysical profile was obtained during pregnancy, each was analyzed individually. Pregnancies with fetal anomalies or obstetrical/medical indications for fetal well-being surveillance were excluded. Analysis of variance and post hoc Tukey tests were used for comparisons. RESULTS: Data were collected for 123 participants, yielding 79, 75, and 72 studies for groups I, II, and III, respectively. The control group included 42 patients, yielding 140 studies. At 30 minutes, 80% (63/79) of the studies in the periviable group had a score of 8 out of 8, as opposed to 100% (140/140) in the control group (P<.001). The mean±standard deviation time in minutes to achieve a biophysical score of 8 out of 8 was 23.3±10.1 in the periviable group, as opposed to 9.4±6.5 in controls (P<.001). Extending the study to +2 standard deviations (43.6 minutes) in the periviable group resulted in 97% (77/79) of the scans scoring 8 out of 8 in the absence of adverse outcomes. In the other groups, a biophysical score of 8 out of 8 within 30 minutes was obtained in 97% (73/75) and 100% (72/72) in groups II and III, respectively; the mean±standard deviation times were 17.1±8.4 minutes (group II) and 13.1±7.3 minutes (group III). No adverse outcomes developed during the study participation in groups I to III. CONCLUSION: Biophysical scores of 8 out of 8 can be successfully achieved in low-risk periviable pregnancies (20 weeks 0 days to 23 weeks 6 days) within an observation time longer than the standard 30-minute duration. The time required to reach a score of 8 out of 8 decreases as gestation progresses. We suggest adjusting the observation time for biophysical profile completion according to the gestational age.

Report of an Experiment With a Fetal Ex-Utero Support System in Piglets.

Extreme prematurity remains one of the leading causes of neonatal death. An ex-utero treatment strategy that allows the fetus to develop beyond this period until capable of tolerating the transition to post-natal physiology would significantly impact the quality of care offered for this pre-viable patient population. In this study, we report our experience with an ex-utero support system for fetal pigs with the goal of support and survival for eight hours. Our experiment included two pigs at a gestational age equivalent to a 32-week human fetus. Following ultrasound assessment and delivery via hysterotomy, the fetuses were transferred to a 40 L glass aquarium filled with warmed lactated Ringer's solution and connected to an arteriovenous (AV) circuit that included a centrifugal pump and a pediatric oxygenator. Fetus 1 was successfully cannulated and survived for seven hours (expected maximum duration of eight hours). Fetus 2 died shortly after hysterotomy, secondary to failure at the cannulation stage. Our results suggest that ex-utero support of the premature fetal pig is feasible, contributing to a scarce body of evidence. However, further studies are needed before effectively translating an artificial placenta system into the clinical arena.

The role of the fetal biophysical profile in the management of fetal growth restriction.

Growth-restricted fetuses are at risk of hypoxemia, acidemia, and stillbirth because of progressive placental dysfunction. Current fetal well-being, neonatal risks following delivery, and the anticipated rate of fetal deterioration are the major management considerations in fetal growth restriction. Surveillance has to quantify the fetal risks accurately to determine the delivery threshold and identify the testing frequency most likely to capture future deterioration and prevent stillbirth. From the second trimester onward, the biophysical profile score correlates over 90% with the current fetal pH, and a normal score predicts a pH >7.25 with a 100% positive predictive value; an abnormal score on the other hand predicts current fetal acidemia with similar certainty. Between 30% and 70% of growth-restricted fetuses with a nonreactive heart rate require biophysical profile scoring to verify fetal well-being, and an abnormal score in 8% to 27% identifies the need for delivery, which is not suspected by Doppler findings. Future fetal well-being is not predicted by the biophysical profile score, which emphasizes the importance of umbilical artery Doppler and amniotic fluid volume to determine surveillance frequency. Studies with integrated surveillance strategies that combine frequent heart rate monitoring with biophysical profile scoring and Doppler report better outcomes and stillbirth rates of between 0% and 4%, compared with those between 8% and 11% with empirically determined surveillance frequency. The variations in clinical behavior and management challenges across gestational age are better addressed when biophysical profile scoring is integrated into the surveillance of fetal growth restriction. This review aims to provide guidance on biophysical profile scoring in the in- and outpatient management of fetal growth restriction.

Clinical Opinion: The diagnosis and management of suspected fetal growth restriction: an evidence-based approach.

