Publications by authors named "Brian M Mercer"

220 Publications

Associations of the Neighborhood Built Environment With Physical Activity Across Pregnancy.

J Phys Act Health 2021 Apr 15:1-7. Epub 2021 Apr 15.

Background: Several features of the neighborhood built environment have been shown to promote leisure-time physical activity (PA) in the general population, but few studies have examined its impact on PA during pregnancy.

Methods: Data were extracted from 8362 Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort participants (2010-2013). Residential address information was linked to 3 built environment characteristics: number of gyms and recreation areas within a 3-km radius of residence and census block level walkability. Self-reported leisure-time PA was measured in each trimester and dichotomized as meeting PA guidelines or not. Relative risks for cross-sectional associations between neighborhood characteristics and meeting PA guidelines were estimated using Poisson regression.

Results: More gyms and recreation areas were each associated with a greater chance of meeting PA guidelines in models adjusted for sociodemographic characteristics and preexisting conditions. Associations were strongest in the third trimester where each doubling in counts of gyms and recreation areas was associated with 10% (95% confidence interval, 1.07-1.13) and 8% (95% confidence interval, 1.03-1.12), respectively, greater likelihood of meeting PA guidelines. Associations were similar though weaker for walkability.

Conclusions: Results from a large, multisite cohort suggest that these built environment characteristics have similar PA-promoting benefits in pregnant women as seen in more general populations.
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http://dx.doi.org/10.1123/jpah.2020-0510DOI Listing
April 2021

Association of Breastfeeding and Child IQ Score at Age 5 Years.

Obstet Gynecol 2021 04;137(4):561-570

Departments of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois, University of Texas, Southwestern, Dallas, Texas, University of Utah Health Sciences Center, Salt Lake City, Utah, Wayne State University, Detroit, Michigan, Columbia University, New York, New York, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, University of Texas Medical Branch at Galveston, Galveston, Texas, University of Alabama at Birmingham, Birmingham, Alabama, Brown University, Providence, Rhode Island, University of Texas, Houston, Houston, Texas, Case Western Reserve University, Cleveland, Ohio, Oregon Health & Science University, Portland, OR, and University of Pittsburgh, Pittsburgh, Pennsylvania; and the George Washington University Biostatistics Center, Washington, DC; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.

Objective: To evaluate whether breastfeeding and its duration are associated with a reduced risk of low IQ scores or other neurodevelopmental problems.

Methods: We conducted a secondary analysis of two parallel multicenter, double-blinded randomized controlled trials in which participants with a singleton pregnancy and either subclinical hypothyroidism or hypothyroxinemia were treated with thyroxine or placebo. Our primary outcome was a low IQ score (less than 85 on the WPPSI-III [Wechsler Preschool and Primary Scale of Intelligence III] at age 5 years). Secondary outcomes included performance measures on other validated neurodevelopmental tests. Univariable and multivariable analyses were performed to evaluate the association between breastfeeding and neurodevelopmental outcomes. Stepwise backward proceeding linear and logistic regression models were used to develop the final adjusted models.

Results: Of the 772 participants studied, 614 (80%) reported breastfeeding. Of these, 31% reported breastfeeding for less than 4 months, 19% for 4-6 months, 11% for 7-9 months, 15% for 10-12 months and 23% for more than 12 months. IQ scores were available for 756 children; mean age-5 scores were higher with any breastfeeding (96.7±15.1) than without (91.2±15.0, mean difference 5.5, 95% CI 2.8-8.2), and low IQ scores were less frequent with any breastfeeding (21.5%) than with no breastfeeding (36.2%, odds ratio 0.48, 95% CI 0.33-0.71). In adjusted analyses, breastfeeding remained associated with reduced odds of low IQ score (adjusted odds ratio [aOR] 0.62, 95% CI 0.41-0.93), and each additional month of breastfeeding was associated with lower odds of a low IQ scores (aOR 0.97, 95% CI 0.939-0.996). No significant associations between breastfeeding and other neurodevelopmental outcomes were identified in adjusted analyses.

Conclusion: Breastfeeding and its duration are associated with lower odds of low IQ score at age 5 years.
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http://dx.doi.org/10.1097/AOG.0000000000004314DOI Listing
April 2021

Early Pregnancy Atherogenic Profile in a First Pregnancy and Hypertension Risk 2 to 7 Years After Delivery.

J Am Heart Assoc 2021 Feb 23;10(5):e017216. Epub 2021 Feb 23.

Northwestern University Feinberg School of Medicine Chicago IL.

Background Cardiovascular risk in young adulthood is an important determinant of lifetime cardiovascular disease risk. Women with adverse pregnancy outcomes (APOs) have increased cardiovascular risk, but the relationship of other factors is unknown. Methods and Results Among 4471 primiparous women, we related first-trimester atherogenic markers to risk of APO (hypertensive disorders of pregnancy, preterm birth, small for gestational age), gestational diabetes mellitus (GDM) and hypertension (130/80 mm Hg or antihypertensive use) 2 to 7 years after delivery. Women with an APO/GDM (n=1102) had more atherogenic characteristics (obesity [34.2 versus 19.5%], higher blood pressure [systolic blood pressure 112.2 versus 108.4, diastolic blood pressure 69.2 versus 66.6 mm Hg], glucose [5.0 versus 4.8 mmol/L], insulin [77.6 versus 60.1 pmol/L], triglycerides [1.4 versus 1.3 mmol/L], and high-sensitivity C-reactive protein [5.6 versus 4.0 nmol/L], and lower high-density lipoprotein cholesterol [1.8 versus 1.9 mmol/L]; <0.05) than women without an APO/GDM. They were also more likely to develop hypertension after delivery (32.8% versus 18.1%, <0.05). Accounting for confounders and factors routinely assessed antepartum, higher glucose (relative risk [RR] 1.03 [95% CI, 1.00-1.06] per 0.6 mmol/L), high-sensitivity C-reactive protein (RR, 1.06 [95% CI, 1.02-1.11] per 2-fold higher), and triglycerides (RR, 1.27 [95% CI, 1.14-1.41] per 2-fold higher) were associated with later hypertension. Higher physical activity was protective (RR, 0.93 [95% CI, 0.87-0.99] per 3 h/week). When evaluated as latent profiles, the nonobese group with higher lipids, high-sensitivity C-reactive protein, and insulin values (6.9% of the cohort) had increased risk of an APO/GDM and later hypertension. Among these factors, 7% to 15% of excess RR was related to APO/GDM. Conclusions Individual and combined first-trimester atherogenic characteristics are associated with APO/GDM occurrence and hypertension 2 to 7 years later. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02231398.
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http://dx.doi.org/10.1161/JAHA.120.017216DOI Listing
February 2021

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

Am J Obstet Gynecol 2021 Feb 20. Epub 2021 Feb 20.

Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, PA.

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.
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http://dx.doi.org/10.1016/j.ajog.2021.02.017DOI Listing
February 2021

The association between personal weight gain goals, provider recommendations, and appropriate gestational weight gain.

Am J Obstet Gynecol MFM 2020 11 22;2(4):100231. Epub 2020 Sep 22.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University, Evanston, IL.

Background: Nearly half of all women exceed the 2009 Institute of Medicine guidelines for gestational weight gain. Excess gestational weight gain is associated with adverse pregnancy outcomes.

Objective: Our objective was to determine whether having a personal gestational weight gain goal consistent with the Institute of Medicine's recommendations for appropriate gestational weight gain and whether having a discussion with one's obstetrical provider regarding that goal were associated with appropriate gestational weight gain.

Study Design: This is a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be study, a prospective cohort study of nulliparous women. We asked women at their first study visit (between 6 and 13 weeks' gestation) whether they had a gestational weight gain goal and what that goal was. Furthermore, we asked whether their provider discussed a gestational weight gain goal and what that goal was. We classified personal and provider-recommended gestational weight gain goals as consistent or inconsistent with the Institute of Medicine guidelines, taking into account a woman's initial body mass index category (underweight, normal weight, overweight, and obese). We included women with live singleton term deliveries (between 37 and 43 weeks' gestation) in this analysis. We classified the primary outcome, which was gestational weight gain (defined as the difference between first visit weight and final weight before delivery), as inadequate, appropriate, or excessive, based on the Institute of Medicine guidelines and initial body mass index category. We used Student t, Wilcoxon rank-sum, and chi-square tests for bivariable analyses, and multinomial logistic regression was performed to control for confounding variables.

Results: Of 6727 eligible women, 3799 (56.5% of all eligible women) stated they had a gestational weight gain goal. Of the 3799 women with a stated goal, 2589 (38.5% of all women) had a goal consistent with the Institute of Medicine's recommendations. In addition, of the 6727 eligible women, 2188 (32.5%) reported that they discussed gestational weight gain with their provider, and 1548 of these (23.0% of all women) recalled that their provider gave a gestational weight gain goal in accordance with the Institute of Medicine guidelines. Although having any gestational weight gain goal was not associated with appropriate gestational weight gain, having a gestational weight gain goal that was consistent with the Institute of Medicine's recommendations was associated with a reduced risk of excessive (adjusted relative risk ratio, 0.77; 95% confidence interval, 0.64-0.92) and inadequate weight gain (adjusted relative risk ratio, 0.66; 95% confidence interval, 0.53-0.82). Conversely, discussing gestational weight gain goals with a provider was not associated with either inadequate or excessive gestational weight gain even if the provider's recommendations for gestational weight gain were consistent with the guidelines.

Conclusion: Nulliparas who delivered singleton pregnancies at term who had a personal gestational weight gain goal consistent with the Institute of Medicine's recommendations were less likely to have excessive or inadequate gestational weight gain. Further study is required to evaluate the most effective way to communicate this information to patients.
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http://dx.doi.org/10.1016/j.ajogmf.2020.100231DOI Listing
November 2020

Later sleep timing is associated with an increased risk of preterm birth in nulliparous women.

Am J Obstet Gynecol MFM 2019 11 9;1(4):100040. Epub 2019 Sep 9.

Department of Obstetrics, Gynecology-Maternal Fetal Medicine & Preventive Medicine, Northwestern University, Chicago, IL.

Background: Although uterine contractions have a diurnal periodicity and increase in frequency during hours of darkness, data on the relationship between sleep duration and sleep timing patterns and preterm birth are limited.

Objective: We sought to examine the relationship of self-reported sleep duration and timing in pregnancy with preterm birth.

Study Design: In the prospective Nulliparous Pregnancy Outcome Study: Monitoring Mothers-to-be cohort, women completed a survey of sleep patterns at 6-13 weeks gestation (visit 1) and again at 22-29 weeks gestation (visit 3). Additionally, at 16-21 weeks gestation (visit 2), a subgroup completed a weeklong actigraphy recording of their sleep. Weekly averages of self-reported sleep duration and sleep midpoint were calculated. A priori, sleep duration of <7 hours was defined as "short," and sleep midpoint after 5 am was defined as "late." The relationships among these sleep characteristics and all preterm birth and spontaneous preterm birth at <37 weeks gestation were examined in univariate analyses. Multivariable logistic regressions that controlled for age and body mass index alone (model 1) and with additional covariates (race, smoking, insurance, and employment schedule) following a backward elimination process (model 2) were performed.

Results: Of the 10,038 women who were enrolled, sleep survey data were available on 7524 women at visit 1 and 7668 women at visit 3. The rate of short sleep duration was 17.1% at visit 1 and 20.7% at visit 3. The proportion with a late sleep midpoint was 11.6% at visit 1 and 12.2% at visit 3. There was no significant relationship between self-reported short sleep and preterm birth across all visits. However, self-reported late sleep midpoint (>5 am) was associated with preterm birth . Women with a late sleep midpoint (>5 am) in early pregnancy had a preterm birth rate of 9.5%, compared with 6.9% for women with sleep midpoint ≤5 am (P=.005). Similarly, women with a late sleep midpoint had a higher rate of spontaneous preterm birth (6.2% vs 4.4%; P=.019). Comparable results were observed for women with a late sleep midpoint at visit 3 (all preterm birth 8.9% vs 6.6%; P=.009; spontaneous preterm birth 5.9% vs 4.3%; P=.023). All adjusted analyses on self-reported sleep midpoint (models 1 and 2) maintained statistical significance (P<.05), except for visit 1, model 2 for spontaneous preterm birth (P=.07). The visit 2 objective data from the smaller subgroup (n=782) demonstrated similar trends in preterm birth rates by sleep midpoint status.

Conclusion: Self-reported late sleep midpoint in both early and late pregnancy, but not short sleep duration, is associated with an increased rate of preterm birth.
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http://dx.doi.org/10.1016/j.ajogmf.2019.100040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757682PMC
November 2019

Preterm Premature Rupture of the Membranes in the Twenty-First Century.

