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Background: Perinatal depression has been suggested to adversely impact child neurodevelopment. However, the complexity of the early childhood environment challenges conclusive findings., Objective: To evaluate whether there is an association between perinatal depressive symptoms and child intelligence quotient (IQ) at 5 years of age., Study Design: Secondary analysis of an ancillary study to a multicenter randomized trial of thyroxine therapy for pregnant individuals with subclinical hypothyroidism. Dyads of infants and birthing parent, with completed Center for Epidemiological Studies-Depression (CES-D) screens during pregnancy and postpartum and child neurodevelopment testing completed at five years of age (n=209) were included. CES-D screening was performed at 11-20 weeks, 34-38 weeks, and one-year postpartum. Depressive symptoms were categorized as antenatal (i.e., a positive screen at any point during pregnancy) or postpartum. The primary outcome was child IQ score < 85 at 5 years of age using the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III) Full Scale test. Secondary outcomes included other assessments of childhood neurodevelopment. Bivariable analyses and multivariable logistic regressions were utilized., Results: Of the 209 birthing people included, 72 (34%) screened positive for depression during pregnancy and 32 (15%) screened positive one year postpartum. Children born to individuals with a positive antenatal depression screen had a higher odds of IQ < 85 at 5 years of age compared with children born to individuals with a CES-D < 16 (35% vs. 18%, OR 2.4, 95% CI 1.2-4.7). Similar findings were seen for children born to individuals with a positive postpartum depression screen (47% vs. 21%, OR 3.3, 95% CI 1.5-7.3). These associations did not persist in multivariable analyses that controlled for social determinants of health and clinical characteristics (adjusted odd ratio [aOR] 1.4, 95% CI 0.7-3.1; aOR 2.1, 95% CI 0.9-5.1, for antenatal and postpartum depressive symptoms, respectively). Similar findings were observed for other adverse neurodevelopmental outcomes., Conclusions: Having a positive perinatal depression screen was not associated with child cognitive outcomes after controlling for covariates including social determinants of health., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To examine the incidence of overt hypothyroidism 1 and 5 years after pregnancies where screening before 21 weeks identified subclinical hypothyroidism (SH) or hypothyroxinemia (HT). Methods: Secondary analysis of two multicenter treatment trials for either SH or HT diagnosed between 8 and 20 weeks gestation. Current analyses focus only on individuals randomized to the placebo groups in the two parallel studies. SH was diagnosed with thyrotropin (TSH) ≥4.0 mU/L and normal free T4 (fT4) (0.86-1.9 ng/dL). HT was diagnosed with normal TSH (0.08-3.99 mU/L) but fT4 <0.86 ng/dL. Serum from initial testing was stored for later thyroid peroxidase (TPO) antibody assay; results were not returned for clinical management. At 1 and 5 years after delivery, participants were asked whether they had either been diagnosed with or were being treated for a thyroid condition. Maternal serum was collected at these visits and thyroid function measured. Subsequent overt hypothyroidism was defined as TSH ≥4.0 mU/L with fT4 <0.86 ng/dL. Results: Data for 1- and 5-year follow-up were available in 307 of the 338 participants with SH and 229 of the 261 with HT. Subsequent hypothyroidism was more common both at year 1 (13.4% vs. 3.1%, p < 0.001) and year 5 (15.6% vs. 2.6%, p < 0.001) for participants with SH compared with those with HT. This progression was more common in individuals with TSH values >10 mIU/mL. Baseline TPO level >50 IU/mL in participants with SH was associated with higher rates of hypothyroidism at year 1 (26.7% vs. 6.5%, odds ratio [OR] = 5.3 [confidence interval (CI) 2.6-10.7]) and year 5 (30.5% vs. 7.5%, OR = 5.4 [CI: 2.8-10.6]) compared with those with TPO levels ≤50 IU/mL. For participants with HT, no differences in overt hypothyroidism were seen at 1 year related to baseline TPO level >50 IU/mL (1/10 (10%) vs. 6/218 (2.8%), OR = 3.9 [CI: 0.43-36.1]), but more participants with TPO levels >50 IU/mL developed hypothyroidism by year 5 (2/10 (20%) vs. 4/218 (1.8%), OR = 13.4 [CI: 2.1-84.1]). Conclusion: SH is associated with higher rates of overt hypothyroidism or thyroid replacement therapy within 5 years of delivery than is HT when these conditions are diagnosed in the first half of pregnancy.

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], P adj 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.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study aimed to assess the association of maternal body mass index (BMI) with a composite of severe maternal outcomes., Study Design: Secondary analysis of a cohort of deliveries on randomly selected days at 25 hospitals from 2008 to 2011. Data on comorbid conditions, intrapartum events, and postpartum course were collected. The reference group (REF, BMI: 18.5-29.9kg/m 2 ), obese (OB; BMI: 30-39.9kg/m 2 ), morbidly obese (MO; BMI: 40-49.9kg/m 2 ), and super morbidly obese (SMO; BMI ≥ 50kg/m 2 ) women were compared. The composite of severe maternal outcomes was defined as death, intensive care unit (ICU) admission, ventilator use, deep venous thrombosis/pulmonary embolus (DVT/PE), sepsis, hemorrhage, disseminated intravascular coagulation (DIC), unplanned operative procedure, or stroke. Patients in the REF group were matched 1:1 with those in all other obesity groups based on propensity score using the baseline characteristics of age, race/ethnicity, previous cesarean, preexisting diabetes, chronic hypertension, parity, cigarette use, and insurance status. Multivariable Poisson's regression was used to estimate adjusted relative risks (aRRs) and 95% confidence intervals (CIs) for the association between BMI and the composite outcome. Because cesarean delivery may be in the causal pathway between obesity and adverse maternal outcomes, models were then adjusted for mode of delivery to evaluate potential mediation., Results: A total of 52,162 pregnant patients are included in the analysis. Risk of composite maternal outcomes was increased for SMO compared with REF but not for OB and MO [OB: aRR=1.06, 95% CI: 0.99-1.14; MO: aRR=1.10, 95% CI: 0.97-1.25; SMO: aRR=1.32, 95% CI: 1.02-1.70]. However, in the mediation analysis, cesarean appears to mediate 46% (95% CI: 31-50%) of the risk of severe morbidity for SMO compared with REF., Conclusion: Super morbid obesity is significantly associated with increased serious maternal morbidity and mortality; however, cesarean appears to mediate this association. Obesity and morbid obesity are not associated with maternal morbidity and mortality., Key Points: · Super morbid obesity is associated with increased morbidity.. · Cesarean appears to mediate the association between super morbid obesity and morbidity.. · Obesity and morbid maternal obesity are not associated with morbidity.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: We conducted a cross-sectional study of pregnant women with acute respiratory illness during delivery hospitalizations during influenza season to describe clinical testing for respiratory viruses and infection prevention practices., Methods: Women had nasal swabs tested for influenza and other respiratory viruses. Among 91 enrolled women, 22 (24%) had clinical testing for influenza., Results: Based on clinical and study testing combined, 41 of 91 (45%) women had samples positive for respiratory viruses. The most common virus was influenza (17 of 91, 19%); 53% (9 of 17) of influenza virus infections were identified through study testing alone. Only 16% of women were on droplet precautions., Conclusions: Peripartum respiratory infections may be underrecognized., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Objective: Headaches affect 88% of reproductive-aged women. Yet data are limited addressing treatment of headache in pregnancy. While many women experience improvement in pregnancy, primary and secondary headaches can develop. Consequently, pregnancy is a time when headache diagnosis can influence maternal and fetal interventions. This study was aimed to summarize existing randomized control trials (RCTs) addressing headache treatment in pregnancy., Study Design: We searched PubMed, CINAHL, EMBASE, ClinicalTrials.gov, Cochrane Library, CINAHL, and SCOPUS from January 1, 1970 through June 31, 2019. Studies were eligible if they were English-language RCTs addressing treatment of headache in pregnancy. Conference abstracts and studies investigating postpartum headache were excluded. Three authors reviewed English-language RCTs addressing treatment of antepartum headache. To be included, all authors agreed each article to meet the following criteria: predefined control group, participants underwent randomization, and treatment of headache occurred in the antepartum period. If inclusion criteria were met no exclusions were made. Our systematic review registration number was CRD42019135874., Results: A total of 193 studies were reviewed. Of the three that met inclusion criteria all were small, with follow-up designed to measure pain reduction and showed statistical significance., Conclusion: Our systematic review of RCTs evaluating treatment of headache in pregnancy revealed only three studies. This paucity of data limits treatment, puts women at risk for worsening headache disorders, and delays diagnosis placing both the mother and fetus at risk for complications., Competing Interests: K.D. was supported in part by an Unrestricted Grant from Research to Prevent Blindness, Inc., New York, NY, to the Department of Ophthalmology and Visual Sciences, University of Utah. M.W.V. was supported in part by the HA and Edna Benning Presidential Chair in Obstetrics and Gynecology., (Thieme. All rights reserved.)

