Publications by authors named "Pauline Mendola"

150 Publications

Joint effects of ethnic enclave residence and ambient volatile organic compounds exposure on risk of gestational diabetes mellitus among Asian/Pacific Islander women in the United States.

Environ Health 2021 May 8;20(1):56. Epub 2021 May 8.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Drive, MSC, Bethesda, MD, 7004, USA.

Background: Asian/Pacific Islander (API) communities in the United States often reside in metropolitan areas with distinct social and environmental attributes. Residence in an ethnic enclave, a socially distinct area, is associated with lower gestational diabetes mellitus (GDM) risk, yet exposure to high levels of air pollution, including volatile organic compounds (VOCS), is associated with increased GDM risk. We examined the joint effects of ethnic enclaves and VOCs to better understand GDM risk among API women, the group with the highest prevalence of GDM.

Methods: We examined 9069 API births in the Consortium on Safe Labor (19 hospitals, 2002-2008). API ethnic enclaves were defined as areas ≥66th percentile for percent API residents, dissimilarity (geographic dispersal of API and White residents), and isolation (degree that API individuals interact with another API individual). High levels of 14 volatile organic compounds (VOC) were defined as ≥75th percentile. Four joint categories were created for each VOC: Low VOC/Enclave (reference group), Low VOC/No Enclave, High VOC/Enclave, High VOC/No Enclave. GDM was reported in medical records. Hierarchical logistic regression estimated odds ratios (OR) and 95% confidence intervals (95%CI) between joint exposures and GDM, adjusted for maternal factors and area-level poverty. Risk was estimated for 3-months preconception and first trimester exposures.

Results: Enclave residence was associated with lower GDM risk regardless of VOC exposure. Preconception benzene exposure was associated with increased risk when women resided outside enclaves [High VOC/No Enclave (OR:3.45, 95%CI:1.77,6.72)], and the effect was somewhat mitigated within enclaves, [High VOC/Enclave (OR:2.07, 95%:1.09,3.94)]. Risks were similar for 12 of 14 VOCs during preconception and 10 of 14 during the first trimester.

Conclusions: API residence in non-enclave areas is associated with higher GDM risk, regardless of VOC level. Ethnic enclave residence may mitigate effects of VOC exposure, perhaps due to lower stress levels. The potential benefit of ethnic enclaves warrants further study.
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http://dx.doi.org/10.1186/s12940-021-00738-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106843PMC
May 2021

Asthma Medication Regimens in Pregnancy: Longitudinal Changes in Asthma Status.

Am J Perinatol 2021 Apr 21. Epub 2021 Apr 21.

Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Objective:  This study aimed to assess the impact of common asthma medication regimens on asthma symptoms, exacerbations, lung function, and inflammation during pregnancy.

Study Design:  A total of 311 women with asthma were enrolled in a prospective pregnancy cohort. Asthma medication regimen was categorized into short-acting β agonist (SABA) alone, SABA + inhaled corticosteroid (ICS), SABA + ICS + long-acting β agonist (LABA), and no asthma medications (reference). We evaluated asthma control at enrollment (< 15 weeks' gestation) and its change into trimesters 2 and 3, including per cent predicted forced expiratory volume in 1 second (%FEV1) and peak expiratory flow (%PEF), pulse oximetry, fractional exhaled nitric oxide (FeNO), asthma symptoms (asthma attacks/month, night symptoms/week), and severe exacerbations. Linear mixed models adjusted for site, age, race, annual income, gestational age, body mass index, and smoking, and propensity scores accounted for asthma control status at baseline.

Results:  Women taking SABA + ICS and SABA + ICS + LABA had better first trimester %PEF (83.5% [75.7-91.3] and 84.6% [76.9-92.3], respectively) compared with women taking no asthma medications (72.7% [66.0-79.3]). Women taking SABA + ICS + LABA also experienced improvements in %FEV1 (+11.1%,  < 0.01) in the third trimester and FeNO in the second (-12.3 parts per billion [ppb],  < 0.01) and third (-11.0 ppb,  < 0.01) trimesters as compared with the trajectory of women taking no medications. SABA + ICS use was associated with increased odds of severe exacerbations in the first (odds ratio [OR]: 2.22 [1.10-4.46]) and second (OR: 3.15 [1.11-8.96]) trimesters, and SABA + ICS + LABA use in the second trimester (OR: 7.89 [2.75-21.47]). Women taking SABA alone were similar to those taking no medication.

Conclusion:  Pregnant women taking SABA + ICS and SABA + ICS + LABA had better lung function in the first trimester. SABA + ICS + LABA was associated with improvements in lung function and inflammation across gestation. However, both the SABA + ICS and SABA + ICS + LABA groups had a higher risk of severe exacerbation during early to mid-pregnancy.

Key Points: · Medication regimens may affect perinatal asthma control.. · Intensive regimens improved lung function/inflammation.. · Women on intensive regimens had more acute asthma events..
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http://dx.doi.org/10.1055/s-0041-1727233DOI Listing
April 2021

Air pollution exposure and risk of adverse obstetric and neonatal outcomes among women with type 1 diabetes.

Environ Res 2021 Jun 18;197:111152. Epub 2021 Apr 18.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Drive, Bethesda, MD, 20892, USA; Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, 401 Kimball Tower, Buffalo, NY, 14214, USA.

Aims/hypothesis: Women with type 1 diabetes have increased risk for poor obstetric outcomes. Prenatal air pollution exposure is also associated with adverse outcomes for women and infants. We examined whether women with type 1 diabetes are more vulnerable than other women to pollution-associated risks during pregnancy.

Methods: In singleton deliveries from the Consortium on Safe Labor (2002-2008), obstetric and neonatal outcomes were compared for women with type 1 diabetes (n = 507) and women without autoimmune disease (n = 204,384). Preconception, trimester, and whole pregnancy average air pollutant exposure (ozone (O), carbon monoxide (CO), particulate matter >10 μm (PM), PM > 2.5 μm (PM), sulfur dioxide (SO), nitrogen oxides (NO)) were estimated using modified Community Multiscale Air Quality models. Poisson regression models with diabetes*pollutant interaction terms estimated relative risks and 95% confidence intervals for adverse outcomes, adjusted for maternal characteristics and geographic region.

Results: For whole pregnancy exposure to SO, women with type 1 diabetes had 15% increased risk (RR:1.15 95%CI:1.01,1.31) and women without autoimmune disease had 5% increased risk (RR:1.05 95%CI:1.05,1.06) for small for gestational age birth (p = 0.09). Additionally, whole pregnancy O exposure was associated with 10% increased risk (RR:1.10 95%CI:1.02,1.17) among women with type 1 diabetes and 2% increased risk (RR:1.02 95%CI:1.00,1.04) among women without autoimmune disease for perinatal mortality (p = 0.08). Similar patterns were observed between PM exposure and spontaneous preterm birth.