Obstet Gynecol Clin North Am 2020 Dec;47(4):xiii-xiv

MetroHealth Medical Center, 2500 Metrohealth Drive, Cleveland, OH 44109, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ogc.2020.09.002DOI Listing
December 2020

Mechanism of Human Fetal Membrane Biomechanical Weakening, Rupture and Potential Targets for Therapeutic Intervention.

Obstet Gynecol Clin North Am 2020 Dec;47(4):523-544

Department of Pediatrics, MetroHealth Medical Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH 44109, USA; Department of Reproductive Biology, MetroHealth Medical Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH 44109, USA.

Using a novel in vitro model system combining biochemical/histologic with bioengineering approaches has provided significant insights into the physiology of fetal membrane weakening and rupture along with potential mechanistic reasons for lack of efficacy of currently clinically used agents to prevent preterm premature rupture of the membranes (pPROM) and preterm births. Likewise, the model has also facilitated screening of agents with potential for preventing pPROM and preterm birth.
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http://dx.doi.org/10.1016/j.ogc.2020.08.010DOI Listing
December 2020

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

Obstet Gynecol 2020 06;135(6):1281-1288

Indiana University, Indianapolis, Indiana; the University of Pittsburgh, Pittsburgh, Pennsylvania; the University of Utah, Salt Lake City, Utah; Northwestern University, Evanston, Illinois; Columbia University, New York, New York; University of California, Irvine, Irvine, California; University of Pennsylvania, Philadelphia, Pennsylvania; Case Western Reserve University, Cleveland, Ohio; and the University of Texas Medical Branch at Galveston, Galveston, Texas.

Objective: To estimate alcohol, tobacco, and recreational drug use during pregnancy among nulliparous women.

Methods: In a cohort of nulliparous women followed through pregnancy from the first-trimester nuMoM2b (Nulliparous Outcomes in Pregnancy: Monitoring Mothers to be) study, self-reported use of alcohol, tobacco, and drugs was chronicled longitudinally at four study visits in this secondary analysis. Rates of use before pregnancy, in each trimester (visit 1, visit 2, visit 3, approximating each trimester), and at the time of delivery (visit 4) were recorded. The amount of alcohol, tobacco, and drug exposure were recorded using validated measures, and trends across pregnancy were analyzed.

Results: Of the 10,038 study participants, 10,028 had information regarding alcohol, tobacco, and drug use at visit 1, 9,412 at visit 2, 9,217 at visit 3, and 7,167 at visit 4. The rates of drinking alcohol, which had been 64.6% in the 3 months before pregnancy, were lower in pregnancy (3.9% at visit 1, 5.6% at visit 2, 7.0% at visit 3, and 6.1% at visit 4, P<.001 for all). Rates later in pregnancy were all greater than in the first trimester (P<.01). The rate of smoking in the 3 months before pregnancy, which was 17.8%, also declined at visit 1 (5.9%), and continued to decline through pregnancy (5.3% at visit 2, 4.7% at visit 3, and 3.9% at visit 4, with all rates lower than that of visit 1 [P<.01]). Although recreational drug use was relatively common in the months before pregnancy (33.8%), it also declined during pregnancy (1.1% at visit 2, 0.7% at visit 3, 0.4% at visit 4).

Conclusions: In this geographically and ethnically diverse cohort of nulliparous women, rates of self-reported alcohol, smoking, and recreational drug use were all significantly lower during than before pregnancy. Nonetheless, rates of alcohol use rose as pregnancy progressed, highlighting the need for continued counseling throughout all trimesters of pregnancy.

Clinical Trial Registration: ClinicalTrials.gov, NCT01322529.
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http://dx.doi.org/10.1097/AOG.0000000000003826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263351PMC
June 2020

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

Matern Child Health J 2020 Aug;24(8):1047-1056

Indiana University, Indianapolis, USA.

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.
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http://dx.doi.org/10.1007/s10995-020-02928-0DOI Listing
August 2020

Weight gain in early, mid, and late pregnancy and hypertensive disorders of pregnancy.

Pregnancy Hypertens 2020 Apr 3;20:50-55. Epub 2020 Mar 3.

Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, Feinberg School of Medicine, Northwestern University, United States.

Objective: To examine the relationship of weight change during early, mid, and late pregnancy with the development of a hypertensive disorder of pregnancy (HDP).

Study Design: These data are from a prospective cohort study of nulliparous women with live singleton pregnancies. "Early" weight change was defined as the difference between self-reported pre-pregnancy weight and weight at the first visit (between 6 and 13 weeks' gestation); "mid" weight change was defined as the weight change between the first and second visits (between 16 and 21 weeks' gestation); "late" weight change was defined as the weight change between the second and third visits (between 22 and 29 weeks' gestation). Weight change in each time period was further characterized as inadequate, adequate, or excessive based on the Institute of Medicine's (IOM's) trimester-specific weekly weight gain goals based on pre-pregnancy body mass index. Multivariable Poisson regression was performed to adjust for potential confounders.

Main Outcome Measure: Development of any hypertensive disorder of pregnancy.

Results: Of 8296 women, 1564 (18.9%) developed a HDP. Weight gain in excess of the IOM recommendations during the latter two time periods was significantly associated with HDP. Specifically, trimester-specific excessive weight gain in the mid period (aIRR 1.16, 95% CI 1.01-1.35) as well as in the late period (aIRR = 1.19, 95% CI = 1.02-1.40) was associated with increased risk of developing HDP. The weight gain preceded the onset of clinically apparent disease.

Conclusions: Excessive weight gain as early as the early second trimester was associated with increased risks of development of HDP.
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http://dx.doi.org/10.1016/j.preghy.2020.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198322PMC
April 2020

Effect of Thyroxine Therapy on Depressive Symptoms Among Women With Subclinical Hypothyroidism.

Obstet Gynecol 2020 04;135(4):812-820

Departments of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, University of Texas - Southwestern, Dallas, Texas, Northwestern University, Chicago, Illinois, University of Utah Health Sciences Center, Salt Lake City, Utah, Wayne State University, Detroit, Michigan, Columbia University, New York, New York, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, University of Alabama at Birmingham, Birmingham, Alabama; Brown University, Providence, Rhode Island, University of Texas - Houston, Houston, Texas, The Ohio State University, Columbus, Ohio, Case Western Reserve University, Cleveland, Ohio, Oregon Health Sciences University, Portland, Oregon, University of Pittsburgh, Pittsburgh, Pennsylvania, Medical University of South Carolina, Charleston, South Carolina; and the George Washington University Biostatistics Center, Washington, DC; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.

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.
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http://dx.doi.org/10.1097/AOG.0000000000003724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103482PMC
April 2020

Quality of periconceptional dietary intake and maternal and neonatal outcomes.

