Association Between Influenza Vaccination and SARS-CoV-2 Infection.

BACKGROUND: Recent data in nonpregnant individuals suggest a protective effect of influenza vaccination against SARS-CoV-2 infection and its severity. OBJECTIVES: Our primary objective was to evaluate whether influenza vaccination was associated with COVID-19 severity and pregnancy and neonatal outcomes among those infected with SARS-CoV-2. The secondary objective was to examine the association between influenza vaccination and SARS-CoV-2 infection. STUDY DESIGN: Secondary analysis of a multicenter retrospective cohort of pregnant people who tested positive for SARS-CoV-2 between March and August 2020, and a cohort of random deliveries during the same time period. The associations between 2019 influenza vaccination and the primary outcome of moderate-to-critical COVID-19 as well as maternal and perinatal outcomes were examined among all people who tested positive for SARS-CoV-2 between March and August 2020. The association between 2019 influenza vaccination and having a positive SARS-CoV-2 test was examined among a cohort of individuals who delivered on randomly selected dates between March and August 2020. Univariable and multivariable analyses were performed. RESULTS: Of 2325 people who tested positive for SARS-CoV-2, 1068 (45.9%) were vaccinated against influenza in 2019. Those who received the influenza vaccine were older, leaner, more likely to have private insurance, and identify as White or Hispanic. They were less likely to smoke tobacco and identify as Black. Overall, 419 (18.0%) had moderate, 193 (8.3%) severe, and 52 (2.2%) critical COVID-19. There was no association between influenza vaccination and moderate-to-critical COVID-19 (29.2% vs. 28.0%, adjusted OR 1.10, 95% CI 0.90-1.34) or adverse maternal and perinatal outcomes among those who tested positive. Of 8152 people who delivered in 2020, 4658 (57.1%) received the influenza vaccine. Prior vaccination was not associated with a difference in the odds of SARS-CoV-2 infection (3.8% vs. 4.2%, adjusted OR 0.94, 95% CI 0.74-1.19). CONCLUSION: Prior influenza vaccination was not associated with decreased severity of COVID-19 or lower odds of SARS-CoV-2 infection in pregnancy.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix: The TOPS Randomized Clinical Trial.

Importance: A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. Objective: To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. Design, Setting, and Participants: We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. Interventions: Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. Main Outcome and Measures: The primary outcome was delivery or fetal death prior to 37 weeks. Results: A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). Conclusions and Relevance: Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02901626.

Maternal and Delivery Characteristics and Self-Reported Perceived Control During Labor.

OBJECTIVE: To evaluate the association between maternal and delivery characteristics and self-reported perceived control during childbirth. METHODS: A secondary analysis of a multicenter randomized trial was conducted to compare labor induction at 39 weeks of gestation with expectant management in low-risk nulliparous people. Six to 96 hours after delivery, participants who experienced labor completed the Labor Agentry Scale, a validated self-administered questionnaire to ascertain perceived control during childbirth. Scores range from 29 to 203, with higher scores indicating a sense of greater control. Multivariable linear regression was used to determine which maternal and delivery characteristics were associated with the Labor Agentry Scale score. Eligible characteristics included age, self-reported race and ethnicity, marital status, employment status, type of insurance, previous pregnancy loss before 20 weeks of gestation, body mass index (BMI), smoking, alcohol use, mode of delivery, labor pain (0-10 points), and a composite of perinatal death or severe neonatal complications. Significant variables ( P <.05) were retained in the final multivariable model, and adjusted mean differences (95% CIs) between groups were estimated. RESULTS: Of 6,106 people enrolled in the trial, 6,038 experienced labor, of whom 5,750 (95.2%) completed the Labor Agentry Scale and were included in this analysis. Mean [95% CI] adjusted Labor Agentry Scale scores were significantly lower among those who identified as Asian (-6.4 [-10.5 to -2.3]) or Hispanic (-3.7 [-5.7 to -1.7]) compared with White, smoked compared with did not smoke (-2.8 [-5.5 to -0.1]), had BMIs of 35 or higher compared with less than 30 (-2.0 [-3.8 to -0.2]), were unemployed (-3.15 [-4.76 to -1.55]), did not have private health insurance (-2.61 [-4.47 to -0.76]), underwent operative vaginal (-5.1 [-7.7 to -2.6]) or cesarean (-14.4 [-16.1 to -12.6]) delivery compared with spontaneous vaginal delivery, and reported greater labor pain score of 8 or higher compared with less than 8 (-11.9 [-13.4 to -10.4]). Mean [95% CI] adjusted Labor Agentry Scale scores were significantly higher among people who were employed compared with unemployed (3.2 [1.6-4.8]) and had private compared with nonprivate insurance (2.6 [0.76-4.5]). CONCLUSION: In nulliparous people at low risk, unemployment, lack of private health insurance, Asian race, Hispanic ethnicity, smoking, operative delivery, and more labor pain were associated with lower perceived control during labor. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01990612.

Maternal Morbidity Risk Factors in Nulliparas.

