Association of Mild Iodine Insufficiency during Pregnancy with Child Neurodevelopment in Patients with Subclinical Hypothyroidism or Hypothyroxinemia.

OBJECTIVE: Our objective was to evaluate whether iodine status in pregnant patients with either subclinical hypothyroidism or hypothyroxinemia in the first half of pregnancy is associated with measures of behavior and neurodevelopment in children through the age of 5 years. STUDY DESIGN: This is a secondary analysis of a multicenter study consisting of two randomized, double-masked, placebo-controlled treatment trials conducted in parallel. Patients with a singleton gestation before 20 weeks' gestation underwent thyroid screening using serum thyrotropin and free thyroxine. Participants with subclinical hypothyroidism or hypothyroxinemia were randomized to levothyroxine replacement or an identical placebo. At randomization, maternal urine was collected and stored for subsequent urinary iodine excretion analysis. Urinary iodine concentrations greater than 150 µg/L were considered iodine sufficient, and concentrations of 150 µg/L or less were considered iodine insufficient. The primary outcome was a full-scale intelligence quotient (IQ) score at the age of 5 years, the general conceptual ability score from the Differential Ability Scales-II at the age of 3 if IQ was not available, or death before 3 years. RESULTS: A total of 677 pregnant participants with subclinical hypothyroidism and 526 with hypothyroxinemia were randomized. The primary outcome was available in 1,133 (94%) of children. Overall, 684 (60%) of mothers were found to have urinary iodine concentrations >150 µg/L. Children of iodine-sufficient participants with subclinical hypothyroidism had similar primary outcome scores when compared to children of iodine-insufficient participants (95 [84-105] vs. 96 [87-109], P adj = 0.73). After adjustment, there was also no difference in IQ scores among children of participants with hypothyroxinemia at 5 to 7 years of age (94 [85 - 102] and 91 [81 - 100], Padj 1/4 0.11). Treatment with levothyroxine was not associated with neurodevelopmental or behavioral outcomes regardless of maternal iodine status (p > 0.05). CONCLUSION: Maternal urinary iodine concentrations ≤150 µg/L were not associated with abnormal cognitive or behavioral outcomes in offspring of participants with either subclinical hypothyroidism or hypothyroxinemia. KEY POINTS: · Most pregnant patients with subclinical thyroid disease are iodine sufficient.. · Mild maternal iodine insufficiency is not associated with lower offspring IQ at 5 years.. · Iodine supplementation in subclinical thyroid disease is unlikely to improve IQ..

Association of Social Determinants of Health and Clinical Factors with Postpartum Hospital Readmissions among Nulliparous Individuals.

OBJECTIVE: Prior data suggest that there are racial and ethnic disparities in postpartum readmission among individuals, especially among those with hypertensive disorders of pregnancy. Existing reports commonly lack granular information on social determinants of health. The objective of this study was to investigate factors associated with postpartum readmission for individuals and address whether such risk factors differed by whether an individual had an antecedent diagnosis of a hypertensive disorder of pregnancy (HDP). STUDY DESIGN: This is a secondary analysis of a large, multicenter prospective cohort study of 10,038 nulliparous participants. The primary outcome of this analysis was postpartum readmission. A priori, participants were analyzed separately based on whether they had HDP. Participant characteristics previously associated with a greater risk of perinatal morbidity or readmission (including social determinants of health, preexisting and chronic comorbidities, and intrapartum characteristics) were compared with bivariable analyses and retained in multivariable models if p < 0.05. Social determinants of health evaluated in this analysis included insurance status, self-identified race and ethnicity (as a proxy for structural racism), income, marital status, primary language, and educational attainment. RESULTS: Of 9,457 participants eligible for inclusion, 1.7% (n = 165) were readmitted following initial hospital discharge. A higher proportion of individuals with HDP were readmitted compared with individuals without HDP (3.4 vs 1.3%, p < 0.001). Among participants without HDP, the only factors associated with postpartum readmission were chorioamnionitis and cesarean delivery. Among participants with HDP, gestational diabetes and postpartum hemorrhage requiring transfusion were associated with postpartum readmission. While the number of postpartum readmissions included in our analysis was relatively small, social determinants of health that we examined were not associated with postpartum readmission for either group. CONCLUSION: In this diverse cohort of nulliparous pregnant individuals, there was a higher frequency of postpartum readmission among participants with HDP. Preexisting comorbidity and intrapartum complications were associated with postpartum readmission among this population engaged in a longitudinal study. KEY POINTS: · Non-HDP patients had higher odds of PPR with chorioamnionitis or cesarean.. · HDP patients had higher odds of PPR if they had GDM or PPH.. · Characterizing PPR may identify and highlight modifiable factors..

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..

The Association between Infant Birth Weight, Head Circumference, and Neurodevelopmental Outcomes.