Objective: To characterize stillbirths associated with pregestational diabetes and gestational diabetes mellitus (GDM) in a large, prospective, U.S. case-control study., Methods: A secondary analysis of stillbirths among patients enrolled in a prospective; multisite; geographically, racially, and ethnically diverse case-control study in the United States was performed. Singleton gestations with complete information regarding diabetes status and with a complete postmortem evaluation were included. A standard evaluation protocol for stillbirth cases included postmortem evaluation, placental pathology, clinical testing as performed at the discretion of the health care professional, and a recommended panel of tests. A potential cause of death was assigned to stillbirth cases using a standardized classification tool. Demographic and delivery characteristics among women with pregestational diabetes and GDM were compared with characteristics of women with no diabetes in pairwise comparisons using χ or two-sample t tests as appropriate. Sensitivity analysis was performed excluding pregnancies with genetic conditions or major fetal malformations., Results: Of 455 stillbirth cases included in the primary analysis, women with stillbirth and diabetes were more likely to be older than 35 years and have a higher body mass index. They were also more likely to have a gestational hypertensive disorder than women without diabetes (28% vs 9.1%; P<.001). Women with pregestational diabetes had more large-for-gestational-age (LGA) neonates (26% vs 3.4%; P<.001). Stillbirths occurred more often at term in women with pregestational diabetes (36%) and those with GDM (52%). Maternal medical complications, including pregestational diabetes and others, were more often identified as a probable or possible cause of death among stillbirths with maternal diabetes (43% vs 4%, P<.001) as compared with stillbirths without diabetes., Conclusion: Compared with stillbirths in women with no diabetes, stillbirths among women with pregestational diabetes and GDM occur later in pregnancy and are associated with hypertensive disorders of pregnancy, maternal medical complications, and LGA.

Objective: To estimate the proportion of accidental drug-related deaths and suicides classified as pregnancy-related from 2013 to 2014 (preimplementation of standardized criteria) and 2015 to 2016 (postimplementation)., Methods: Based on Centers for Disease Control and Prevention pregnancy-related death criteria, the Utah Perinatal Mortality Review Committee developed a standardized evaluation tool to assess accidental drug-related death and suicide beginning in 2015. We performed a retrospective case review of all pregnancy-associated deaths (those occurring during pregnancy or 1 year postpartum for any reason) and pregnancy-related deaths (those directly attributable to the pregnancy or postpartum events) evaluated by Utah's Perinatal Mortality Review Committee from 2013 to 2016. We compared the proportion of accidental drug-related deaths and suicides meeting pregnancy-related criteria preimplementation and postimplementation of a standardized criteria checklist tool using Fisher's exact test. We assessed the change in pregnancy-related mortality ratio in Utah from 2013 to 2014 and 2015 to 2016 using test of trend., Results: From 2013 to 2016, there were 80 pregnancy-associated deaths in Utah (2013-2014: n=40; 2015-2016: n=40), and 41 (51%) were pregnancy-related (2013-2014: n=15, 2015-2016: n=26). In 2013-2014 (preimplementation), 12 women died of drug-related deaths or suicides, and only two of these deaths were deemed pregnancy-related (17%). In 2015-2016 (postimplementation), 18 women died of drug-related deaths or suicide, and 94% (n=17/18) of these deaths met one or more of the pregnancy-related criteria on the checklist (P<.001). From 2013 to 2014 to 2015-2016, Utah's overall pregnancy-related mortality ratio more than doubled, from 11.8 of 100,000 to 25.7 of 100,000 (P=.08)., Conclusion: After application of standardized criteria, the Utah Perinatal Mortality Review Committee determined that pregnancy itself was the inciting event leading to the majority of accidental drug-related deaths or suicides among pregnant and postpartum women. Other maternal mortality review committees may consider a standardized approach to assessing perinatal suicides and accidental drug-related deaths.

Objective: To estimate whether the frequency of adverse maternal and neonatal outcomes differs between low-risk nulliparous and multiparous women at 39-41 weeks of gestation., Methods: This is a secondary analysis of an observational obstetrics cohort of maternal-neonatal dyads at 25 hospitals. Low-risk women with nonanomalous singletons who delivered between 39 0/7 and 41 6/7 weeks of gestation were included. The composite neonatal adverse outcome included 5-minute Apgar score less than five, ventilator support or cardiopulmonary resuscitation, seizure, hypoxic ischemic encephalopathy, sepsis, bronchopulmonary dysplasia, persistent pulmonary hypertension, necrotizing enterocolitis, birth injury or perinatal death. The composite maternal adverse outcome included infection, third- or fourth-degree perineal laceration, thromboembolism, transfusion of blood products, or maternal death. Small for gestational age (SGA), large for gestational age (LGA), and shoulder dystocia requiring maneuvers were also evaluated. Multivariable regression was used to estimate adjusted relative risks (aRRs) and adjusted odds ratios (aORs) with 95% CIs., Results: Of the 115,502 women in the overall cohort, 39,870 (34.5%) met eligibility criteria for this analysis; 18,245 (45.8%) were nulliparous. The risk of the composite neonatal adverse outcome (1.5% vs 1.0%, aRR 1.80, 95% CI 1.48-2.19), composite maternal adverse outcome (15.1% vs 3.3%, aRR 5.04, 95% CI 4.62-5.49), and SGA (8.9% vs 5.8%, aOR 1.45, 95% CI 1.33-1.57) was significantly higher in nulliparous than multiparous patients. The risk of LGA (aOR 0.65, 95% CI 0.60-0.71) and shoulder dystocia with maneuvers (aRR 0.68, 95% CI 0.60-0.77) was significantly lower in nulliparous rather than multiparous patients., Conclusion: The risk of composite adverse outcomes and SGA among low-risk nulliparous women at 39-41 weeks of gestation is significantly higher than among multiparous counterparts. However, nulliparous women had a lower risk of shoulder dystocia with maneuvers and LGA.