OBJECTIVE: For every incidence of maternal mortality, maternal morbidity is thought to occur in another 50 to 100 individuals in the United States. Multiple risk factors for severe maternal morbidity have been identified, but counseling about specific risk in pregnancy remains difficult, particularly nulliparous individuals as prior obstetric history is one of the factors influencing risk for severe maternal morbidity. The objective of this study is to examine the association between sociodemographic and laboratory assessments in the first trimester and maternal morbidity in nulliparas. STUDY DESIGN: This was a secondary analysis of a large, multicenter prospective observational cohort of nulliparas. The primary maternal outcome was a composite of hypertensive disorders of pregnancy (HDP), hemorrhage (transfusion, hemorrhage, hysterectomy, other surgery, readmission for bleeding), infection (endometritis, wound infection or dehiscence, pneumonia, sepsis, infection during labor and delivery, readmission for infection through day 14), venous thromboembolic events (VTE) (deep venous thrombosis, or pulmonary embolus), or maternal death within 14 days of delivery. Sociodemographic and clinical factors were compared between people with and without maternal morbidity. Relative risk and 95% confidence interval for maternal morbidity was calculated using log-binomial regression, adjusted for baseline characteristics that had a significant independent relationship with maternal morbidity with a p-value <0.05. RESULTS: Of 9,445 pregnant people in the analysis, 18.2% (n = 1,716) experienced the composite maternal morbidity; the most common component was HDP (13.1%, n = 1,244) followed by infection (4.43%, n = 420), hemorrhage (2.27%, n = 215), VTE (0.12%, n = 11), and death (0.01%, n = 1). In a multivariable model, self-identified Black race, first trimester obesity, pregestational diabetes, chronic hypertension, and chronic kidney disease were significantly associated with the primary maternal outcome. CONCLUSION: More than one in six nulliparas experienced the composite maternal morbidities. Maternal morbidity was associated with self-identified Black race, obesity, and multiple preexisting medical comorbidities. KEY POINTS: · One in six nulliparas experience maternal morbidity in their first pregnancy related to hypertensive disorders of pregnancy, infection, hemorrhage, and venous thromboembolism.. · Risk factors for maternal morbidity in nulliparas include Black race, prepregnancy body mass index, and preexisting medical conditions.. · The preexisting medical conditions with the strongest association with maternal morbidity included pregestational diabetes, chronic hypertension, and chronic kidney disease..

Tranexamic Acid to Prevent Obstetrical Hemorrhage after Cesarean Delivery.

BACKGROUND: Prophylactic use of tranexamic acid at the time of cesarean delivery has been shown to decrease the calculated blood loss, but the effect on the need for blood transfusions is unclear. METHODS: We randomly assigned patients undergoing cesarean delivery at 31 U.S. hospitals to receive either tranexamic acid or placebo after umbilical-cord clamping. The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days post partum, whichever came first. Key secondary outcomes were estimated intraoperative blood loss of more than 1 liter (prespecified as a major secondary outcome), interventions for bleeding and related complications, the preoperative-to-postoperative change in the hemoglobin level, and postpartum infectious complications. Adverse events were assessed. RESULTS: A total of 11,000 participants underwent randomization (5529 to the tranexamic acid group and 5471 to the placebo group); scheduled cesarean delivery accounted for 50.1% and 49.2% of the deliveries in the respective groups. A primary-outcome event occurred in 201 of 5525 participants (3.6%) in the tranexamic acid group and in 233 of 5470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% confidence interval [CI], 0.74 to 1.07; P = 0.19). Estimated intraoperative blood loss of more than 1 liter occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI, 0.79 to 1.05). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82 to 0.97); the change in the hemoglobin level was -1.8 g per deciliter and -1.9 g per deciliter, respectively (mean difference, -0.1 g per deciliter; 95% CI, -0.2 to -0.1); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI, 1.02 to 1.61). The frequencies of thromboembolic events and other adverse events were similar in the two groups. CONCLUSIONS: Prophylactic use of tranexamic acid during cesarean delivery did not lead to a significantly lower risk of a composite outcome of maternal death or blood transfusion than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT03364491.).

Neighborhood disadvantage and the racial disparity in postpartum hypertension.