Am J Obstet Gynecol 2020 07 23;223(1):121.e1-121.e8. Epub 2020 Jan 23.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL.

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.
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http://dx.doi.org/10.1016/j.ajog.2020.01.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321878PMC
July 2020

Association of Acculturation With Adverse Pregnancy Outcomes.

Obstet Gynecol 2020 02;135(2):301-309

Northwestern University, Chicago, Illinois; the University of Utah Health and Intermountain Healthcare, Salt Lake City, Utah; Indiana University, Indianapolis, Indiana; the University of Pittsburgh, Pittsburgh, Pennsylvania; the University of California, Irvine, Irvine, California; the University of Pennsylvania, Philadelphia, Pennsylvania; Case Western Reserve University, Cleveland, Ohio; The Ohio State University, Columbus, Ohio; the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland; the University of Texas Medical Branch, Galveston, Galveston, Texas.

Objective: To evaluate the relationship between acculturation and adverse pregnancy outcomes, and whether these relationships differ across racial or ethnic groups.

Methods: This is a planned secondary analysis of the nuMoM2b study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be), a prospective observational cohort study of 10,038 pregnant women at eight academic health care centers in the United States. Nulliparous pregnant women with singleton gestations were recruited between 6 0/7 and 13 6/7 weeks of gestation from October 2010-September 2013. Acculturation was defined by birthplace (United States vs non-United States), language used during study visits (English or Spanish), and self-rated English proficiency. The adverse pregnancy outcomes of interest were preterm birth (less than 37 weeks of gestation, both iatrogenic and spontaneous), preeclampsia or eclampsia, gestational hypertension, gestational diabetes, stillbirth, small for gestational age, and large for gestational age. Multivariable regression modeling was performed, as was an interaction analysis focusing on the relationship between acculturation and adverse pregnancy outcomes by maternal race or ethnicity.

Results: Of the 10,006 women eligible for this analysis, 8,100 (80.9%) were classified as more acculturated (eg, born in the United States with high English proficiency), and 1,906 (19.1%) were classified as having less acculturation (eg, born or not born in the United States with low proficiency in English or use of Spanish as the preferred language during study visits). In multivariable logistic regression modeling, more acculturation was significantly associated with higher frequency of preterm birth (odds ratio [OR] 1.46, adjusted odds ratio [aOR] 1.50, 95% CI 1.16-1.95); spontaneous preterm birth (OR 1.54, aOR 1.62, 95% CI 1.14-2.24); preeclampsia or eclampsia (OR 1.39, aOR 1.31, 95% CI 1.03-1.67); preeclampsia without severe features (OR 1.44, aOR 1.43, 95% CI 1.03-2.01); and gestational hypertension (OR 1.68, aOR 1.48, 95% CI 1.22-1.79). These associations did not differ by self-described race or ethnicity.

Conclusion: In a large cohort of nulliparous women, more acculturation, regardless of self-described race or ethnicity, was associated with increased odds of several adverse pregnancy outcomes.

Clinical Trial Registration: ClinicalTrials.gov, NCT01322529.
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http://dx.doi.org/10.1097/AOG.0000000000003659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054005PMC
February 2020

The Association of Public Insurance with Postpartum Contraception Preference and Provision.

Open Access J Contracept 2019 19;10:103-110. Epub 2019 Dec 19.

Department of Obstetrics and Gynecology, MetroHealth Medical Center, Cleveland, OH, USA.

Background: Prior studies have noted that public insurance status is associated with increased uptake of postpartum contraception whereas others have pointed to public insurance as a barrier to accessing highly effective forms of contraception.

Objective: To assess differences in planned method and provision of postpartum contraception according to insurance type.

Study Design: This is a secondary analysis of a retrospective cohort study examining postpartum women delivered at a single hospital in Cleveland, Ohio from 2012-2014. Contraceptive methods were analyzed according to Tier-based effectiveness as defined by the Centers for Disease Control and Prevention. The primary outcome was postpartum contraception method preference. Additional outcomes included method provision, postpartum visit attendance, and subsequent pregnancy within 365 days of delivery.

Results: Of the 8281 patients in the study cohort, 1372 (16.6%) were privately and 6990 (83.4%) were publicly insured. After adjusting for the potentially confounding clinical and demographic factors through propensity score analysis, public insurance was not associated with preference for a Tier 1 versus Tier 2 postpartum contraceptive method (matched adjusted odds ratio [maOR] 0.89, 95% CI 0.69-1.15), but was associated with a preference for Tier 1/2 vs Tier 3/None (maOR 1.41, 95% CI 1.17-1.69). There was no difference between women with private or public insurance in terms of method provision by 90 days after delivery (maOR 0.94, 95% CI 0.75-1.17). Public insurance status was also associated with decreased postpartum visit attendance (maOR 0.54, 95% CI 0.43-0.68) and increased rates of subsequent pregnancy within 365 days of delivery (maOR 1.29, 95% CI 1.05-1.59).

Conclusion: Public insurance status does not serve as a barrier to either the preference or provision of effective postpartum contraception. Women desiring highly- or moderately effective methods of contraception should have these methods provided prior to hospital discharge to minimize barriers to method provision.
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http://dx.doi.org/10.2147/OAJC.S231196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927572PMC
December 2019

Desired Sterilization Procedure at the Time of Cesarean Delivery According to Insurance Status.

Obstet Gynecol 2019 12;134(6):1171-1177

Department of Obstetrics and Gynecology, MetroHealth Medical Center, the Cleveland Institute for Computational Biology, and the School of Medicine, Case Western Reserve University, Cleveland, Ohio.

Objective: To evaluate whether women with Medicaid are less likely than their privately insured counterparts to receive a desired sterilization procedure at the time of cesarean delivery.

Methods: This is a secondary analysis of a single-center retrospective cohort examining 8,654 postpartum women from 2012 to 2014, of whom 2,205 (25.5%) underwent cesarean delivery. Insurance was analyzed as Medicaid compared with private insurance. The primary outcome was sterilization at the time of cesarean delivery. Reason for sterilization noncompletion and Medicaid sterilization consent form validity were recorded. Secondary outcomes included postpartum visit attendance, outpatient postpartum sterilization, and subsequent pregnancy within 365 days of delivery.