Conclusions: Pregnant women with type 1 diabetes may be at greater risk for adverse outcomes when exposed to air pollution than women without autoimmune disease.
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http://dx.doi.org/10.1016/j.envres.2021.111152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190832PMC
June 2021

Conception by fertility treatment and offspring deoxyribonucleic acid methylation.

Fertil Steril 2021 Apr 3. Epub 2021 Apr 3.

Department of Epidemiology and Biostatistics, University at Albany School of Public Health, Albany, New York.

Objective: To investigate whether deoxyribonucleic acid (DNA) methylation at birth and in childhood differ by conception using assisted reproductive technologies (ART) or ovulation induction compared with those in children conceived without fertility treatment.

Design: Upstate KIDS is a matched exposure cohort which oversampled on newborns conceived by treatment.

Setting: New York State (excluding New York City).

Patient(s): This analysis included 855 newborns and 152 children at approximately 9 years of age.

Intervention(s): None.

Main Outcome Measure(s): DNA methylation levels were measured using the Illumina EPIC platform. Single CpG and regional analyses at imprinting genes were conducted.

Result(s): Compared to no fertility treatment, ART was associated with lower mean DNA methylation levels at birth in 11 CpGs (located in/near SYCE1, SPRN, KIAA2013, MYO1D, GET1/WRB-SH4BGR, IGF1R, SORD, NECAB3/ACTL10, and GET1) and higher mean methylation level in 1 CpG (KLK4; all false discovery rate P<.05). The strongest association (cg17676129) was located at SYCE1, which codes for a synaptonemal complex that plays a role in meiosis and therefore infertility. This CpG remained associated with newborn hypomethylation when the analysis was limited to those conceived with ICSI, but this may be because of underlying male infertility. In addition, nine regions in maternally imprinted genes (IGF1R, PPIEL, SVOPL GNAS, L3MBTL, BLCAP, HYMAI/PLAGL1, SNU13, and MEST) were observed to have decreased mean DNA methylation levels among newborns conceived by ART. In childhood, hypomethylation of the maternally imprinted gene, GNAS, persisted. No CpGs or regions were associated with ovulation induction.

Conclusion(s): ART but not ovulation induction was associated with hypomethylation at birth, but only one difference at an imprinting region appeared to persist in childhood.
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http://dx.doi.org/10.1016/j.fertnstert.2021.03.011DOI Listing
April 2021

Chronic exposure to air pollution and risk of mental health disorders complicating pregnancy.

Environ Res 2021 05 26;196:110937. Epub 2021 Feb 26.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Drive, Bethesda, MD, 20892, USA; Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, USA. Electronic address:

Background: Air pollution is associated with mental health in the general population, but its influence on maternal mental health during pregnancy has not been assessed.

Objective: We evaluated the relationship between unspecified mental disorders complicating pregnancy and depression with average air pollution exposure during 3-months preconception, first trimester and whole pregnancy.

Methods: Ambient air pollution was derived from a modified Community Multiscale Air Quality model and mental health diagnoses were based on electronic intrapartum medical records. Logistic regression models assessed the odds of unspecified mental disorder complicating pregnancy (n = 11,577) and depression (n = 9793) associated with an interquartile range increase in particulate matter (PM) less than 2.5 μm (PM), PM, carbon monoxide (CO), nitrogen dioxide (NO), nitrogen oxide (NO), sulfur dioxide (SO), and ozone (O). Pregnancies without mental health disorders were the reference group (n = 211,645). Models were adjusted for maternal characteristics and study site; analyses were repeated using cases with no additional mental health co-morbidity.

Results: Whole pregnancy exposure to PM, PM, NO, and NO was associated with a 29%-74% increased odds of unspecified mental disorders complicating pregnancy while CO was associated with 31% decreased odds. Results were similar for depression: whole pregnancy exposure to PM, PM, NO, and NO was associated with 11%-21% increased odds and CO and O were associated with 16%-20% decreased odds. SO results were inconsistent, with increased odds for unspecified mental disorders complicating pregnancy and decreased odds for depression. While most findings were similar or stronger among cases with no co-morbidity, PM and NO were associated with reduced risk and SO with increased risk for depression only.

Discussion: Whole pregnancy exposure to PM, PM, NO, and NO were associated with unspecified mental disorder complicating pregnancy and depression, but some results varied for depression only. These risks merit further investigation.
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http://dx.doi.org/10.1016/j.envres.2021.110937DOI Listing
May 2021

Admixture mapping identifies African and Amerindigenous local ancestry loci associated with fetal growth.

Hum Genet 2021 Jul 15;140(7):985-997. Epub 2021 Feb 15.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6710B Rockledge Dr, 6710B-3204, Bethesda, MD, 20892-7004, USA.

Fetal growth is an important determinant of cardiometabolic disease risk during childhood and adulthood. The genetic architecture of fetal growth remains largely understudied in ancestrally diverse populations. We conducted genome-wide admixture mapping scan and analysis of genetic ancestry among Hispanic American, African American, European American, and Asian American pregnant women to identify genetic loci associated with fetal growth measures across 13-40 weeks gestation. Fetal growth measures were associated with genome-wide average African, European, Amerindigenous and East Asian ancestry proportions (P ranged from10 to 4.8 × 10). Admixture mapping analysis identified ten African ancestry loci and three Amerindigenous ancestry loci significantly associated with fetal growth measures at Bonferroni-corrected levels of significance (P ranged from 2.18 × 10 to 3.71 × 10). At the chr2q23.3-24.2 locus in which higher African ancestry was associated with long bone (femur and humerus) lengths, the T allele of rs13030825 (GALNT13) was associated with longer humerus length in African Americans (β = 0.44, P = 6.25 × 10 at week 27; β = 0.39, P = 7.72 × 10 at week 40). The rs13030825 SNP accounted for most of the admixture association at the chr2q23.3-24.2 locus and has substantial allele frequency difference between African and European reference samples (F = 0.55, P = 0.03). Regulatory annotation shows that rs13030825 overlaps with the serum response factor (SRF) transcription factor previously implicated in postnatal bone development of mice. Overall, we identified ancestry-related maternal genetic loci that influence fetal growth, shedding light on molecular pathways that regulate fetal growth and potential effects on health across the lifespan.Clinical trials registration ClinicalTrials.gov, NCT00912132.
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http://dx.doi.org/10.1007/s00439-021-02265-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197736PMC
July 2021

Household mold, pesticide use, and childhood asthma: A nationwide study in the U.S.

Int J Hyg Environ Health 2021 Apr 6;233:113694. Epub 2021 Feb 6.

