Short Term Coping-Behaviors and Postpartum Health in a Population-Based Study of Women with a Live Birth, Stillbirth, or Neonatal Death.

OBJECTIVE: Responding to the National Institutes of Health Working Group's call for research on the psychological impact of stillbirth, we compared coping-related behaviors by outcome of an index birth (surviving live birth or perinatal loss - stillbirth or neonatal death) and, among individuals with loss, characterized coping strategies and their association with depressive symptoms 6-36 months postpartum. METHODS: We used data from the Stillbirth Collaborative Research Network follow-up study (2006-2008) of 285 individuals who experienced a stillbirth, 691 a livebirth, and 49 a neonatal death. We conducted a thematic analysis of coping strategies individuals recommended following their loss. We fit logistic regression models, accounting for sampling and inverse probability of follow-up weights to estimate associations between pregnancy outcomes and coping-related behaviors and, separately, coping strategies and probable depression (Edinburgh Postnatal Depression Scale > 12) for those with loss. RESULTS: Compared to those with a surviving live birth and adjusting for pre-pregnancy drinking and smoking, history of stillbirth, and age, individuals who experienced a loss were more likely to report increased drinking or smoking in the two months postpartum (adjusted OR: 2.7, 95% CI = 1.4-5.4). Those who smoked or drank more had greater odds of probable depression at 6 to 36 months postpartum (adjusted OR 6.4, 95% CI = 2.5-16.4). Among those with loss, recommended coping strategies commonly included communication, support groups, memorializing the loss, and spirituality. DISCUSSION: Access to a variety of evidence-based and culturally-appropriate positive coping strategies may help individuals experiencing perinatal loss avoid adverse health consequences.

Preeclampsia at delivery is associated with lower serum vitamin D and higher antiangiogenic factors: a case control study.

BACKGROUND: Preeclampsia is characterized by decreased trophoblastic angiogenesis leading to abnormal invasion of spiral arteries, shallow implantation and resulting in compromised placentation with poor uteroplacental perfusion. Vitamin D plays an important role in pregnancy influencing implantation, angiogenesis and placental development. The objective of this study was to determine whether there is an association between serum vitamin D levels, and anti-angiogenic factors at the time of delivery and the occurrence of preeclampsia. METHODS: This nested case control study analyzed frozen serum samples at the time of delivery and related clinical data from women with singleton liveborn pregnancies who had participated in studies of the NICHD Stillbirth Collaborative Research Network. Women with a recorded finding of preeclampsia and who had received magnesium sulfate treatment prior to delivery were considered index cases (N = 56). Women without a finding of preeclampsia were controls (N = 341). RESULTS: Women with preeclampsia had 14.5% lower serum vitamin D levels than women in the control group (16.5 ng/ml vs. 19 ng/ml, p = 0.014) with 64.5% higher sFlt-1 levels (11,600 pg/ml vs. 7050 pg/ml, p < 0.001) and greater than 2 times higher endoglin levels (18.6 ng/ml vs. 8.7 ng/ml, < 0.001). After controlling for gestational age at delivery and maternal BMI, vitamin D levels were 0.88 times lower (P = 0.051), while endoglin levels were 2.5 times higher and sFlt-1 levels were 2.1 times higher than in control pregnancies (P < 0.001). CONCLUSIONS: Women with preeclampsia at time of delivery have higher maternal antiangiogenetic factors and may have lower maternal serum vitamin D levels. These findings may lead to a better understanding of the underlying etiology of preeclampsia as well as possible modifiable treatment options which could include assuring adequate levels of maternal serum vitamin D prior to pregnancy.

DLK1: A Novel Biomarker of Placental Insufficiency in Stillbirth and Live Birth.

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..

Chronic Stress and Preconception Health Among Latina Women in Metro Atlanta.