BACKGROUND: Postpartum hypertension is the leading cause of postpartum readmission and has long-lasting cardiovascular effects. Black patients have higher incidence rates of hypertensive disorders after delivery and subsequent severe maternal morbidity. Neighborhood advantage, a marker of social determinants of health, has not been studied concerning postpartum hypertension. Moreover, the interplay between race and neighborhood advantage and their effect on postpartum hypertension have not been previously explored. OBJECTIVE: This study aimed to evaluate the association between neighborhood-level social determinants of health and postpartum hypertension and explore whether these factors explain previously documented racial disparities. STUDY DESIGN: This study included a retrospective cohort of people enrolled in a remote monitoring program of postpartum hypertension at the time of delivery within 1 health network from March 2019 to September 2021. Patients were eligible for enrollment after a diagnosis of hypertensive disorder during pregnancy or delivery. We further limited the cohort to self-reported Black and White patients with blood pressures recorded at 3 weeks and 6 weeks postpartum. The neighborhood advantage for each person at the time of delivery was classified using the area deprivation index, an accepted surrogate of social determinants of health and our primary exposure. The secondary exposure was self-reported race. Study outcomes of interest were hypertensive status (stage 1 hypertension: ≥130 to 139/80 to 89 mm Hg; stage 2 hypertension: ≥140/90 mm Hg) at 3 and 6 weeks after delivery. In addition, hypertensive status by neighborhood area deprivation index using logistic regression was molded. In secondary analyses, a case-control cohort matched on the area deprivation index was created, and conditional logistic regression was used to evaluate race. Finally, mixed-effects models modeling hypertension by race and clustering within the area deprivation index were used. RESULTS: Of 4193 people enrolled, 2722 were Black or White and had blood pressure data recorded at 3 weeks after delivery, and 1126 had blood pressure data recorded at 6 weeks after delivery. After accounting for prenatal body mass index, smoking status, type of hypertension, and antihypertensives prescribed at discharge, persons living in the most disadvantaged neighborhoods were twice as likely (adjusted odds ratio, 2.03; 95% confidence interval, 1.53-2.69) to develop stage 2 hypertension at 21 days after delivery and 1.67 times more likely (95% confidence interval, 1.06-2.64) to develop stage 2 hypertension at 6 weeks after delivery than persons living in the most advantaged neighborhoods. Both associations were attenuated after adjusting for race. When people with stage 2 hypertension were matched on area deprivation index with normotensive counterparts, Black patients were still 3 to 4 times more likely to develop stage 2 hypertension at 3 (adjusted odds ratio, 3.00; 95% confidence interval, 1.95-4.63) and 6 (adjusted odds ratio, 4.61; 95% confidence interval, 2.05-10.36) weeks after delivery. This association remained after clustering within a neighborhood at 3 (adjusted odds ratio, 3.12; 95% confidence interval, 2.41-4.06) and 6 (adjusted odds ratio, 2.99; 95% confidence interval, 1.96-4.54) weeks after delivery. There was no significant difference in stage 1 hypertension. CONCLUSION: Neighborhood advantage was associated with the development of persistent hypertension at 3 and 6 weeks after delivery. This association did not explain the racial disparity in sustained high blood pressure.

Serum Cotinine and Adverse Cardiovascular Outcomes: A Cross-sectional Secondary Analysis of the nuMoM2b Heart Health Study.

OBJECTIVE: We aimed to (1) compare serum cotinine with self-report for ascertaining smoking status among reproductive-aged women; (2) estimate the relative odds of adverse cardiovascular (CV) outcomes among women by smoking status; (3) assess whether the association between adverse pregnancy outcomes (APOs) and CV outcomes varies by smoking status. STUDY DESIGN: We conducted a cross-sectional study of the nuMoM2b Heart Health Study. Women attended a study visit 2 to 7 years after their first pregnancy. The exposure was smoking status, determined by self-report and by serum cotinine. Outcomes included incident chronic hypertension (HTN), metabolic syndrome (MetS), and dyslipidemia. Multivariable logistic regression estimated odds ratios (ORs) for each outcome by smoking status. RESULTS: Of 4,392 women with serum cotinine measured, 3,610 were categorized as nonsmokers, 62 as secondhand smoke exposure, and 720 as smokers. Of 3,144 women who denied tobacco smoke exposure, serum cotinine was consistent with secondhand smoke exposure in 48 (1.5%) and current smoking in 131 (4.2%) After adjustment for APOs, smoking defined by serum cotinine was associated with MetS (adjusted OR [aOR] = 1.52, 95% confidence interval [CI]: 1.21, 1.91) and dyslipidemia (aOR = 1.28, 95% CI: 1.01, 1.62). When stratified by nicotine exposure, nonsmokers with an APO in their index pregnancy had higher odds of stage 1 (aOR = 1.64, 95% CI: 1.32, 2.03) and stage 2 HTN (aOR = 2.92, 95% CI: 2.17, 3.93), MetS (aOR = 1.76, 95% CI: 1.42, 2.18), and dyslipidemia (aOR = 1.55, 95% CI: 1.25, 1.91) relative to women with no APO. Results were similar when smoking exposure was defined by self-report. CONCLUSION: Whether determined by serum cotinine or self-report, smoking is associated with subsequent CV outcomes in reproductive-aged women. APOs are also independently associated with CV outcomes in women. KEY POINTS: · Cotinine was detected in 5.7% of reported nonsmokers.. · Smoking and APOs were independently associated with CV health.. · Smoking was associated with MetS and dyslipidemia..

Allostatic Load and Adverse Pregnancy Outcomes.