Kaiser Permanente Northern California Division of Research, Oakland, CA, United States; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, United States. Electronic address:

Objectives: To investigate the associations of household mold and pesticide use with risk of childhood asthma and examine the potential effect modification by child's sex at a national level in the U.S.

Methods: Nationally representative data were drawn from the cross-sectional 2017 and 2018 National Surveys of Children's Health. Household mold and pesticide exposures during the past 12 months and physician-diagnosed childhood asthma were assessed by standard questionnaires administered to primary caregivers. Multivariable logistic regression models were used to calculate adjusted odds ratios (aOR) for current asthma, adjusting for child, caregiver, and household covariates. We also examined potential effect modification by child's sex. Sampling weights accounted for the complex survey design.

Results: Among 41,423 U.S. children in 2017-2018, the weighted prevalence of current asthma was 10.8% in household mold-exposed children, compared with 7.2% in non-exposed children (P < 0.001). After adjusting for covariates including child's obesity, children with household mold exposure compared to those with no household mold exposure had a 1.41-fold (95% CI: 1.07, 1.87) higher odds of current asthma. Associations between household mold and current asthma were pronounced among boys (aOR 1.57; 95% CI: 1.03-2.38) but not girls (aOR 1.28; 0.90-1.83; P for interaction <0.001). No significant associations were observed between household pesticide use and current asthma, after adjusting for covariates.

Conclusions: Our findings suggest that household mold is associated with current asthma among children, independent of other major risk factors including child's obesity status. Our findings may inform strategies targeting mitigation of household mold as an important indoor environment factor to address childhood asthma.
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http://dx.doi.org/10.1016/j.ijheh.2021.113694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965337PMC
April 2021

Does maternal race or ethnicity modify the association between maternal psychiatric disorders and preterm birth?

Ann Epidemiol 2021 04 24;56:34-39.e2. Epub 2020 Oct 24.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD. Electronic address:

Purpose: Preterm birth risk has been linked to maternal racial and ethnic background, particularly African American heritage; however, the association of maternal race and ethnicity with psychiatric disorders and preterm birth has received relatively limited attention.

Methods: The Consortium on Safe Labor (2002-2008) is a nationwide U.S. cohort study with 223,394 singleton pregnancies. Clinical data were obtained from electronic medical records, including maternal diagnoses of psychiatric disorders. Relative risk (RR) and 95% confidence intervals (CI) were estimated for the association between maternal psychiatric disorders and preterm birth (<37 completed weeks) using log-binomial regression with generalized estimating equations. The interaction effect of maternal psychiatric disorders with race and ethnicity was also evaluated.

Results: Non-Hispanic White (RR, 1.42; 95% CI, 1.35-1.49), Hispanic (RR, 1.44; 95% CI, 1.29-1.60), and non-Hispanic Black (RR, 1.21, 95% CI, 1.13-1.29) women with any psychiatric disorder were at increased risk for delivering preterm infants, compared with women without any psychiatric disorder. However, non-Hispanic Black women with any psychiatric disorder, depression, bipolar disorder, and schizophrenia had a significantly lower increase in preterm birth risk than non-Hispanic White women.

Conclusions: Despite the significant association between maternal psychiatric disorders and preterm birth risk, psychiatric disorders did not appear to contribute to racial and ethnic disparities in preterm birth.
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http://dx.doi.org/10.1016/j.annepidem.2020.10.009DOI Listing
April 2021

Perfluorooctanoic acid (PFOA) or perfluorooctane sulfonate (PFOS) and DNA methylation in newborn dried blood spots in the Upstate KIDS cohort.

Environ Res 2021 03 30;194:110668. Epub 2020 Dec 30.

Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6710B Rockledge Drive, Bethesda, MD, 20892, United States. Electronic address:

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are persistent organic pollutants which may alter prenatal development, potentially through epigenetic modifications. Prior studies examining PFOS/PFOA and DNA methylation have relatively few subjects (n < 200) and inconsistent results. We examined relations of PFOA/PFOS with DNA methylation among 597 neonates in the Upstate KIDS cohort study. PFOA/PFOS were quantified in newborn dried blood spots (DBS) using high-performance liquid chromatography/tandem mass spectrometry. DNA methylation was measured using the Infinium MethylationEPIC BeadChip with DNA extracted from DBS. Robust linear regression was used to examine the associations of PFOA/PFOS with DNA methylation at individual CpG sites. Covariates included sample plate, estimated cell type, epigenetically derived ancestry, infant sex and plurality, indicators of maternal socioeconomic status, and prior pregnancy loss. In supplemental analysis, we restricted the analysis to 2242 CpG sites previously identified as Correlated Regions of Systemic Interindividual Variation (CoRSIVs) which include metastable epialleles. At FDR<0.05, PFOA concentration >90th percentile was related to DNA methylation at cg15557840, near SCRT2, SRXN1; PFOS>90th percentile was related to 2 CpG sites in a sex-specific manner (cg19039925 in GVIN1 in boys and cg05754408 in ZNF26 in girls). When analysis was restricted to CoRSIVs, log-scaled, continuous PFOS concentration was related to DNA methylation at cg03278866 within PTBP1. In conclusion, there was limited evidence of an association between high concentrations of PFOA/PFOS and DNA methylation in newborn DBS in the Upstate KIDS cohort. These findings merit replication in populations with a higher median concentration of PFOA/PFOS.
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http://dx.doi.org/10.1016/j.envres.2020.110668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946760PMC
March 2021

Gestational and Postpartum Weight Trajectories Among Women With and Without Asthma.

Am J Epidemiol 2021 05;190(5):744-754

Asthma leads to increased weight gain in nonpregnant populations, but studies have not examined this association within the context of pregnancy. The association between asthma and perinatal weight trajectories was examined in the Breathe-Wellbeing, Environment, Lifestyle, and Lung Function Study (2015-2019). Multilevel linear spline models were adjusted for age, race/ethnicity, income, marital status, education, cigarette smoking, parity, study site, and prepregnancy body mass index were used to examine differences in perinatal weight trajectories between women with (n = 299) and without (n = 101) asthma. Secondary analyses were conducted to assess whether associations differed by asthma phenotypes. At 40 weeks' gestation, women with asthma gained 16.2 kg (95% confidence interval (CI): 14.6, 17.7) and women without asthma gained 13.1 kg (95% CI: 10.9, 15.4). At 3 months postpartum, women with asthma retained 10.4 kg (95% CI: 8.9, 11.9) and women without asthma retained 8.0 kg (95% CI: 5.9, 10.2). Among women with asthma, exercise-induced asthma and step 3 asthma medications were associated with excess gestational weight gain. These study findings suggest women with asthma gain and retain more weight during pregnancy and postpartum than do women without asthma.
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http://dx.doi.org/10.1093/aje/kwaa248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096479PMC
May 2021

Ambient temperature and stillbirth: Risks associated with chronic extreme temperature and acute temperature change.