BACKGROUND: Underserved subgroups are less likely to have optimal health prior to pregnancy. We describe preconception health indicators (behavior, pregnancy intention, and obesity) among pregnant Latina women with and without chronic stress in metro Atlanta. DESIGN: We surveyed 110 pregnant Latina women enrolled in prenatal care at three clinics in Atlanta. The survey assessed chronic stress, pregnancy intention, preconception behavior changes (taking folic acid or prenatal vitamins, seeking healthcare advice, any reduction in smoking or drinking), and previous trauma. RESULTS: Specific behaviors to improve health prior to pregnancy were uncommon (e.g., taking vitamins (25.5%) or improving nutrition (20.9%)). Just under half of women were experiencing a chronic stressor at the time of conception (49.5%). Chronically stressed women were more likely to be obese (aOR: 3.0 (1.2, 7.4)), less likely to intend their pregnancy (aOR: 0.3 (0.1, 0.7)), and possibly less likely to report any PHB (45.5% vs. 57.4%; aOR: 0.5 (0.2-1.1)). CONCLUSIONS: Chronically stress women were less likely to enter prenatal care with optimal health. However, preconception behaviors were uncommon overall.

Stressful Life Events Among New Mothers in Georgia: Variation by Race, Ethnicity and Nativity.

INTRODUCTION: Prior research has identified psychosocial stress as a risk factor for adverse maternal and infant outcomes for non-Hispanic Black and White women. However, whether psychosocial stress differs in its profile and association with preterm birth across diverse racial-ethnic-nativity groups in the Southeast remains unexamined. Both foreign-born and Hispanic women represent important proportions of new mothers in many Southeastern states. The objective of this paper is to describe the prevalence of categories of prenatal life events among Georgia mothers, the variation across race, ethnicity and nativity, and the association of prenatal stress with prevalence of preterm birth. METHODS: We calculated racial-ethnic-nativity specific prevalence of stress categories (emotional/traumatic, financial, or partner-related) with data from the 2012 to 2015 Georgia PRAMS. Maternal race, ethnicity, and nativity were reported on birth certificates. We used logistic regression to examine the association of different categories of stress with preterm birth. We conducted a bias analysis to estimate the potential impact of recall bias on observed associations. RESULTS: The sample was 20.2% foreign born overall, 15.5% non-Hispanic White, 45.7% non-Hispanic Black, 32.3% Hispanic, and 6.5% non-Hispanic other. The prevalence of specific stressors varied by race-ethnicity-nativity. Women who experienced financial stress had a slightly elevated prevalence of preterm birth (prevalence ratio: 1.32 (0.97-1.79)). DISCUSSION: Prenatal and preconception stress were common among women who gave birth between 2012 and 2015 in Georgia and may have implications for preterm and postpartum maternal mental health.

Associations Between Features of Placental Morphology and Birth Weight in Dichorionic Twins.

Low birth weight is associated with perinatal and long-term morbidity and mortality, and may be a result of abnormal placental development and function. In studies of singletons, associations have been reported between features of placental morphology and birth weight. Evaluating similar associations within twin pairs offers a unique opportunity to control for key confounders shared within a twin pair, including gestational age, parental characteristics, and intrauterine environment. Data from 3 studies in the United States that were completed from 2012 to 2013, 2006 to 2008, and 1959 to 1966 were used in our analysis of 208 sets of dichorionic twins with unfused placentas. We used linear regression to model difference in birth weight within a twin pair as a function of differences in placental characteristics (i.e., thickness, 2-dimensional surface area, intraplacental difference in diameter). After controlling for sex discordance, a 75.3- cm2 difference in placental surface area, which reflects the interquartile range, was associated with a difference in birth weight of 142.1 g (95% confidence interval (CI): 62.9, 221.3). The magnitude of the association also may be larger for same-sex male pairs than same-sex female pairs (males: 265.8 g, 95% CI: 60.8, 470.8; females: 133.0 g, 95% CI: 15.7, 250.3). Strong associations between surface area and birth weight are consistent with reported results for singleton pregnancies.

The association of stillbirth with placental abnormalities in growth-restricted and normally grown fetuses.