OBJECTIVE: The aim of this study was to evaluate whether being small for gestational age (SGA) or large for gestational age (LGA) or having a small or large head circumference (HC) at birth is associated with adverse neurodevelopmental outcomes. STUDY DESIGN: This is a secondary analysis of a multicenter negative randomized trial of thyroxine therapy for subclinical hypothyroid disorders in pregnancy. The primary outcome was child intelligence quotient (IQ) at 5 years of age. Secondary outcomes included several neurodevelopmental measures. Associations between the outcomes in children with SGA (<10th percentile) or LGA (>90th percentile) birth weights, using ethnicity- and sex-specific population nomogram as well as nomograms from the National Fetal Growth (NFG) study, were compared with the referent of those with appropriate for gestational age (AGA) birth weight. Similar analyses were performed for HC. RESULTS: Using the population nomogram, 90 (8.2%) were SGA and 112 (10.2%) were LGA. SGA neonates were more likely to be born preterm to mothers who were younger, smoked, and were less likely to have less than a high school education, whereas LGA neonates were more likely to be born to mothers who were older and have higher body mass index, compared with AGA neonates. SGA at birth was associated with a decrease in the child IQ at 5 years of age by 3.34 (95% confidence interval [CI], 0.54-6.14) points, and an increase in odds of child with an IQ < 85 (adjusted odds ratio [aOR], 1.9; 95% CI, 1.1-3.2). There was no association between SGA and other secondary outcomes, or between LGA and the primary or secondary outcomes. Using the NFG standards, SGA at birth remained associated with a decrease in the child IQ at 5 years of age by 3.14 (95% CI, 0.22-6.05) points and higher odds of an IQ < 85 (aOR, 2.3; 95% CI, 1.3-4.1), but none of the other secondary outcomes. HC was not associated with the primary outcome, and there were no consistent associations of these standards with the secondary outcomes. CONCLUSION: In this cohort of pregnant individuals with hypothyroid disorders, SGA birth weight was associated with a decrease in child IQ and greater odds of child IQ < 85 at 5 years of age. Using a fetal growth standard did not appear to improve the detection of newborns at risk of adverse neurodevelopment.

Genetic Predisposition to Adverse Neurodevelopmental Outcome of Extremely Low Birth Weight Infants.

OBJECTIVE: This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants. STUDY DESIGN: We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication. The discovery case-control analysis utilized anonymized DNA samples and evaluated 1,614 single-nucleotide polymorphisms (SNPs) in 145 genes concentrated in inflammation, angiogenesis, brain development, and oxidation pathways. Cases were children who died by age one or who were diagnosed with cerebral palsy (CP) or neurodevelopmental delay (Bayley II mental developmental index [MDI] or psychomotor developmental index [PDI] < 70) by 18 to 22 months. Controls were survivors with normal neurodevelopment. We assessed significant epidemiological variables and SNPs associated with the combined outcome of CP or death, CP, mental delay (MDI < 70) and motor delay (PDI < 70). Multivariable analyses adjusted for gestational age at birth, small for gestational age, sex, antenatal corticosteroids, multiple gestation, racial admixture, and multiple comparisons. SNPs associated with adverse neurodevelopmental outcomes with p < 0.01 were selected for validation in the replication cohort. Successful replication was defined as p < 0.05 in the replication cohort. RESULTS: Of 1,013 infants analyzed (452 cases, 561 controls) in the discovery cohort, 917 were successfully genotyped for >90% of SNPs and passed quality metrics. After adjusting for covariates, 26 SNPs with p < 0.01 for one or more outcomes were selected for replication cohort validation, which included 362 infants (170 cases and 192 controls). A variant in SERPINE1, which encodes plasminogen activator inhibitor (PAI1), was associated with the combined outcome of CP or death in the discovery analysis (p = 4.1 × 10-4) and was significantly associated with CP or death in the replication cohort (adjusted odd ratio: 0.4; 95% confidence interval: 0.2-1.0; p = 0.039). CONCLUSION: A genetic variant in SERPINE1, involved in inflammation and coagulation, is associated with CP or death among ELBW infants. KEY POINTS: · Early preterm and ELBW infants have dramatically increased risks of CP and developmental delay.. · A genetic variant in SERPINE1 is associated with CP or death among ELBW infants.. · The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor..

Associations of the Neighborhood Built Environment with Gestational Weight Gain.