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is frequently defined as one with an estimated fetal weight of <10th percentile. This condition has been considered syndromic and has been frequently attributed to fetal growth restriction, a constitutionally small fetus, congenital infections, chromosomal abnormalities, or genetic conditions. Small for gestational age is not synonymous with fetal growth restriction, which is defined by deceleration of fetal growth determined by a change in fetal growth velocity. An abnormal umbilical artery Doppler pulsatility index reflects an increased impedance to flow in the umbilical circulation and is considered to be an indicator of placental disease. The combined finding of an estimated fetal weight of <10th percentile and abnormal umbilical artery Doppler velocimetry has been widely accepted as indicative of fetal growth restriction. Clinical studies have shown that the gestational age at diagnosis can be used to subclassify suspected fetal growth restriction into early and late, depending on whether the condition is diagnosed before or after 32 weeks of gestation. The early type is associated with umbilical artery Doppler abnormalities, whereas the late type is often associated with a low pulsatility index in the middle cerebral artery. A large randomized clinical trial indicated that in the context of early suspected fetal growth restriction, the combination of computerized cardiotocography and fetal ductus venosus Doppler improves outcomes, such that 95% of surviving infants have a normal neurodevelopmental outcome at 2 years of age. A low middle cerebral artery pulsatility index is associated with an adverse perinatal outcome in late fetal growth restriction; however, there is no evidence supporting its use to determine the time of delivery. Nonetheless, an abnormality in middle cerebral artery Doppler could be valuable to increase the surveillance of the fetus at risk. We propose that fetal size, growth rate, uteroplacental Doppler indices, cardiotocography, and maternal conditions (ie, hypertension) according to gestational age are important factors in optimizing the outcome of suspected fetal growth restriction.

Neonatal blood pressure before and after delayed umbilical cord clamping.

OBJECTIVE: To describe values of blood pressure (BP) before and after delayed cord clamping (DCC) in healthy term neonates born to low risk pregnancies, examine differences in the temporal patterns of BP during this transition, and assess potential correlation of these parameters with maternal and perinatal clinical and demographic variables. METHODS: Prospective observational study of term infants eligible for DCC born vaginally from uncomplicated pregnancies. Neonatal BP was estimated noninvasively before DCC, at 30 min and 24 h of life. Median, minimum, maximum, mean and standard deviation, as well as percentiles for BP values were calculated. Pearson correlation assessed the correlation between demographic and clinical variables and BP measurements. Spearman correlation studied the association between BP parameters prior to DCC and Apgar scores. Repeated measures ANOVA and Tukey post hoc analyses were used to compare BP measurements over time. A p-value of <.05 was considered significant. RESULTS: A total of 54 patients were included. Mean neonatal birthweight was 3185 g and gestational age 39/3 weeks. The mean values for the systolic, diastolic, and mean BP prior to DCC were 97 ± 24.9 mmHg, 58 ± 21.9 mmHg and 67 ± 27.7 mmHg respectively. A statistically significant difference was detected when comparing BP values obtained before DCC with those measured afterwards (Figure 1). A positive correlation was found between SBP and MAP prior to DCC and Apgar scores at 1 min.[Figure: see text]. CONCLUSION: We describe novel values of BP before DCC in healthy term infants following vaginal delivery. Data suggest that neonates whose cord is clamped in a delayed fashion experience an increase blood pressures immediately after birth, followed by a significant drop within 30 min to levels that remain unchanged at 24 h of life. BP values obtained after DCC in our study are similar to those found by previous authors. Further studies are needed to determine the clinical significance of these findings and assess the potential of BP prior to DCC to evaluate immediate postnatal adaptation. LIMITATIONS: Results generalizability may have been limited by varying degrees of neonatal resuscitation, inability to perform more than one measurement before cord clamping ensued, as well as an unequal distribution of self-reported race in our cohort. Also, noninvasive BP estimates have proven less accurate that invasive methods. Finally, our cohort was comprised by a relatively small sample and larger studies will be required to corroborate our findings.

Uterine artery pulsatility index for the prediction of obstetrical complications in preterm prelabor rupture of membranes.

