The timing, duration, and severity of nausea and vomiting of pregnancy and adverse birth outcomes among controls without birth defects in the National Birth Defects Prevention Study.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) occurs in approximately 70% of pregnant people, with varying severity and duration. Treatments include pharmacologic and herbal/natural medications. The associations between NVP and birth outcomes, including preterm birth, small for gestational age (SGA), and low birth weight are inconclusive. OBJECTIVE: To determine whether NVP and reported medications are associated with adverse birth outcomes. METHODS: We used data from the population-based, multisite National Birth Defects Prevention Study (1997-2011) to evaluate whether self-reported NVP according to timing, duration, and severity or its specific treatments were associated with preterm birth, SGA, and low birth weight among controls without birth defects. Odds ratios (aOR) and 95% confidence intervals (CI) were adjusted for sociodemographic, reproductive, and medical factors. For any NVP, duration, treatment use, and severity score analyses, the comparison group was participants with no reported NVP. For timing analyses, the comparison group was women with no reported NVP in the same trimester of pregnancy. RESULTS: Among 6018 participants, 4339 (72.1%) reported any NVP. Among those with NVP, moderate or severe symptoms were more common than mild symptoms. Any versus no NVP was not associated with any of the outcomes of interest. NVP in months 4-6 (aOR 1.21, 95% CI: 1.00, 1.47) and 7-9 (aOR 1.57, 95% CI: 1.22, 2.01) of pregnancy were associated with an increase in the risk of preterm birth. NVP lasting one trimester in duration was associated with decrease in risk of SGA (aOR: 0.74, 95% CI: 0.58, 0.95), and NVP present in every trimester of pregnancy had a 50% increase in risk of preterm birth (aOR: 1.50, 95% CI: 1.11, 2.05). For NVP in months 7-9 and preterm birth, ORs were elevated for moderate (aOR: 1.82, 95% CI: 1.26, 2.63), and severe (aOR: 1.53, 95% CI: 1.06, 2.19) symptoms. NVP was not significantly associated with low birth weight. Our analyses of medications were limited by small numbers, but none suggested increased risk of adverse outcomes associated with use of the medication. CONCLUSION: Mild NVP and NVP limited to early pregnancy appear to have no effect or a small protective effect on birth outcomes. Long-lasting NVP, severe NVP, and NVP later in pregnancy may increase risk of preterm birth and SGA.

Trimester and severity of SARS-CoV-2 infection during pregnancy and risk of hypertensive disorders in pregnancy.

OBJECTIVE: SARS-CoV-2 infection during pregnancy has been linked with an increased risk of hypertensive disorders of pregnancy (HDP). The aim of this study was to examine how both trimester and severity of SARS-CoV-2 infection impact HDP. METHODS: We conducted a cohort study of SARS-CoV-2-infected individuals during pregnancy (n = 205) and examined the association between trimester and severity of infection with incidence of HDP using modified Poisson regression models to calculate risk ratios (RR) and 95% confidence intervals (CI). We stratified the analysis of trimester by severity to understand the role of timing of infection among those with similar symptomatology and also examined timing of infection as a continuous variable. RESULTS: Compared to a reference cohort from 2018, SARS-CoV-2 infection did not largely increase the risk of HDP (RR: 1.17; CI:0.90, 1.51), but a non-statistically significant higher risk of preeclampsia was observed (RR: 1.33; CI:0.89, 1.98), in our small sample. Among the SARS-CoV-2 cohort, severity was linked with risk of HDP, with infections requiring hospitalization increasing the risk of HDP compared to asymptomatic/mild infections. Trimester of infection was not associated with risk of HDP, but a slight decline in the risk of HDP was observed with later gestational week of infection. Among patients with asymptomatic or mild symptoms, SARS-CoV-2 in the first trimester conferred a higher risk of HDP compared to the third trimester (RR: 1.70; CI:0.77, 3.77), although estimates were imprecise. CONCLUSION: SARS-CoV-2 infection in early pregnancy may increase the risk of HDP compared to infection later in pregnancy.

Bias analyses to investigate the impact of differential participation: Application to a birth defects case-control study.