OBJECTIVE: This study aimed to determine whether specific factors of the built environment related to physical activity and diet are associated with inadequate and excessive gestational weight gain (GWG). STUDY DESIGN: This analysis is based on data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be, a prospective cohort of nulliparous women who were followed from the beginning of their pregnancies through delivery. At each study visit, home addresses were recorded and geocoded. Locations were linked to several built-environment characteristics such as the census tract National Walkability Score (the 2010 Walkability Index) and the number of gyms, parks, and grocery stores within a 3-km radius of residential address. The primary outcome of GWG (calculated as the difference between prepregnancy weight and weight at delivery) was categorized as inadequate, appropriate, or excessive based on weight gained per week of gestation. Multinomial regression (generalized logit) models evaluated the relationship between each factor in the built environment and excessive or inadequate GWG. RESULTS: Of the 8,182 women in the analytic sample, 5,819 (71.1%) had excessive GWG, 1,426 (17.4%) had appropriate GWG, and 937 (11.5%) had inadequate GWG. For the majority of variables examined, built environments more conducive to physical activity and healthful food availability were associated with a lower odds of excessive or inadequate GWG category. For example, a higher number of gyms or parks within 3 km of a participant's residential address was associated with lower odds of having excessive (gyms: adjusted odds ratio [aOR] = 0.93 [0.89-0.96], parks: 0.94 [0.90-0.98]) or inadequate GWG (gyms: 0.91 [0.86-0.96]; parks: 0.91 [0.86-0.97]). Similarly, a higher number of grocery stores was associated with lower odds of having excessive GWG (0.94 [0.91-0.97]). CONCLUSION: Among a diverse population of nulliparous women, multiple aspects of the built environment are associated with excessive and inadequate GWG. KEY POINTS: · There are little data on the association between the built environment and pregnancy outcomes.. · Multiple aspects of the built environment are associated with excessive and inadequate GWG.. · These results suggest the role that neighborhood investment may play in improving pregnancy outcomes..

Cannabis Exposure and Adverse Pregnancy Outcomes Related to Placental Function.

Importance: Cannabis use is increasing among reproductive-age individuals and the risks associated with cannabis exposure during pregnancy remain uncertain. Objective: To evaluate the association between maternal cannabis use and adverse pregnancy outcomes known to be related to placental function. Design, Setting, and Participants: Ancillary analysis of nulliparous individuals treated at 8 US medical centers with stored urine samples and abstracted pregnancy outcome data available. Participants in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort were recruited from 2010 through 2013; the drug assays and analyses for this ancillary project were completed from June 2020 through April 2023. Exposure: Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol using frozen stored urine samples from study visits during the pregnancy gestational age windows of 6 weeks and 0 days to 13 weeks and 6 days (visit 1); 16 weeks and 0 days to 21 weeks and 6 days (visit 2); and 22 weeks and 0 days to 29 weeks and 6 days (visit 3). Positive results were confirmed with liquid chromatography tandem mass spectrometry. The timing of cannabis exposure was defined as only during the first trimester or ongoing exposure beyond the first trimester. Main Outcome and Measure: The dichotomous primary composite outcome included small-for-gestational-age birth, medically indicated preterm birth, stillbirth, or hypertensive disorders of pregnancy ascertained by medical record abstraction by trained perinatal research staff with adjudication of outcomes by site investigators. Results: Of 10 038 participants, 9257 were eligible for this analysis. Of the 610 participants (6.6%) with cannabis use, 32.4% (n = 197) had cannabis exposure only during the first trimester and 67.6% (n = 413) had ongoing exposure beyond the first trimester. Cannabis exposure was associated with the primary composite outcome (25.9% in the cannabis exposure group vs 17.4% in the no exposure group; adjusted relative risk, 1.27 [95% CI, 1.07-1.49]) in the propensity score-weighted analyses after adjustment for sociodemographic characteristics, body mass index, medical comorbidities, and active nicotine use ascertained via urine cotinine assays. In a 3-category cannabis exposure model (no exposure, exposure only during the first trimester, or ongoing exposure), cannabis use during the first trimester only was not associated with the primary composite outcome; however, ongoing cannabis use was associated with the primary composite outcome (adjusted relative risk, 1.32 [95% CI, 1.09-1.60]). Conclusions and Relevance: In this multicenter cohort, maternal cannabis use ascertained by biological sampling was associated with adverse pregnancy outcomes related to placental dysfunction.

Trajectories of antenatal depression and adverse pregnancy outcomes.