BACKGROUND: Stillbirth, defined as foetal death ≥20 weeks' gestation, is associated with poor foetal growth and is often attributed to placental abnormalities, which are also associated with poor foetal growth. Evaluating inter-relationships between placental abnormalities, poor foetal growth, and stillbirth may improve our understanding of the underlying mechanisms for some causes of stillbirth. OBJECTIVE: Our primary objective was to determine whether poor foetal growth, operationalised as small for gestational age (SGA), mediates the relationship between placental abnormalities and stillbirth. METHODS: We used data from the Stillbirth Collaborative Research Network study, a population-based case-control study conducted from 2006-2008. Our analysis included 266 stillbirths and 1135 livebirths. We evaluated associations of stillbirth with five types of placental characteristics (developmental disorders, maternal and foetal inflammatory responses, and maternal and foetal circulatory disorders) and examined mediation of these relationships by SGA. We also assessed exposure-mediator interaction. Models were adjusted for maternal age, race/ethnicity, education, body mass index, parity, and smoking status. RESULTS: All five placental abnormalities were more prevalent in cases than controls. After adjustment for potential confounders, maternal inflammatory response (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.77, 3.75), maternal circulatory disorders OR 4.14, 95% CI 2.93, 5.84, and foetal circulatory disorders OR 4.58, 95% CI 3.11, 6.74 were strongly associated with stillbirth, and the relationships did not appear to be mediated by SGA status. Associations for developmental disorders and foetal inflammatory response diverged for SGA and non-SGA births, and strong associations were only observed when SGA was not present. CONCLUSIONS: Foetal growth did not mediate the relationships between placental abnormalities and stillbirth. The relationships of stillbirth with maternal and foetal circulatory disorders and maternal inflammatory response appear to be independent of poor foetal growth, while developmental disorders and foetal inflammatory response likely interact with foetal growth to affect stillbirth risk.

Associations Between the Features of Gross Placental Morphology and Birthweight.

The placenta plays a critical role in regulating fetal growth. Recent studies suggest that there may be sex-specific differences in placental development. The purpose of our study was to evaluate the associations between birthweight and placental morphology in models adjusted for covariates and to assess sex-specific differences in these associations. We analyzed data from the Stillbirth Collaborative Research Network's population-based case-control study conducted between 2006 and 2008, which recruited cases of stillbirth and population-based controls in 5 states. Our analysis was restricted to singleton live births with a placental examination (n = 1229). Characteristics of placental morphology evaluated include thickness, surface area, difference in diameters, shape, and umbilical cord insertion site. We used linear regression to model birthweight as a function of placental morphology and covariates. Surface area had the greatest association with birthweight; a reduction in surface area of 83 cm2, which reflects the interquartile range, is associated with a 260.2-g reduction in birthweight (95% confidence interval, -299.9 to -220.6), after adjustment for other features of placental morphology and covariates. Reduced placental thickness was also associated with lower birthweight. These associations did not differ between males and females. Our results suggest that reduced placental thickness and surface area are independently associated with lower birthweight and that these relationships are not related to sex.

The association between gestational weight gain z-score and stillbirth: a case-control study.

BACKGROUND: There is limited information on potentially modifiable risk factors for stillbirth, such as gestational weight gain (GWG). Our purpose was to explore the association between GWG and stillbirth using the GWG z-score. METHODS: We analyzed 479 stillbirths and 1601 live births from the Stillbirth Collaborative Research Network case-control study. Women with triplets or monochorionic twins were excluded from analysis. We evaluated the association between GWG z-score (modeled as a restricted cubic spline with knots at the 5th, 50th, and 95th percentiles) and stillbirth using multivariable logistic regression with generalized estimating equations, adjusting for pre - pregnancy body mass index (BMI) and other confounders. In addition, we conducted analyses stratified by pre - pregnancy BMI category (normal weight, overweight, obese). RESULTS: Mean GWG was 18.95 (SD 17.6) lb. among mothers of stillbirths and 30.89 (SD 13.3) lb. among mothers of live births; mean GWG z-score was - 0.39 (SD 1.5) among mothers of cases and - 0.17 (SD 0.9) among control mothers. In adjusted analyses, the odds of stillbirth were elevated for women with very low GWG z-scores (e.g., adjusted odds ratio (aOR) and 95% Confidence Interval (CI) for z-score - 1.5 SD versus 0 SD: 1.52 (1.30, 1.78); aOR (95% CI) for z-score - 2.5 SD versus 0 SD: 2.36 (1.74, 3.20)). Results differed slightly by pre - pregnancy BMI. The odds of stillbirth were slightly elevated among women with overweight BMI and GWG z-scores ≥1 SD (e.g., aOR (95% CI) for z-score of 1.5 SD versus 0 SD: 1.84 (0.97, 3.50)). CONCLUSIONS: GWG z-scores below - 1.5 SD are associated with increased odds of stillbirth.