Objective: To estimate the effect of antenatal treatment of subclinical hypothyroidism on maternal depressive symptoms., Methods: We conducted an ancillary study to a multicenter trial in women with singleton pregnancies diagnosed with subclinical hypothyroidism randomized to antenatal thyroxine therapy or placebo. Treatment was discontinued at the end of pregnancy. Women with overt thyroid disease, diabetes, autoimmune disease, and those diagnosed with depression were excluded. Participants were assessed for depressive symptoms using the Center for Epidemiological Studies-Depression scale (CES-D) before starting the study drug (between 11 and 20 weeks of gestation), between 32 and 38 weeks of gestation, and at 1 year postpartum. The primary outcome was maternal depressive symptoms score as assessed using the CES-D. Secondary outcome was the percentage of women who scored 16 or higher on the CES-D, as such a score is considered screen-positive for depression., Results: Two hundred forty-five (36.2% of parent trial) women with subclinical hypothyroidism were allocated to thyroxine (n=124) or placebo (n=121). Median CES-D scores and the proportion of participants with positive scores were similar at baseline between the two groups. Treatment with thyroxine was not associated with differences in CES-D scores (10 [5-15] vs 10 [5-17]; P=.46) or in odds of screening positive in the third trimester compared with placebo, even after adjusting for baseline scores (24.3% vs 30.1%, adjusted odds ratio 0.63, 95% CI 0.31-1.28, P=.20). At 1 year postpartum, CES-D scores were not different (6 [3-11] vs 6 [3-12]; P=.79), nor was the frequency of screen-positive CES-D scores in the treated compared with the placebo group (9.7% vs 15.8%; P=.19). Treatment with thyroxine during pregnancy was also not associated with differences in odds of screening positive at the postpartum visit compared with placebo even after adjusting for baseline scores. Sensitivity analysis including women who were diagnosed with depression by the postpartum visit did not change the results., Conclusions: This study did not achieve its planned sample size, thus our conclusions may be limited, but in this cohort of pregnant women with subclinical hypothyroidism, antenatal thyroxine replacement did not improve maternal depressive symptoms.

Objective: To assess whether treatment of pregnant women with subclinical hypothyroidism or hypothyroxinemia alters neonatal TSH results., Study Design: A planned secondary analysis of data from two multi-center randomized, double-masked, placebo-controlled thyroxine replacement trials in pregnant women with either subclinical hypothyroidism or hypothyroxinemia. Infant heel-stick specimens were obtained before discharge. We compared TSH levels between neonates born to mothers allocated to treatment or placebo within each trial and between neonates in the placebo groups. Multiples of means were generated for day-of-life-specific data., Results: Neonatal TSH values were available for 573/677 (84.6%) newborns from the subclinical hypothyroidism trial and 461/526 (87.6%) newborns from the hypothyroxinemia trial. Neonatal TSH values did not differ in either trial by treatment group or between placebo groups (P > 0.05 for all comparisons)., Conclusions: Neonatal TSH values did not differ with thyroid hormone replacement in pregnancies diagnosed with subclinical hypothyroidism or hypothyroxinemia.

Background: Obesity is associated with increased risk of stillbirth, although the mechanisms are unknown. Obesity is also associated with inflammation. Serum ferritin, C-reactive protein, white blood cell count, and histologic chorioamnionitis are all markers of inflammation., Objective: This article determines if inflammatory markers are associated with stillbirth and body mass index (BMI). Additionally, we determined whether inflammatory markers help to explain the known relationship between obesity and stillbirth., Study Design: White blood cell count was assessed at admission to labor and delivery, maternal serum for assessment of various biomarkers was collected after study enrollment, and histologic chorioamnionitis was based on placental histology. These markers were compared for stillbirths and live births overall and within categories of BMI using analysis of variance on logarithmic-transformed markers and logistic regression for dichotomous variables. The impact of inflammatory markers on the association of BMI categories with stillbirth status was assessed using crude and adjusted odds ratios (COR and AOR, respectively) from logistic regression models. The interaction of inflammatory markers and BMI categories on stillbirth status was also assessed through logistic regression. Additional logistic regression models were used to determine if the association of maternal serum ferritin with stillbirth is different for preterm versus term births. Analyses were weighted for the overall population from which this sample was derived., Results: A total of 497 women with singleton stillbirths and 1,414 women with live births were studied with prepregnancy BMI (kg/m 2 ) categorized as normal (18.5-24.9), overweight (25.0-29.9), or obese (30.0 + ). Overweight (COR, 1.48; 95% confidence interval [CI]: 1.14-1.94) and obese women (COR, 1.60; 95% CI: 1.23-2.08) were more likely than normal weight women to experience stillbirth. Serum ferritin levels were higher (geometric mean: 37.4 ng/mL vs. 23.3, p  < 0.0001) and C-reactive protein levels lower (geometric mean: 2.9 mg/dL vs. 3.3, p  = 0.0279), among women with stillbirth compared with live birth. Elevated white blood cell count (15.0 uL × 10 3 or greater) was associated with stillbirth (21.2% SB vs. 10.0% live birth, p  < 0.0001). Histologic chorioamnionitis was more common (33.2% vs. 15.7%, p  < 0.0001) among women with stillbirth compared with those with live birth. Serum ferritin, C-reactive protein, and chorioamnionitis had little impact on the ORs associating stillbirth with overweight or obesity. Adjustment for elevated white blood cell count did not meaningfully change the OR for stillbirth in overweight versus normal weight women. However, the stillbirth OR for obese versus normal BMI changed by more than 10% when adjusting for histologic chorioamnionitis (AOR, 1.38; 95% CI: 1.02-1.88), indicating confounding. BMI by inflammatory marker interaction terms were not significant. The association of serum ferritin levels with stillbirth was stronger among preterm births ( p  = 0.0066)., Conclusion: Maternal serum ferritin levels, elevated white blood cell count, and histologic chorioamnionitis were positively and C-reactive protein levels negatively associated with stillbirth. Elevated BMIs, both overweight and obese, were associated with stillbirth when compared with women with normal BMI. None of the inflammatory markers fully accounted for the relationship between obesity and stillbirth. The association of maternal serum ferritin with stillbirth was stronger in preterm than term stillbirths., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: The objective of this study is to examine perinatal outcomes associated with cholestasis of pregnancy according to bile acid level and antenatal testing practice., Study Design: Retrospective cohort study of women with symptoms and bile acid testing from 2005 to 2014. Women were stratified by bile acid level: no cholestasis (<10 μmol/L), mild (10-39 μmol/L), moderate (40-99 μmol/L), and severe (≥100 μmol/L). The primary outcome was composite neonatal morbidity (hypoxic ischemic encephalopathy, severe intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, or death)., Results: 785 women were included; 487 had cholestasis (347 mild, 108 moderate, 32 severe) and 298 did not. After controlling for gestational age (GA), severe cholestasis was associated with the composite neonatal outcome (aRR 5.6, 95% CI 1.3-23.5) and meconium-stained fluid (aRR 4.82, 95%CI 1.6-14.2). Bile acid levels were not correlated with the frequency of testing (p = .50). Women who underwent twice weekly testing were delivered earlier (p = .016) than women tested less frequently, but the difference in GA was ≤4 d. Abnormal testing prompting delivery was uncommon. Among women with cholestasis, there were three stillbirths. One of these women was undergoing antenatal testing, which was normal 1 d prior to the fetal demise., Conclusion: Severe cholestasis is associated with neonatal morbidity which antenatal testing may not predict.

Objective: To estimate the proportion of potentially preventable stillbirths in the United States., Methods: We conducted a secondary analysis of 512 stillbirths with complete evaluation enrolled in the Stillbirth Collaborative Research Network from 2006 to 2008. The Stillbirth Collaborative Research Network was a multisite, geographically, racially, and ethnically diverse, population-based case-control study of stillbirth in the United States. Cases of stillbirth underwent standard evaluation that included maternal interview, medical record abstraction, biospecimen collection, postmortem examination, placental pathology, and clinically recommended evaluation. Each stillbirth was assigned probable and possible causes of death using the Initial Causes of Fetal Death algorithm system. For this analysis, we defined potentially preventable stillbirths as those occurring in nonanomalous fetuses, 24 weeks of gestation or greater, and weighing 500 g or greater that were 1) intrapartum, 2) the result of medical complications, 3) the result of placental insufficiency, 4) multiple gestation (excluding twin-twin transfusion), 5) the result of spontaneous preterm birth, or 6) the result of hypertensive disorders of pregnancy., Results: Of the 512 stillbirths included in our cohort, causes of potentially preventable stillbirth included placental insufficiency (65 [12.7%]), medical complications of pregnancy (31 [6.1%]), hypertensive disorders of pregnancy (20 [3.9%]), preterm labor (16 [3.1%]), intrapartum (nine [1.8%]), and multiple gestations (four [0.8%]). Twenty-seven stillbirths fit two or more categories, leaving 114 (22.3%) potentially preventable stillbirths., Conclusion: Based on our definition, almost one fourth of stillbirths are potentially preventable. Given the predominance of placental insufficiency among stillbirths, identification and management of placental insufficiency may have the most immediate effect on stillbirth reduction.

