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Objective Maternal preconception diet influences pregnancy health and fetal outcomes. We examined the relationship between preconception fatty acid (FA) intake and uterine artery indices in mid-gestation in a large, heterogeneous cohort of nulliparous individuals. Study Design This is a secondary analysis of the nuMom2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be) study. Dietary ω-6 and ω-3 FA intake was assessed with food frequency questionnaires and uterine artery indices were obtained via Doppler studies in the second trimester. For our primary outcome of pulsatility index (PI) > 1.6, we compared proportions by each dichotomous FA exposure and tested differences with chi-square test. Results For PI > 1.6, odds ratio for the unfavorable FA quartile compared with remaining quartiles for the exposures were 0.96 to 1.25, p = 0.157 (ω-6 FA); 0.97 to 1.26, p = 0.124 (ω-3 FA); 0.87 to 1.14, p = 1.00 (ω-6:ω-3 FA ratio). Conclusion No significant associations between self-reported maternal preconception ω-6 and ω-3 FA intake and uterine artery Doppler indices measured during the second trimester were observed. Key Points Maternal diet impacts pregnancy health/fetal outcomes. ω-3 and ω-6 FA intake influences cardiovascular health. FA intake may affect blood flow to fetoplacental unit. Results are limited by inadequate adherence to dietary recommendations. [ABSTRACT FROM AUTHOR]

Objective Delta-like homolog 1 (DLK1) is a growth factor that is reduced in maternal sera in pregnancies with small for gestational age neonates. We sought to determine if DLK1 is associated with stillbirth (SB), with and without placental insufficiency. Study Design A nested case-control study was performed using maternal sera from a multicenter case-control study of SB and live birth (LB). SB and LB were stratified as placental insufficiency cases (small for gestational age <5% or circulatory lesions on placental histopathology) or normal placenta controls (appropriate for gestational age and no circulatory lesions). Enzyme-linked immunosorbent assay (ELISA) was used to measure DLK1. The mean difference in DLK1 was compared on the log scale in an adjusted linear regression model with pairwise differences, stratified by term/preterm deliveries among DLK1 results in the quantifiable range. In exploratory analysis, geometric means were compared among all data and the proportion of "low DLK1" (less than the median value for gestational age) was compared between groups and modeled using linear and logistic regression, respectively. Results Overall, 234 SB and 234 LB were analyzed; 246 DLK1 values were quantifiable within the standard curve. Pairwise comparisons of case and control DLK1 geometric means showed no significant differences between groups. In exploratory analysis of all data, adjusted analysis revealed a significant difference for the LB comparison only (SB: 71.9 vs. 99.1 pg/mL, p = 0.097; LB: 37.6 vs. 98.1 pg/mL, p = 0.005). In exploratory analysis of "low DLK1," there was a significant difference between the odds ratio of having "low DLK1" between preterm cases and controls for both SB and LB. There were no significant differences in geometric means nor "low DLK1" between SB and LB. Conclusion In exploratory analysis, more placental insufficiency cases in preterm SB and LB had "low DLK1." However, low DLK1 levels were not associated with SB. Key Points Maternally circulating DLK1 is correlated with placental insufficiency. Maternally circulating DLK1 is not correlated with SB. DLK1 is a promising marker for placental insufficiency. [ABSTRACT FROM AUTHOR]