BACKGROUND: Antenatal depression affects approximately 1 of 7 pregnancies, with an increasing prevalence across gestation. Data regarding the associations between antenatal depression and adverse pregnancy outcomes yielded conflicting results. However, previous studies evaluated the cross-sectional prevalence of depression at various time points and not the depressive symptom trajectory across gestation. OBJECTIVE: This study aimed to identify whether the trajectory of antenatal depressive symptoms is associated with different risks of adverse pregnancy outcomes. STUDY DESIGN: This was a secondary analysis of a large multisite prospective cohort of nulliparous women across the United States. The Edinburgh Postpartum Depression Scale was administered at 2 study visits: between 6 and 14 weeks' gestation and between 22 and 30 weeks' gestation. The Edinburgh Postpartum Depression Scale score trajectories were categorized as improved, stable, or worsened based on whether the scores changed by at least 1 standard deviation between the 2 visits. The frequencies of adverse pregnancy outcomes (hypertensive disorders of pregnancy, abruption, cesarean delivery, preterm birth [ie, <37 weeks' gestation], small for gestational age neonates, neonatal intensive care unit admission, and maternal readmission) were compared with depression trajectories across gestation in bivariable and multivariable analyses. Secondary analyses evaluated the frequencies of spontaneous and medically indicated preterm births and frequencies of spontaneous and medically indicated preterm births before 35, 32, and 28 weeks' gestation. RESULTS: Of the 8784 women who completed the 2 antenatal Edinburgh Postpartum Depression Scale screens, 1141 (13.0%) had improved, 6663 (75.9%) had stable, and 980 (11.2%) had worsened depressive symptom trajectories across gestation. Compared with women with improved or stable depressive symptoms, those with worsened symptoms were more likely to experience preterm birth (8.3% vs 7.4% vs 9.9%, respectively; P=.018). After controlling for potential confounders, worsened depressive symptoms remained associated with more frequent preterm birth (adjusted odds ratio, 1.68; 95% confidence interval, 1.10-2.57). CONCLUSION: Women with depression symptoms that worsen as pregnancy progresses have increased odds of preterm birth. Future research is warranted to optimize and implement effective prevention, screening, and treatment protocols for antenatal depressive symptoms as a strategy to prevent preterm birth.

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).

Prediction of Cerebral Palsy or Death among Preterm Infants Who Survive the Neonatal Period.

OBJECTIVE: To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death. STUDY DESIGN: This is a secondary analysis of data from a multicenter placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes (n = 11) and demographic and clinical factors (n = 10) evident by the time of discharge among surviving infants (n = 1889) and the primary outcome of death or moderate/severe CP at age 2 (n = 73) was estimated, and a prediction model was created. RESULTS: Gestational age in weeks at delivery (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.67-0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1-13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6-104.6), and male gender (OR: 2.5, CI: 1.4-4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78-0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants. CONCLUSION: IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae. KEY POINTS: · Factors known at hospital discharge are identified which are independently associated with death or CP by age 2.. · A model was created and validated using these findings to counsel parents.. · The risk of death or CP can be calculated at the time of hospital discharge..

Association between Hypertensive Disorders of Pregnancy and Long-Term Neurodevelopmental Outcomes in the Offspring.

OBJECTIVE: The long-term impact of hypertensive disorders of pregnancy (HDP) exposure on offspring health is an emerging research area. The objective of this study was to evaluate the association between a maternal diagnosis of HDP (gestational hypertension and preeclampsia) and adverse neurodevelopmental outcomes in the offspring. STUDY DESIGN: This was a secondary analysis of two parallel multicenter clinical trials of thyroxine therapy for subclinical hypothyroid disorders in pregnancy. Women with singleton nonanomalous gestations diagnosed with subclinical hypothyroidism or hypothyroxinemia were randomized to thyroxine therapy or placebo. The primary outcome was child intelligence quotient (IQ) at 5 years of age. Secondary outcomes included several neurodevelopmental measures, including the Bayley-III cognitive, motor, and language scores at 12 and 24 months, Differential Ability Scales-II (DAS-II) scores at 36 months, the Conners' rating scales-revised at 48 months, and scores from the Child Behavior Checklist at 36 and 60 months. Thyroxine therapy did not influence neurodevelopment in either of the primary studies. Associations between neurodevelopment outcomes and maternal HDP were examined using univariable and multivariable analyses. RESULTS: A total of 112 woman-child dyads with HDP were compared with 1,067 woman-child dyads without HDP. In univariable analysis, mean maternal age (26.7 ± 5.9 vs. 27.8 ± 5.7 years, p = 0.032) and the frequency of nulliparity (45.5 vs. 31.0%, p = 0.002) differed significantly between the two groups. Maternal socioeconomic characteristics did not differ between the groups. After adjusting for potential confounders, there were no significant differences in any primary or secondary neurodevelopment outcome between offspring exposed to HDP and those unexposed. However, when dichotomized as low or high scores, we found higher rates of language delay (language scores <85: -1 standard deviation) at 2 years of age among offspring exposed to HDP compared with those unexposed (46.5 vs. 30.5%, adjusted odds ratio = 2.22, 95% confidence interval [CI]: 1.44-3.42). CONCLUSION: In this cohort of pregnant women, HDP diagnosis was associated with language delay at 2 years of age. However, other long-term neurodevelopmental outcomes in offspring were not associated with HDP. KEY POINTS: · No differences were found in neurodevelopment between offspring exposed to HDP and controls.. · Higher rates of language delay at 2 years of age were found in offspring exposed to HDP.. · The results did not differ when analysis was stratified by preterm birth..