BACKGROUND: Certain associations observed in the National Birth Defects Prevention Study (NBDPS) contrasted with other research or were from areas with mixed findings, including no decrease in odds of spina bifida with periconceptional folic acid supplementation, moderately increased cleft palate odds with ondansetron use and reduced hypospadias odds with maternal smoking. OBJECTIVES: To investigate the plausibility and extent of differential participation to produce effect estimates observed in NBDPS. METHODS: We searched the literature for factors related to these exposures and participation and conducted deterministic quantitative bias analyses. We estimated case-control participation and expected exposure prevalence based on internal and external reports, respectively. For the folic acid-spina bifida and ondansetron-cleft palate analyses, we hypothesized the true odds ratio (OR) based on prior studies and quantified the degree of exposure over- (or under-) representation to produce the crude OR (cOR) in NBDPS. For the smoking-hypospadias analysis, we estimated the extent of selection bias needed to nullify the association as well as the maximum potential harmful OR. RESULTS: Under our assumptions (participation, exposure prevalence, true OR), there was overrepresentation of folic acid use and underrepresentation of ondansetron use and smoking among participants. Folic acid-exposed spina bifida cases would need to have been ≥1.2× more likely to participate than exposed controls to yield the observed null cOR. Ondansetron-exposed cleft palate cases would need to have been 1.6× more likely to participate than exposed controls if the true OR is null. Smoking-exposed hypospadias cases would need to have been ≥1.2 times less likely to participate than exposed controls for the association to falsely appear protective (upper bound of selection bias adjusted smoking-hypospadias OR = 2.02). CONCLUSIONS: Differential participation could partly explain certain associations observed in NBDPS, but questions remain about why. Potential impacts of other systematic errors (e.g. exposure misclassification) could be informed by additional research.

Periconceptional intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further reduce the risk of neural tube defects in offspring: a United States population-based case-control study of women meeting the folic acid recommendations.

BACKGROUND: Neural tube defects (NTDs) still occur among some women who consume 400 µg of folic acid for prevention. It has been hypothesized that intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further protect against NTDs. OBJECTIVES: To investigate whether intakes of vitamin B6, vitamin B12, choline, betaine, methionine, thiamine, riboflavin, and zinc, individually or in combination, were associated with NTD risk reduction in offspring of women meeting the folic acid recommendations. METHODS: Data were from the National Birth Defects Prevention Study (United States population-based, case-control). We restricted deliveries between 1999 and 2011 with daily periconceptional folic acid supplementation or estimated dietary folate equivalents ≥400 µg. NTD cases were live births, stillbirths, or terminations affected by spina bifida, anencephaly, or encephalocele (n = 1227). Controls were live births without a major birth defect (n = 7095). We categorized intake of each micronutrient as higher or lower based on a combination of diet (estimated from a food frequency questionnaire) and periconceptional vitamin supplementation. We estimated NTD associations for higher compared with lower intake of each micronutrient, individually and in combination, expressed as odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, race/ethnicity, education, and study center. RESULTS: NTD associations with each micronutrient were weak to modest. Greater NTD reductions were observed with concurrent higher-amount intakes of multiple micronutrients. For instance, NTD odds were ∼50% lower among participants with ≥4 micronutrients with higher-amount intakes than among participants with ≤1 micronutrient with higher-amount intake (adjusted OR: 0.53; 95% CI: 0.33, 0.86). The strongest reduction occurred with concurrent higher-amount intakes of vitamin B6, vitamin B12, choline, betaine, and methionine (adjusted OR: 0.26; 95% CI: 0.09, 0.77) compared with ≤1 micronutrient with higher-amount intake. CONCLUSIONS: Our findings support that NTD prevention, in the context of folic acid fortification, could be augmented with intakes of methyl donors and other micronutrients involved in folate metabolism.

Prenatal exposure to acetaminophen and adolescent assessment of behavior: Discrepancies by age and reporter.