Environ Res 2020 10 19;189:109958. Epub 2020 Jul 19.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Drive, Bethesda, MD, USA. Electronic address:

Background: Ambient temperature events are increasing in frequency and intensity. Our prior work in a U.S. nationwide study suggests a strong association between both chronic and acute temperature extremes and stillbirth risk.

Objective: We attempted to replicate our prior study by assessing stillbirth risk associated with average whole-pregnancy temperatures and acute ambient temperature changes in a low-risk U.S.

Population:

Methods: Singleton deliveries in the NICHD Consecutive Pregnancies Study (Utah, 2002-2010; n = 112,005) were identified using electronic medical records. Ambient temperature was derived from the Weather Research and Forecasting model. Binary logistic regression determined the adjusted odds ratio (aOR) and 95% confidence interval (95% CI) for stillbirth associated with whole-pregnancy exposure to extreme cold (<10th percentile) and hot (>90th percentile) versus moderate (10th-90th percentiles) average temperature, adjusting for maternal demographics, season of conception, hypertensive disorders of pregnancy, and gestational diabetes. In a case-crossover analysis, we estimated the stillbirth aOR and 95% CI for each 1° Celsius increase during the week prior to delivery using conditional logistic regression. In both models, we adjusted for relative humidity, ozone, and fine particulates.

Results: We observed 500 stillbirth cases among 498 mothers. Compared to moderate temperatures, whole-pregnancy exposure to extreme cold (aOR: 4.42, 95% CI:3.43, 5.69) and hot (aOR: 5.06, 95% CI: 3.34, 7.68) temperatures were associated with stillbirth risk. Case-crossover models observed a 7% increased odds (95% CI: 1.04, 1.10) associated with each 1° Celsius increase during the week prior to delivery.

Discussion: Both chronic and acute ambient temperature were associated with odds of stillbirth in this low-risk population, similar to our prior nationwide findings. Future increases in temperature extremes are likely and the observed risk in a low-risk population suggests this association merits attention.
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http://dx.doi.org/10.1016/j.envres.2020.109958DOI Listing
October 2020

Preconception Blood Pressure and Its Change Into Early Pregnancy: Early Risk Factors for Preeclampsia and Gestational Hypertension.

Hypertension 2020 09 3;76(3):922-929. Epub 2020 Aug 3.

From the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (C.J.N., P.M., S.L.M., K.K., V.C.A., M.C., L.S., N.J.P., E.F.S.).

Preeclampsia and gestational hypertension are common complications of pregnancy associated with significant maternal and infant morbidity. Despite extensive research evaluating risk factors during pregnancy, most women who develop a hypertensive disorder of pregnancy are not considered high-risk and strategies for prevention remain elusive. We evaluated preconception blood pressure and its change into early pregnancy as novel risk markers for development of a hypertensive disorder of pregnancy. The EAGeR (Effects of Aspirin in Gestation and Reproduction) trial (2007-2011) randomized 1228 healthy women with a history of pregnancy loss to preconception-initiated low-dose aspirin versus placebo and followed participants for up to 6 menstrual cycles attempting pregnancy and throughout pregnancy if they became pregnant. Blood pressure was measured during preconception and throughout early gestation. The primary outcomes, preterm preeclampsia, term preeclampsia, and gestational hypertension, were abstracted from medical records. Among 586 women with a pregnancy >20 weeks' gestation, preconception blood pressure levels were higher for preterm preeclampsia (87.3±6.7 mm Hg mean arterial pressure), term preeclampsia (88.3±9.8 mm Hg), and gestational hypertension (87.9±9.1 mm Hg) as compared with no hypertensive disorder of pregnancy (83.9±8.6 mm Hg). Change in blood pressure from preconception into very early pregnancy was associated with development of preeclampsia (relative risk, 1.13 [95% CI, 1.02-1.25] per 2 mm Hg increase in mean arterial pressure at 4 weeks' gestation), particularly preterm preeclampsia (relative risk, 1.21 [95% CI, 1.01-1.45]). Randomization to aspirin did not alter blood pressure trajectory or risk of hypertension in pregnancy. Preconception blood pressure and longitudinal changes during early pregnancy are underexplored but crucial windows in the detection and prevention of hypertensive disorders of pregnancy. Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00467363.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456510PMC
September 2020

Family history of autoimmune disease in relation to time-to-pregnancy, pregnancy loss, and live birth rate.

J Transl Autoimmun 2020 1;3:100059. Epub 2020 Jun 1.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Dr. MSC 7004, Bethesda, MD 20892, United States.

Several autoimmune conditions have adverse effects on reproductive outcomes, but the relationship between family history of autoimmune disease in women without these conditions and pregnancy is uncertain. The objective of this study was to determine if there is an association between a family history of an autoimmune condition and time-to-pregnancy (TTP), pregnancy loss, and live birth. This was a prospective cohort study from a RCT of 1228 adult women ages 18-40, who were healthy, had no history of infertility, were actively attempting to conceive, and had one or two prior pregnancy losses. Of these, 1172 women had data available regarding family history of autoimmune conditions. Women with an affected first-degree relative had similar TTP when compared to those without a FHx (fecundability odds ratio 0.90, 95% confidence interval [CI] 0.70, 1.15). Women with an affected first-degree relative had a lower likelihood of live birth (relative risk [RR] 0.83, 95% CI 0.69, 0.99). Among women who achieved pregnancy, FHx of autoimmune disease was associated with a higher likelihood of pregnancy loss (RR 1.49, 95% CI 1.10, 2.03). Women who had a first-degree relative with an autoimmune disease had a similar TTP as unaffected women but a lower likelihood of live birth and higher risk of pregnancy loss. This information may encourage clinicians to evaluate women with a family history of autoimmune conditions prior to pregnancy and highlights the need for further studies to ascertain the effects of autoimmunity and pregnancy.
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http://dx.doi.org/10.1016/j.jtauto.2020.100059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388372PMC
June 2020

Early pregnancy dyslipidemia is associated with placental DNA methylation at loci relevant for cardiometabolic diseases.

Epigenomics 2020 06 17;12(11):921-934. Epub 2020 Jul 17.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD 20892-7004, USA.