Associations Between Maternal Exposure to Child Abuse, Preterm Birth, and Very Preterm Birth in Young, Nulliparous Women.

Objectives Preterm birth (PTB) is a leading cause of infant morbidity and mortality. One goal of Healthy People 2020 is to understand the role of preconception lifecourse exposures in relation to pregnancy outcomes, including PTB. The objective of this study was to examine the relationship between maternal exposure to multiple forms of childhood abuse and PTB and very preterm birth (vPTB), utilizing a national, population-based sample. MethodsThis study utilized retrospective self-reported maternal exposure to parent/adult caregiver perpetrated emotional, physical, and sexual abuse; non-parental/adult caregiver perpetrated sexual abuse; and history of PTB and vPTB in the National Longitudinal Study of Adolescent to Adult Health. The cross-sectional analytic study population consisted of first deliveries to 4181 nulliparous women (mean age at time of delivery = 21.7 years). Results With one exception, we did not observe associations between experiences of child abuse and the likelihood of PTB or vPTB. Only sexual abuse, accompanied by physical force and perpetrated by a non-parent/adult caregiver, was associated with an increased odds of vPTB (aOR = 1.94 (95% CI 1.10, 3.44)), particularly in women for whom abuse began after age 9 (aOR = 2.32 (95% CI 1.25, 4.28)).Conclusions for Practice The relationship between maternal exposure to child abuse and PTB may be limited to specific abuse and PTB subtypes, namely non-parent/caregiver perpetrated sexual abuse by force and vPTB. Future studies should also examine possible effect modifiers, such as maternal age and resilience, which may have the potential to inform interventions that can mitigate effects of maternal early life adversity.

Screening for Pregnancy Status in a Population-Based Sample: Characteristics Associated with Item Nonresponse.

OBJECTIVES: Population-based recruitment of a cohort of women who are currently pregnant or who may become pregnant in a given timeframe presents challenges unique to identifying pregnancy status or the likelihood of future pregnancy. Little is known about the performance of individual eligibility items on pregnancy screeners although they are critical to participant recruitment. This paper examined the patterns and respondent characteristics of key pregnancy screener items used in a large national study. METHODS: Cross-sectional analyses were conducted. Descriptive statistics and multivariable logistic regression models were used to examine nonresponse patterns to three questions (currently pregnant, trying to get pregnant and able to get pregnant). The questions were asked of 50,529 women in 17 locations across the US, as part of eligibility screening for the National Children's Study Vanguard Study household-based recruitment. RESULTS: Most respondents were willing to provide information about current pregnancy, trying, and able to get pregnant: 99.3% of respondents answered all three questions and 97.4% provided meaningful answers. Nonresponse ranged from 0.3 to 2.5% for individual items. Multivariable logistic regression results identified small but statistically significant differences in nonresponse by respondent age, marital status, race/ethnicity-language, and household-based recruitment group. CONCLUSIONS FOR PRACTICE: The high levels of response to pregnancy-related items are impressive considering that the eligibility questions were fairly sensitive, were administered at households, and were not part of a respondent-initiated encounter.

Complement Activation During Early Pregnancy and Clinical Predictors of Preterm Birth in African American Women.

Complement activation is essential for select physiologic processes during pregnancy; however, excess activation has been associated with an increased risk for preterm birth (PTB). African American (AA) women experience disproportionately higher rates of inflammation-associated PTB than other groups of women; thus, the purpose of this study was to explore the relationship between complement activation and perinatal outcomes among AA women. A plasma sample was collected between 8 and 14 weeks' gestation from a cohort of healthy AA women (N = 144) enrolled in a larger PTB cohort study. Medical record review was conducted to collect information on clinical factors (cervical length, health behaviors, gestational age at delivery). Multiple regression analysis was used to explore the relationships between complement marker (C3a/Bb) concentrations and the outcomes of interest after adjusting for baseline characteristics. C3a/Bb concentrations were not significant predictors of the gestational age at delivery, cervical length, or behavioral risk factors for PTB in this sample. Complement markers may not influence pregnancy outcomes among AA women in the same way as in predominantly white populations; however, more studies are needed to define complement dysregulation and the relationship with outcomes among AA women.

Association of participation in a supplemental nutrition program with stillbirth by race, ethnicity, and maternal characteristics.