Acetaminophen, which is one of the most commonly used medications during pregnancy, has been linked to adverse neurodevelopmental outcomes among offspring during childhood. Less is known about associations with outcomes occurring later in adolescence. Methods: We conducted a follow-up study of children born between 1996 and 2002. Data on illnesses and medications, including acetaminophen, during pregnancy were collected through a standardized interview after delivery. Behavioral assessments were conducted at two subsequent time points, childhood (ages 5-10) and adolescence (ages 11-17). Outcomes examined included internalizing, externalizing, and total behavior problems based on the parent-completed Child Behavior Checklist (CBCL), the teacher-completed Teacher Report Form (TRF), and the youth-completed Youth Self Report (YSR, adolescent follow-up only). Adjusted linear regression models were used to calculate mean differences (MD) and 95% confidence intervals (95% CI) in T-scores comparing those with prenatal acetaminophen exposure to those without. Stabilized inverse probability weights were used to account for attrition. Results: Among the 216 mother-child dyads with completed parent and teacher behavioral assessments at both childhood and adolescence, prenatal acetaminophen exposure was not associated with behavioral problems according to either parent or teacher assessments. Modest increases in externalizing and total behavior problems were observed according to youth report (MD: 1.9). Compared to associations observed during the childhood follow-up, associations at adolescence were attenuated according to parent-report. Conclusion: Reported associations between prenatal acetaminophen exposure and behavioral outcomes were not consistent over time nor between reporters.

Weight gain patterns among pregnancies with obesity and small- and large-for-gestational-age births.

OBJECTIVE: This case-cohort study estimated associations between gestational weight gain (GWG) and small-for-gestational-age (SGA) and large-for-gestational-age (LGA) births stratified by obesity class (I: 30-34.9 kg/m2 ; II: 35-39.9 kg/m2 ; III: ≥40 kg/m2 ) (Magee-Womens Hospital, Pittsburgh, Pennsylvania, 1998-2011). METHODS: First-trimester GWG was categorized as being below (<0.2 kg), within (0.2-2.0 kg), or above (>2.0 kg) the Institute of Medicine recommendations. For second- and third-trimester GWG, four linear trajectories were derived: approximating maintenance (slope -0.05 ± 0.03 kg/wk), approximating the recommendations (0.27 ± 0.01 kg/wk; reference), higher than the recommendations (0.54 ± 0.01 kg/wk), and highest among those above the recommendations (0.91 ± 0.02 kg/wk). RESULTS: For classes I, II, and III, respectively, there were 1290, 1247, and 1198 pregnancies in the subcohort; 262, 171, and 123 SGA cases; and 353, 286, and 257 LGA cases. First-trimester GWG was not associated with SGA/LGA births. Second- and third-trimester weight maintenance was associated with potentially lower LGA risk (risk ratio [RR]: 0.80; 95% confidence interval [CI]: 0.55-1.1) but not higher SGA risk (RR: 0.98; 95% CI: 0.64-1.5) for class III. In addition, some sensitivity analyses supported no increased SGA risk with second- and third-trimester weight maintenance for classes I and II. CONCLUSIONS: Second- and third-trimester weight maintenance may be associated with more optimal birth weight for gestational age. However, how this could be achieved (e.g., through diet and exercise interventions) is unclear, given the observational design of our study.

Maternal, Infant, and Breast Milk Antibody Response Following COVID-19 Infection in Early Versus Late Gestation.

BACKGROUND: Coronavirus disease 2019 [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] infection at varying time points during the pregnancy can influence antibody levels after delivery. We aimed to examine SARS-CoV-2 IgG, IgM and IgA receptor binding domain of the spike protein and nucleocapsid protein (N-protein) reactive antibody concentrations in maternal blood, infant blood and breastmilk at birth and 6 weeks after SARS-CoV-2 infection in early versus late gestation. METHODS: Mothers with SARS-CoV-2 infection during pregnancy were enrolled between July 2020 and May 2021. Maternal blood, infant blood and breast milk samples were collected at delivery and 6 weeks postpartum. Samples were analyzed for SARS-CoV-2 spike and N-protein reactive IgG, IgM and IgA antibodies. Antibody concentrations were compared at the 2 time points and based on trimester of infection ("early" 1st/2nd vs. "late" 3rd). RESULTS: Dyads from 20 early and 11 late trimester infections were analyzed. For the entire cohort, there were no significant differences in antibody levels at delivery versus 6 weeks with the exception of breast milk levels which declined over time. Early gestation infections were associated with higher levels of breastmilk IgA to spike protein ( P = 0.04). Infant IgG levels to spike protein were higher at 6 weeks after late infections ( P = 0.04). There were strong correlations between maternal and infant IgG levels at delivery ( P < 0.01), and between breastmilk and infant IgG levels. CONCLUSIONS: SARS-CoV-2 infection in early versus late gestation leads to a persistent antibody response in maternal blood, infant blood and breast milk over the first 6 weeks after delivery.