Cervical length distribution and other sonographic ancillary findings of singleton nulliparous patients at midgestation.

BACKGROUND: Short cervix at midgestation, the presence of intraamniotic debris, and cervical funneling are risk factors for preterm birth; however, cervical length measurements and cutoffs are not well documented among pregnant patients of different gestational ages and self-reported races and ethnicities. OBJECTIVE: This study aimed to describe the distribution of cervical length and frequency of funneling and debris at midgestation in nulliparous women by gestational age and race/ethnicity. STUDY DESIGN: This secondary analysis of screening data from a multicenter treatment trial of singleton nulliparous patients with short cervix was conducted at 14 geographically distributed, university-affiliated medical centers in the United States. Singleton nulliparous patients with no known risk factors for preterm birth were screened for trial participation and asked to undergo a transvaginal ultrasound to measure cervical length by a certified sonographer. The distribution of cervical length and the frequency of funneling and debris were assessed for each gestational age week (16-22 weeks) and stratified by self-reported race and ethnicity, which for this study were categorized as White, Black, Hispanic, and other. Patients enrolled in the randomized trial were excluded from this analysis. RESULTS: A total of 12,407 nulliparous patients were included in this analysis. The racial or ethnic distribution of the study participants was as follows: White, 41.6%; Black, 29.6%; Hispanic, 24.2%; and others, 4.6%. The 10th percentile cervical length for the entire cohort was 31.1 mm and, when stratified by race and ethnicity, 31.9 mm for White, 30.2 mm for Black, 31.4 mm for Hispanic, and 31.2 mm for patients of other race and ethnicity (P<.001). At each gestational age, the cervical length corresponding to the tenth percentile was shorter in Black patients. The 25 mm value commonly used to define a short cervix and thought to represent the 10th percentile ranged from 1.3% to 5.4% across gestational age weeks and 1.0% to 3.8% across race and ethnicity groups. Black patients had the highest rate of funneling (2.6%), whereas Hispanic and Black patients had higher rates of intraamniotic debris than White and other patients (P<.001). CONCLUSION: Black patients had shorter cervical length and higher rates of debris and funneling than White patients. The racial and ethnic disparities in sonographic midtrimester cervical findings may provide insight into the racial disparity in preterm birth rates in the United States.

Is Exposure to Intrapartum Prostaglandins for Labor Induction Associated with a Lower Incidence of Neonatal Respiratory Distress Syndrome?

OBJECTIVE: Respiratory distress syndrome (RDS) is implicated in 30% of neonatal deaths. Since prostaglandins promote surfactant secretion and labor is associated with a lower risk of RDS in term neonates, it is plausible that synthetic prostaglandin (sPG) exposure is associated with a lower risk of RDS. Thus, we evaluated the association between sPG exposure and RDS in neonates born after the induction of labor (IOL). STUDY DESIGN: Secondary analysis of women with singleton pregnancies undergoing IOL at 340/7 to 420/7 weeks in the nuMoM2b study, a multicenter prospective cohort of nulliparous women. RDS rates and secondary neonatal outcomes in neonates with intrapartum sPG exposure were compared with those who had IOL with non-sPG methods (e.g., balloon catheter, amniotomy, oxytocin, and laminaria). Logistic regression models estimated the association of sPG with RDS and with secondary outcomes after adjustment for clinical and demographic factors (including gestational age). A sensitivity analysis was performed in which analysis was restricted to those with an admission cervical dilation ≤2 cm. RESULTS: Of 10,038 women in the total cohort, 3,071 met inclusion criteria; 1,444 were exposed and 1,627 were unexposed to sPGs. Antenatal corticosteroid exposure rates were low (3.0%) and similar between groups. In univariable analysis, neonates with sPG exposure had higher rates of RDS (3.2 vs. 2.0%, odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.01-2.50). This relationship was similar by gestational age at delivery (term vs. preterm, interaction p = 0.14). After adjustment, the association between sPG and RDS was no longer significant (adjusted odds ratio: 1.4, 95% CI: 0.9-2.3). When analysis was restricted to subjects with admission cervical dilation of ≤2 cm, there was also no association between sPG exposure and RDS. CONCLUSION: In pregnancies between 34 and 42 weeks of gestation, exposure to sPG for cervical ripening or labor induction was not associated with newborn RDS. KEY POINTS: · RDS is implicated in 30% of neonatal deaths.. · sPG exposure was not associated with RDS.. · Avoiding preterm birth remains crucial in RDS prevention..

Gestational Weight Gain and Pregnancy Outcomes among Nulliparous Women.