To identify placental DNA methylation changes that are associated with early pregnancy maternal dyslipidemia. We analyzed placental genome-wide DNA methylation (n = 262). Genes annotating differentially methylated CpGs were evaluated for gene expression in placenta (n = 64). We found 11 novel significant differentially methylated CpGs associated with high total cholesterol, low-density lipoprotein cholesterol and triglycerides, and low high-density lipoprotein cholesterol. High triglycerides were associated with decreased methylation of cg02785814 () and decreased expression of in placenta. Genes annotating the differentially methylated CpGs play key roles in lipid metabolism and were enriched in dyslipidemia pathways. Functional annotation found -methylation quantitative trait loci for genetic loci in and . Our findings lend novel insights into potential placental epigenetic mechanisms linked with maternal dyslipidemia. ClinicalTrials.gov, NCT00912132.
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http://dx.doi.org/10.2217/epi-2019-0293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466909PMC
June 2020

Concentrations of persistent organic pollutants in maternal plasma and epigenome-wide placental DNA methylation.

Clin Epigenetics 2020 07 11;12(1):103. Epub 2020 Jul 11.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6710B Rockledge Drive, Bethesda, MD, 20892-7004, USA.

Background: Prenatal maternal plasma persistent organic pollutant (POP) concentrations have been associated with neonatal outcomes. However, the underlying mechanisms remain unknown. Placental epigenetic mechanisms may be involved, but no prior epigenome-wide studies have investigated the impact of maternal POPs on placental DNA methylation. We studied the association between maternal plasma POP concentration in early pregnancy and epigenome-wide placental DNA methylation among 260 pregnant women from the NICHD Fetal Growth Studies.

Results: Our analysis focused on POPs with more than 80% plasma concentrations above the limit of quantification, including 3 organochlorine pesticides (hexachlorobenzene, trans-nonachlor, p,p'-dichlorodiphenyldichloroethylene), 1 polybrominated diphenyl ether (PBDE 47), 3 polychlorinated biphenyls (138/158, 153, 180), and 6 poly- and perfluorinated alkyl substances (PFASs) (perfluorodecanoic acid, perfluorohexanesulfonic acid, perfluorononanoic acid, perfluorooctanesulfonic acid, perfluoroundecanoic acid (PFUnDA)). Using 5% false discovery rate, POPs were associated with a total of 214 differentially methylated CpG sites (nominal p values ranging from 2.61 × 10 to 2.11 × 10). Out of the 214 CpG sites, 24 (11%) were significantly correlated with placental expression of 21 genes. Notably, higher PFUnDA was associated with increased methylation at 3 CpG sites (cg13996963, cg12089439, cg18145877) annotated to TUSC3, and increased methylation at those 3 CpG sites was correlated with decreased expression of TUSC3 in the placenta. Increased methylation at cg18145877 (TUSC3) and decreased expression of TUSC3 were correlated with shorter birth length. Out of the 214 CpG sites, methylation at 44 CpG sites was correlated (p value < 0.10) with at least one neonatal anthropometry measure (i.e., birth weight, birth length, and head circumference). Seven CpG sites mediated (p value < 0.05) the association between PBDE 47 and neonatal anthropometry measures. Genes annotating the top differentially methylated CpG sites were enriched in pathways related to differentiation of embryonic cells (PBDE 47) and in pathways related to brain size and brain morphology (PFASs).

Conclusions: DNA methylation changes in the placenta were significantly associated with maternal plasma POPs concentration. The findings suggest that placental DNA methylation and gene expression mechanism may be involved in the prenatal toxicity of POPs and their association with neonatal anthropometry measures.
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http://dx.doi.org/10.1186/s13148-020-00894-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371466PMC
July 2020

Air Pollution Exposure Monitoring among Pregnant Women with and without Asthma.

Int J Environ Res Public Health 2020 07 7;17(13). Epub 2020 Jul 7.

Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.

: We monitored exposure to fine particulates (PM), ozone, nitrogen dioxide (NO), and ambient temperature for pregnant women with and without asthma. : Women ( = 40) from the Breathe-Well-Being, Environment, Lifestyle, and Lung Function Study (2015-2018) were enrolled during pregnancy and monitored for 2-4 days. Daily pollutants were measured using personal air monitors, indoor air monitors, and nearest Environmental Protection Agency's stationary monitors based on GPS tracking and home address. : Personal-monitor measurements of PM, ozone, and NO did not vary by asthma status but exposure profiles significantly differed by assessment methods. EPA stationary monitor-based methods appeared to underestimate PM and temperature exposure and overestimate ozone and NO exposure. Higher indoor-monitored PM exposures were associated with smoking and the use of gas appliances. The proportion of waking-time during which personal monitors were worn was ~56%. Lower compliance was associated with exercise, smoking, being around a smoker, and the use of a prescription drug. : Exposure did not vary by asthma status but was influenced by daily activities and assessment methods. Personal monitors may better capture exposures but non-compliance merits attention. Meanwhile, larger monitoring studies are warranted to further understand exposure profiles and the health effects of air pollution during pregnancy.
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http://dx.doi.org/10.3390/ijerph17134888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369909PMC
July 2020

The associations of maternal polycystic ovary syndrome and hirsutism with behavioral problems in offspring.

Fertil Steril 2020 02;113(2):435-443

Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. Electronic address:

Objective: To study the associations between maternal polycystic ovary syndrome (PCOS) and hirsutism with offspring attention-deficit/hyperactivity disorder (ADHD), anxiety, conduct disorder, and behavioral problems.

Design: Prospective birth cohort study.

Setting: Not applicable.

Patient(s): A total of 1,915 mother-child dyads.

Intervention(s): None.

Main Outcome Measure(s): Maternal report of offspring ADHD, anxiety, or conduct disorder diagnosis at 7 to 8 years; emotional symptoms, behavioral problems (including peer relationship, conduct, hyperactivity/inattention), and prosocial problems measured with the Strengths and Difficulties Questionnaire (SDQ) at 7 years.

Result(s): Prevalence of PCOS and hirsutism were 12.0% and 3.9%; 84% of women with hirsutism had PCOS. After adjustment for sociodemographic covariates, prepregnancy body mass index, and parental history of affective disorders, children born to mothers with PCOS had higher risk of anxiety (adjusted risk ratio [aRR] 1.62; 95% confidence interval [CI], 1.02-2.57) and borderline emotional symptoms (aRR 1.66; 95% CI, 1.18-2.33) compared with children born to mothers without PCOS. The associations between maternal PCOS and offspring ADHD were positive but imprecise. Maternal hirsutism was related to a higher risk of children's ADHD (aRR 2.33; 95% CI, 1.28-4.24), conduct disorder (aRR 2.54; 95% CI 1.18-5.47), borderline emotional symptoms, peer relationship problems, and conduct problems (aRRs 2.61; 95% CI, 1.69-4.05; 1.92; 95% CI, 1.16-3.17; and 2.22; 95% CI, 1.30-3.79, respectively).