Prepregnancy Cardiovascular Disease Risk Factors and Adverse Pregnancy Outcomes in a Safety-Net Hospital.

Background: Many adverse pregnancy outcomes (APOs) are associated with elevated cardiovascular disease (CVD) risk. However, APO data in the context of pre-existing CVD risk factors, and from diverse populations, are limited. We assessed the occurrence of APOs among individuals with and without prepregnancy CVD risk factors, overall and by race/ethnicity. Methods: We conducted a retrospective study using electronic medical record data from a large urban safety-net hospital. Individuals with prenatal care and delivery between 2016 and 2018 at the hospital were included, and data from prenatal intake through the delivery hospitalization were captured. The exposure, prepregnancy CVD risk factors (hypertension, diabetes, tobacco use, and obesity), and the outcome, APOs (hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, low birth weight, and stillbirth), were identified from electronic medical records. Results: We identified 3760 unique delivering individuals, of whom 55.1% self-identified as Black non-Hispanic and 17% as Hispanic. Prepregnancy CVD risk factor prevalence was 45.6%, most commonly obesity (26.6%). APO prevalence was 35.6%, most commonly a hypertensive disorder of pregnancy (20.1%). Overall, 45.7% of APOs occurred in the absence of recognized prepregnancy CVD risk factors, representing 16.3% of the total sample. Among individuals without prepregnancy CVD risk factors, APO prevalence was 30.0% and did not vary by race/ethnicity. Conclusions: In this racially and ethnically diverse hospital-based sample, APOs were present in one in three parous individuals without prepregnancy CVD risk factors-a group with potentially elevated CVD risk who might otherwise be missed by traditional CVD risk factor screening.

Cytokine levels in maternal and infant blood after COVID-19 vaccination during pregnancy in comparison with unvaccinated controls.

The objective of this study was to compare maternal and infant cytokine profiles at delivery among those vaccinated against SARS-CoV-2 during pregnancy to unvaccinated controls. Mother-infant dyads were enrolled in this prospective cohort study, and maternal blood and infant and/or cord blood collected. Samples were analyzed utilizing a LEGENDplex 13-plex human anti-viral response cytokine panel. Maternal IP-10 and IFN-λ2/3 were lower in the vaccinated cohort. In the infants, levels were lower for IL-1ß, IFN-λ2/3, and GM-CSF, and higher for IFN-λ1 in the vaccinated cohort. Vaccination against SARS-CoV-2 during pregnancy did not lead to elevations in cytokines in mothers or infants.

De Novo Postpartum Hypertension: Incidence and Risk Factors at a Safety-Net Hospital.

BACKGROUND: Postpartum hypertension can be persistent, following a pregnancy complicated by hypertension, or new onset (de novo), following a normotensive pregnancy. The aim of this study is to estimate the incidence and identify risk factors for de novo postpartum hypertension (dn-PPHTN) among a diverse safety-net hospital population. METHODS: We conducted a retrospective cohort study of 3925 deliveries from 2016 to 2018. All blood pressure (BP) measures during pregnancy through 12 months postpartum were extracted from medical records. Patients with chronic hypertension or hypertensive disorders of pregnancy were excluded. dn-PPHTN was defined as 2 separate BP readings with systolic BP ≥140 mm Hg and diastolic BP ≥90 mm Hg at least 48 hours after delivery. Severe dn-PPHTN was defined as systolic BP ≥160 and diastolic BP ≥110. We examined risk factors individually and in combination and timing of diagnosis. RESULTS: Among the 2465 patients without a history of hypertension, 12.1% (n=298) developed dn-PPHTN; 17.1% of whom had severe dn-PPHTN (n=51). Compared to those without dn-PPHTN; cases were more likely to be ≥35 years, delivered via cesarean, or be current or former smokers. Patients with all of these characteristics had a 29% risk of developing dn-PPHTN, which was elevated among non-Hispanic Black patients (36%). Approximately 22% of cases were diagnosed after 6 weeks postpartum. CONCLUSIONS: More than 1 in 10 patients with normotensive pregnancies experience dn-PPHTN in the year after delivery. Opportunities to monitor and manage patients at the highest risk of dn-PPHTN throughout the entire year postpartum could mitigate cardiovascular related maternal morbidity.