Results: Of the 481 women included in this analysis, 78 of 86 (90.7%) women with private insurance and 306 of 395 (77.4%) women with Medicaid desiring sterilization obtained sterilization at the time of cesarean delivery (relative risk 0.85, 95% CI 0.78-0.94). After multivariable logistic regression, gestational age at delivery (1.02 [1.00-1.03]), adequacy of prenatal care (1.30 [1.18-1.43]), and marital status (1.09 [1.01-1.19]) were associated with achievement of sterilization at the time of cesarean delivery. Sixty-four (66.0%) women who desired but did not receive sterilization at the time of cesarean delivery did not have valid, signed Medicaid sterilization forms, and 10 (10.3%) sterilizations were not able to be completed at the time of surgery owing to adhesions. Sterilization during cesarean delivery was not associated with less frequent postpartum visit attendance for either the Medicaid or privately insured population. Rates of outpatient postpartum sterilization were similar among those with Medicaid compared with private insurance. Among patients who did not receive sterilization at the time of delivery, 15 patients (each with Medicaid) had a subsequent pregnancy within the study period.

Conclusion: Women with Medicaid insurance received sterilization at the time of cesarean delivery less frequently than privately insured counterparts, most commonly due to the absence of a valid Medicaid sterilization consent form as well as adhesive disease. The constraints surrounding the Medicaid form serve as a significant barrier to achieving desired sterilization.
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http://dx.doi.org/10.1097/AOG.0000000000003552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905118PMC
December 2019

Granulocyte macrophage colony stimulating factor (GM-CSF), the critical intermediate of inflammation-induced fetal membrane weakening, primarily exerts its weakening effect on the choriodecidua rather than the amnion.

Placenta 2020 01 5;89:1-7. Epub 2019 Oct 5.

Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA; Reproductive Biology, Case Western Reserve University, Cleveland, OH, USA. Electronic address:

Introduction: We have previously demonstrated two associations of PPROM, (1) inflammation/infection (modeled by tumor necrosis factor (TNF)) and (2) decidual bleeding (modeled by thrombin), both decrease fetal membrane (FM) rupture strength in-vitro. Furthermore, Granulocyte-Macrophage-Colony-Stimulating-Factor (GM-CSF) induced by both TNF and thrombin is a critical intermediate, necessary and sufficient for weakening by either agent. The amnion is the strength component of FM and must weaken for FM to rupture. It is unclear whether GM-CSF weakens amnion (AM) directly, or initially targets choriodecidua (CD) which secondarily releases agents to act on amnion.

Methods: Full thickness FM fragments were treated with/without GM-CSF. Some were preincubated with alpha-lipoic acid (LA), a known inhibitor of FM weakening. The FM fragments were then strength-tested. Separately, FM fragments were initially separated to AM and CD. AM fragments were cultured with Medium ± GM-CSF and then strength-tested. In other experiments, CD fragments were cultured with Medium, GM-CSF, LA, or LA + GM-CSF. Conditioned medium from each group was then incubated with AM. AM was then strength-tested. Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Matrix Metalloproteinases (TIMPs) were analyzed by Mutiplex Elisa.

Results: GM-CSF weakened intact FM which was blocked by LA. GM-CSF did not weaken isolated AM. However, GM-CSF conditioned CD media weakened AM and this weakening was inhibited by LA. GM-CSF treatment of CD increased MMPs 2, 9, and 10, and decreased TIMPs 1-3. LA reversed these effects.

Conclusions: GM-CSF does not weaken amnion directly; GM-CSF acts on CD to increase proteases and decrease anti-proteases which secondarily weaken the amnion.
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http://dx.doi.org/10.1016/j.placenta.2019.10.003DOI Listing
January 2020

Association of Adverse Pregnancy Outcomes With Hypertension 2 to 7 Years Postpartum.

J Am Heart Assoc 2019 10 30;8(19):e013092. Epub 2019 Sep 30.

University of Texas Medical Branch Galveston TX.

Background Identifying pregnancy-associated risk factors before the development of major cardiovascular disease events could provide opportunities for prevention. The objective of this study was to determine the association between outcomes in first pregnancies and subsequent cardiovascular health. Methods and Results The Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be Heart Health Study is a prospective observational cohort that followed 4484 women 2 to 7 years (mean 3.2 years) after their first pregnancy. Adverse pregnancy outcomes (defined as hypertensive disorders of pregnancy, small-for-gestational-age birth, preterm birth, and stillbirth) were identified prospectively in 1017 of the women (22.7%) during this pregnancy. The primary outcome was incident hypertension (HTN). Women without adverse pregnancy outcomes served as controls. Risk ratios (RR) and 95% CIs were adjusted for age, smoking, body mass index, insurance type, and race/ethnicity at enrollment during pregnancy. The overall incidence of HTN was 5.4% (95% CI 4.7% to 6.1%). Women with adverse pregnancy outcomes had higher adjusted risk of HTN at follow-up compared with controls (RR 2.4, 95% CI 1.8-3.1). The association held for individual adverse pregnancy outcomes: any hypertensive disorders of pregnancy (RR 2.7, 95% CI 2.0-3.6), preeclampsia (RR 2.8, 95% CI 2.0-4.0), and preterm birth (RR 2.7, 95% CI 1.9-3.8). Women who had an indicated preterm birth and hypertensive disorders of pregnancy had the highest risk of HTN (RR 4.3, 95% CI 2.7-6.7). Conclusions Several pregnancy complications in the first pregnancy are associated with development of HTN 2 to 7 years later. Preventive care for women should include a detailed pregnancy history to aid in counseling about HTN risk. Clinical Trial Registration URL: http://www.clinicaltrials.gov Unique identifier: NCT02231398.
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http://dx.doi.org/10.1161/JAHA.119.013092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806043PMC
October 2019

Prospective Evaluation of Maternal Sleep Position Through 30 Weeks of Gestation and Adverse Pregnancy Outcomes.

Obstet Gynecol 2019 10;134(4):667-676

University of Utah, Salt Lake City, Utah; RTI International, Research Triangle Park, North Carolina; Yale University, New Haven, Connecticut; University of Pittsburgh, Pittsburgh, Pennsylvania; Oregon Health & Science University, Portland, Oregon; Northwestern University, Evanston, Illinois; Case Western Reserve University, Cleveland, Ohio; Indiana University, Bloomington, Indiana; University of Pennsylvania, Philadelphia, Pennsylvania; Columbia University, New York, New York; University of South Florida, Tampa, Florida; University of California-Irvine, Irvine, California; Johns Hopkins Medicine, Baltimore, Maryland; University of Texas Medical Branch at Galveston, Galveston, Texas; and Brigham and Women's Hospital, Boston, Massachusetts.

Objective: To examine the relationship between prospectively assessed maternal sleep position and subsequent adverse pregnancy outcomes.