OBJECTIVE: To assess the association between allostatic load, as an estimate of chronic stress, and adverse pregnancy outcomes. METHODS: This was a secondary analysis of nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be), a prospective observational cohort study. Our primary exposure was dichotomous high allostatic load in the first trimester, defined as 4 or more of 12 biomarkers in the "worst" quartile. The primary outcome was a composite adverse pregnancy outcome: hypertensive disorders of pregnancy (HDP), preterm birth, small for gestational age (SGA), and stillbirth. Secondary outcomes included components of the composite. Multivariable logistic regression was used to test the association between high allostatic load and adverse pregnancy outcomes, adjusted for potential confounders. Mediation and moderation analyses were conducted to assess the role of allostatic load along the causal pathway between racial disparities and adverse pregnancy outcomes. RESULTS: Among 4,266 individuals, 34.7% had a high allostatic load. Composite adverse pregnancy outcome occurred in 1,171 (27.5%): 14.0% HDP, 8.6% preterm birth (48.0% spontaneous and 52.2% indicated), 11.0% SGA, and 0.3% stillbirth. After adjustment for maternal age, gravidity, smoking, bleeding in the first trimester, and health insurance, high allostatic load was significantly associated with a composite adverse pregnancy outcome (adjusted odds ratio [aOR] 1.5, 95% CI 1.3, 1.7) and HDP (aOR 2.5, 95% CI 2.0-2.9), but not preterm birth or SGA. High allostatic load partially mediated the association between self-reported race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race, but not for a composite adverse pregnancy outcome, preterm birth, or SGA. CONCLUSION: High allostatic load in the first trimester is associated with adverse pregnancy outcomes, particularly HDP. Allostatic load was a partial mediator between race and adverse pregnancy outcomes. The association between allostatic load and HDP differed by self-reported race.

Periconceptional diet quality is associated with gestational diabetes risk and glucose concentrations among nulliparous gravidas.

Background: Gestational diabetes mellitus (GDM) and elevated glucose concentrations below the threshold for GDM diagnosis have been associated with adverse pregnancy and offspring outcomes. Dietary interventions initiated during pregnancy have demonstrated inconsistent beneficial effects. Limited data exist regarding the effects of periconceptional diet on gestational glycemia. Objective: To evaluate independent associations between periconceptional diet quality with GDM frequency and glucose concentrations from GDM screening and diagnostic tests among nulliparous gravidas. Design: This is a secondary analysis of N=7997 participants from the NuMoM2b multicenter, prospective, observational cohort study of first pregnancies. The Alternative Healthy Eating Index (AHEI)-2010 was computed from food frequency questionnaires completed in early pregnancy (6-13 weeks), reporting usual dietary intake over the preceding 3 months. GDM screening was performed either by non-fasting 1-hour 50g glucose load (N=6845), followed by 3-hour 100g glucose tolerance test (GTT) for those with raised glucose concentrations (N=1116; at risk for GDM), or by a single 2-hour 75g GTT (N=569; all GDM risk levels). Logistic and linear regression were used to estimate the associations between the AHEI-2010 score with odds of GDM, having raised blood glucose on the 1-hour screening test, and continuous glucose concentrations on screening and diagnostic tests. All models were adjusted for a priori covariates: maternal age, race/ethnicity, early-pregnancy body mass index, smoking habits, rate of gestational weight gain, energy intake, nausea and vomiting in early pregnancy, study site. Results: Poorer periconceptional diet quality was observed among participants who were younger, with higher BMI, lower income levels, and of non-Hispanic Black or Hispanic ethnicity. The GDM rate was 4%. Each 1-point increase in AHEI-2010 score was associated with a 1% decrease in the odds of being diagnosed with GDM (beta=-0.015, p=0.022, OR=0.986, 95% CI 0.973 to 0.998). Diet quality was inversely associated with each post glucose load concentration on the non-fasting screening test and the 2-hour and 3-hour GTT. Conclusion: Poor periconceptional diet quality is independently associated with an increased risk of GDM and with minor elevations in serum glucose concentrations on GDM screening and diagnostic tests, in a diverse cohort of nulliparas. Periconception intervention studies targeting diet quality are warranted.

Factors associated with duration of breastfeeding in women giving birth for the first time.

OBJECTIVE: To examine maternal, psychosocial, and pregnancy factors associated with breastfeeding for at least 6 months in those giving birth for the first time. METHODS: We performed a planned secondary analysis of an observational cohort study of 5249 women giving birth for the first time. Women were contacted at least 6 months after delivery and provided information regarding breastfeeding initiation, duration, and exclusivity. Maternal demographics, psychosocial measures, and delivery methods were compared by breastfeeding groups. RESULTS: 4712 (89.8%) of the women breastfed at some point, with 2739 (58.2%) breastfeeding for at least 6 months. Of those who breastfed, 1161 (24.7% of the entire cohort), breastfed exclusively for at least 6 months. In the multivariable model among those who ever breastfed, not smoking in the month prior to delivery (adjusted odds ratio [aOR] 2.04, 95%CI 1.19-3.45), having a Master's degree of higher (aOR 1.89, 95%CI 1.51-2.36), having a planned pregnancy (aOR 1.48, 95%CI 1.27-1.73), older age (aOR 1.02, 95% CI, 1.01-1.04), lower BMI (aOR 0.96 95% CI 0.95-0.97), and having less anxiety measured during pregnancy (aOR 0.990, 95%CI 0.983-0.998) were associated with breastfeeding for at least 6 months. Compared to non-Hispanic White women, Hispanic women, while being more likely to breastfeed initially (aOR 1.40, 95%CI 1.02-1.92), were less likely to breastfeed for 6 months (aOR 0.72, 95%CI 0.59-0.88). While non-Hispanic Black women were less likely than non-Hispanic White women to initiate breastfeeding (aOR 0.68, 95%CI 0.51-0.90), the odds of non-Hispanic Black women of continuing to breastfeed for at least 6 months was similar to non-Hispanic White women (aOR 0.92, 95%CI 0.71-1.19). CONCLUSIONS: In this cohort of women giving birth for the first time, duration of breastfeeding was associated with several characteristics which highlight groups at greater risk of not breastfeeding as long as currently recommended. TRIAL REGISTRATION: NCT01322529 (nuMoM2b) and NCT02231398 (nuMoM2b-Heart Health).