OBJECTIVE: To determine the association between total gestational weight gain and perinatal outcomes. STUDY DESIGN: Data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be (NuMoM2b) study were used. Total gestational weight gain was categorized as inadequate, adequate, or excessive based on the 2009 Institute of Medicine guidelines. Outcomes examined included hypertensive disorders of pregnancy, mode of delivery, shoulder dystocia, large for gestational age or small for-gestational age birth weight, and neonatal intensive care unit admission. RESULTS: Among 8,628 women, 1,666 (19.3%) had inadequate, 2,945 (34.1%) had adequate, and 4,017 (46.6%) had excessive gestational weight gain. Excessive gestational weight gain was associated with higher odds of hypertensive disorders (adjusted odds ratio [aOR] = 2.05, 95% confidence interval [CI]: 1.78-2.36) Cesarean delivery (aOR = 1.24, 95% CI: 1.09-1.41), and large for gestational age birth weight (aOR = 1.49, 95% CI: 1.23-1.80), but lower odds of small for gestational age birth weight (aOR = 0.59, 95% CI: 0.50-0.71). Conversely, inadequate gestational weight gain was associated with lower odds of hypertensive disorders (aOR = 0.75, 95% CI: 0.62-0.92), Cesarean delivery (aOR = 0.77, 95% CI: 0.65-0.92), and a large for gestational age birth weight (aOR = 0.72, 95% CI: 0.55-0.94), but higher odds of having a small for gestational age birth weight (aOR = 1.64, 95% CI: 1.37-1.96). CONCLUSION: Both excessive and inadequate gestational weight gain are associated with adverse maternal and neonatal outcomes.

Fetal Tachycardia in the Setting of Maternal Intrapartum Fever and Perinatal Morbidity.

OBJECTIVE: The fetal consequences of intrapartum fetal tachycardia with maternal fever or clinical chorioamnionitis are not well studied. We evaluated the association between perinatal morbidity and fetal tachycardia in the setting of intrapartum fever. STUDY DESIGN: Secondary analysis of a multicenter randomized control trial that enrolled 5,341 healthy laboring nulliparous women ≥36 weeks' gestation. Women with intrapartum fever ≥ 38.0°C (including those meeting criteria for clinical chorioamnionitis) after randomization were included in this analysis. Isolated fetal tachycardia was defined as fetal heart rate (FHR) ≥160 beats per minute for at least 10 minutes in the absence of other FHR abnormalities. FHR abnormalities other than tachycardia were excluded from the analysis. The primary outcome was a perinatal composite (5-minute Apgar's score ≤3, intubation, chest compressions, or mortality). Secondary outcomes included low arterial cord pH (pH < 7.20), base deficit ≥12, and cesarean delivery. RESULTS: A total of 986 (18.5%) of women in the trial developed intrapartum fever, and 728 (13.7%) met criteria to be analyzed; of these, 728 women 336 (46.2%) had maternal-fetal medicine (MFM) reviewer-defined fetal tachycardia, and 349 of the 550 (63.5%) women during the final hour of labor had validated software (PeriCALM) defined fetal tachycardia. After adjusting for confounders, isolated fetal tachycardia was not associated with a significant difference in the composite perinatal outcome (adjusted odds ratio [aOR] = 3.15 [0.82-12.03]) compared with absence of tachycardia. Fetal tachycardia was associated with higher odds of arterial cord pH <7.2, aOR = 1.48 (1.01-2.17) and of infants with a base deficit ≥ 12, aOR = 2.42 (1.02-5.77), but no significant difference in the odds of cesarean delivery, aOR = 1.33 (0.97-1.82). CONCLUSION: Fetal tachycardia in the setting of intrapartum fever or chorioamnionitis is associated with significantly increased fetal acidemia defined as a pH <7.2 and base excess ≥12 but not with a composite perinatal morbidity. KEY POINTS: · The perinatal outcomes associated with fetal tachycardia in the setting of maternal fever are undefined.. · Fetal tachycardia was not significantly associated with perinatal morbidity although the sample size was limited.. · Fetal tachycardia was associated with an arterial cord pH <7.2 and base deficit of 12 or greater..

Treatment of Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy.

