Postconceptual Neonatal Dating by Transmastoid Ultrasound of Transcerebellar Diameter-Comparison to Crown Rump Length Measurement: A Proof of Concept Paper.

OBJECTIVES: Transcerebellar diameter (TCD) has been utilized prenatally as a tool to estimate gestational age (GA) when fetal growth aberrations are suspected. Traditionally, first trimester ultrasound (1TUS) has been the gold standard of dating a pregnancy in spontaneous pregnancies. We sought to determine if neonatal TCD measurement was as accurate as 1TUS in the estimation of postconceptual gestational age (PCGA). METHODS: A retrospective cohort from a registry of high-quality transmastoid views of consecutive patients from July 2019 to November 2020, delivered from 24 to 34 weeks GA, and with a 1TUS were included. The reference PCGA was the sum of the GA at delivery by 1TUS and day of life. The PCGA by TCD was calculated from Chang et al for GA by TCD. Reference and experimental values were compared by correlation, agreement within 7 days, and Bland-Altman analysis. RESULTS: Of the 154 individual patients in the registry of high-quality transmastoid views during the study period, 62 met inclusion and exclusion criteria. PCGA by 1TUS and TCD were highly correlated (r = 0.86, P < .001; κ = 47% agreement within 7 days of PCGA). The bias of PCGA by TCD was 4.6 days earlier than the PCGA by 1TUS (95% confidence interval of agreement: -29.2, 20). CONCLUSIONS: PCGA estimation by neonatal transmastoid TCD was highly correlated with that of 1TUS. It generally underestimates GA by 4.6 days. This relationship warrants further investigation to determine if this method of estimating PCGA in undated gestations is generalizable.

Birthweight and Apgar at 5 minutes of life for the prediction of severe neonatal outcomes in preterm prelabor rupture of membranes.

OBJECTIVE: The aim of our study was to investigate the predictive accuracy of clinical variables available after delivery for severe neonatal outcomes (SNO) in pregnancies complicated by PPROM. MATERIALS AND METHODS: This was a secondary analysis of a prospective cohort of pregnancies complicated by PPROM. We included expectant mothers from 13-46 years of age who were between 23 and 36 6/7 weeks of gestation. We excluded multiple gestations, complex fetal anomalies, those with fetal demise and outborn infants. Our primary outcome was a composite of SNO (respiratory distress syndrome, necrotizing enterocolitis, Intra-ventricular hemorrhage, sepsis, and death). The variables assessed where gestational age at delivery, birthweight, Apgar score at 5 min of life, Apgar <7 at 5 min of life, small for gestational age, sex, umbilical artery pH, and mode of delivery. Logistic regression was performed to evaluate the predictive accuracy of each of these variables. Stepwise multivariable logistic regression was utilized to assess the effect of variables with univariate analysis p value <.10 and those baseline characteristics with a statistically significant association with our composite score. RESULTS: We included 108 infants. SNO was diagnosed in 44 (41%) neonates. The Apgar score at 5 min (AUC = 0.89; p= <.001), the birthweight (AUC = 0.88; p= <.001), gestational age at delivery (AUC = 0.87; p= <.001), and the Apgar score < 7 at 5 min (AUC = 0.73; p= <0.001) were statistical significant predictors of SNO. Sex (p=.15), mode of delivery (p=.15), umbilical artery Ph (p=.28), SGA (p=.85) were not statistically significant predictors of SNO. After stepwise multivariable logistic regression only the Apgar at 5 min and birth weight remained statistically significant predictors for SNO (AUC = 0.94). CONCLUSIONS: In pregnancies complicated by PPROM the birthweight and the Apgar at 5 min of life are accurate predictors of a composite score of SNO. We acknowledge the need for larger and more diverse studies to corroborate our findings. BRIEF RATIONALE: We assessed the predictive accuracy of clinical variables available after delivery for severe neonatal outcomes in pregnancies complicated by PPROM. We found that the birthweight and the Apgar score at 5 min were accurate predictors of such outcomes in this population. Our results may aid providers in the counseling of premature infants born after PPROM.

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.

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.

Perinatal maternal antibiotic exposure augments lung injury in offspring in experimental bronchopulmonary dysplasia.