Objective  The study aimed to assess the feasibility of creating and transplanting human umbilical cord mesenchymal stem cell sheets applied to a rat model of hysterotomy, and additionally to determine benefits of human umbilical cord mesenchymal stem cell sheet transplantation in reducing uterine fibrosis and scarring. Study Design  Human umbilical cord mesenchymal stem cell sheets are generated by culturing human umbilical cord mesenchymal stem cells on thermo-responsive cell culture plates. The temperature-sensitive property of these culture dishes facilitates normal cell culture in a thin contiguous layer and allows for reliable recovery of intact stem cell sheets without use of destructive proteolytic enzymes. We developed a rat hysterotomy model using nude rats. The rat uterus has two distinct horns: one horn provided a control/untreated scarring site, while the second horn was the cell sheet transplantation site. On day 14 following surgery, complete uteri were harvested and subjected to histologic evaluations of all hysterotomy sites. Results  The stem cell sheet culture process yielded human umbilical cord mesenchymal stem cell sheets with surface area of approximately 1 cm 2. Mean myometrial thickness in the cell sheet-transplanted group was 274 μm compared with 191 μm in the control group (p  = 0.02). Mean fibrotic surface area in the human umbilical cord mesenchymal stem cell sheet-transplanted group was 95,861 μm 2 compared with 129,185 μm 2 in the control group. Compared with control horn sites, cell sheet-transplanted horns exhibited significantly smaller fibrotic-to-normal myometrium ratios (0.18 vs. 0.27, respectively, p  = 0.029). Mean number of fibroblasts in cell sheet-transplanted horns was significantly smaller than the control horns (483 vs. 716/mm 2 , respectively, p  = 0.001). Conclusion  Human umbilical cord mesenchymal stem cell sheet transplantation is feasible in a rat model of hysterotomy. Furthermore, use of stem cell sheets reduces fibroblast infiltration and uterine scar fibrotic tissue formation during hysterotomy healing, potentially mitigating risks of uterine scar formation. Key Points Stem cell sheet transplanted to hysterotomy promotes myometrial regeneration and reduced fibrotic tissue formation. This study demonstrates the feasibility of using human umbilical cord mesenchymal stem cell sheets. [ABSTRACT FROM AUTHOR]

Objective  Marijuana use is associated with placenta-mediated adverse pregnancy outcomes including fetal growth restriction, but the mechanism remains uncertain. The objective was to evaluate the association between maternal marijuana use and the feto-placental weight ratio (FPR). Secondarily, we aimed to compare placental histology of women who used marijuana to those who did not. Study Design  This was a secondary analysis of singleton pregnancies enrolled in a multicenter and case–control stillbirth study. Prior marijuana use was detected by electronic medical record abstraction or cord homogenate positive for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. Prior tobacco use was detected by self-report or presence of maternal serum cotinine. Stillbirths and live births were considered separately. The primary outcome was FPR. Association of marijuana use with FPR was estimated with multivariable linear modeling adjusted for fetal sex, preterm birth, and tobacco use. Comparisons between groups for placental histology were made using Chi-square and stratified by live birth and stillbirth, term and preterm deliveries, and fetal sex. Results  Of 1,027 participants, 224 were stillbirths and 803 were live births. Overall, 41 (4%) women used marijuana during the pregnancy. The FPR ratio was lower among exposed offspring but reached statistical significance only for term stillbirths (mean 6.84 with marijuana use vs. mean 7.8 without use, p  < 0.001). In multivariable modeling, marijuana use was not significantly associated with FPR (p  = 0.09). There were no differences in histologic placental features among those with and without marijuana use overall or in stratified analyses. Conclusion  Exposure to marijuana may not be associated with FPR. Similarly, there were no placental histologic features associated with marijuana exposure. Further study of the influence of maternal marijuana use on placental development and function is warranted to better understand the association between prenatal marijuana use and poor fetal growth. Key Points Maternal marijuana exposure was not associated with the feto-placental weight ratio. Marijuana exposure was not associated with differences in placental histology. Concerning trend toward lower feto-placental weight ratios among marijuana-exposed stillbirths. [ABSTRACT FROM AUTHOR]