BACKGROUND: Subclinical thyroid disease during pregnancy may be associated with adverse outcomes, including a lower-than-normal IQ in offspring. It is unknown whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children. METHODS: We screened women with a singleton pregnancy before 20 weeks of gestation for subclinical hypothyroidism, defined as a thyrotropin level of 4.00 mU or more per liter and a normal free thyroxine (T4) level (0.86 to 1.90 ng per deciliter [11 to 24 pmol per liter]), and for hypothyroxinemia, defined as a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T4 level (<0.86 ng per deciliter). In separate trials for the two conditions, women were randomly assigned to receive levothyroxine or placebo. Thyroid function was assessed monthly, and the levothyroxine dose was adjusted to attain a normal thyrotropin or free T4 level (depending on the trial), with sham adjustments for placebo. Children underwent annual developmental and behavioral testing for 5 years. The primary outcome was the IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years. RESULTS: A total of 677 women with subclinical hypothyroidism underwent randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia at a mean of 17.8 weeks of gestation. In the subclinical hypothyroidism trial, the median IQ score of the children was 97 (95% confidence interval [CI], 94 to 99) in the levothyroxine group and 94 (95% CI, 92 to 96) in the placebo group (P=0.71). In the hypothyroxinemia trial, the median IQ score was 94 (95% CI, 91 to 95) in the levothyroxine group and 91 (95% CI, 89 to 93) in the placebo group (P=0.30). In each trial, IQ scores were missing for 4% of the children. There were no significant between-group differences in either trial in any other neurocognitive or pregnancy outcomes or in the incidence of adverse events, which was low in both groups. CONCLUSIONS: Treatment for subclinical hypothyroidism or hypothyroxinemia beginning between 8 and 20 weeks of gestation did not result in significantly better cognitive outcomes in children through 5 years of age than no treatment for those conditions. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00388297 .).

Quality of periconceptional dietary intake and maternal and neonatal outcomes.

BACKGROUND: Periconceptional diet quality is commonly suboptimal and sociodemographic disparities in diet quality exist. However, it is unknown whether individual periconceptional diet quality is associated with obstetric outcomes. OBJECTIVE: Our objective was to assess differences in maternal and neonatal outcomes according to maternal periconceptional diet quality. STUDY DESIGN: This is a secondary analysis of a large, multicenter prospective cohort study of 10,038 nulliparous women receiving obstetrical care at 8 United States centers. Women underwent 3 antenatal study visits and had detailed maternal and neonatal data abstracted by trained research personnel. In the first trimester (between 6 and 13 weeks), women completed the modified Block 2005 Food Frequency Questionnaire, a semiquantitative assessment of usual dietary intake for the 3 months around conception. Responses were scored using the Healthy Eating Index-2010, which assesses adherence to the 2010 Dietary Guidelines for Americans. Higher scores on the Healthy Eating Index represent better adherence. Healthy Eating Index scores were analyzed by quartile; quartile 4 represents the highest dietary quality. Bivariable and multivariable analyses were performed to assess associations between diet quality and outcomes. A sensitivity analysis in which markers of socioeconomic status were included in the multivariable Poisson regression models was performed. RESULTS: In the cohort of 8259 women with Healthy Eating Index data, the mean Healthy Eating Index score was 63 (±13) of 100. Women with the lowest quartile Healthy Eating Index scores were more likely to be younger, non-Hispanic black and Hispanic, publicly insured, low income, and tobacco users. They were more likely to have comorbidities (obesity, chronic hypertension, pregestational diabetes, mental health disorders), a higher prepregnancy body mass index, and less education. Women with lowest quartile scores experienced less frequent major perineal lacerations and more frequent postpartum hemorrhage requiring transfusion and hypertensive disorders of pregnancy, which persisted on multivariable analyses (controlling for age, body mass index, tobacco use, chronic hypertension, pregestational diabetes mellitus, and mental health disorders) comparing women in each quartile with quartile 4. Additionally, women in quartiles 1 and 2 experienced greater adjusted relative risk of cesarean delivery compared with women in quartile 4. Neonatal outcomes also differed by dietary quartile, with women in the lowest Healthy Eating Index quartile experiencing greater adjusted relative risk of preterm birth, neonatal intensive care unit admission, small for gestational age infant, and low birthweight, and lower risk of macrosomia; all neonatal findings also persisted in multivariable analyses. The sensitivity analysis with inclusion of markers of socioeconomic status (race/ethnicity, insurance status, marital status) in the multivariable models supported these findings. CONCLUSION: Periconceptional diet quality among women in the United States is poor. Poorer periconceptional dietary quality is associated with adverse maternal and neonatal outcomes, even after controlling for potential comorbidities and body mass index, suggesting periconceptional diet may be an important social or biological determinant of health underlying existing health disparities.

Associations of perceived prenatal stress and adverse pregnancy outcomes with perceived stress years after delivery.