Methods: This was a secondary analysis of a prospective observational multicenter cohort study of nulliparous women with singleton gestations who were enrolled between October 2010 and May 2014. Participants had three study visits that were not part of clinical care. They prospectively completed in-depth sleep questionnaires between 6 0/7 and 13 6/7 weeks of gestation and 22 0/7 and 29 6/7 weeks of gestation, the first and third study visits. A subset of women also underwent level 3 home sleep tests using the Embletta Gold device. The primary outcome was a composite of adverse pregnancy outcomes such as stillbirth, a small-for-gestational-age newborn, and gestational hypertensive disorders.

Results: A total of 8,706 (of 10,038) women had data from at least one sleep questionnaire and for pregnancy outcomes, and they comprised the population for this analysis. The primary outcome occurred in 1,903 pregnancies (22%). There was no association between reported non-left lateral or supine sleep during the last week of the first visit (adjusted odds ratio [aOR] 1.00 [95% CI 0.89-1.14]) or third visit (aOR 0.99 [95% CI 0.89-1.11] and the composite or any individual outcome, except for an apparent protective effect for stillbirth at the third visit (aOR 0.27 (95% CI 0.09-0.75). Women with objectively measured supine sleep position for at least 50% of the time were no more likely than those in the supine position 50% or less of the time to have the composite adverse outcome.

Conclusions: Going to sleep in the supine or right lateral position, as self-reported before the development of pregnancy outcome and objectively assessed through 30 weeks of gestation, was not associated with an increased risk of stillbirth, a small-for-gestational-age newborn, or gestational hypertensive disorders.
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http://dx.doi.org/10.1097/AOG.0000000000003458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768734PMC
October 2019

Gestational Weight Gain and Pregnancy Outcomes among Nulliparous Women.

Am J Perinatol 2021 01 6;38(2):182-190. Epub 2019 Sep 6.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

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.
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http://dx.doi.org/10.1055/s-0039-1696640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071163PMC
January 2021

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

Arch Womens Ment Health 2020 06 29;23(3):361-369. Epub 2019 Jun 29.

Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL, USA.

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.
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http://dx.doi.org/10.1007/s00737-019-00970-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935433PMC
June 2020

Blood pressure trajectory and category and risk of hypertensive disorders of pregnancy in nulliparous women.

Am J Obstet Gynecol 2019 09 27;221(3):277.e1-277.e8. Epub 2019 Jun 27.

Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

Background: Recently updated American College of Cardiology/ American Heart Association (ACC/AHA) guidelines redefine blood pressure categories as stage 1 hypertension (systolic, 130-139 mm Hg or diastolic, 80-89 mm Hg), elevated (systolic, 120-129 mm Hg and diastolic, <80 mm Hg), and normal (<120/<80 mm Hg), but their relevance to an obstetric population is uncertain.

Objective: We sought to evaluate the risk of gestational hypertension or preeclampsia based on early pregnancy blood pressure category and trajectory.

Study Design: We utilized data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort, a prospective observational study of nulliparous women with singleton pregnancies conducted at 8 clinical sites between 2010 and 2014. Women included in this analysis had no known history of prepregnancy hypertension (blood pressure, ≥140/90 mm Hg) or diabetes. We compared the frequency of hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension, among women based on ACC/AHA blood pressure category at a first-trimester study visit and blood pressure trajectory between study visits in the first and second trimesters. Blood pressure trajectories were categorized based on blood pressure difference between visits 1 and 2 as stable (<5 mm Hg difference), upward (≥5 mm Hg), or downward (≤-5 mm Hg). Associations of blood pressure category and trajectory with preeclampsia and gestational hypertension were assessed via univariate analysis and multinomial logistic regression analysis with covariates identified a priori.

Results: A total of 8899 women were included in the analysis. Study visit 1 occurred at a mean gestational age of 11.6 ± 1.5 weeks and study visit 2 at a mean gestational age of 19.0 ± 1.6 weeks. First-trimester blood pressure category was significantly associated with both preeclampsia and gestational hypertension, with increasing blood pressure category associated with a higher risk of all hypertensive disorders of pregnancy. Elevated blood pressure was associated with an adjusted relative risk of 1.54 (95% confidence interval, 1.18-2.02) and stage 1 hypertension was associated with adjusted relative risk of 2.16 (95% confidence interval, 1.31-3.57) of any hypertensive disorder of pregnancy. Stage 1 hypertension was associated with the highest risk of preeclampsia with severe features, with an adjusted relative risk of 2.48 (95% confidence interval, 1.38-8.74). Both systolic and diastolic blood pressure trajectories were also significantly associated with the risk of hypertensive disorders of pregnancy independent of blood pressure category (P < .001). Women with a blood pressure categorized as normal and with an upward systolic trajectory had a 41% increased risk of any hypertensive disorder of pregnancy (adjusted relative risk, 1.41; 95% confidence interval, 1.20-1.65) compared to women with a downward systolic trajectory.

Conclusion: In nulliparous women, blood pressure category and trajectory in early pregnancy are independently associated with risk of preeclampsia and gestational hypertension. Our study demonstrates that blood pressure categories with lower thresholds than those traditionally used to identify individuals as hypertensive may identify more women at risk for preeclampsia and gestational hypertension.
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http://dx.doi.org/10.1016/j.ajog.2019.06.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732036PMC
September 2019

Cord Blood Haptoglobin, Cerebral Palsy and Death in Infants of Women at Risk for Preterm Birth: A Secondary Analysis of a Randomised Controlled Trial.

EClinicalMedicine 2019 Mar 22;9:11-18. Epub 2019 Mar 22.

Centre for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States of America.

Background: Antenatal exposure to intra-uterine inflammation results in precocious Haptoglobin (Hp) expression (switch-on status). We investigated the relationships between foetal Hp expression at birth with newborn and childhood outcomes.

Methods: We evaluated cord blood samples from 921 newborns of women at imminent risk for preterm delivery randomised to either placebo (n = 471, birth gestational age (GA) median [min-max]: 31 [24-41] weeks) or magnesium sulphate (n = 450, GA 31 [24-42] weeks]). Primary outcome was infant death by 1 year and/or cerebral palsy (CP) ≥ 2 years of corrected age. Adjusted odd ratios (aOR) for neonatal and childhood outcomes were calculated controlling for GA, birth weight, sex, and magnesium exposure.