During the newborn period, intestinal commensal bacteria influence pulmonary mucosal immunology via the gut-lung axis. Epidemiological studies have linked perinatal antibiotic exposure in human newborns to an increased risk for bronchopulmonary dysplasia, but whether this effect is mediated by the gut-lung axis is unknown. To explore antibiotic disruption of the newborn gut-lung axis, we studied how perinatal maternal antibiotic exposure influenced lung injury in a hyperoxia-based mouse model of bronchopulmonary dysplasia. We report that disruption of intestinal commensal colonization during the perinatal period promotes a more severe bronchopulmonary dysplasia phenotype characterized by increased mortality and pulmonary fibrosis. Mechanistically, metagenomic shifts were associated with decreased IL-22 expression in bronchoalveolar lavage and were independent of hyperoxia-induced inflammasome activation. Collectively, these results demonstrate a previously unrecognized influence of the gut-lung axis during the development of neonatal lung injury, which could be leveraged to ameliorate the most severe and persistent pulmonary complication of preterm birth.

Termination of Pregnancy as a Means to Reduce Maternal Mortality in Pregnant Women With Medical Comorbidities.

The United States is the world's only developed country with a rising maternal mortality rate, with an increase of 26% between 2000 and 2014. Of the approximately 700 pregnancy-related deaths per year in the United States, nearly 30% are attributable to preexisting disease. Maternal-fetal medicine physicians are in a unique position-they are tasked with counseling patients regarding the risks of pregnancy in the context of their medical comorbidities. Individual physicians' opinions regarding the level of risk of death at which a termination of pregnancy would be considered "medically indicated" are highly variable and are influenced by where physicians are from, where they trained, and their knowledge regarding the safety of termination of pregnancy. Additionally, 43 states have legislated restrictions to abortion access that contain exceptions to protect women's life or health, but what constitutes a risk to a woman's life or health is not well-defined and appropriates medical terminology for political purposes. The current statements from the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine advocate for safe, legal, and unobstructed access to pregnancy termination services. These statements attempt to remove health care providers' own biases regarding the exact risk level at which they would consider an abortion to be medically indicated. Because the risk of death from a first- or second-trimester termination is less than that of a traditional delivery, any medical problem that increases that risk of death could be considered an indication for counseling patients regarding the option of termination of pregnancy as a means to reduce mortality or morbidity.

Fungi form interkingdom microbial communities in the primordial human gut that develop with gestational age.

Fungal and bacterial commensal organisms play a complex role in the health of the human host. Expansion of commensal ecology after birth is a critical period in human immune development. However, the initial fungal colonization of the primordial gut remains undescribed. To investigate primordial fungal ecology, we performed amplicon sequencing and culture-based techniques of first-pass meconium, which forms in the intestine prior to birth, from a prospective observational cohort of term and preterm newborns. Here, we describe fungal ecologies in the primordial gut that develop complexity with advancing gestational age at birth. Our findings suggest homeostasis of fungal commensals may represent an important aspect of human biology present even before birth. Unlike bacterial communities that gradually develop complexity, the domination of the fungal communities of some preterm infants by Saccromycetes, specifically Candida, may suggest a pathologic association with preterm birth.-Willis, K. A., Purvis, J. H., Myers, E. D., Aziz, M. M., Karabayir, I., Gomes, C. K., Peters, B. M., Akbilgic, O., Talati, A. J., Pierre, J. F. Fungi form interkingdom microbial communities in the primordial human gut that develop with gestational age.

Physiologic proteinuria in labor and postpartum: The results of the postpartum proteinuria trial (PoPPy).

The urine protein to creatinine ratio (PC) is a sensitive and specific means of diagnosing preeclampsia in the antepartum period, but the 0.3 g protein per gram of creatinine threshold may be non-specific postpartum due to physiologic proteinuria after delivery. The objective of this study was to examine the reliability of PC in labor and postpartum and to determine if PC is affected by mode of delivery. This is the first study of its kind to examine physiologic proteinuria by catheterized PC in individual patients before and after delivery. This single-center prospective cohort study included two groups: term uncomplicated nulliparous patients in labor with epidural analgesia and patients for scheduled repeat cesarean deliveries. Patients with hypertension, antepartum proteinuria, renal disease, gross hematuria, or evidence of infection were excluded. Catheterized pre- and post-delivery urine PC were compared using paired t-tests. 27 and 40 patients were included in the vaginal and cesarean delivery groups, respectively. 52% of the vaginal delivery and 58% of the cesarean delivery groups were positive for proteinuria at the 0.3 g protein per g creatinine threshold. Pre- and post-delivery specimens were significantly different in the vaginal (mean difference 0.28, p = 0.05) and cesarean (mean difference 0.25, p < 0.01) delivery groups. The conclusions reached included the finding that PC measurements are unreliable in the immediate postpartum period regardless of mode of delivery, and utilizing the 0.3 threshold to diagnose preeclampsia in close proximity to delivery would contribute to increased false positive tests.