Placental protein levels in maternal serum are associated with adverse pregnancy outcomes in nulliparous patients.

BACKGROUND: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be was established to investigate the underlying causes and pathophysiological pathways associated with adverse pregnancy outcomes in nulliparous gravidas. OBJECTIVE: This study aimed to study placental physiology and identify novel biomarkers concerning adverse pregnancy outcomes, including preterm birth (medically indicated and spontaneous), preeclampsia, small-for-gestational-age neonates, and stillbirth. We measured levels of placental proteins in the maternal circulation in the first 2 trimesters of pregnancy. STUDY DESIGN: Maternal serum samples were collected at 2 study visits (6-13 weeks and 16-21 weeks), and levels of 9 analytes were measured. The analytes we measured were vascular endothelial growth factor, placental growth factor, endoglin, soluble fms-like tyrosine kinase-1, A disintegrin and metalloproteinase domain-containing protein 12, pregnancy-associated plasma protein A, free beta-human chorionic gonadotropin, inhibin A, and alpha-fetoprotein. The primary outcome was preterm birth between 20 0/7 and 36 6/7 weeks of gestation. The secondary outcomes were spontaneous preterm births, medically indicated preterm births, preeclampsia, small-for-gestational-age neonates, and stillbirth. RESULTS: A total of 10,038 eligible gravidas were enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort, from which a nested case-control study was performed comparing 800 cases with preterm birth (466 spontaneous preterm births, 330 medically indicated preterm births, and 4 unclassified preterm births), 568 with preeclampsia, 406 with small-for-gestational-age birth, and 49 with stillbirth with 911 controls who delivered at term without complications. Although levels of each analyte generally differed between cases and controls at 1 or 2 visits, the odds ratios revealed a <2-fold difference between cases and controls in all comparisons. Receiver operating characteristic curves, generated to determine the relationship between analyte levels and preterm birth and the other adverse pregnancy outcomes, resulted in areas under the receiver operating characteristic curves that were relatively low (range, 0.50-0.64) for each analyte. Logistic regression modeling demonstrated that areas under the receiver operating characteristic curves for predicting adverse pregnancy outcomes were greater using baseline clinical characteristics and combinations of analytes than baseline characteristics alone, but areas under the receiver operating characteristic curves remained relatively low for each outcome (range, 0.65-0.78). CONCLUSION: We have found significant associations between maternal serum levels of analytes evaluated early in pregnancy and subsequent adverse pregnancy outcomes in nulliparous gravidas. However, the test characteristics for these analytes do not support their use as clinical biomarkers to predict adverse pregnancy outcomes, either alone or in combination with maternal clinical characteristics.

Association of N-Terminal Pro-Brain Natriuretic Peptide Concentration in Early Pregnancy With Development of Hypertensive Disorders of Pregnancy and Future Hypertension.

IMPORTANCE: Hypertensive disorders of pregnancy are associated with future cardiovascular disease, perhaps because of subclinical cardiac dysfunction before pregnancy leading to impaired adaptation to pregnancy. Natriuretic peptides are promising biomarkers for detecting subclinical cardiac dysfunction outside of pregnancy. OBJECTIVE: To investigate whether higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in early pregnancy would be associated with hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study, a prospective multicenter observational study. A total of 4103 nulliparous women with complete data and no prepregnancy hypertension or diabetes who were treated at 8 clinical sites were included. Women were followed up with for 2 to 7 years after pregnancy. Data were collected from October 2010 to October 2017, and data were analyzed from August 2020 to November 2021. EXPOSURES: NT-proBNP concentration, measured using an electrochemiluminescence immunoassay from a first-trimester blood sample. MAIN OUTCOMES AND MEASURES: Hypertensive disorders of pregnancy and incident hypertension (systolic blood pressure of 130 mm Hg or diastolic blood pressure of 80 mm Hg or use of antihypertensive agents) at follow-up visit. RESULTS: A total of 4103 women met inclusion criteria; the mean (SD) age was 27.0 (5.6) years. Among these women, 909 (22.2%) had an adverse pregnancy outcome, and 817 (19.9%) had hypertension at the follow-up visit. Higher NT-proBNP concentrations were associated with a lower risk of hypertensive disorders of pregnancy (adjusted odds ratio per doubling, 0.81; 95% CI, 0.73-0.91), which persisted after adjustment for age, self-reported race and ethnicity, early-pregnancy body mass index, smoking, and aspirin use. Similarly, higher NT-proBNP concentration in early pregnancy was also associated with a lower risk of incident hypertension 2 to 7 years after delivery (adjusted odds ratio per doubling, 0.84; 95% CI, 0.77-0.93), an association that persisted after controlling for confounders, including hypertensive disorders of pregnancy. CONCLUSIONS AND RELEVANCE: In this cohort study, higher NT-proBNP concentrations in early pregnancy were associated with a lower risk of hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum. These findings suggest that normal early-pregnancy cardiovascular physiology, as assessed by NT-proBNP concentration, may provide biologic insights into both pregnancy outcome and cardiovascular disease risk.