BACKGROUND: Participation in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) has been associated with lower risk of stillbirth. We hypothesized that such an association would differ by race/ethnicity because of factors associated with WIC participation that confound the association. METHODS: We conducted a secondary analysis of the Stillbirth Collaborative Research Network's population-based case-control study of stillbirths and live-born controls, enrolled at delivery between March 2006 and September 2008. Weighting accounted for study design and differential consent. Five nested models using multivariable logistic regression examined whether the WIC participation/stillbirth associations were attenuated after sequential adjustment for sociodemographic, health, healthcare, socioeconomic, and behavioral factors. Models also included an interaction term for race/ethnicity x WIC. RESULTS: In the final model, WIC participation was associated with lower adjusted odds (aOR) of stillbirth among non-Hispanic Black women (aOR: 0.34; 95% CI 0.16, 0.72) but not among non-Hispanic White (aOR: 1.69; 95% CI: 0.89, 3.20) or Hispanic women (aOR: 0.91; 95% CI 0.52, 1.52). CONCLUSIONS: Contrary to our hypotheses, control for potential confounding factors did not explain disparate findings by race/ethnicity. Rather, WIC may be most beneficial to women with the greatest risk factors for stillbirth. WIC-eligible, higher-risk women who do not participate may be missing the potential health associated benefits afforded by WIC.

Identifying bottlenecks in the iron and folic acid supply chain in Bihar, India: a mixed-methods study.

BACKGROUND: Maternal anaemia prevalence in Bihar, India remains high despite government mandated iron supplementation targeting pregnant women. Inadequate supply has been identified as a potential barrier to iron and folic acid (IFA) receipt. Our study objective was to examine the government health system's IFA supply and distribution system and identify bottlenecks contributing to insufficient IFA supply. METHODS: Primary data collection was conducted in November 2011 and July 2012 across 8 districts in Bihar, India. A cross-sectional, observational, mixed methods approach was utilized. Auxiliary Nurse Midwives were surveyed on current IFA supply and practices. In-depth interviews (n = 59) were conducted with health workers at state, district, block, health sub-centre, and village levels. RESULTS: Overall, 44% of Auxiliary Nurse Midwives were out of IFA stock. Stock levels and supply chain practices varied greatly across districts. Qualitative data revealed specific bottlenecks impacting IFA forecasting, procurement, storage, disposal, lack of personnel, and few training opportunities for key players in the supply chain. CONCLUSIONS: Inadequate IFA supply is a major constraint to the IFA supplementation program, the extent of which varies widely across districts. Improvements at all levels of infrastructure, practices, and effective monitoring will be critical to strengthen the IFA supply chain in Bihar.

The Development of the Healthy Pregnancy Stress Scale, and Validation in a Sample of Low-Income African American Women.

Objectives The association of stress with pregnancy health is well-known. However, few studies take a mixed methods approach to understand the stressors contributing to a woman's pregnancy-related stress. Among African American women, exposure to stressors during pregnancy likely contributes to disparities in pregnancy health outcomes. This work aimed to understand the types and magnitude of stressors African American women are exposed to during pregnancy. Methods Using a mixed methods research design, we developed and administered the Healthy Pregnancy Stress Scale to measure stressors within the stress environment of African American women living in poverty. Results Exploratory factor analysis with one random split-half sample (N = 85) identified a two-factor model. Factor 1, defined as general pregnancy stressors, had significant loadings for ten items that ranged in magnitude from 0.319 to 0.724. Factor 2, defined as relationship strain, had significant loadings for three items ranging in magnitude from 0.613 to 0.856. Confirmatory factor analysis in the second random split-half sample (N = 88) showed a strong fit for the two factor model with factor loadings similar in magnitude. Standard fit statistics and those that adjust for item non-normality suggested an adequate fit to the data (RMSEA = 0.057, CFI = 0.947, TLI = 0.932; Satorra-Bentler RMSEA = 0.037, CFI = 0.972, TLI = 0.965). Conclusions for Practice Our measurement tool may provide a way to determine differences in pregnancy stress experiences across diverse populations of women. Future research should include a test for construct validity by correlating the scale with other measures that should have a specific directional relationship in diverse populations.

Smith-Lemli-Opitz Mutations in Unexplained Stillbirths.