Machine learning-based placental clusters and their associations with adverse pregnancy outcomes.

BACKGROUND: Placental abnormalities have been described in clinical convenience samples, with predominately adverse outcomes. Few studies have described placental patterns in unselected samples. OBJECTIVE: We aimed to investigate associations between co-occurring placental features and adverse pregnancy outcomes in a prospective cohort of singletons. METHODS: Data were from the Safe Passage study (U.S. and South Africa, 2007-2015). Before 24 weeks' gestation, participants were randomly invited to donate placental tissue at delivery for blinded, standardised pathological examination. We used hierarchical clustering to construct statistically derived groups using 60 placental features. We estimated associations between the placental clusters and select adverse pregnancy outcomes, expressed as unadjusted and adjusted risk ratios (RRs) and robust 95% confidence intervals (CI). RESULTS: We selected a 7-cluster model. After collapsing 2 clusters to form the reference group, we labelled the resulting 6 analytic clusters according to the overarching category of their most predominant feature(s): severe maternal vascular malperfusion (n = 117), fetal vascular malperfusion (n = 222), other vascular malperfusion (n = 516), inflammation 1 (n = 269), inflammation 2 (n = 175), and normal (n = 706). Risks for all outcomes were elevated in the severe maternal vascular malperfusion cluster. For instance, in unadjusted analyses, this cluster had 12 times the risk of stillbirth (RR 12.07, 95% CI 4.20, 34.68) and an almost doubling in the risk of preterm delivery (RR 1.93, 95% CI 1.27, 2.93) compared with the normal cluster. Small infant size was more common among the abnormal clusters, with the highest unadjusted RRs observed in the fetal vascular malperfusion cluster (small for gestational age birth RR 2.99, 95% CI 2.24, 3.98, head circumference <10th percentile RR 2.86, 95% CI 1.60, 5.12). Upon adjustment for known risk factors, most RRs attenuated but remained >1. CONCLUSION: Our study adds to the growing body of epidemiologic research, finding adverse pregnancy outcomes may occur through etiologic mechanisms involving co-occurring placental abnormalities.

The association of nausea and vomiting of pregnancy, its treatments, and select birth defects: Findings from the National Birth Defect Prevention Study.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) occurs in approximately 70% of pregnant people. Treatments include pharmacologic and herbal/natural products. Research on the associations between NVP and its treatments and birth defects is limited. METHODS: We used data from the case-control National Birth Defects Prevention Study (1997-2011) to examine whether first-trimester NVP or its specific treatments were associated with 37 major birth defects. Odds ratios (aOR) and 95% confidence intervals (CIs) were adjusted for sociodemographic and reproductive factors. RESULTS: Mothers of 66.6% of 28,628 cases and 69.9% of 11,083 controls reported first-trimester NVP. Compared to no NVP, mothers with NVP had ≥10% reduction in risk of cardiac and noncardiac defects overall, and of 18 specific defects. Over-the-counter antiemetic use, compared to untreated NVP, was associated with ≥10% increase in risk for nine defect groups (heterotaxy, hypoplastic left heart syndrome [HLHS], aortic stenosis, cataracts, anophthalmos/microphthalmos, biliary atresia, transverse limb deficiency, omphalocele, and gastroschisis), whereas use of prescription antiemetics increased risk ≥10% for seven defect groups (tetralogy of Fallot, HLHS, spina bifida, anopthlamos/microphthalmos, cleft palate, craniosynostosis, and diaphragmatic hernia). We observed increased risks for promethazine and tetralogy of Fallot (aOR: 1.49, 95% CI: 1.05-2.10), promethazine and craniosynostosis (1.44, 1.08-1.92), ondansetron and cleft palate (1.66, 1.18-2.31), pyridoxine and heterotaxy (3.91, 1.49-10.27), and pyridoxine and cataracts (2.57, 1.12-5.88). CONCLUSIONS: NVP does not increase risks of birth defects. Our findings that some treatments for NVP increase risk of specific birth defects should be investigated further before clinical recommendations are made.