Perinatal Outcomes of Two Screening Strategies for Gestational Diabetes Mellitus: A Randomized Controlled Trial.

OBJECTIVE: To evaluate differences in short-term perinatal outcomes between the two prominent screening strategies for gestational diabetes mellitus, the International Association of Diabetes and Pregnancy Study Groups (IADPSG) and Carpenter-Coustan. METHODS: In this single-site, blinded, randomized, comparative effectiveness trial, participants received a nonfasting 50-g oral glucose tolerance test and, if less than 200 mg/dL (less than 11.1 mmol/L), were randomized to further screening with either IADPSG or Carpenter-Coustan criteria. Gestational diabetes treatment occurred per routine clinical care. The primary outcome was incidence of large-for-gestational-age (LGA) neonates. Prespecified secondary outcomes included small-for-gestational-age (SGA) neonates, cesarean birth, and neonatal and maternal composites of adverse perinatal outcomes. Assuming a 15% incidence of LGA neonates in the Carpenter-Coustan group, 782 participants provided more than 80% power to detect a 7% absolute risk reduction with the use of IADPSG; planned recruitment was 920 for anticipated attrition. RESULTS: From June 2015 to February 2019, 1,016 participants were enrolled and 921 were randomized to IADPSG (n=461) or Carpenter-Coustan (n=460) groups. Gestational diabetes incidence (14.4% vs 4.5%, P<.001) and diabetes medication use (9.3% vs 2.4%; P<.001) were more common in the IADPSG group; there were no differences in LGA neonates, either overall (risk reduction 0.90, 97.5% CI 0.53-1.52) or among women without gestational diabetes (risk reduction 0.85, 97.5% CI 0.49-1.48). Those screened with IADPSG had higher rates of neonatal morbidity but fewer study-related adverse events. Rates of SGA neonates, cesarean birth, and maternal morbidity composite did not differ significantly between study groups. CONCLUSIONS: The IADPSG screening criteria resulted in more women diagnosed and treated for gestational diabetes than Carpenter-Coustan without reducing the incidence of LGA birth weight or maternal or neonatal morbidity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02309138.

Racial differences across pregnancy in maternal pro-inflammatory immune responsivity and its regulation by glucocorticoids.

BACKGROUND: The distribution of adverse pregnancy, birth and subsequent child developmental and health outcomes in the U.S. is characterized by pronounced racial (particularly Black-white) disparities. In this context, chronic stress exposure represents a variable of considerable importance, and the immune/inflammatory system represents a leading candidate biological pathway of interest. Previous pregnancy studies examining racial disparities in immune processes have largely utilized circulating cytokine levels, and have yielded null or mixed results. Circulating cytokines primarily represent basal secretion and do not necessarily represent functional features of immune responsivity and regulation. Thus, in order to conduct a more in-depth characterization of racial differences in functional immune properties during pregnancy, we utilized an ex vivo stimulation assay, a dynamic measure of immune function at the cellular level, to investigate Black-white racial differences in in mid- and late-gestation in i) pro-inflammatory (IL-6) responsivity of leukocytes to antigen [lipopolysaccharide (LPS)] challenge, and ii) regulation (dampening) of this pro-inflammatory response by glucocorticoids. METHOD: 177 women (N = 42 Black (24%), n = 135 white (76%)) with a singleton, intrauterine pregnancy provided 20 mL venous blood in mid- (16.6 ± 2.4 wks) and late (33.3 ± 1.1 wks) pregnancy. Maternal pro-inflammatory responsivity of leukocytes was quantified by assessing the release of the pro-inflammatory cytokine IL-6 in response to LPS stimulation, and regulation of the pro-inflammatory response was quantified by assessing the suppression of the stimulated IL-6 response after co-incubation with progressively increasing levels of dexamethasone [10-7, 10-6, 10-5 M] (i.e., glucocorticoid receptor resistance (GRR)). A priori model covariates included maternal age, parity, SES (socioeconomic status), and pre-pregnancy BMI. RESULTS: Maternal pro-inflammatory responsivity (LPS-stimulated IL-6) and GRR increased significantly across mid- and late gestation (adjusted ß = 0.157, p = 0.007; ß = 0.627, p < 0.001, respectively). Across both time points in pregnancy Black women exhibited significantly higher LPS-stimulated IL-6 release and reduced glucocorticoid regulation of the IL-6 response (i.e., higher GRR) relative to white women, before and after adjusting for covariates (ß = 0.381, p = 0.0030; ß = 0.391, p = 0.0075, respectively). There was no racial difference in the concentrations of circulating IL-6 (p = 0.9199). CONCLUSION: Our findings support the hypothesis postulating significant racial (Black-white) differences in key functional properties of the maternal immune system in pregnancy, which were not apparent using circulating cytokine measures. These data elucidate a potentially important physiological mechanism underlying the transduction of environmental conditions into racial disparities in reproductive and subsequent child health outcomes, and the use of these ex vivo measures should be considered in future studies.