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 (T 4 ) 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 T 4 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 T 4 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 .).

Objective: To evaluate whether pregnancy-associated hypertension (preeclampsia or gestational hypertension) among women with varying degrees of glucose intolerance during pregnancy is associated with maternal metabolic syndrome 5-10 years later., Methods: This was an observational cohort study of women previously enrolled in a treatment trial of mild gestational diabetes mellitus or an observational study of lesser degrees of glucose intolerance evaluated 5-10 years after their index pregnancy. At follow-up, women underwent anthropometric and blood pressure measurements and analysis of fasting glucose and serum lipids., Results: A total of 825 women (47% of eligible women from the original study) were included in this analysis and evaluated at a median 7 years after their index pregnancy at a median age of 35 years. Overall, 239 (29%) had subsequent metabolic syndrome. The frequency of metabolic syndrome and its components was highest in the women who had pregnancy-associated hypertension and delivered preterm. After adjusting for confounding factors, pregnancy-associated hypertension in women who delivered preterm was associated with subsequent hypertension (130/85 mm Hg or greater; relative risk 3.06, 95% confidence interval [CI] 1.95-4.80, P<.001), high triglycerides (150 mg/dL or greater; relative risk 1.82, 95% CI 1.06-3.14, P=.03), and metabolic syndrome (per the American Heart Association and National Heart Lung and Blood Institute Scientific Statement; relative risk 1.78, 95% CI 1.14-2.78, P=.01) compared with women who remained normotensive throughout their index pregnancy and were delivered at term., Conclusion: Women with varying degrees of glucose intolerance who experienced pregnancy-associated hypertension and then delivered preterm had a higher frequency of subsequent hypertension, high triglycerides, and metabolic syndrome 5-10 years later.

Objective: We sought to evaluate whether the presence of condition-specific obstetric protocols within a hospital was associated with better maternal and neonatal outcomes., Study Design: This was a cohort study of a random sample of deliveries performed at 25 hospitals over 3 years. Condition-specific protocols were collected from all hospitals and categorized independently by 2 authors. Data on maternal and neonatal outcomes, as well as data necessary for risk adjustment were collected. Risk-adjusted outcomes were compared according to whether the patient delivered in a hospital with condition-specific obstetric protocols at the time of delivery., Results: Hemorrhage-specific protocols were not associated with a lower rate of postpartum hemorrhage or with fewer cases of estimated blood loss >1000 mL. Similarly, in the presence of a shoulder dystocia protocol, there were no differences in the frequency of shoulder dystocia or number of shoulder dystocia maneuvers used. Conversely, preeclampsia-specific protocols were associated with fewer intensive care unit admissions (odds ratio, 0.28; 95% confidence interval, 0.18-0.44) and fewer cases of severe maternal hypertension (odds ratio, 0.86; 95% confidence interval, 0.77-0.96)., Conclusion: The presence of condition-specific obstetric protocols was not consistently shown to be associated with improved risk-adjusted outcomes. Our study would suggest that the presence or absence of a protocol does not matter and regulations to require protocols are not fruitful., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The aim of the article is to determine whether maternal body mass index (BMI) influences the beneficial effects of diabetes treatment in women with gestational diabetes mellitus (GDM)., Study Design: Secondary analysis of a multicenter randomized treatment trial of women with GDM. Outcomes of interest were elevated umbilical cord c-peptide levels (> 90th percentile 1.77 ng/mL), large for gestational age (LGA) birth weight (> 90th percentile), and neonatal fat mass (g). Women were grouped into five BMI categories adapted from the World Health Organization International Classification of normal, overweight, and obese adults. Outcomes were analyzed according to treatment group assignment., Results: A total of 958 women were enrolled (485 treated and 473 controls). Maternal BMI at enrollment was not related to umbilical cord c-peptide levels. However, treatment of women in the overweight, Class I, and Class II obese categories was associated with a reduction in both LGA birth weight and neonatal fat mass. Neither measure of excess fetal growth was reduced with treatment in normal weight (BMI < 25 kg/m(2)) or Class III (BMI ≥ 40 kg/m(2)) obese women., Conclusion: There was a beneficial effect of treatment on fetal growth in women with mild GDM who were overweight or Class I and Class II obese. These effects were not apparent for normal weight and very obese women., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: The purpose of this study was to determine whether hospital differences in the frequency of adverse obstetric outcomes are related to differences in care., Study Design: The Assessment of Perinatal EXcellence cohort comprises 115,502 women and their neonates who were born in 25 hospitals in the United States between March 2008 and February 2011. Hierarchical logistic regression was used to quantify the amount of variation in postpartum hemorrhage, peripartum infection, severe perineal laceration, and a composite adverse neonatal outcome among hospitals that is explained by differences in patient characteristics, hospital characteristics, and obstetric care provided., Results: The study included 115,502 women. For most outcomes, 20-40% of hospital differences in outcomes were related to differences in patient populations. After adjusting for patient-, provider-, and hospital-level factors, multiple care processes were associated with the predefined adverse outcomes; however, these care processes did not explain significant variation in the frequency of adverse outcomes among hospitals. Ultimately, 50-100% of the interhospital variation in outcomes was unexplained., Conclusion: Hospital differences in the frequency of adverse obstetric outcomes could not be explained by differences in frequency of types of care provided., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth., Methods and Findings: We conducted a population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings., Conclusions: Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies. Please see later in the article for the Editors' Summary.

Objective: To estimate the frequency of severe maternal morbidity, assess its underlying etiologies, and develop a scoring system to predict its occurrence.Supplemental Digital Content is Available in the Text., Methods: This was a secondary analysis of a Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network cohort of 115,502 women and their neonates born in 25 hospitals across the United States over a 3-year period. Women were classified as having severe maternal morbidity according to a scoring system that takes into account the occurrence of red blood cell transfusion (more than three units), intubation, unanticipated surgical intervention, organ failure, and intensive care unit admission. The frequency of severe maternal morbidity was calculated and the underlying etiologies determined. Multivariable analysis identified patient factors present on admission that were independently associated with severe maternal morbidity; these were used to develop a prediction model for severe maternal morbidity., Results: Among 115,502 women who delivered during the study period, 332 (2.9/1,000 births, 95% confidence interval 2.6-3.2) experienced severe maternal morbidity. Postpartum hemorrhage was responsible for approximately half of severe maternal morbidity. Multiple patient factors were found to be independently associated with severe maternal morbidity and were used to develop a predictive model with an area under the receiver operating characteristic curve of 0.80., Conclusion: Severe maternal morbidity occurs in approximately 2.9 per 1,000 births, is most commonly the result of postpartum hemorrhage, and occurs more commonly in association with several identifiable patient characteristics., Level of Evidence: : II.