Medication use during pregnancy among women with congenital physical disabilities.

BACKGROUND: Medication use during pregnancy is common, with up to 90% of pregnant women taking at least one medication. Women with congenital physical disabilities often report co-occurring conditions during pregnancy that may warrant pharmaceutical treatment, however, research is limited. We aim to describe medication use during pregnancy including: pain, psychotropic, and antibacterial medication, among women with and without congenital physical disabilities. METHODS: We used data from the Slone Birth Defects Study (1976-2015), a case-control study that collected information on pre-pregnancy health conditions and exposures among participating mothers. Women with congenital physical disabilities (n = 132) included women with spina bifida, cerebral palsy, muscular dystrophy, limb deficiencies, and other skeletal/connective tissue conditions and were matched by interview year and study site to women without congenital physical disabilities (n = 528). Proportions and difference in proportions for each medication were compared between groups. Simple proportions were also calculated for duration and multiple medication use variables. RESULTS: Women with congenital physical disabilities more frequently reported use of pain (acetaminophen and opioids), psychotropic (antidepressants), and antibacterial medications during pregnancy. Women with congenital physical disabilities used pain and psychotropic medications for longer, frequent durations, and more frequently reported haven taken multiple medications during pregnancy. CONCLUSION: Women with congenital physical disabilities report higher medication use during pregnancy compared to women without physical disabilities. Patterns may be attributable to co-occurring conditions or increased risk of pregnancy complications in this population. Further research is needed to describe the patterns of medication use for clinical decisions regarding treatment of pregnant women with disabilities.

Evaluation of maternal-infant dyad inflammatory cytokines in pregnancies affected by maternal SARS-CoV-2 infection in early and late gestation.

OBJECTIVE: SARS-CoV-2 infection induces significant inflammatory cytokine production in adults, but infant cytokine signatures in pregnancies affected by maternal SARS-CoV-2 are less well characterized. We aimed to evaluate cytokine profiles of mothers and their infants following COVID-19 in pregnancy. STUDY DESIGN: Serum samples at delivery from 31 mother-infant dyads with maternal SARS-CoV-2 infection in pregnancy (COVID) were examined in comparison to 29 control dyads (Control). Samples were evaluated using a 13-plex cytokine assay. RESULTS: In comparison with controls, interleukin (IL)-6 and interferon gamma-induced protein 10 (IP-10) were higher in COVID maternal and infant samples (p < 0.05) and IL-8 uniquely elevated in COVID infant samples (p < 0.05). Significant elevations in IL-6, IP-10, and IL-8 were found among both early (1st/2nd Trimester) and late (3rd Trimester) maternal SARS-CoV-2 infections. CONCLUSIONS: Maternal SARS-CoV-2 infections throughout gestation are associated with increased maternal and infant inflammatory cytokines at birth with potential to impact long-term infant health.

Birth outcomes among women with congenital neuromuscular disabilities.

BACKGROUND: Women with disabilities are at an increased risk for adverse birth outcomes; however, research among women with congenital neuromuscular disabilities (cNMD) is limited. OBJECTIVE: To describe characteristics and compare birth outcomes among women with and without cNMD. METHODS: Data were from the Slone Birth Defects Study (case-control, conducted from 1976 to 2015), which collected information on demographic, reproductive, and lifestyle characteristics. cNMD included spina bifida, cerebral palsy, muscular dystrophy, contractures, or arthrogryposis and were identified by participant report. Those with cNMD were matched to participants without cNMD by interview year and study site. We use modified Poisson regression to estimate relative risks (RR) for low birthweight, macrosomia, preterm birth, and small/large-for-gestational age (SGA/LGA). Given the case-control design and overrepresentation of infants with congenital anomalies, data were weighted to reflect a 3% national prevalence of infants with congenital anomalies. RESULTS: Women with cNMD (n = 125) were more likely to be white, nulliparous, have a cesarean section, have an unplanned pregnancy, report a pre-pregnancy BMI ≥25 kg/m2, smoke during pregnancy, and report genitourinary infections. Women with cNMD had infants with shorter gestational length (mean difference: -7.44 days, 95% CI: -13.94, -0.95) compared to women without cNMD. cNMD was associated with higher risk of preterm birth (RR = 3.98, 95% CI: 1.33, 11.95) and SGA (RR = 2.14, 95% CI: 0.74, 6.15). CONCLUSION: Women with cNMD were more likely to deliver preterm and have an SGA infant. These findings highlight disparities faced by women with cNMD and stress the need to provide optimal perinatal and reproductive care.