Findings: Primary outcome occurred in 2.8% of offspring. Newborns were classified in three pre-defined categorisation groups by cord blood Hp switch status and IL-6 levels: inflammation-nonexposed (Category 1, n = 432, 47%), inflammation-exposed haptoglobinemic (Category 2, n = 449, 49%), and inflammation-exposed anhaptoglobinemic or hypohaptoglobinemic (Category 3, n = 40, 4%). Newborns, found anhaptoglobinemic or hypohaptoglobinemic (Category 3) had increased OR for intraventricular haemorrhage (IVH) and/or death (aOR: 7.0; 95% CI: 1.4-34.6, p = 0.02) and for CP and/or death (aOR: 6.27; 95% CI: 1.7-23.5, p = 0.006) compared with Category 2. Foetal ability to respond to inflammation by haptoglobinemia resulted in aOR similar to inflammation-nonexposed newborns. Hp1-2 or Hp2-2 phenotypes protected against retinopathy of prematurity (aOR = 0.66; 95% CI 0.48-0.91, p = 0.01).

Interpretation: Foetal ability to switch-on Hp expression in response to inflammation was associated with reduction of IVH and/or death, and CP and/or death. Foetuses unable to mount such a response had an increased risk of adverse outcomes.: clinicaltrials.gov Identifier: NCT00014989.
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http://dx.doi.org/10.1016/j.eclinm.2019.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510719PMC
March 2019

Discordance in Antenatal Corticosteroid Use and Resuscitation Following Extremely Preterm Birth.

J Pediatr 2019 05 6;208:156-162.e5. Epub 2019 Feb 6.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

Objective: To describe discordance in antenatal corticosteroid use and resuscitation following extremely preterm birth and its relationship with infant survival and neurodevelopment.

Study Design: A multicenter cohort study of 4858 infants 22-26 weeks of gestation born 2006-2011 at 24 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, with follow-up through 2013. Survival and neurodevelopmental outcomes were available at 18-22 months of corrected age for 4576 (94.2%) infants. We described antenatal interventions, resuscitation, and infant outcomes. We modeled the effect on infant outcomes of each hospital increasing antenatal corticosteroid exposure for resuscitated infants born at 22-24 weeks of gestation to rates observed at 25-26 weeks of gestation.

Results: Discordant antenatal corticosteroid use and resuscitation, where one and not the other occurred, were more frequent for births at 22 and 23 but not 24 weeks (rate ratio [95% CI] at 22 weeks: 1.7 [1.3-2.2]; 23 weeks: 2.6 [2.2-3.2]; 24 weeks: 1.0 [0.8-1.2]) when compared with 25-26 weeks. Among infants resuscitated at 23 weeks, adjusting each hospital's rate of antenatal corticosteroid use to the average at 25-26 weeks (89.2%) was projected to increase infant survival by 7.1% (95% CI 5.4-8.8%) and survival without severe impairment by 6.4% (95% CI 4.7-8.1%). No significant change in outcomes was projected for infants resuscitated at 22 weeks, where few (n = 22) resuscitated infants received antenatal corticosteroids.

Conclusions: Infants born at 23 weeks were more frequently resuscitated without antenatal corticosteroids than other extremely preterm infants. When resuscitation is intended, consistent provision of antenatal corticosteroids may increase infant survival and survival without impairment.

Trial Registration: ClinicalTrials.govNCT00063063 (Generic Database) and NCT00009633 (Follow-Up Study).
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http://dx.doi.org/10.1016/j.jpeds.2018.12.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486854PMC
May 2019

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

Am J Perinatol 2020 02 7;37(3):281-290. Epub 2019 Feb 7.

Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania.

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 (MgSO) 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 MgSO-corticosteroid exposures. Holm-Bonferroni corrections, adjusting for multiple comparisons ( < 7.3 × 10), 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;  = 0.001), but not in males (OR: 0.8, 95% CI: 0.5-1.2;  = 0.33). The sex-specific effect difference was significant ( = 7.0 × 10) and was unaffected by MgSO exposure. No other gene-sex associations were significant.

Conclusion: An gene locus may confer susceptibility to ANO in females, but not males, after EPTB.
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http://dx.doi.org/10.1055/s-0039-1678535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685763PMC
February 2020

Association of Adverse Pregnancy Outcomes With Self-Reported Measures of Sleep Duration and Timing in Women Who Are Nulliparous.

J Clin Sleep Med 2018 12 15;14(12):2047-2056. Epub 2018 Dec 15.

Department of Obstetrics and Gynecology Medicine, Northwestern University, Chicago, Illinois.

Study Objectives: To examine the relationship of self-reported sleep during pregnancy with adverse pregnancy outcomes. A secondary objective was to describe the concordance between self-reported and objectively assessed sleep during pregnancy.

Methods: In this prospective cohort, women completed a survey of sleep patterns at 6 to 13 weeks' gestation (visit 1) and again at 22 to 29 weeks' gestation (visit 3). Additionally, at 16 to 21 weeks (visit 2), a subgroup completed a week-long sleep diary coincident with an actigraphy recording. Weekly averages of self-reported sleep duration and sleep midpoint were calculated. A priori, sleep duration < 7 hours was defined as "short," and sleep midpoint after 5:00 AM was defined as "late." The relationship of these sleep abnormalities with hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) was determined.

Results: Of the 10,038 women enrolled, sleep survey data were available for 7,524 women at visit 1 and 7,668 women at visit 3. A total of 752 women also provided ≥ 5 days of sleep diary data coincident with actigraphy at visit 2. We did not observe any consistent relationship between self-reported short sleep and HDP or GDM. There was an association between self-reported late sleep midpoint and GDM (visit 1 adjusted odds ratio 1.67, 95% confidence interval 1.17, 2.38; visit 2 adjusted odds ratio 1.73, 95% confidence interval 1.23, 2.43). At visit 2, 77.1% of participants had concordance between their diary and actigraphy for short sleep duration, whereas 94.3% were concordant for sleep midpoint.

Conclusions: Self-reported sleep midpoint, which is more accurate than self-reported sleep duration, is associated with the risk of GDM.

Clinical Trial Registration: Registry: ClinicalTrials.gov, Title: Pregnancy as a Window to Future Cardiovascular Health: Adverse Pregnancy Outcomes as Predictors of Increased Risk Factors for Cardiovascular Disease, Identifier: NCT02231398, URL: https://clinicaltrials.gov/ct2/show/NCT02231398.
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http://dx.doi.org/10.5664/jcsm.7534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287730PMC
December 2018

Impact of training level on postplacental levonorgestrel 52 mg intrauterine device expulsion.

Contraception 2019 02 16;99(2):94-97. Epub 2018 Nov 16.