Objective: To assess the relationship between a low 50-g 1-hour glucose loading test (GLT) and maternal and neonatal outcomes in women without diabetes., Study Design: This was a secondary analysis of a multicenter observational cohort from a randomized trial of treatment for mild gestational diabetes. Maternal and neonatal outcomes were compared between women with GLT values < 90 mg/dL and those with results 90 to 119 mg/dL., Results: Of 436 enrolled women, 297 (68.1%) had a GLT result of 90 to 119 mg/dL and 139 (31.9%) had a result of < 90 mg/dL. There was a lower incidence of neonatal hypoglycemia in those with a GLT < 90 mg/dL (5.7% versus 16.5%, p = 0.006). Other outcomes were not associated with test results., Conclusion: A GLT result < 90 mg/dL compared with 90 to 119 mg/dL is associated with a lower risk of neonatal hypoglycemia, but no other significant findings., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To estimate the cost-effectiveness of a trial of labor after one previous cesarean (TOLAC) when incorporating long-term events and outcomes., Methods: A Markov model comparing TOLAC with elective repeat cesarean delivery (ERCD) was developed for a hypothetical cohort with no contraindication to a TOLAC. Women were selected from a prospective study to derive probability estimates for potential events through three subsequent pregnancies. Probabilities for cerebral palsy and stress urinary incontinence, cost data, and quality-adjusted life-years (QALYs) were obtained from the literature. The primary outcome was cost-effectiveness measured as the marginal cost per QALY gained, with a $50,000 threshold per QALY used to define cost-effectiveness., Results: The TOLAC strategy dominated the ERCD strategy at baseline, with $164.2 million saved and 500 QALYs gained per 100,000 women. The model was sensitive to six variables: the probability of uterine rupture and successful TOLAC among women with no prior vaginal delivery, the frequency of stress urinary incontinence, and the costs of failed TOLAC, successful TOLAC, and ERCD. When the probability of TOLAC success was at the base value, 67.2%, TOLAC was preferred if the probability of uterine rupture was 3.1% or less. When the probability of uterine rupture was at the base value, 0.8%, the TOLAC strategy was preferred as long as the probability of success was 47.2% or more. Probabilistic sensitivity analysis confirmed the base-case analysis., Conclusions: Under baseline circumstances, TOLAC is less expensive and more effective than an ERCD when considering long-term consequences when the likelihood of success is 47.2% or more., (Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.)

Myasthenia gravis is an autoimmune disease of the neuromuscular junction characterized by painless fluctuating skeletal muscle weakness. Disease exacerbations are more likely to occur in the first trimester or puerperium. A number of medications commonly used in obstetric practice can exacerbate the disease. The effect of pregnancy on myasthenia varies substantially from woman to woman and also from pregnancy to pregnancy in the same woman. Mainstay treatments involve acetylcholine esterase inhibitors, corticosteroids and other immunosuppressants, and adequate rest. Newborns may suffer in utero or neonatal consequences, usually transient, of transplacental antibody exposure.

Over 25,000 epileptic women deliver viable pregnancies each year in the United States. Although medical management is the first line of treatment, many physiological changes associated with pregnancy can make optimal treatment challenging. Medication dosage is adjusted based on side effects and seizure frequency, with the goal being no seizures with the lowest medication dosage(s) and side-effect profile possible. Whenever possible, monotherapy is preferred. Many antiepileptic drugs have teratogenic potential, so preconceptional optimization of medication dosage(s) is recommended. Epilepsy has associated neurological comorbidities, the most common being migraines and sleep disorders.

Objective: To compare population versus customized fetal growth norms in identifying neonates at risk for adverse outcomes (APO) associated with small for gestational age (SGA)., Study Design: Secondary analysis of an intrapartum fetal pulse oximetry trial in nulliparous women at term. Birth weight percentiles were calculated using ethnicity- and gender-specific population norms and customized norms (Gardosi)., Results: Of the studied neonates, 508 (9.9%) and 584 (11.3%) were SGA by population (SGApop) and customized (SGAcust) norms, respectively. SGApop infants were significantly associated with a composite adverse neonatal outcome, neonatal intensive care admission, low fetal oxygen saturation, and reduced risk of cesarean delivery; both SGApop and SGAcust infants were associated with a 5-minute Apgar score < 4. The ability of customized and population birth weight percentiles in predicting APO was poor (12 of 14 APOs had area under the curve of <0.6)., Conclusion: In this intrapartum cohort, neither customized nor normalized population norms adequately identified neonates at risk of APO related to SGA., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To evaluate whether neonates born to women who previously had received antenatal corticosteroids and then delivered a late-preterm-birth neonate had less respiratory morbidity compared with those not exposed to antenatal corticosteroids., Methods: This is a secondary analysis from a multicenter observational study regarding mode of delivery after previous cesarean delivery. We compared women who received one course of antenatal corticosteroids with unexposed parturients and evaluated various respiratory outcomes among those having a singleton, late-preterm-birth neonate. We controlled for potential confounders including gestational age at delivery, diabetes, mode of delivery, and maternal race., Results: Five thousand nine hundred twenty-four patients met the inclusion criteria; 550 received steroids and 5,374 did not. In the univariable model, compared with unexposed women, those who received antenatal corticosteroids appeared more likely to have neonates who required ventilatory support (11.5% compared with 8.6%, P=.022), had respiratory distress syndrome (RDS) (17.1% compared with 12.2%, P=.001), developed transient tachypnea of the newborn (12.9% compared with 9.8%, P=.020), or required resuscitation in the delivery room (55.8% compared with 49.7%, P=.007). After controlling for confounding factors, we found no significant differences among the groups regarding all of the above outcomes with an odds ratio for RDS of 0.78 (95% confidence interval, 0.60-1.02) and ventilator support of 0.75 (95% confidence interval, 0.55-1.03)., Conclusion: Exposure to antenatal corticosteroids does not significantly affect respiratory outcomes among those with a subsequent late-preterm birth.

Objective: To determine if maternal asthma or asthma severity affects newborn morphometry., Study Design: A secondary analysis was performed on data collected in a multicenter prospective observational cohort study of asthma in pregnancy. Patients enrolled included women with asthma stratified by severity of disease and controls. Asthma severity was defined according to the classification proposed by the National Asthma Education Program (NAEP) Report of the Working Group on Asthma and Pregnancy, modified to include medication requirements. Newborn morphometry measurements included birth weight (BW) and multiples of the median birth weight (BW-MOM), head circumference (HC), length (L), HC:BW ratio, and ponderal index (PI)., Results: Of 2480 patients there were 828 nonasthmatic controls, 828 with mild, 775 with moderate, and 49 with severe disease. Comparing all groups, there were statistically significant differences in maternal age (p < .001), race (p = .005), parity (p = .006), prepregnancy weight (p = .028), and medical care source (p = .001), with the severe asthma group having the highest mean maternal age (25.7 years), and proportion of African Americans (71.4%), proportion of multiparous patients (63.3%), and proportion of patients receiving government assistance (85.7%). When the control group was excluded from the comparisons, differences in prepregnancy weight and medical care source were no longer significant. BW-MOM and L did not differ between groups. The HC:BW ratio increased with asthma severity (p = .029) and was increased compared to controls (p = .010). This remained significant after controlling for confounding variables (both p <.001). HC was statistically significantly different between all groups (p = .032), as well as among women with varying degrees of asthma severity (p = .013), which was not clinically significant. After covariates adjustment, HC was not significantly different among all groups (p = .228), nor the asthma groups (p = .144)., Conclusion: Asthma severity is associated with an increased HC:BW ratio. Severity was not found to impact HC, BW-MOM, L, or PI independently. However, the magnitudes of the effects were too small to suggest a clinically significant effect of asthma on neonatal morphometry in this large prospectively studied sample.

Background: The article was designed to estimate the effect of active and passive household cigarette smoke exposure on asthma severity and obstetric and neonatal outcomes in pregnant women with asthma., Methods: We used a secondary observational analysis of pregnant women with mild and moderate-severe asthma enrolled in a prospective observational cohort study of asthma in pregnancy and a randomized clinical trial (RCT) comparing inhaled beclomethasone and oral theophylline. A baseline questionnaire detailing smoking history and passive household smoke exposure was given to each patient. Smoking status was confirmed in the RCT using cotinine levels. Data on asthma severity and obstetric and neonatal outcomes were collected and analyzed with respect to self-reported tobacco smoke exposure. Kruskal-Wallis and Pearson chi(2) statistics were used to test for significance., Results: A total of 2,210 women were enrolled: 1,812 in the observational study and 398 in the RCT. Four hundred and eight (18%) women reported current active smoking. Of the nonsmokers, 790 (36%) women reported passive household smoke exposure. Active smoking was associated with more total symptomatic days (P < .001) and nights of sleep disturbance (P < .001). Among the newborns of active smokers, there was a greater risk of small for gestational age < 10th percentile (P < .001), and a lower mean birth weight (P < .001). There were no differences in symptom exacerbation or outcome between nonsmokers with and without passive household cigarette smoke exposure., Conclusions: Among pregnant women with asthma, active but not passive smoking is associated with increased asthma symptoms and fetal growth abnormalities.