Interpregnancy interval and prevalence of selected birth defects: A multistate study.

BACKGROUND: Both short and long interpregnancy intervals (IPIs) have been associated with adverse birth outcomes. We undertook a multistate study to describe the prevalence of selected birth defects by IPI. METHODS: We obtained data from nine population-based state birth defects registries for singleton live births in 2000-2009 among mothers with a previous live birth identified through birth certificates. IPI was calculated as the difference between prior birthdate and start of the current pregnancy (conception date). We estimated prevalence of selected defects per 10,000 live births and prevalence ratios (PRs) with 95% confidence intervals (CIs) overall and stratified by maternal age at previous birth and race/ethnicity. Primary analyses focused on short IPI < 6 months and long IPI ≥ 60 months compared to 18-23 months (referent). Sensitivity analyses limited to active-surveillance states and those with<10% missing IPI. RESULTS: Among 5,147,962 eligible births, 6.3% had short IPI while 19.8% had long IPI. Compared to referent, prevalence with short IPI was elevated for gastroschisis (3.7, CI: 3.0-4.5 vs. 2.0, CI: 1.6-2.4) and with both short and long IPI for tetralogy of Fallot (short: 3.4, 2.8-4.2 long: 3.8, 3.4-4.3 vs. 2.7, 2.3-3.2) and cleft lip ± palate (short: 9.9, 8.8-11.2 long: 9.2, 8.5-9.8 vs. 8.4, 7.6-9.2). Stratified analyses identified additional associations, including elevated prevalence of anencephaly with short IPI in younger mothers and limb defects with long IPI in those ages 25-34 at prior birth. Sensitivity analyses showed similar results. CONCLUSION: In this population-based study, we observed increased prevalence of several birth defects with short and long IPI.

Inequities in Adverse Maternal and Perinatal Outcomes: The Effect of Maternal Race and Nativity.

OBJECTIVES: To evaluate the effect of race and ethnicity on differences in maternal and perinatal outcomes among U.S.-born and foreign-born women, as well as racial and ethnic disparities in outcomes within these groups. METHODS: This retrospective study analyzed singleton pregnancies (n = 11,518) among women delivering at Boston Medical Center from January 2010-March 2015. Outcomes of interest included preterm birth, early preterm birth, cesarean delivery, hypertensive disorders, diabetes, low birth weight at term (LBW, < 2500 g), NICU admission and intrauterine fetal demise (IUFD). Prevalence ratios and 95% confidence intervals comparing outcomes between U.S.- and foreign-born women were calculated and stratified by race. Obstetric outcomes among Black and Hispanic women were compared to those of white women within both U.S.- and foreign-born groups. RESULTS: Preterm birth, hypertensive disorders, LBW and NICU admission were more likely to occur among U.S.-born women and their neonates compared to foreign-born women. Controlling for sociodemographic characteristics did not significantly impact these disparities. Among foreign-born women, Black women had a higher prevalence of many maternal and neonatal complications, while Hispanic women had a lower prevalence of some complications compared to white women. Black woman and infants consistently exhibit worse outcomes regardless of their nativity, while Hispanic women foreign-born women experience less disparate outcomes. CONCLUSIONS FOR PRACTICE: Overall, women born in the United States are at higher risk of several adverse perinatal outcomes compared to foreign-born women. Racial and ethnic disparities in birth outcomes exist in both groups. However, the complex interplay between biopsychosocial influences that mediate these inequities appear to have different effects among U.S- and foreign- born women. A better understanding of these factors can be used to combat disparities and improve outcomes for all women.