Conclusion(s): Maternal PCOS was associated with offspring anxiety, and hirsutism was related to other offspring behavioral problems. These findings should be interpreted with caution as replication is needed in prospective cohort studies that assess PCOS and hirsutism diagnoses using medical records.
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http://dx.doi.org/10.1016/j.fertnstert.2019.09.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185046PMC
February 2020

Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial.

JAMA 2020 01;323(1):35-48

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.

Importance: Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth.

Objective: To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth.

Design, Setting, And Participants: The Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged ≥18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019.

Interventions: Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months.

Main Outcomes And Measures: The co-primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization.

Results: Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, -0.9% [95% CI, -4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]).

Conclusions And Relevance: Among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples' live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility.

Trial Registration: ClinicalTrials.gov Identifier: NCT01857310.
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http://dx.doi.org/10.1001/jama.2019.18714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990807PMC
January 2020

Association of Maternal Exposure to Persistent Organic Pollutants in Early Pregnancy With Fetal Growth.

JAMA Pediatr 2020 02;174(2):149-161

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland.

Importance: Prenatal exposure to persistent organic pollutants (POPs) has been associated with birth size, but data on fetal growth and among racially/ethnically diverse pregnant women remain scarce.

Objectives: To assess the association between maternal plasma POPs in early pregnancy and fetal growth and by infant sex and maternal race/ethnicity.

Design, Setting, And Participants: This cohort study used the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton cohort, which recruited nonobese, low-risk pregnant women before 14 weeks' gestation between July 1, 2009, and January 31, 2013, in 12 community-based clinics throughout the United States. Participants self-identified their race/ethnicity, self-reported their behavioral risk factors, and were followed up throughout their pregnancy. Data were analyzed from July 31, 2018, to June 3, 2019.

Exposures: Levels of 76 POPs in early gestation plasma were measured: 11 perfluoroalkyl and polyfluoroalkyl substances, 1 polybrominated biphenyl, 9 polybrominated diphenyl ethers (PBDEs), 44 polychlorinated biphenyls (PCBs), and 11 organochlorine pesticides (OCPs). The bayesian kernel machine regression method was used to examine chemical class mixtures, and generalized additive mixed model was used to analyze individual chemicals.

Main Outcomes And Measures: Fourteen fetal biometrics were measured, including head circumference, abdominal circumference, and femur length, within 5 ultrasonography appointments.

Results: A total of 2284 low-risk pregnant women were included: 606 women (26.5%) self-identified as white with a mean (SD) age of 30.3 (4.4) years, 589 (25.8%) as black with a mean (SD) age of 25.5 (5.5) years, 635 (27.8%) as Hispanic with a mean (SD) age of 27.1 (5.5) years, and 454 (19.9%) as Asian with a mean (SD) age of 30.5 (4.5) years. A comparison between the 75th and 25th percentile of exposure revealed that the OCP mixture was negatively associated with most fetal growth measures, with a reduction of 4.7 mm (95% CI, -6.7 to -2.8 mm) in head circumference, 3.5 mm (95% CI, -4.7 to -2.2 mm) in abdominal circumference, and 0.6 mm (95% CI, -1.1 to -0.2 mm) in femur length. Higher exposure to the PBDE mixture was associated with reduced abdominal circumference (-2.4 mm; 95% CI, -4.0 to -0.5 mm) and femur length (-0.5 mm; 95% CI, -1.0 to -0.1 mm), and the dioxin-like PCB mixture was associated with reduced head circumference (-6.4 mm; 95% CI, -8.4 to -4.3 mm) and abdominal circumference (-2.4 mm; 95% CI, -3.9 to -0.8 mm). Associations with individual chemicals were less consistent. There were some interactions by fetal sex, although most of the results did not vary by maternal race/ethnicity. For example, oxychlordane (-0.98 mm; 95% CI, -1.60 to -0.36 mm; P for interaction <.001), trans-nonachlor (-0.31 mm; 95% CI, -0.54 to -0.08 mm; P for interaction = .005), and p,p'-dichlorodiphenyldichloroethylene (-0.19 mm; 95% CI, -0.22 to -0.09 mm; P for interaction = .006) were associated with shorter femur length among boys only.

Conclusions And Relevance: This study found that, among pregnant women with low POP levels, a mixture of OCPs was negatively associated with most fetal growth measures and that mixtures of PBDEs and dioxin-like PCBs were associated with reduced abdominal circumference. These findings suggested that, although exposures may be low, associations with fetal growth are apparent.
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http://dx.doi.org/10.1001/jamapediatrics.2019.5104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990715PMC
February 2020

Vital Status Ascertainment for a Historic Diverse Cohort of U.S. Women.

Epidemiology 2020 03;31(2):310-316

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD.

Background: Studies linking large pregnancy cohorts with mortality data can address critical questions about long-term implications of gravid health, yet relevant US data are scant. We examined the feasibility of linking the Collaborative Perinatal Project, a large multiracial U.S. cohort study of pregnant women (n = 48,197; 1959-1966), to death records.

Methods: We abstracted essential National Death Index (NDI) (1979-2016) (n = 46,428). We performed a linkage to the Social Security Administration Death Master File through 2016 (n = 46,450). Genealogists manually searched vital status in 2016 for a random sample of women (n = 1,249). We conducted agreement analyses for women with abstracted data among the three sources. As proof of concept, we calculated adjusted associations between mortality and smoking and other sociodemographic factors using Cox proportional hazards regression.

Results: We successfully abstracted identifying information for most of the cohort (97%). National Death Index identified the greatest proportion of participants deceased (35%), followed by genealogists (31%) and Death Master File (23%). Estimates of agreement (κ [95% confidence interval]) between National Death Index and Death Master File were lower (0.52 [0.51, 0.53]) than for National Death Index and genealogist (0.66 [0.61, 0.70]). As expected, compared with nonsmokers, smoking ≥1 pack per day was associated with elevated mortality for all vital sources and was strongest for National Death Index.

Conclusions: Linking this historic cohort with mortality records was feasible and agreed reasonably on vital status when compared with other data sources. Such linkage enables future examination of pregnancy conditions in relation to mortality in a diverse U.S. cohort.
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http://dx.doi.org/10.1097/EDE.0000000000001134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042706PMC
March 2020

The influences of sleep duration, chronotype, and nightwork on the ovarian cycle.