INTRODUCTION: Abnormal uterine artery Doppler studies have been associated with an increased risk of preeclampsia, fetal growth restriction (FGR), placental abruption, and fetal demise. These obstetrical complications can affect pregnancies with preterm prelabor rupture of membranes (PPROM). Therefore, our objective was to assess the prediction accuracy of the uterine artery pulsatility index (UtAPI) to detect these complications in pregnancies with PPROM. MATERIALS AND METHODS: This was a prospective study of pregnancies complicated by PPROM from October 2015 to May 2018. We included mothers aged 13-46 years old with singleton pregnancies from 23 to 36 + 6 weeks with PPROM. Those without UtAPI measurements and complex fetal anomalies were excluded. Our primary outcome was a composite of obstetrical complications, defined as having one or more of the following: gestational hypertension or preeclampsia, placenta abruption, FGR, or fetal demise. The UtAPI was obtained at the time of enrollment. Logistic regression models with receiver operating curves were used to determine the predictive value of the UtAPI for obstetrical complications. A p value of <.05 was considered significant. RESULTS: A total of 103 patients met inclusion criteria, of those 37 (36%) developed an obstetrical complication (FGR = 22 (21.5%); preeclampsia or gestational hypertension = 9 (9%); placental abruption = 8 (8%); fetal demise = 1 (1%)). Six mothers had more than one complication. The UtAPI was not a statistically significant predictor of a composite of obstetrical complications (AUC = 0.61; p = .07) or for any of the individual complications studied. CONCLUSIONS: The UtAPI appears to have limited clinical value for the prediction of obstetrical complications previously associated with abnormal uterine artery Doppler indices in pregnancies with PPROM. Larger and more diverse studies are needed to corroborate our findings. BRIEF RATIONALE: An accurate prediction for adverse outcomes in patients with PPROM may help identify those that may benefit from increased surveillance protocols.

Estimated fetal weight and severe neonatal outcomes in preterm prelabor rupture of membranes.

Objectives Our aim was to study the association of clinical variables obtainable before delivery for severe neonatal outcomes (SNO) and develop a clinical tool to calculate the prediction probability of SNO in preterm prelabor rupture of membranes (PPROM). Methods This was a prospective study from October 2015 to May 2018. We included singleton pregnancies with PPROM and an estimated fetal weight (EFW) two weeks before delivery. We excluded those with fetal anomalies or fetal death. We examined the association between SNO and variables obtainable before delivery such as gestational age (GA) at PPROM, EFW, gender, race, body mass index, chorioamnioitis. SNO was defined as having at least one of the following: respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, neonatal sepsis, or neonatal death. The most parsimonious logistic regression models was constructed using the best subset selection model approach, and receiver operator curves were utilized to evaluate the prognostic accuracy of these clinical variables for SNO. Results We included 106 pregnancies, 42 had SNO (39.6%). The EFW (area under the receiver operating characteristic curve [AUC]=0.88) and GA at PPROM (AUC=0.83) were significant predictors of SNO. The addition of any of the other variables did not improve the predictive probability of EFW for the prediction of SNO. Conclusions The EFW had the strongest association with SNO in in our study among variables obtainable before delivery. Other variables had no significant effect on the prediction probability of the EFW. Our findings should be validated in larger studies.

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.

Middle cerebral artery peak systolic velocity in perinatal cytomegalovirus infection.

A middle cerebral artery peak systolic velocity value (MCA-PSV) persistently greater than 1.5 times the median of the normal population is utilized to detect moderate and severe anemia in fetuses at risk. Cytomegalovirus (CMV) is the most common perinatal infection and can cause fetal anemia. We present four cases with CMV perinatal infection. Although their MCA-PSV values were the highest recorded in normal as well as in anemic fetuses, only two of them developed moderate or severe anemia. These findings suggest that high MCA-PSV values in cases with perinatal CMV infection may have a different pathophysiologic mechanism than anemia.

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.

Fetal anemia.

The diagnosis and management of fetal anemia has been at the forefront of advances in the fields of fetal physiology, immunology, fetal imaging, and fetal therapy among others. Alloimmunization and parvovirus infection are the leading cause of fetal anemia in the United States. The middle cerebral artery peak systolic velocity (MCA-PSV) diagnoses fetal anemia. Its discovery is considered one of the most important achievements in fetal medicine. Accumulation of experience in recent years as well as refinement of surgical techniques have led to safer invasive procedures. It is expected that long term follow-up of affected pregnancies, continues to reflect all these improvements in care. It is also expected that treatment of other less common causes of fetal anemia becomes more frequently reported and that the management principles of fetal anemia are successfully applied to other fetal pathologies.

Bilateral salpingectomy versus bilateral partial salpingectomy during cesarean delivery.