Pre-pregnancy body mass index and parent and teacher-reported behavioral outcomes among offspring in childhood.

OBJECTIVE: Pre-pregnancy obesity has been linked to childhood neurodevelopmental outcomes, including autism and attention-deficit hyperactivity disorder. The aim of our study was to examine the association between pre-pregnancy body mass index (BMI) and scores on behavioral scales according to both mother and teacher report. METHODS: We conducted a longitudinal study of 469 mother-child pairs. Information on pre-pregnancy body mass index (BMI) was collected from standardized maternal interviews conducted after delivery and assessment of childhood behavioral problems was measured at 5-12 years of age according to maternal-report using the Child Behavior Checklist (CBCL) and teacher-report using the Teacher Report Form (TRF). Using normal pre-pregnancy BMI (18.5-24.9 kg/m2) as the reference (n = 305), we calculated adjusted mean differences (MD) for t-scores on broadband and syndrome scales of behavior for children of mothers with pre-pregnancy overweight (n = 101) or obese (n = 63) BMI. We also examined associations with scores in the clinical range using risk ratios (RR) and compared results across informants. To account for loss to follow-up between the initial interview and the childhood behavioral assessment, we weighted models using stabilized inverse probability weights. RESULTS: Pre-pregnancy obesity was associated with a mean increase in child's total behavior problem t-scores according to both mother and teacher report, after adjustment for confounders and weighted for loss to follow-up (MD: 0.7, 95% CI: -2.2, 3.6 on CBCL; MD: 3.1, 95% CI: 0.5, 5.7 on TRF), indicating poorer behavioral outcomes. Comparing the magnitude of associations between mother and teacher-report, mean differences for pre-pregnancy obesity and most behavioral problem scales were larger for teacher-reported outcomes than mother-reported outcomes. Pre-pregnancy obesity was associated with increased risks of externalizing behaviors in the clinical range regardless of informant (CBCL RR: 1.6, 95% CI: 0.8, 3.2 and TRF RR: 1.7, 95% CI: 0.8, 3.5). Pre-pregnancy obesity was also associated with increased risks of internalizing behaviors according to teacher-report (TRF RR: 2.6, 95% CI:1.5, 4.6). CONCLUSIONS: Pre-pregnancy obesity, compared to pre-pregnancy normal weight, is associated with generally higher scores on both mother and teacher reported childhood behavioral assessments, indicating an increased likelihood of behavioral problems.

Periconceptional nonsteroidal anti-inflammatory drug use, folic acid intake, and the risk of spina bifida.

BACKGROUND: Use of nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy may increase risk for neural tube defects (NTDs), including spina bifida. Folic acid intake can prevent NTDs, but it is not known whether it modifies any risks associated with NSAID use. OBJECTIVES: To assess the impact of periconceptional NSAID use on the risk of spina bifida overall and stratified by folic acid intake. STUDY DESIGN: We analyzed 1998-2015 data from the Slone Epidemiology Center Birth Defects Study, a multi-site, case-control study. Mothers were interviewed to identify sociodemographic factors, behaviors, and exposures during pregnancy. Periconceptional NSAID use was defined as use of aspirin, ibuprofen, naproxen, or COX2 inhibitors within the month before or after the last menstrual period. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for NSAID use, adjusted for study center and race/ethnicity stratified by average daily folic acid intake above ("high FA") or below ("low FA") 400 mcg/day. RESULTS: We compared mothers of 267 infants with spina bifida to mothers of 6,233 nonmalformed controls. Among control mothers, 20% used NSAIDS periconceptionally (16% ibuprofen, 4% aspirin, 3% naproxen, and <1% COX-2 inhibitors). For any NSAID use, the aORs among low FA and high FA women were 1.70 (95% CI [1.13, 2.57]) and 1.09 (95% CI [0.69, 1.71]), respectively. CONCLUSIONS: We observed a small increase in the risk for spina bifida among infants born to women who used NSAIDs periconceptionally, but this risk was limited to those who had inadequate folic acid intake.