Association of second trimester uterine artery Doppler parameters with maternal hypertension 2-7 years after delivery.

BACKGROUND: Reduced uterine artery compliance is associated with adverse pregnancy outcomes (APOs) and may indicate underlying maternal cardiovascular pathology. We investigated associations between second trimester uterine artery Doppler (UAD) parameters and incident maternal hypertension 2-7 years after delivery. METHODS: A cohort of 10,038 nulliparous US participants was recruited early in pregnancy. A subgroup of 3739, without baseline hypertension and with complete follow-up visits 2-7 years after delivery, were included in this analysis. We investigated UAD indicators of compliance including: 1) early diastolic notch; 2) resistance index (RI); and 3) pulsatility index (PI). We defined hypertension as systolic blood pressure ≥130 mmHg, diastolic ≥80 mmHg, or antihypertensive medication use. We calculated odds ratios (OR) and 95 % confidence intervals (95%CI) for associations between UAD parameters and hypertension, adjusting for age, obesity, race/ethnicity, insurance, smoking, and APOs. RESULTS: A total of 187 (5 %) participants developed hypertension after the index pregnancy. Presence of early diastolic notch on UAD was not associated with incident hypertension. Increased RI and PI correlated with higher odds of hypertension (RI: adjusted OR 1.15 [95 % CI 1.03-1.30]; PI: adjusted OR 1.03 [95%CI 1.01-1.05] for each 0.1 unit increase). Maximum RI above 0.84 or maximum PI above 2.3 more than doubled the odds of incident hypertension (RI: adjusted OR 2.49, 95%CI 1.45-4.26; PI: adjusted OR 2.36, 95%CI 1.45-3.86). CONCLUSION: Higher resistance and pulsatility indices measured on second trimester UAD were associated with increased odds of incident hypertension 2-7 years later, and may be biomarkers of higher maternal cardiovascular risk.

The impact of setting a pregnancy weight gain goal on total weight gain.

BACKGROUND: Expert groups recommend that women set a pregnancy weight gain goal with their care provider to optimise weight gain. OBJECTIVE: Our aim was to describe the concordance between first-trimester personal and provider pregnancy weight gain goals with the Institute of Medicine (IOM) recommendations and to determine the association between these goals and total weight gain. METHODS: We used data from 9353 women in the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be. In the first trimester, women reported their personal pregnancy weight gain goal and their provider weight gain goal, and we categorised personal and provider weight gain goals and total weight gain according to IOM recommendations. We used log-binomial or linear regression models to relate goals to total weight gain, adjusting for confounders including race/ethnicity, maternal age, education, smoking, marital status and planned pregnancy. RESULTS: Approximately 37% of women reported no weight gain goals, while 24% had personal and provider goals, 31% had only a personal goal, and 8% had only a provider goal. Personal and provider goals were outside the recommended ranges in 12%-23% of normal-weight women, 31%-41% of overweight women and 47%-63% of women with obesity. Women with both personal and provider pregnancy weight gain goals were 6%-14% more likely than their counterparts to have a goal within IOM-recommended ranges. Having any goal or a goal within the IOM-recommended ranges was unrelated to pregnancy weight gain. Excessive weight gain occurred in approximately half of normal-weight or obese women and three-quarters of overweight women, regardless of goal setting group. CONCLUSIONS: These findings do not support the effectiveness of early-pregnancy personal or provider gestational weight gain goal setting alone in optimising weight gain. Multifaceted interventions that address a number of mediators of goal setting success may assist women in achieving weight gain consistent with their goals.

Prospective association of maternal immune pro-inflammatory responsivity and regulation in pregnancy with length of gestation.