Objective  Randomized controlled trials (RCTs) are considered the highest level of evidence to inform clinical practice. However, the reproducibility crisis has raised concerns about the scientific rigor of published RCT findings. Some advocate for a lower p -value threshold. We aimed to review published OB/Gyn topical RCTs in three representative OB/Gyn journals and three high impact non-OB/Gyn journals to determine if their interpretations would change with adoption of a p -value threshold for significance of 0.005. Secondarily, we evaluated if there were differences in methodologic characteristics between those that did and did not lose significance. Study Design  A manual search was performed to identify all OB/Gyn RCTs published in the selected journals between July 2017 and June 2019. Data were collected on primary outcome(s), methodology, and p -values. We determined the proportion of primary outcomes that would remain statistically significant with adoption of a p -value significance threshold of 0.005 versus be reinterpreted as "suggestive" (defined as p -value between 0.005 and 0.05). Chi-square or Fisher's exact test were used to compare study characteristics. Results  Overall, 202 RCTs met inclusion criteria; 52% in obstetrics and 48% in gynecology. Of 90 studies considered significant with p <0.05 at the time of publication, 54.4% (n  = 49) would maintain significant (p  < 0.005), while 45.6% (n  = 41) would become suggestive using the lower threshold. Most RCTs utilized a single (90.1%) versus composite (8.9%) primary outcome type, used an intent-to-treat analysis (73.3%), and studied a drug intervention (46.5%). Methodologically, 23.7% did not prespecify analysis type, 28.2% did not meet the pre-determined sample size, and 9.4% did not report an a priori sample size calculation. Studies maintaining significance were more likely to be international and report a funding source. Conclusion  Adopting a p -value significance threshold of 0.005 would require reinterpretation of almost half of RCT results in the OB/Gyn literature. Highly variable methodological quality was identified. Key Points New p -value threshold results in reinterpretation of nearly half of RCT results in OB/Gyn literature. Highly variable methodological quality was identified. Reduced use of binary interpretations of significance is necessary. [ABSTRACT FROM AUTHOR]

Objective  Respiratory distress syndrome (RDS) is implicated in 30% of neonatal deaths. Since prostaglandins promote surfactant secretion and labor is associated with a lower risk of RDS in term neonates, it is plausible that synthetic prostaglandin (sPG) exposure is associated with a lower risk of RDS. Thus, we evaluated the association between sPG exposure and RDS in neonates born after the induction of labor (IOL). Study Design  Secondary analysis of women with singleton pregnancies undergoing IOL at 34 0/7 to 42 0/7 weeks in the nuMoM2b study, a multicenter prospective cohort of nulliparous women. RDS rates and secondary neonatal outcomes in neonates with intrapartum sPG exposure were compared with those who had IOL with non-sPG methods (e.g., balloon catheter, amniotomy, oxytocin, and laminaria). Logistic regression models estimated the association of sPG with RDS and with secondary outcomes after adjustment for clinical and demographic factors (including gestational age). A sensitivity analysis was performed in which analysis was restricted to those with an admission cervical dilation ≤2 cm. Results  Of 10,038 women in the total cohort, 3,071 met inclusion criteria; 1,444 were exposed and 1,627 were unexposed to sPGs. Antenatal corticosteroid exposure rates were low (3.0%) and similar between groups. In univariable analysis, neonates with sPG exposure had higher rates of RDS (3.2 vs. 2.0%, odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.01–2.50). This relationship was similar by gestational age at delivery (term vs. preterm, interaction p  = 0.14). After adjustment, the association between sPG and RDS was no longer significant (adjusted odds ratio: 1.4, 95% CI: 0.9–2.3). When analysis was restricted to subjects with admission cervical dilation of ≤2 cm, there was also no association between sPG exposure and RDS. Conclusion  In pregnancies between 34 and 42 weeks of gestation, exposure to sPG for cervical ripening or labor induction was not associated with newborn RDS. Key Points RDS is implicated in 30% of neonatal deaths. sPG exposure was not associated with RDS. Avoiding preterm birth remains crucial in RDS prevention. [ABSTRACT FROM AUTHOR]