Maternal stress is a risk factor for adverse pregnancy outcomes (APOs). This study evaluates the associations of prenatal stress and APOs with maternal stress years after pregnancy. The 10-item Perceived Stress Scale (PSS) (0-40 range) was completed in the first and third trimesters, and 2-7 years after delivery among a subsample (n = 4161) of nulliparous women enrolled at eight US medical centers between 2010 and 2013 in a prospective, observational cohort study. Demographics, medical history, and presence of APOs (gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), preeclampsia (PE), and medically indicated or spontaneous preterm birth (miPTB, sPTB)) were obtained. The associations of prenatal PSS and the presence of APOs with PSS scores years after delivery were estimated using multivariable linear regression. Mean PSS scores were 12.5 (95% CI 12.3, 12.7) and 11.3 (95% CI 11.1, 11.5) in the first and third trimesters respectively and 14.9 (95% CI 14.7, 15.1) 2-7 years later, an average increase of 2.4 points (95% CI 2.2, 2.6) from the start of pregnancy. Regressing PSS scores after delivery on first-trimester PSS and PSS increase through pregnancy showed positive associations, with coefficients (95% CI) of 2.8 (2.7, 3.0) and 1.5 (1.3, 1.7) per 5-point change, respectively. Adding APO indicator variables separately showed higher PSS scores for women with HDP (0.7 [0.1, 1.3]), PE (1.3 [0.6, 2.1]), and miPTB (1.3 [0.2, 2.4]), but not those with GDM or sPTB. In this geographically and demographically diverse sample, prenatal stress and some APOs were positively associated with stress levels 2-7 years after pregnancy.ClinicalTrials.gov Registration number NCT02231398.

Psychosocial and Sociodemographic Contributors to Breastfeeding Intention in First-Time Mothers.

OBJECTIVE: Breastfeeding has multiple benefits for women and babies. Understanding factors contributing to intention to exclusively breastfeed may allow for improving the rates in first-time mothers. The study objective was to examine factors associated with a woman's intention to breastfeed her first child. METHODS: A secondary analysis of the prospective "Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be" (nuMoM2b) study of nulliparous women in the U.S. with singleton pregnancies was performed. Sociodemographic and psychosocial factors were analyzed for associations with breastfeeding intention. RESULTS: For the 6443 women with complete information about breastfeeding intention and all factors under consideration, women who intended to breastfeed (either exclusively or any breastfeeding) were more likely to be older, not black, have reached a higher level of education, have higher incomes, have a lower body mass index (BMI), and be nonsmokers. Reporting a planned pregnancy and several psychosocial measures were also associated with intention to breastfeed. In the multivariable analysis for exclusive breastfeeding, in addition to age, BMI, race, income, education, and smoking, of the psychosocial measures assessed, only women with higher hassle intensity ratios on the Pregnancy Experience Scale had lower odds of exclusive breastfeeding intention (OR 0.71, 95% CI 0.55-0.92). Other psychosocial measures were not associated with either exclusive breastfeeding or any breastfeeding after controlling for demographic characteristics. CONCLUSIONS FOR PRACTICE: Several sociodemographic factors, having a planned pregnancy, and fewer intense pregnancy hassles compared to uplifts are associated with intention to exclusively breastfeed. Identifying these factors may allow providers to identify women for focused, multilevel efforts to enhance breastfeeding rates.

Sex-Specific Genetic Susceptibility to Adverse Neurodevelopmental Outcome in Offspring of Pregnancies at Risk of Early Preterm Delivery.

OBJECTIVE: To evaluate sex-specific genetic susceptibility to adverse neurodevelopmental outcome (ANO, defined as cerebral palsy [CP], mental, or psychomotor delay) at risk for early preterm birth (EPTB, < 32 weeks). STUDY DESIGN: Secondary case-control analysis of a trial of magnesium sulfate (MgSO4) before anticipated EPTB for CP prevention. Cases are infants who died by the age of 1 year or developed ANO. Controls, matched by maternal race and infant sex, were neurodevelopmentally normal survivors. Neonatal DNA was evaluated for 80 polymorphisms in inflammation, coagulation, vasoregulation, excitotoxicity, and oxidative stress pathways using Taqman assays. The primary outcome for this analysis was sex-specific ANO susceptibility. Conditional logistic regression estimated each polymorphism's odds ratio (OR) by sex stratum, adjusting for gestational age, maternal education, and MgSO4-corticosteroid exposures. Holm-Bonferroni corrections, adjusting for multiple comparisons (p < 7.3 × 10-4), accounted for linkage disequilibrium between markers. RESULTS: Analysis included 211 cases (134 males; 77 females) and 213 controls (130 males; 83 females). An interleukin-6 (IL6) polymorphism (rs2069840) was associated with ANO in females (OR: 2.6, 95% confidence interval [CI]: 1.5-4.7; p = 0.001), but not in males (OR: 0.8, 95% CI: 0.5-1.2; p = 0.33). The sex-specific effect difference was significant (p = 7.0 × 10-4) and was unaffected by MgSO4 exposure. No other gene-sex associations were significant. CONCLUSION: An IL6 gene locus may confer susceptibility to ANO in females, but not males, after EPTB.