PROBLEM: The immune system represents a leading pathway of interest in the pathophysiology of preterm birth. The majority of human clinical studies interrogating this pathway have utilized circulating immune biomarkers; however, these concentrations typically reflect only basal production but not key functional properties of the immune system, particularly variation in the pro-inflammatory response to antigen challenge and the regulation of this response. Thus, in this study, we utilized an ex vivo stimulation protocol that quantifies these processes, and we examined their prospective association with the gestation length and risk of preterm birth. METHOD OF STUDY: Immune responsiveness and regulation were assessed in 128 pregnant women in mid-gestation using an ex vivo stimulation protocol. Maternal pro-inflammatory responsivity of leukocytes was quantified by assessing the release of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1ß in response to antigen stimulation, and regulation of the pro-inflammatory response was quantified by assessing the suppression of stimulated cytokine response upon co-incubation with increasing dexamethasone concentrations (ie, glucocorticoid receptor resistance; GRR). RESULTS: Higher maternal GRR, indicating impaired regulation of the pro-inflammatory response, was significantly and independently associated with shorter gestational length (ß = -0.42, p = .0091) and a 3.0-fold increase in risk for preterm birth (OR = 3.01, 95% CI = 1.17-7.70, p = .0218). Basal circulating IL-6 and TNF-α were not associated with either outcome. CONCLUSION: The association of maternal GRR with length of gestation and preterm birth risk suggests that the processes represented by this measure-maternal pro-inflammatory propensity and immune regulation-may provide further mechanistic insight into the pathophysiology of preterm birth.

Profile of Reported Alcohol, Tobacco, and Recreational Drug Use in Nulliparous Women.

OBJECTIVE: To estimate alcohol, tobacco, and recreational drug use during pregnancy among nulliparous women. METHODS: In a cohort of nulliparous women followed through pregnancy from the first-trimester nuMoM2b (Nulliparous Outcomes in Pregnancy: Monitoring Mothers to be) study, self-reported use of alcohol, tobacco, and drugs was chronicled longitudinally at four study visits in this secondary analysis. Rates of use before pregnancy, in each trimester (visit 1, visit 2, visit 3, approximating each trimester), and at the time of delivery (visit 4) were recorded. The amount of alcohol, tobacco, and drug exposure were recorded using validated measures, and trends across pregnancy were analyzed. RESULTS: Of the 10,038 study participants, 10,028 had information regarding alcohol, tobacco, and drug use at visit 1, 9,412 at visit 2, 9,217 at visit 3, and 7,167 at visit 4. The rates of drinking alcohol, which had been 64.6% in the 3 months before pregnancy, were lower in pregnancy (3.9% at visit 1, 5.6% at visit 2, 7.0% at visit 3, and 6.1% at visit 4, P<.001 for all). Rates later in pregnancy were all greater than in the first trimester (P<.01). The rate of smoking in the 3 months before pregnancy, which was 17.8%, also declined at visit 1 (5.9%), and continued to decline through pregnancy (5.3% at visit 2, 4.7% at visit 3, and 3.9% at visit 4, with all rates lower than that of visit 1 [P<.01]). Although recreational drug use was relatively common in the months before pregnancy (33.8%), it also declined during pregnancy (1.1% at visit 2, 0.7% at visit 3, 0.4% at visit 4). CONCLUSIONS: In this geographically and ethnically diverse cohort of nulliparous women, rates of self-reported alcohol, smoking, and recreational drug use were all significantly lower during than before pregnancy. Nonetheless, rates of alcohol use rose as pregnancy progressed, highlighting the need for continued counseling throughout all trimesters of pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01322529.

Competing demands in postpartum care: a national survey of U.S. providers' priorities and practice.

BACKGROUND: A new movement towards improved postpartum care calls for restructuring how that care is provided. As professional guidelines evolve, understanding how providers prioritize and practice postpartum care can offer insights about elements of care that may be currently performed more routinely than providers deem a priority to do so, as well as those that may warrant more routine practice. METHODS: We surveyed 600 randomly-sampled U.S. postpartum care providers about their priorities for and the frequency with which specific elements of care are provided, as well as the feasibility of remote delivery of postpartum care provision (i.e., telemedicine). RESULTS: The survey response rate was 43% across medical specialties. Providers reported an average of only 24.4 ± 11.7 min available to spend on the postpartum visit. Certain types of postpartum care were highly prioritized and routinely performed, such as depression screening. Yet, there were also noted discrepancies between prioritized and performed care, revealing competing demands on providers' time. For example, pelvic exams were performed more often than similarly prioritized care, whereas screening for intimate partner violence and substance use were performed less often than similarly-prioritized care. Certain types of care were identified as important that are not explicitly addressed by national practice guidelines (e.g. transitioning to parenthood). Approximately 25% of respondents regarded telemedicine as a feasible remote care delivery alternative to much of the care currently provided in-person. CONCLUSIONS: The time providers have available to offer comprehensive postpartum care is constrained. Understanding how certain elements of care may be competing with one another at a single postpartum visit highlights those elements of care, which may be currently underperformed, as well as those elements of care that may warrant evaluation for future inclusion in standard care. For some providers experiencing time constraints, complementary remote care represents a potentially viable approach to implementing recommendations for transitioning the traditional visit to a more frequent, ongoing postpartum care process. In calling for a new approach to postpartum care delivery, professional organizations should consider the practices and priorities of their constituency as they revise guidelines and shape future research about the value of specific postpartum services.