Chronobiol Int 2020 02 28;37(2):260-271. Epub 2019 Nov 28.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

Despite research indicating that sleep disorders influence reproductive health, the effects of sleep on reproductive hormone concentrations are poorly characterized. We prospectively followed 259 regularly menstruating women across one to two menstrual cycles (the BioCycle Study, 2005-2007), measuring fasting serum hormone concentrations up to eight times per cycle. Women provided information about daily sleep in diaries and chronotype and night/shift work on a baseline questionnaire. We evaluated percent differences in mean hormone concentrations, the magnitude of shifts in the timing and amplitude of hormone peaks, and the risk for sporadic anovulation associated with self-reported sleep patterns and night/shift work. We estimated chronotype scores - categorizing women below and above the interquartile range (IQR) as "morning" and "evening" chronotypes, respectively. For every hour increase in daily sleep duration, mean estradiol concentrations increased by 3.9% (95% confidence interval [CI] 2.0, 5.9%) and luteal phase progesterone by 9.4% (CI 4.0, 15.2%). Receiving less than 7 hours of sleep per day was associated with slightly earlier rises in peak levels for several hormones. Women reporting night/shift work (n = 77) had lower testosterone relative to women employed without night/shift work (percent difference: -9.9%, CI -18.4, -0.4%). Women with morning chronotypes (n = 47) had earlier rises in estradiol during their cycles and potentially an earlier rise in luteinizing hormone. Compared to those who had intermediate chronotypes, women with evening chronotypes (n = 42) had a later luteinizing hormone peak of borderline statistical significance. A reduced risk for sporadic anovulation was suggested, but imprecise, for increasing hours of daily sleep leading up to ovulation (risk ratio 0.79, CI 0.59, 1.06), while an imprecise increased risk was observed for women with morning chronotypes (risk ratio 2.50, CI 0.93, 6.77). Sleep-related hormonal changes may not greatly alter ovarian function in healthy women, but have the potential to influence gynecologic health.
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http://dx.doi.org/10.1080/07420528.2019.1694938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054152PMC
February 2020

Ethnic Enclaves and Pregnancy and Behavior Outcomes Among Asian/Pacific Islanders in the USA.

J Racial Ethn Health Disparities 2020 04 14;7(2):224-233. Epub 2019 Nov 14.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Drive, MSC, Bethesda, MD, 7004, USA.

Objectives: Ethnic enclaves are ethnically, spatially, and socially distinct communities that may promote health through access to culturally appropriate resources and reduced exposure to discrimination. This study examined ethnic enclave residence and pregnancy outcomes among Asian/Pacific Islander (API) women in the USA.

Design: We examined 9206 API births in the Consortium on Safe Labor (2002-2008). Ethnic enclaves were defined as hospital regions with high percentage of API residents (> 4%), high dissimilarity index (> 0.41; distribution of API and white residents within a geographic area), and high isolation index (> 0.03; interaction between API and white residents in an area). Gestational diabetes mellitus (GDM), preterm birth (PTB), small for gestational age (SGA), and smoking and alcohol use during pregnancy were reported in medical records supplemented with ICD-9 codes. Hierarchical logistic regression models estimated associations between ethnic enclaves and pregnancy outcomes, adjusted for maternal factors, area-level poverty, and air pollution.

Results: Women in enclaves had lower odds of GDM (OR 0.61; 95%CI 0.45, 0.82), PTB (OR 0.74; 95%CI 0.56, 0.99), and SGA (OR 0.68; 95%CI 0.52, 0.89) compared with women in non-enclaves. Prenatal smoking and alcohol use appeared less likely in enclaves, but estimates were imprecise. Within enclaves, about 10.5% of homes speak an API language, compared with 6.0% in non-enclaves. The mean percent of foreign-born API populations was 67.4% in enclaves and 68.8% in non-enclaves.

Conclusions: API women residing in ethnic enclaves had better pregnancy outcomes than API women residing in non-enclave areas. Access to culturally appropriate social supports and resources may be important for health promotion among API populations.
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http://dx.doi.org/10.1007/s40615-019-00650-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104626PMC
April 2020

A Randomized Trial to Evaluate the Effects of Folic Acid and Zinc Supplementation on Male Fertility and Livebirth: Design and Baseline Characteristics.

Am J Epidemiol 2020 01;189(1):8-26

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

The Folic Acid and Zinc Supplementation Trial (FAZST) was a multicenter, double-blind, block-randomized, placebo-controlled trial to determine whether folic acid and zinc supplementation in men improves semen quality and increases livebirth rate among couples seeking infertility treatment (2013-2017). Eligible men were aged 18 years or older with female partners aged 18-45 years, seeking infertility treatment. Men were randomized (1:1) to 5 mg folic acid and 30 mg elemental zinc daily or matching placebo for 6 months. Randomization was stratified by site and intended infertility treatment (in vitro fertilization (IVF), non-IVF/study site, and non-IVF/outside clinic). Follow-up of men continued for 6 months, and female partners were passively followed for a minimum of 9 months. Women who conceived were followed throughout pregnancy. Overall, 2,370 men were randomized during 2013-2017 (1,185 folic acid and zinc, 1,185 placebo); they had a mean age of 33 years and body mass index (weight (kg)/height (m)2) of 29.8. Most participants were white (82%), well educated (83% with some college), and employed (72%). Participant characteristics were balanced across intervention arms. Study visits were completed by 89%, 77%, and 75% of men at months 2, 4, and 6, respectively. Here we describe the study design, recruitment, data collection, lessons learned, and baseline participant characteristics.
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http://dx.doi.org/10.1093/aje/kwz217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204144PMC
January 2020

Air Pollution and Preterm Birth: Do Air Pollution Changes over Time Influence Risk in Consecutive Pregnancies among Low-Risk Women?

Int J Environ Res Public Health 2019 09 12;16(18). Epub 2019 Sep 12.

Division of Intramural Population Health Research, Epidemiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Drive, Bethesda, MD 20895, USA.

Since the 2000s, air pollution has generally continued to decrease in the U.S. To investigate preterm birth (PTB) risk associated with air pollutants in two consecutive pregnancies, we estimated exposures using modified Community Multiscale Air Quality models linked to the NICHD Consecutive Pregnancy Study. Electronic medical records for delivery admissions were available for 50,005 women with singleton births in 20 Utah-based hospitals between 2002-2010. We categorized whole pregnancy average exposures as high (>75th percentile), moderate (25-75) and low (<25). Modified Poisson regression estimated second pregnancy PTB risk associated with persistent high and moderate exposure, and increasing or decreasing exposure, compared to persistent low exposure. Analyses were adjusted for prior PTB, interpregnancy interval and demographic and clinical characteristics. Second pregnancy PTB risk was increased when exposure stayed high for sulfur dioxide (32%), ozone (17%), nitrogen oxides (24%), nitrogen dioxide (43%), carbon monoxide (31%) and for particles < 10 microns (29%) versus consistently low exposure. PTB risk tended to increase to a lesser extent for repeated PTB (19-21%) than for women without a prior PTB (22-79%) when exposure increased or stayed high. Area-level changes in air pollution exposure appear to have important consequences in consecutive pregnancies with increasing exposure associated with higher risk.
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http://dx.doi.org/10.3390/ijerph16183365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765877PMC
September 2019

Acute air pollution exposure and NICU admission: a case-crossover analysis.