Objective  Our objective was to test the association of fetal adrenal size with perinatal morbidity among fetuses with fetal growth restriction (FGR; estimated fetal weight [EFW] < 10th percentile). Study Design  This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) adrenal study, which measured fetal adrenal gland size at 22 to 30 weeks' gestation. We analyzed the transverse adrenal area (TAA) and fetal zone area (absolute measurements and corrected for fetal size) and the ratio of the fetal zone area to the total transverse area using a composite perinatal outcome of stillbirth, neonatal intensive care unit admission, respiratory distress syndrome, necrotizing enterocolitis, retinopathy of prematurity, sepsis, mechanical ventilation, seizure, or death. Among fetuses with FGR, adrenal measurements were compared between those that did and did not experience the composite perinatal outcome. Results  There were 1,709 eligible neonates. Seven percent (n  = 120) were diagnosed with FGR at the time of adrenal measurement, and 14.7% (n  = 251) experienced perinatal morbidity. EFW-corrected and absolute adrenal measurements were similar among fetuses with and without FGR as well as among those who did and did not experience morbidity. The area under the curve for corrected TAA was 0.52 (95% confidence interval 0.38–0.67). Conclusion  In our cohort, adrenal size was not associated with risk of morbidity among fetuses with FGR. [ABSTRACT FROM AUTHOR]

Objective  Substance use disorders often coexist with depression. The objective of this study was to establish whether pregnant women who report depressive symptomatology were more likely to report use of alcohol, tobacco, and marijuana during pregnancy. Study Design  This was a secondary analysis of prospectively collected data from the Maternal-Fetal Medicine Units Network Preterm Prediction Study. Self-reported history of alcohol, tobacco, and marijuana use was compared between pregnant women with and without depressive symptomatology with adjustment for demographic factors. Results  After adjustment for demographic factors, women with depressive symptomatology were more likely to report: any alcohol use (odds ratio [OR]: 1.4, 95% confidence interval [CI]: 1.1–1.8), >1 drink per week (OR: 1.3, 95% CI: 1.0–1.8), and >1 drink per day (OR: 2.2, 95% CI: 1.5–3.4). Women with depressive symptomatology were also more likely to report use of marijuana (OR: 1.8, 95% CI: 1.2–2.6) and cigarettes (OR: 1.4, 95% CI: 1.1–1.7). Conclusion  Depressive symptomatology was associated with an increase in self-reported the use of alcohol, tobacco, and marijuana during pregnancy. These data reveal the importance of targeted screening of pregnant women with depressive symptomatology for substance use. [ABSTRACT FROM AUTHOR]

Objective  We aimed to assess whether marijuana legalization was associated with a difference in prevalence of prenatal use or an increase in incidence of adverse perinatal outcomes. Study Design  The present study is a retrospective cohort of September and October deliveries in the years 2012 through 2015 at a tertiary center in Colorado. Primary outcome of the study was use of marijuana, defined by self-report or biodetection. Secondary outcomes of the study included growth restriction, spontaneous preterm birth, stillbirth, preeclampsia, and neonatal or maternal death. Marijuana use prevalence was compared by year, and secondary outcomes between two periods, before and after the opening of the first recreational dispensary. Results  A total of 2,392 pregnant women were included (1,165 before legalization and 1,227 after). More women used marijuana over the period of legalization (trend p  = 0.01). Odds of marijuana use were higher after legalization versus before (adjusted odds ratio [aOR] = 1.8, 95% confidence interval [CI]: 1.2–2.6). Incidence of growth restriction was higher after legalization (2.9 vs. 5.1%, p  = 0.0084). This difference persisted after adjustment for ethnicity and other drugs in multivariable modeling (aOR = 1.9, 95%CI: 1.2–3.0). Conclusion  The prevalence of prenatal marijuana use increased over the time of legalization. Further investigation into the population impact of legalization on obstetrical outcomes is warranted given the observed increase in growth restriction. [ABSTRACT FROM AUTHOR]