Objective: Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of prematurity. We hypothesized that, when controlled for delivery gestational age, potential prolonged exposure to inflammation/infection could be harmful to the developing fetus., Study Design: We studied a retrospective cohort of pregnancies with PPROM at 22.0-33.9 weeks' gestation. The primary outcome was perinatal survival without major morbidity (grade III/IV intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia). Regression models assessed predictors of perinatal morbidity., Results: Three hundred six women were included. PPROM occurred at a median of 29.4 weeks' gestation (interquartile range [IQR], 24.7-32.1 weeks' gestation). Median latency was 8 days (IQR, 3-15 days). Median delivery age was 31.4 weeks' gestation (IQR, 27.4-33.3 weeks' gestation). Two hundred seventy-seven infants (91%) survived; 233 infants (84% of survivors, 76% of all babies) did not have major morbidities. Gestational age (odds ratio, 0.60; 95% confidence interval, 0.53-0.68) and congenital sepsis (odds ratio, 13.2; 95% confidence interval, 3.9-44.5), but not latency, predicted perinatal morbidity in multivariate models., Conclusion: Latency does not appear to worsen outcomes in pregnancies that are complicated by PPROM.

Objective: To estimate success rates and risks with a trial of labor after one previous cesarean delivery for multifetal gestation compared with one previous cesarean delivery for a singleton pregnancy., Methods: Patients from the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network Cesarean Registry with one previous cesarean delivery and a current term singleton pregnancy were identified. Cases had one previous cesarean delivery for a multifetal pregnancy. Controls had one previous cesarean delivery for a singleton pregnancy., Results: Of cases, 556 of 944 (58.9%) attempted a trial of labor. Of controls, 13,923 of 29,329 (47.5%) attempted a trial of labor. The trial of labor success rate was 85.6% among cases and 73.1% among controls (odds ratio 2.19, 95% confidence interval 1.72-2.78). Compared with trial of labor controls, cases had no statistically increased risk of transfusion, endometritis, intensive care unit admissions, uterine rupture, or perinatal complications. Cases in this analysis with a successful trial of labor were more likely to have previously had a successful vaginal birth after cesarean (37.1% compared with 14.1%, P<.001)., Conclusion: Women with one previous cesarean delivery for a multifetal gestation have high trial of labor success rates and low complication rates.

To examine whether the magnitude-squared coherence between uterine and umbilical blood flow velocity waveforms can, in conjunction with estimated fetal weight, uterine and umbilical pulsatility indices, fetal and maternal heart rates, diastolic notching and the amniotic fluid index, create a sensitive and specific model for the prediction of placental dysfunction. Binary logistic prediction models are created for preeclampsia, pregnancy induced hypertension and intrauterine growth restriction in a study group of 284 unselected midtrimester pregnancies. In each study group, the median value of derived parameters were compared with the uncomplicated pregnancy control group. The magnitude-squared coherence function between the uterine and umbilical flow velocity waveforms was found to be a statistically significant predictor of preeclampsia during the midtrimester of pregnancy. The magnitude-squared coherence did not improve the prediction of intrauterine growth restriction or pregnancy induced hypertension. The inclusion of magnitude-squared coherence as one of the prediction parameters may improve the early identification of pregnancies subsequently complicated by preeclampsia.

Objective: To evaluate whether maternal obesity is associated with pulmonary and nonpulmonary pregnancy complications in asthmatic women., Methods: This is a secondary analysis of the prospective cohort Asthma During Pregnancy Study. Asthma patients were classified as having either mild or moderate to severe disease at the beginning of the study. Rates of pulmonary complications of asthma in asthmatic women and rates of nonpulmonary complications of pregnancy among asthma patients and controls, were compared between obese (body mass index > or = 30 kg/m2) and nonobese women., Results: Maternal body mass index and pregnancy outcome data were available for 1,699 of 1,812 asthmatic women and for 867 of 881 controls. Of the asthma subjects, 30.7% (521) were obese compared with 25.5% of the controls, P = .006. Obese women, regardless of whether they had asthma, were more likely to undergo cesarean delivery (OR 1.6, 95% confidence interval [CI]1.3-2.0) to develop preeclampsia or gestational hypertension (OR 1.7 95% CI 1.3-2.3) and gestational diabetes (OR 4.2, 95% CI 2.8-6.3). There were no differences in the rates of overall asthma improvement (20.6% compared with 23.6%, P = .36) or deterioration (33.3% compared with 28.8%, P = .20) between obese and nonobese asthma patients. After adjustment for confounding variables, obesity, not asthma, was associated with nonpulmonary complications of pregnancy, and obesity was associated with an increase in asthma exacerbations as well (OR 1.3, 95% CI 1.1-1.7)., Conclusion: Obesity is associated with an increased risk of asthma exacerbations during pregnancy. The increased rate of nonpulmonary complications of pregnancy in asthma patients is associated with obesity in this population and not with asthma status., Level of Evidence: II-1.

Objective: Assess effects of body mass index (BMI) on trial of labor after previous cesarean delivery and determine whether morbidly obese women have greater maternal and perinatal morbidity with trial of labor compared with elective repeat cesarean delivery., Methods: Secondary analysis from a prospective observational study included all term singletons undergoing trial of labor after previous cesarean delivery. Body mass index groups were as follows: normal 18.5-24.9, overweight 25.0-29.9, obese 30.0-39.9, morbidly obese 40.0 kg/m2 or greater, and were compared for failure and maternal and neonatal morbidities. The morbidly obese trial of labor and elective repeat cesarean delivery were compared for maternal and neonatal morbidities. Multivariable logistic regression analysis controlled for confounding variables., Results: There were 14,142 trial of labor participants and 14,304 elective repeat cesarean delivery participants. Increasing BMI was directly associated with failed trial of labor after previous cesarean delivery: from 15.2% in normal weight (1,344) to 39.3% in morbidly obese (1,638), with combined risk of rupture/dehiscence increasing from 0.9% to 2.1% in morbidly obese women. Among morbidly obese women, trial of labor carried greater than five-fold risk of uterine rupture/dehiscence (2.1% versus 0.4%), almost a two-fold increase in composite maternal morbidity (7.2% versus 3.8%) and five-fold risk of neonatal injury (1.1% versus 0.2%) (fractures, brachial plexus injuries, and lacerations), but no neonatal encephalopathy. Morbidly obese women failing a trial of labor had six-fold greater composite maternal morbidity than those undergoing a successful trial of labor (14.2% versus 2.6%)., Conclusion: Body mass index correlates with outcomes in trial of labor after previous cesarean delivery. Morbidly obese women undergoing a trial of labor were at increased risk for failure. Increased BMI was associated with greater composite morbidity and neonatal injury compared with elective repeat cesarean delivery, but absolute morbidities were small. Increased risks should be considered before trial of labor after previous cesarean delivery., Level of Evidence: II-2.

Objective: This study was undertaken to characterize risk factors associated with nonanomalous stillborn (SB) infants and to ascribe the probability of fetal survival by gestational age among high-risk pregnancies., Study Design: We compiled a database of all SB infants and an equivalent number of controls using information obtained from Utah Birth and Fetal Death Certificates during the years 1992 through 2002. Adjusted and unadjusted odds ratios for risk factors associated with SB were generated. Cox proportional hazard models were used to generate survival curves comparing pregnancies complicated by chronic hypertension or gestational hypertension with those of controls., Results: Infants with major anomalies were eliminated from both cases and controls, to generate 1566 nonanomalous SBs and 2720 nonanomalous controls. In a logistic regression model controlling for multiple maternal and fetal factors, placental abruption, hydramnios, cord prolapse, and essential hypertension were associated with an increased risk of SB. In pregnancies complicated by essential hypertension, the survival curve diverged from that of controls at those gestational ages approaching term (hazard ratio 2.24; 95% CI 1.52-3.32)., Conclusion: SB in nonanomalous infants in Utah is more common among pregnancies complicated by placental abruption, hydramnios, cord prolapse, and essential hypertension.