Department of Obstetrics and Gynecology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH 44109. Electronic address:

Objective: To determine the association between provider training level and postplacental intrauterine device (IUD) outcomes following insertion instruction by email only.

Study Design: We conducted a single-center chart review of demographics, insertion and clinical outcomes within 6 months of delivery for 116 patients who underwent postplacental levonorgestrel 52 mg IUD placement from October 1, 2016, to March 31, 2017.

Results: We confirmed IUD retention, removal or expulsion in 87 of 116 (75.0%) patients by 6 months after delivery. Complete expulsion or removal for malposition occurred in 20 (23.0%) patients and more frequently after vaginal than cesarean delivery (30.2% vs. 4.2%, OR 9.93 [95% CI 1.25-78.96]) and when a postgraduate year (PGY) 1 physician placed the IUD compared to a PGY 2-4 or attending physician (37.5% vs. 14.5%, OR 3.52 [95% CI 1.25-9.94]).

Conclusion: Postplacental levonorgestrel 52 mg IUD expulsion rates are associated with provider training level as well as delivery route, though the individual association of each of these factors is difficult to ascertain given the high degree of collinearity between these two variables in our study.
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http://dx.doi.org/10.1016/j.contraception.2018.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351181PMC
February 2019

Child Neurodevelopmental Outcomes by Prepregnancy Body Mass Index and Gestational Weight Gain.

Obstet Gynecol 2018 12;132(6):1386-1393

Departments of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois, University of Utah Health Sciences Center, Salt Lake City, Utah, University of Texas-Southwestern, Dallas, Texas, Wayne State University, Detroit, Michigan, Columbia University, New York, New York, University of North Carolina, Chapel Hill, North Carolina, University of Texas Medical Branch, Galveston, Texas, University of Alabama at Birmingham, Birmingham, Alabama, Brown University, Providence, Rhode Island, University of Texas-Houston, Houston, Texas, The Ohio State University, Columbus, Ohio, Case Western Reserve University, Cleveland, Ohio, Oregon Health Sciences University, Portland, Oregon, and University of Pittsburgh, Pittsburgh, Pennsylvania; the George Washington University Biostatistics Coordinating Center, Washington, DC; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, Bethesda, Maryland.

Objective: To study the association of prepregnancy body mass index (BMI) and gestational weight gain with child neurodevelopmental outcomes.

Methods: We performed a secondary analysis of data from two parallel, multicenter, randomized, double-blind, placebo-controlled thyroxine replacement trials in pregnant women with either hypothyroxinemia or subclinical hypothyroidism who delivered at term. Body mass index was categorized as normal (18.5-24.9), overweight (25.0-29.9), or obese (30 or greater). We also evaluated early (20 weeks of gestation or less), late (greater than 20 weeks of gestation), and total gestational weight gain and categorized gestational weight gain as inadequate, adequate, and excessive per 2009 Institute of Medicine guidelines. Neurodevelopmental outcomes included 5-year Wechsler Preschool and Primary Scale of Intelligence and 3-year Differential Ability Scales-II. Linear and logistic regression analyses were performed and adjusted for maternal age, race-ethnicity, education, insurance status, parity, smoking and alcohol use, thyroid status (subclinical hypothyroidism or hypothyroxinemia), treatment group, gestational age at delivery, and neonatal sex.

Results: Of the 948 women included, 380 (40%), 305 (32%), and 263 (28%) had normal, overweight, and obese prepregnancy BMI, respectively. A total of 106 (11%), 212 (22%), and 630 (66%) of women had inadequate, adequate, and excessive total rates of gestational weight gain, respectively. Maternal differences among the BMI categories included race-ethnicity, education, insurance type, parity, and thyroid status (all P<.01), whereas the gestational weight gain groups only differed by parity (P<.001). In unadjusted analysis, children of obese (93.2±12.8; 88.5±13.3) and overweight (94.1±15.6; 89.6±16.0) women had lower Wechsler Preschool and Primary Scale of Intelligence and Differential Ability Scales-II scores, respectively, than normal-weight women (97.4±15.4; 93.9±16.0; P<.001 for all comparisons); however, in adjusted analysis, there were no differences in neurodevelopmental outcomes by maternal BMI. The association was primarily accounted for by race-ethnicity and education. In unadjusted and adjusted analyses, there were no differences in neurodevelopmental outcomes by adequacy of early, late, or total gestational weight gain.

Conclusion: In women with either subclinical hypothyroidism or hypothyroxinemia, neither prepregnancy BMI nor gestational weight gain was associated with neurodevelopmental outcomes among children born at term in adjusted analyses.
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http://dx.doi.org/10.1097/AOG.0000000000002974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249049PMC
December 2018

Risk of Ischemic Placental Disease in Relation to Family History of Preeclampsia.

Am J Perinatol 2019 05 3;36(6):624-631. Epub 2018 Oct 3.

Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan.

Objective: To assess the risk of ischemic placental disease (IPD) including preeclampsia, small for gestational age (SGA), and abruption, in relation to preeclampsia in maternal grandmother, mother, and sister(s).

Study Design: We performed a secondary analysis of data from a randomized trial of vitamins C and E for preeclampsia prevention. Data on family history of preeclampsia were based on recall by the proband. The associations between family history of preeclampsia and the odds of IPD were evaluated from alternating logistic regressions.

Results: Of the 9,686 women who delivered nonmalformed, singleton live births, 17.1% had IPD. Probands provided data on preeclampsia in 55.5% ( = 5,374) on all three family members, 26.5% ( = 2,562) in mother and sister(s) only, and 11.6% ( = 1,125) in sister(s) only. The pairwise odds ratio (pOR) of IPD was 1.16 (95% confidence interval [CI]: 1.00-1.36) if one or more of the female relatives had preeclampsia. The pORs of preeclampsia were 1.54 (95% CI: 1.12-2.13) and 1.35 (95% CI: 1.03-1.77) if the proband's mother or sister(s) had a preeclamptic pregnancy, respectively, but no associations were seen for SGA infant or abruption.

Conclusion: This study suggests that IPD may share a predisposition with preeclampsia, suggesting a familial inheritance.
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http://dx.doi.org/10.1055/s-0038-1672177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447463PMC
May 2019

Thyroid function in neonates of women with subclinical hypothyroidism or hypothyroxinemia.

J Perinatol 2018 11 5;38(11):1490-1495. Epub 2018 Sep 5.

University of Pittsburgh, Pittsburgh, PA, USA.

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.
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http://dx.doi.org/10.1038/s41372-018-0213-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215529PMC
November 2018