OBJECTIVE: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive syndrome caused by a defect in cholesterol biosynthesis with mutations in 7-dehydrocholesterol reductase (DHCR7). A total of 3% of Caucasians carry DHCR7 mutations, theoretically resulting in a homozygote frequency of 1/4000. However, SLOS occurs in only 1/20,000 to 60,000 live births. Our objective was to assess DHCR7 mutations in unexplained stillbirths. STUDY DESIGN: Prospective, multicenter, population-based case-control study of all stillbirths and a representative sample of live births enrolled in five geographic areas. Cases with stillbirth due to obstetric complications, infection, or aneuploidy, and those with poor quality deoxyribonucleic acid (DNA) were excluded. DNA was extracted from placental tissue stored at -80°C, and exons 3 to 9 of the DCHR7 gene were amplified, purified, and subjected to bidirectional sequencing to identify mutations. RESULTS: One-hundred forty four stillbirths were unexplained and had adequate DNA for analysis. Nine stillbirths of 139 (6.5%) had a single mutation in one allele in coding exons 3 to 9 of DHCR7 (Table 1). One case (0.7%) was a compound heterozygote for mutations in exons 3 to 9 of DHCR7; this fetus had no clinical or histologic features of SLOS. CONCLUSION: We detected SLOS mutations in only 0.7% of stillbirths. This does not support a strong association between unrecognized DHCR7 mutations and stillbirth.

Stillbirth, Inflammatory Markers, and Obesity: Results from the Stillbirth Collaborative Research Network.

BACKGROUND: Obesity is associated with increased risk of stillbirth, although the mechanisms are unknown. Obesity is also associated with inflammation. Serum ferritin, C-reactive protein, white blood cell count, and histologic chorioamnionitis are all markers of inflammation. OBJECTIVE: This article determines if inflammatory markers are associated with stillbirth and body mass index (BMI). Additionally, we determined whether inflammatory markers help to explain the known relationship between obesity and stillbirth. STUDY DESIGN: White blood cell count was assessed at admission to labor and delivery, maternal serum for assessment of various biomarkers was collected after study enrollment, and histologic chorioamnionitis was based on placental histology. These markers were compared for stillbirths and live births overall and within categories of BMI using analysis of variance on logarithmic-transformed markers and logistic regression for dichotomous variables. The impact of inflammatory markers on the association of BMI categories with stillbirth status was assessed using crude and adjusted odds ratios (COR and AOR, respectively) from logistic regression models. The interaction of inflammatory markers and BMI categories on stillbirth status was also assessed through logistic regression. Additional logistic regression models were used to determine if the association of maternal serum ferritin with stillbirth is different for preterm versus term births. Analyses were weighted for the overall population from which this sample was derived. RESULTS: A total of 497 women with singleton stillbirths and 1,414 women with live births were studied with prepregnancy BMI (kg/m2) categorized as normal (18.5-24.9), overweight (25.0-29.9), or obese (30.0 + ). Overweight (COR, 1.48; 95% confidence interval [CI]: 1.14-1.94) and obese women (COR, 1.60; 95% CI: 1.23-2.08) were more likely than normal weight women to experience stillbirth. Serum ferritin levels were higher (geometric mean: 37.4 ng/mL vs. 23.3, p < 0.0001) and C-reactive protein levels lower (geometric mean: 2.9 mg/dL vs. 3.3, p = 0.0279), among women with stillbirth compared with live birth. Elevated white blood cell count (15.0 uL × 103 or greater) was associated with stillbirth (21.2% SB vs. 10.0% live birth, p < 0.0001). Histologic chorioamnionitis was more common (33.2% vs. 15.7%, p < 0.0001) among women with stillbirth compared with those with live birth. Serum ferritin, C-reactive protein, and chorioamnionitis had little impact on the ORs associating stillbirth with overweight or obesity. Adjustment for elevated white blood cell count did not meaningfully change the OR for stillbirth in overweight versus normal weight women. However, the stillbirth OR for obese versus normal BMI changed by more than 10% when adjusting for histologic chorioamnionitis (AOR, 1.38; 95% CI: 1.02-1.88), indicating confounding. BMI by inflammatory marker interaction terms were not significant. The association of serum ferritin levels with stillbirth was stronger among preterm births (p = 0.0066). CONCLUSION: Maternal serum ferritin levels, elevated white blood cell count, and histologic chorioamnionitis were positively and C-reactive protein levels negatively associated with stillbirth. Elevated BMIs, both overweight and obese, were associated with stillbirth when compared with women with normal BMI. None of the inflammatory markers fully accounted for the relationship between obesity and stillbirth. The association of maternal serum ferritin with stillbirth was stronger in preterm than term stillbirths.