Are Women With Threatened Preterm Labor More Dehydrated Than Women Without It?

OBJECTIVE: To determine if women who present to the labor and delivery unit at 23 0/7 to 36 6/7 weeks gestation with threatened preterm labor (TPTL) are more likely to be dehydrated than women who present at the same gestational age for other reasons. DESIGN: Retrospective cohort study. SETTING: An academic medical center in the northeastern United States. PARTICIPANTS: All women at preterm gestational ages 23 0/7 to 36 6/7 weeks who presented to the labor and delivery unit for care in 2014. METHODS: We compared hydration status by urine specific gravity of women with TPTL to that of women with other chief complaints. Women for whom data were missing and those with hypertension, diabetes, renal disease, vaginal bleeding, ruptured membranes, advanced dilation (>3 cm), multiple gestation, or fetal demise were excluded. Chi-square statistic and a receiver operating characteristic (ROC) curve were used for data analysis. RESULTS: A total of 840 women at 23 0/7 to 36 6/7 weeks gestation presented during the study period; 188 of these had TPTL, 261 had other chief complaints, and 391 were excluded. The proportion of women diagnosed with dehydration was similar between those with TPTL (39%) and those with other complaints (46%, p = .12). An ROC curve showed no association between TPTL and hydration status (area under the curve = 0.57, 95% confidence interval [0.46, 0.67]). CONCLUSION: At 23 0/7 to 36 6/7 weeks gestation, the hydration status of women with TPTL was not different from those without TPTL. Because there is no relationship, it is unlikely that hydration is a worthwhile therapy for women with TPTL, although additional prospective study is warranted.

Is preeclampsia an independent predictor of diastolic dysfunction? A retrospective cohort study.

OBJECTIVE: To determine if preeclampsia is an independent predictor of diastolic dysfunction and what factors among patients with preeclampsia are associated with diastolic dysfunction. METHODS: This is a retrospective cohort study of patients who delivered between 2008 and 2013 at a single institution who had a maternal echocardiogram during their pregnancy or within 5months of delivery. Patients with structural heart disease, ejection fraction less than 45%, pulmonary embolus, or age over 45years were excluded. Medical records were reviewed for medical and obstetric complications and echocardiogram findings. Demographic characteristics and rate of diastolic dysfunction were compared between patients with preeclampsia and without preeclampsia. Multivariate logistic regression was performed controlling for age, ethnicity, gestational age at delivery, diabetes, preeclampsia, intrauterine growth restriction (IUGR), antihypertensive use and magnesium sulfate administration. RESULTS: Sixty-six patients were identified, of which 39 (59%) had preeclampsia. Past history of preeclampsia, IUGR in the current pregnancy, antihypertensive use and magnesium sulfate use were higher in the preeclampsia group. Fifteen patients (39%) in the preeclampsia group were African-American compared to 2 (3%) in the control group (p<0.01). Seventeen (44%) of the patients with preeclampsia were found to have diastolic dysfunction compared to 3 (11%) controls (OR=6.18, 95% CI 1.59,24.02; p=0.006). Logistic regression analysis did not reveal other independent predictors of diastolic dysfunction. In the patients with preeclampsia, history of preeclampsia with severe features and IUGR were not associated with diastolic dysfunction. CONCLUSIONS: Our study supports previous findings that preeclampsia is associated with diastolic dysfunction.

Association Between 6-Minute Walk Test and All-Cause Mortality, Coronary Heart Disease-Specific Mortality, and Incident Coronary Heart Disease.

OBJECTIVE: To examine the association between 6-min walk test (6 MWT) performance and all-cause mortality, coronary heart disease mortality, and incident coronary heart disease in older adults. METHOD: We conducted a time-to-event analysis of 1,665 Cardiovascular Health Study participants without prevalent cardiovascular disease with a 6 MWT. RESULTS: During a mean follow-up of 8 years, there were 305 incident coronary heart disease events, and 504 deaths of which 100 were coronary heart disease-related deaths. The 6 MWT performance in the shortest two distance quintiles was associated with increased risk of all-cause mortality (290-338 m: hazard ratio [HR] = 1.7; 95% confidence interval [CI] = [1.2, 2.5]; <290 m: HR = 2.1; 95% CI = [1.4, 3.0]). The adjusted risk of coronary heart disease mortality incident events among those with a 6 MWT < 290 m was not significant. DISCUSSION: Performance on the 6 MWT is independently associated with all-cause mortality and is of prognostic utility in community-dwelling older adults.