Objective: The purpose of this study was to test the hypothesis that maternal asthma symptoms and pulmonary function are related to adverse perinatal outcomes., Study Design: Asthmatic patients were recruited from the 16 centers of the Maternal Fetal Medicine Units. Forced expiratory volume in 1 second was obtained at enrollment and at monthly study visits, and the frequency of asthma symptoms was assessed from enrollment to delivery. Perinatal data were obtained at postpartum chart reviews., Results: The final cohort included 2123 participants with asthma. After adjustment for demographic characteristics, smoking, acute asthmatic episodes, and oral corticosteroid use, significant relationships were demonstrated between gestational hypertension and preterm birth and lower maternal gestational forced expiratory volume in 1 second. The data did not show any significant independent relationship between asthma symptom frequency and perinatal outcomes., Conclusion: Lower pulmonary function during pregnancy is associated with increased gestational hypertension and prematurity in the pregnancies of women with asthma, which may be due to inadequate asthma control or factors that are associated with increased asthma severity.

Objective: This study aims to identify recent population-based trends in maternal overweight and obesity and adverse outcomes., Study Design: Statewide retrospective cohort study of birth certificate data for live singleton births to women in Utah between 1991 and 2001., Results: Prepregnancy overweight and obesity increased from 25.1% in 1991 to 35.2% in 2001, a 40.2% increase (prevalence ratio [PR] 1.40 [1.37-1.43]), whereas maternal obesity at delivery rose 36.2% from 28.7% to 39.1% (PR 1.36 [1.33-1.39]). The attributable fraction of cesarean delivery in overweight and obese women was 0.388 (0.369-0.407). Statewide, among all women having a cesarean delivery in 2001, 1 in 7 is attributable to overweight and obesity., Conclusion: This is the first state-wide analysis of maternal obesity trends demonstrating a significant increase in maternal overweight and obesity. Overweight and obese women are at increased risk of cesarean delivery, preeclampsia, eclampsia, dystocia, and macrosomia, risks that increase as the body mass index rises.

Background: Maternal asthma has been reported to increase the risk of preeclampsia, preterm deliveries, and lower-birth-weight infants, but the mechanisms of this effect are not defined., Objective: We sought to evaluate the relationship between the use of contemporary asthma medications and adverse perinatal outcomes., Methods: Asthmatic patients were recruited from the 16 centers of the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network from December 1994 through February 2000. Gestational medication use was determined on the basis of patient history at enrollment and at monthly visits during pregnancy. Perinatal data were obtained at postpartum chart reviews. Perinatal outcome variables included gestational hypertension, preterm births, low-birth-weight infants, small-for-gestational-age infants, and major malformations., Results: The final cohort included 2123 asthmatic participants. No significant relationships were found between the use of inhaled beta-agonists (n=1828), inhaled corticosteroids (n=722), or theophylline (n=273) and adverse perinatal outcomes. After adjusting for demographic and asthma severity covariates, oral corticosteroid use was significantly associated with both preterm birth at less than 37 weeks' gestation (odds ratio, 1.54; 95% CI, 1.02-2.33) and low birth weight of less than 2500 g (odds ratio, 1.80; 95% CI, 1.13-2.88)., Conclusions: Use of inhaled beta-agonists, inhaled steroids, and theophylline do not appear to increase perinatal risks in pregnant asthmatic women. The mechanism of the association between maternal oral corticosteroid use and prematurity remains to be determined.

Objective: This study was undertaken to compare the efficacy of inhaled beclomethasone dipropionate to oral theophylline for the prevention of asthma exacerbation(s) requiring medical intervention., Study Design: A prospective, double-blind, double placebo-controlled randomized clinical trial of pregnant women with moderate asthma was performed., Results: There was no significant difference (P=.554) in the proportion of asthma exacerbations among the 194 women in the beclomethasone cohort (18.0%) versus the 191 in the theophylline cohort (20.4%; risk ratio [RR]=0.9, 95% CI=0.6-1.3). The beclomethasone cohort had significantly lower incidences of discontinuing study medications caused by side effects (RR=0.3, 95% CI=0.1-0.9; P=.016), and proportion of study visits with forced expiratory volume expired in 1 second (FEV1) less than 80% predicted (0.284+/-0.331 vs 0.284+/-0.221, P=.039). There were no significant differences in treatment failure, compliance, or proportion of peak expiratory flow rate less than 80% predicted. There were no significant differences in maternal or perinatal outcomes., Conclusion: The treatment of moderate asthma with inhaled beclomethasone versus oral theophylline resulted in similar rates of asthma exacerbations and similar obstetric and perinatal outcomes. These results favor the use of inhaled corticosteroids for moderate asthma during pregnancy because of the improved FEV1 and because theophylline had more side effects and requires serum monitoring.

Background: The 1993 National Asthma Education Program Working Group on Asthma and Pregnancy defined asthma severity as mild, moderate, or severe on the basis of symptoms and spirometry, but no studies have evaluated the relationship between this classification system and subsequent asthma morbidity during pregnancy., Objective: The objective of this study was to evaluate the relationship between asthma severity classification during pregnancy and gestational asthma exacerbations., Methods: Asthma severity was defined according to the 1993 classification, adjusted to include medication requirements, in a volunteer sample of 1739 pregnant asthmatic patients who were less than 26 weeks' gestation., Results: Initial asthma classification (mild, moderate, or severe) was significantly related to subsequent asthma morbidity during pregnancy (hospitalizations, unscheduled visits, corticosteroid requirements, and asthma symptoms during labor and delivery). Exacerbations during pregnancy occurred in 12.6% of patients initially classified as mild, 25.7% of patients classified as moderate, and 51.9% of patients classified as severe (P <.001). Asthma morbidity was similar, whether patients were classified as moderate or severe by symptoms and spirometry or by medication requirement. Thirty percent of initially mild patients were reclassified as moderate-severe during pregnancy, and 23% of the initially moderate-severe patients were reclassified as mild later in pregnancy; asthma morbidity in these patients changed accordingly., Conclusion: The National Asthma Education Program Working Group on Asthma and Pregnancy classification of asthma severity, adapted to include medication use, predicts subsequent asthma morbidity during pregnancy.

ObjectiveRegulatory bodies and insurers evaluate hospital quality using obstetrical outcomes, however meaningful comparisons should take preexisting patient characteristics into account. Furthermore, if risk-adjusted outcomes are consistent within a hospital, fewer measures and resources would be needed to assess obstetrical quality. Our objective was to establish risk-adjusted models for 5 obstetric outcomes and assess hospital performance across these outcomes.Study designWe studied a cohort of 115,502 women and their neonates born in 25 hospitals in the United States from March 2008 through February 2011. Hospitals were ranked according to their unadjusted and risk-adjusted frequency of venous thromboembolism, postpartum hemorrhage, peripartum infection, severe perineal laceration, and a composite neonatal adverse outcome. Correlations between hospital risk-adjusted outcome frequencies were assessed.ResultsVenous thromboembolism occurred too infrequently (0.03%; 95% confidence interval [CI], 0.02-0.04%) for meaningful assessment. Other outcomes occurred frequently enough for assessment (postpartum hemorrhage, 2.29%; 95% CI, 2.20-2.38, peripartum infection, 5.06%; 95% CI, 4.93-5.19, severe perineal laceration at spontaneous vaginal delivery, 2.16%; 95% CI, 2.06-2.27, neonatal composite, 2.73%; 95% CI, 2.63-2.84). Although there was high concordance between unadjusted and adjusted hospital rankings, several individual hospitals had an adjusted rank that was substantially different (as much as 12 rank tiers) than their unadjusted rank. None of the correlations between hospital-adjusted outcome frequencies was significant. For example, the hospital with the lowest adjusted frequency of peripartum infection had the highest adjusted frequency of severe perineal laceration.ConclusionEvaluations based on a single risk-adjusted outcome cannot be generalized to overall hospital obstetric performance.