Objective We aimed to evaluate which patient-level factors influence mode of delivery among candidates for operative vaginal delivery. Study Design Cross-sectional study of candidates for operative vaginal delivery from 18 hospitals over 8 years. Probabilities of mode of delivery were estimated using hierarchical logistic modeling adjusting for clustering within physician and hospital. Results Total 3,771 (64%) women delivered with forceps, 1,474 (25%) vacuums, and 665 (11%) cesareans. Odds of forceps versus vacuum were higher with induction (OR = 2.16, 95% CI: 1.76-2.65), nulliparity (OR = 2.06, 95% CI: 1.59-2.66), epidural (OR = 2.05, 95% CI: 1.19-3.56), maternal indication (OR = 1.53, 95% CI 1.16-2.02), older maternal age (OR 1.18, 95% CI 1.06-1.31 per 5 years), and longer second stage (OR = 1.10, 95% CI: 1.01-1.20 per hour). Odds of cesarean versus operative vaginal delivery were higher with maternal indication (OR = 9.0, 95% CI: 7.23-11.20), a perinatologist (OR = 2.51, 95% CI: 1.09-5.78), longer second stage (OR = 1.79, 95% CI: 1.65-1.93 per hour), older gestational age (OR = 1.10, 95% CI: 1.01-1.20 per week), and longer labor (OR = 1.02, 95% CI: 1.01- 1.04 per hour). Conclusion Patient-level factors influence the decision to proceed with an operative vaginal delivery and the choice of instrument, thereby emphasizing the importance of maintaining availability of both forceps and vacuums. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to determine if maternal smoking modifies the effectiveness of 17 α-hydroxyprogesterone caproate (17OHP-C). Study Design Secondary analysis of the Maternal-Fetal Medicine Units Network trial of 17OHP-C. The prevalence of preterm birth (PTB) by smoking status and treatment group was compared by chi-squared analysis and analysis of variance was used to compare gestational age (GA) at birth. Multivariable modeling was used to estimate the effect of smoking on 17OHP-C treatment. Results In this study, 459 women were included. Maternal smoking significantly modified the effectiveness of 17OHP-C treatment. In smokers, 17OHP-C significantly reduced the prevalence of multiple outcomes (PTB < 37 and < 35 weeks, spontaneous PTB < 37 and < 35 weeks), while in nonsmokers, only PTB < 37 weeks was reduced. Delivery GA was later in 17OHP-C versus placebo treated smokers (36.4 vs. 34.3 weeks, p = 0.041) but not nonsmokers (36.3 vs. 35.5 weeks, p = nonsignificant). In multivariable modeling, 17OHP-C was more effective in smokers than nonsmokers as measured by multiple outcomes (PTB < 37 weeks [p = 0.041] and < 35 weeks [p = 0.036] and spontaneous PTB < 37 weeks [p = 0.029]). Conclusion In this cohort of women with a prior PTB, maternal smoking status significantly modified the effectiveness of 17OHP-C treatment. [ABSTRACT FROM AUTHOR]

Objective We aimed to determine if obese women undergoing trial of labor after cesarean (TOLAC) were more likely to undergo repeat cesarean for arrest disorders prior to active labor, and whether this was due to decreased use of standard interventions to achieve vaginal birth. Study Design This was a secondary analysis of a prospective registry. Women undergoing TOLAC with one prior cesarean and a singleton, term gestation who had a repeat cesarean for an arrest disorder were included. The primary outcome was repeat cesarean prior to active labor (cervical dilation < 6 cm). Obese (body mass index ≥30 kg/m²) and nonobese women were compared. Multivariable logistic regression was used to estimate the association between obesity and repeat cesarean prior to active labor. Clinical interventions were compared between groups using t-test and χ² test. Results Among 2,098 women undergoing TOLAC, 1,454 (69%) were obese. Obese women were more likely to undergo repeat cesarean for an arrest disorder prior to active labor (odds ratio, 1.4; 95% confidence interval, 1.1 -1.7) despite being allowed longer labors and receiving higher maximum doses of oxytocin for a longer duration than nonobese women. Conclusion Obese women were more likely to undergo repeat cesarean prior to active labor despite more clinical interventions to achieve vaginal birth. [ABSTRACT FROM AUTHOR]