Maternal marijuana use, adverse pregnancy outcomes, and neonatal morbidity.

BACKGROUND: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Stillbirth Collaborative Research Network previously demonstrated an association between stillbirth and maternal marijuana use as defined by the presence of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in the umbilical cord homogenate. However, the relationship between marijuana use and perinatal complications in live births is uncertain. OBJECTIVE: Our aim was to examine if maternal marijuana use is associated with increased odds of adverse pregnancy outcomes and neonatal morbidity among live-born controls in the Stillbirth Collaborative Research Network cohort. STUDY DESIGN: We conducted a secondary analysis of singleton, live-born controls in the Stillbirth Collaborative Research Network data set. Marijuana use was measured by self-report and/or the presence of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in umbilical cord homogenate. Tobacco use was measured by self-report and/or presence of any cotinine in maternal serum. Adverse pregnancy outcome was a composite of small for gestational age, spontaneous preterm birth resulting from preterm labor with or without intact membranes, and hypertensive disorders of pregnancy. Neonatal morbidity included neonatal intensive care unit admission and composite neonatal morbidity (pulmonary morbidity, necrotizing enterocolitis, seizures, retinopathy of prematurity, infection morbidity, anemia requiring blood transfusion, neonatal surgery, hyperbilirubinemia, neurological morbidity, or death prior to hospital discharge). Effect of maternal marijuana use on the probability of an adverse outcome was estimated using weighted methodology to account for oversampling in the original study. 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid cord homogenate analysis was performed in the subset of women for whom biospecimens were available. Comparisons using logistic modeling, χ2, and t tests were weighted to account for oversampling of preterm births and non-Hispanic blacks. Results are reported as weighted percent and unweighted frequencies. RESULTS: Maternal marijuana use was identified in 2.7% (unweighted frequency 48/1610) of live births. Use was self-reported by 1.6% (34/1610) and detected by 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in cord homogenate for 1.9% (17/897), n = 3 overlapping. Rate of tobacco use was 12.9% (217/1610), with 10.7% (167/1607) by self-report and 9.5% (141/1313) by serum cotinine. The composite adverse pregnancy outcome was not significantly increased in women with marijuana use compared to nonusers (31.2% vs 21.2%; P = .14). After adjustment for tobacco, clinical, and socioeconomic factors, marijuana use was not associated with the composite adverse pregnancy outcome (adjusted odds ratio, 1.29; 95% confidence interval, 0.56-2.96). Similarly, among women with umbilical cord homogenate and serum cotinine data (n = 765), marijuana use was not associated with adverse pregnancy outcomes (adjusted odds ratio, 1.02; 95% confidence interval, 0.18-5.66). Neonatal intensive care unit admission rates were not statistically different between groups (16.9% users vs 9.5% nonusers, P = .12). Composite neonatal morbidity or death was more frequent among neonates of mothers with marijuana use compared to nonusers (14.1% vs 4.5%; P = .002). In univariate comparisons, the components of the composite outcome that were more frequent in neonates of marijuana users were infection morbidity (9.8% vs 2.4%; P < .001) and neurologic morbidity (1.4% vs 0.3%; P = .002). After adjustment for tobacco, race, and other illicit drug use, marijuana use was still associated with composite neonatal morbidity or death (adjusted odds ratio, 3.11; 95% confidence interval, 1.40-6.91). CONCLUSION: Maternal marijuana use was not associated with a composite of small for gestational age, spontaneous preterm birth, or hypertensive disorders of pregnancy. However, it was associated with an increased risk of neonatal morbidity.

Correction to: Protocol for the Emory University African American Vaginal, oral, and gut microbiome in pregnancy cohort study.

Following publication of the original article [1], the authors pointed out that the Methods included one step that is no longer necessary but which was inadvertently carried over from an earlier protocol.