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. [ABSTRACT FROM AUTHOR]

Background Data about the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among pregnant individuals are needed to inform infection-prevention guidance and counseling for this population. Methods We prospectively followed a cohort of pregnant individuals during August 2020–March 2021 at 3 US sites. The 3 primary outcomes were incidence rates of any SARS-CoV-2 infection, symptomatic infection, and asymptomatic infection, during pregnancy during periods of SARS-CoV-2 circulation. Participants self-collected weekly midturbinate nasal swabs for SARS-CoV-2 reverse transcription–polymerase chain reaction testing, completed weekly illness symptom questionnaires, and submitted additional swabs with coronavirus disease 2019 (COVID-19)–like symptoms. An overall SARS-CoV-2 infection incidence rate weighted by population counts of women of reproductive age in each state was calculated. Results Among 1098 pregnant individuals followed for a mean of 10 weeks, 9% (99/1098) had SARS-CoV-2 infections during the study. Population-weighted incidence rates of SARS-CoV-2 infection were 10.0 per 1000 (95% confidence interval, 5.7–14.3) person-weeks for any infection, 5.7 per 1000 (1.7–9.7) for symptomatic infections, and 3.5 per 1000 (0–7.1) for asymptomatic infections. Among 96 participants with SARS-CoV-2 infections and symptom data, the most common symptoms were nasal congestion (72%), cough (64%), headache (59%), and change in taste or smell (54%); 28% had measured or subjective fever. Median symptom duration was 10 (interquartile range, 6–16) days. Conclusions Pregnant individuals in this study had a 1% risk of SARS-CoV-2 infection per week, underscoring the importance of COVID-19 vaccination and other prevention measures during pregnancy while SARS-CoV-2 is circulating in the community. [ABSTRACT FROM AUTHOR]

Objective  To estimate the actual excess costs of care for delivery admissions complicated by severe maternal morbidity (SMM) compared with uncomplicated deliveries. Study Design  This is a retrospective cohort study of all deliveries between October 2015 and September 2018 at a single tertiary academic center. Pregnant individuals ≥ 20 weeks' gestation who delivered during a hospital admission (i.e., a "delivery admission") were included. The primary exposure was SMM, as defined by Centers for Disease Control and Prevention (CDC) criteria, CDC criteria excluding blood transfusion, or by validated hospital-defined criteria (intensive care unit admission or ≥ 4 units of blood products). Potential SMM events identified via administrative and blood bank data were reviewed to confirm SMM events had occurred. Primary outcome was total actual costs of delivery admission derived from time-based accounting and acquisition costs in the institutional Value Driven Outcomes database. Cost of delivery admissions with SMM events was compared with the cost of uncomplicated delivery using adjusted generalized linear models, with separate models for each of the SMM definitions. Relative cost differences are reported due to data restrictions. Results  Of 12,367 eligible individuals, 12,361 had complete cost data. Two hundred and eighty individuals (2.3%) had confirmed SMM events meeting CDC criteria. CDC criteria excluding transfusion alone occurred in 1.0% (n  = 121) and hospital-defined SMM in 0.6% (n  = 76). In adjusted models, SMM events by CDC criteria were associated with a relative cost increase of 2.45 times (95% confidence interval [CI]: 2.29–2.61) the cost of an uncomplicated delivery. SMM by CDC criteria excluding transfusion alone was associated with a relative increase of 3.26 (95% CI: 2.95–3.60) and hospital-defined SMM with a 4.19-fold (95% CI: 3.64–4.83) increase. Each additional CDC subcategory of SMM diagnoses conferred a relative cost increase of 1.60 (95% CI: 1.43–1.79). Conclusion  SMM is associated with between 2.5- and 4-fold higher cost than uncomplicated deliveries. Key Points Severe maternal morbidity as defined by CDC criteria confers a 2.5-fold increase in delivery hospitalization costs. Intensive care unit admission or ≥ 4 units of blood products confer a fourfold increase in cost. Costs of maternal morbidity may motivate SMM review. [ABSTRACT FROM AUTHOR]

Objective  Our objective was to compare outcomes among low-risk parous women who underwent elective labor induction at 39 weeks versus expectant management. Study Design  This is a secondary analysis of an observational cohort of 115,502 mother–infant dyads who delivered at 25 hospitals between 2008 and 2011. The inclusion criteria for this analysis were low-risk parous women with nonanomalous singletons with at least one prior vaginal delivery after 20 weeks, who delivered at ≥39 0/7 weeks. Women who electively induced between 39 0/7 and 39 6/7 weeks were compared with women who expectantly managed ≥39 0/7 weeks. The primary outcome for this analysis was cesarean delivery. Secondary outcomes were composites of maternal adverse outcome and neonatal adverse outcome. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR). Results  Of 20,822 women who met inclusion criteria, 2,648 (12.7%) were electively induced at 39 weeks. Cesarean delivery was lower among women who underwent elective induction at 39 weeks than those who did not (2.4 vs. 4.6%, adjusted odds ratio [aOR]: 0.70, 95% confidence interval [CI]: 0.53–0.92). The frequency of the composite maternal adverse outcome was significantly lower for the elective induction cohort as well (1.6 vs. 3.1%, aOR: 0.66, 95% CI: 0.47–0.93). The composite neonatal adverse outcome was not significantly different between the two groups (0.3 vs. 0.6%; aOR: 0.60, 95% CI: 0.29–1.23). Conclusion  In low-risk parous women, elective induction of labor at 39 weeks was associated with decreased odds of cesarean delivery and maternal morbidity, without an increase in neonatal adverse outcomes. Key Points 39-week elective induction is associated with decreased cesarean delivery in low-risk parous women. Compared with expectant management, maternal adverse outcomes were lower with elective induction. Neonatal adverse outcomes are unchanged between elective and expectant management groups. [ABSTRACT FROM AUTHOR]

Background: Hypertensive disorders of pregnancy (HDP) and short-term adverse outcomes have long been recognized; however, survivors remain at risk of long-term complications. We investigated whether HDP is associated with the development of choroidal neovascular age-related macular degeneration (CNV AMD). Methods: We identified 31,454 women who experienced HDP based on Utah birth certificates and 62,908 unexposed women matched 2:1 to the exposed. Risk of CNV AMD was estimated using Cox models. Findings: Women with HDP exhibited an 80% higher risk for early CNV AMD (age < 70 y; 95%CI 1.23-2.58). Conclusion: Our findings may have implications forearlier CNV AMD screening and detection. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to examine perinatal outcomes associated with cholestasis of pregnancy according to bile acid level and antenatal testing practice.Study Design: Retrospective cohort study of women with symptoms and bile acid testing from 2005 to 2014. Women were stratified by bile acid level: no cholestasis (<10 μmol/L), mild (10-39 μmol/L), moderate (40-99 μmol/L), and severe (≥100 μmol/L). The primary outcome was composite neonatal morbidity (hypoxic ischemic encephalopathy, severe intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, or death).Results: 785 women were included; 487 had cholestasis (347 mild, 108 moderate, 32 severe) and 298 did not. After controlling for gestational age (GA), severe cholestasis was associated with the composite neonatal outcome (aRR 5.6, 95% CI 1.3-23.5) and meconium-stained fluid (aRR 4.82, 95%CI 1.6-14.2). Bile acid levels were not correlated with the frequency of testing (p = .50). Women who underwent twice weekly testing were delivered earlier (p = .016) than women tested less frequently, but the difference in GA was ≤4 d. Abnormal testing prompting delivery was uncommon. Among women with cholestasis, there were three stillbirths. One of these women was undergoing antenatal testing, which was normal 1 d prior to the fetal demise.Conclusion: Severe cholestasis is associated with neonatal morbidity which antenatal testing may not predict. [ABSTRACT FROM AUTHOR]