OBJECTIVE: To compare surgical outcomes in patients undergoing bilateral salpingectomy (salpingectomy group) with those who had partial salpingectomy (partial salpingectomy group) during cesarean delivery. MATERIALS AND METHODS: A chart review from July 2015 to November 2016 was performed. We included women who had sterilization during cesarean delivery. We excluded sterilization by occlusive methods. Our primary outcomes were total operative time and a composite score of transfusion rate, internal organ injury, hospital readmission, and endometritis. Secondary outcomes included menstrual abnormalities, pelvic pain, quality of life assessment, and regrets rate. We compared these outcomes between women in the salpingectomy and partial salpingectomy groups. Chi-squared, Fisher's exact, t-test, and Mann-Whitney U were utilized for statistical analysis where appropriate. A P<0.05 was considered significant. RESULTS: We included a total of 160 pregnancies. Of these, 41 were in the salpingectomy and 119 in the partial salpingectomy group. The median total operative time was longer for the salpingectomy group (62 [IQR 54, 71] vs 60 minutes [IQR 46, 72]; P=0.03). The composite of surgical complications (19.5% vs 12.6%; P=0.28) was not significantly different between our study groups. Menstrual irregularities (P≥0.99), quality of life (P≥0.99), dyspareunia (P≥0.99), dysmenorrhea (P=0.36), and regrets (P≥0.99) were not different between groups. CONCLUSION: Salpingectomy during cesarean delivery increased the median operative time by 2 minutes and may not be associated with an increased risk of surgical complications. We acknowledge the need for larger multi-center trials to corroborate our outcomes.

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.

A conceptual framework for the impact of obesity on risk of cesarean delivery.

Cesarean deliveries accounted for 32.2% of nearly 4 million births in the United States in 2014. Obesity affects a third of reproductive-age women and is associated with worse cesarean delivery outcomes. Studies have shown that increasing maternal body mass index correlates linearly with cesarean delivery rates, but little is known about the potential mediating and moderating mechanisms. Thus, a conceptual framework for understanding how obesity correlates with risk of cesarean delivery is crucial to determining safe ways to reduce the cesarean delivery rate among obese gravidas. Based on an extensive review and synthesis of the literature, we present a conceptual framework that posits how obesity may operate through several pathways to lead to a cesarean delivery. Our framework explores the complexity of obesity as an exposure that operates through potential mediating pathways, a moderator of cesarean delivery risk, and a covariate with other cesarean delivery risk factors. Among nulliparas, obesity appears to operate through 3 main proximal mediating mechanisms to increase risk of cesarean delivery including: (1) preexisting comorbidities and obstetric complications; (2) a slower progression of first-stage labor, potentially increasing the risk of cesarean delivery secondary to failure to progress; and (3) a prolongation of pregnancy, which is associated with risk of maternal postdates. For multiparas, a fourth proximal mediator of prior uterine scar may also increase cesarean delivery risk. Distal mediating mechanisms, which operate through one of the proximal mechanisms, may include an induction of labor or planned prelabor cesarean delivery. Obesity may also moderate the likelihood of cesarean delivery by interacting with clinician-level or hospital-level factors. Future research should assess the validity of this framework and seek to understand the relative contributions of each potential pathway between obesity and cesarean delivery. This will allow for evidence-based recommendations to reduce preventable cesareans among obese women by targeting modifiable mediators and moderators of the relationship between obesity and increased risk of cesarean delivery.

Factors Associated With Improvements in Mortality and Morbidity Rates of Very-Low-Birth-Weight Infants: A Cohort Study.

Objective. The objective of this study was to determine factors contributing to improvements in infant mortality rates (IMR) and composite morbidity-mortality in very-low-birth-weight (VLBW) infants after initiating a new perinatal program in 2009 at Regional One Health (ROH). VLBW infants account for 67% of infant deaths. Design. This is a pre-/postintervention cohort study of prospectively gathered data. Population. VLBW infants delivered at ROH during the 2004 to 2015 study period. Setting. ROH is a Regional Perinatal Center affiliated with the University of Tennessee Health Science Center. Methods. We studied 2364 consecutive VLBW infants. Multivariate models were applied to determine factors contributing significantly to the reduction in the outcome measures as well as trends over time. Main Outcome Measures. Primary outcomes were IMR and composite morbidity-mortality rates. Standardized, risk-adjusted mortality and composite morbidity ratios were also reported as defined by the Vermont Oxford Network. Results. Mortality declined from 15.5% in Pre-Implementation to 13.1% in Post-Implementation (P = .093), corresponding to an 18% reduction in odds. The combined factors of composite morbidity-mortality rate decreased from 55.7% in Pre-Implementation to 43.9% in Post-Implementation (P < .0001), representing a 38% reduction in odds. Standardized, risk-adjusted mortality and composite morbidity ratios improved during the study period from 20% above to 20% below the expected rate. Increases in the administration of antenatal steroids, surfactant administration, cesarean delivery, and perhaps other programmatic changes that were observational and unaccounted in the model were associated with improvements in outcome measures. Conclusions. Decreased mortality and composite morbidity-mortality in VLBW infants delivered at ROH were found following the initiation of a new perinatal program.

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.