Ann Epidemiol 2019 09 12;37:64-70.e2. Epub 2019 Jul 12.

Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD. Electronic address:

Purpose: Neonatal intensive care unit (NICU) admission rates have increased over time. Air pollution is associated with adverse pregnancy outcomes, but the relationship between prenatal air pollution exposure and NICU admission has not been investigated.

Methods: In the Consortium on Safe Labor (2002-2008), 27,189 singletons were admitted to the NICU. Modified Community Multiscale Air Quality models estimated exposures for criteria air pollutants and constituents of particles less than or equal to 2.5 microns (PM). Case-crossover analyses calculated odds ratios and 95% confidence intervals for interquartile range increases in pollutant exposure, comparing exposures during the week of delivery to control periods before and after delivery.

Results: In models that adjusted for PM, exposure to PM constituents during the week before delivery was significantly associated with increased odds of NICU admission: elemental carbon (35%), ammonium ions (37%), nitrate compounds (16%), organic compounds (147%), and sulfate compounds (35%). Odds were also significantly increased by day of and day before delivery exposures to carbon monoxide (4%-5%), nitrogen dioxide (13%), nitrogen oxides (4%-8%), particles less than or equal to 10 microns (2%), particles less than or equal to 2.5 microns (2%), and sulfur dioxide (3%-6%). No associations were observed for ozone.

Conclusions: Acute exposures to PM constituents and several traffic-related pollutants during the week before delivery, the day of delivery, and day before delivery appear to increase the odds of NICU admissions. These novel associations suggest infants exposed in utero to common air pollutants may require additional care during the newborn hospital admission.
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http://dx.doi.org/10.1016/j.annepidem.2019.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755057PMC
September 2019

Race-ethnic differences in the associations of maternal lipid trait genetic risk scores with longitudinal fetal growth.

J Clin Lipidol 2019 Sep - Oct;13(5):821-831. Epub 2019 Jun 29.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Background: Fetal growth, an important predictor of cardiometabolic diseases in adults, is influenced by maternal and fetal genetic and environmental factors.

Objective: We investigated the association between maternal lipid genetic risk score (GRS) and fetal growth among 4 US racial-ethnic populations (Whites, Blacks, Hispanics, and Asians).

Methods: We extracted genotype data for 2008 pregnant women recruited in the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton cohort with up to 6 standardized ultrasound examinations. GRS was calculated using 240 single-nucleotide polymorphisms previously associated with higher total cholesterol (GRS), low-density lipoprotein cholesterol (GRS), and triglycerides (GRS) and lower high-density lipoprotein cholesterol (GRS).

Results: At 40 weeks' gestation, a unit increase in GRS was associated with 11.4 g higher fetal weight (95% confidence interval [CI] 2.8-20.0 g) among normal-weight Whites, 26.3 g (95% CI 6.0-46.6 g) among obese Blacks, and 30.8 g (95% CI 6.3-55.3 g) among obese Hispanics. Higher GRS was associated with increased fetal weight across 36 to 40 weeks among normal-weight Whites and across 13 to 20 weeks among normal-weight Asians, but with decreased fetal weight across 26 to 40 weeks among normal-weight Hispanics. Higher GRS was suggestively associated with increased fetal weight in males and decreased in females. Associations remained consistent after adjustment for serum lipids.

Conclusion: Associations between fetal weight and maternal lipid GRS appear to vary by maternal race-ethnic group, obesity status, and offspring sex. Genetic susceptibility to unfavorable lipid profiles contributes to fetal growth differences even among normal-weight women suggesting a potential future application in predicting aberrant fetal growth.
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http://dx.doi.org/10.1016/j.jacl.2019.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885118PMC
July 2020

Differential Effect of Ambient Air Pollution Exposure on Risk of Gestational Hypertension and Preeclampsia.

Hypertension 2019 08 24;74(2):384-390. Epub 2019 Jun 24.

From the Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD (C.J.N., A.W., M.O., P.M.).

Although ambient air pollution may increase hypertension risk through endothelial damage and oxidative stress, evidence is inconsistent regarding its effect on hypertension in pregnancy. Prior research has evaluated a limited scope of pollution species and often not differentiated preeclampsia, which may have a placental origin, from gestational hypertension. Among 49 607 women with at least 2 singleton deliveries in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Consecutive Pregnancies Study (2002-2010), we estimated criteria pollutant and volatile organic compound levels during pregnancy using Community Multiscale Air Quality models and abstracted gestational hypertension and preeclampsia diagnoses from medical records. Generalized estimating equations accounted for repeat pregnancies and adjusted for ambient temperature and maternal age, race/ethnicity, body mass index, smoking, alcohol, parity, insurance, marital status, and asthma. Air pollution levels were low to moderate (eg, median 41.6 ppb [interquartile range, 38.9-43.7 ppb] for ozone and 35.1 ppb [28.9-40.3 ppb] for nitrogen oxides). Higher levels of most criteria pollutants during preconception and the first trimester were associated with lower preeclampsia risk, while higher second-trimester levels were associated with greater gestational hypertension risk. For example, an interquartile increase in first-trimester carbon monoxide was associated with a relative risk of 0.88 (95% CI, 0.81-0.95) for preeclampsia and second-trimester carbon monoxide a relative risk of 1.14 (95% CI, 1.07-1.22) for gestational hypertension. Volatile organic compounds, conversely, were not associated with gestational hypertension but consistently associated with higher preeclampsia risk. These findings further suggest air pollution may affect the development of hypertension in pregnancy, although differing causes of preeclampsia and gestational hypertension may alter these relationships.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.12731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620155PMC
August 2019

Obstetric and neonatal complications among women with autoimmune disease.

J Autoimmun 2019 09 27;103:102287. Epub 2019 May 27.

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA. Electronic address:

Background: The impact of autoimmune diseases on pregnancy remains understudied on a population level. Examination of obstetric and neonatal outcomes among women with autoimmune disease and their infants can provide important insights for clinical management.

Methods: Autoimmune diseases and outcomes were identified using medical records. Cesarean delivery, preterm birth, preeclampsia, small for gestational age (SGA), neonatal intensive care (NICU) admission, neonatal respiratory distress syndrome (RDS), and perinatal mortality risk was assessed. Poisson regression with robust standard errors estimated relative risks (RR) and 95% confidence intervals (95% CI) with adjustment for maternal characteristics and other chronic conditions.

Results: Women with T1DM were at increased risk for nearly all outcomes including RDS (RR: 3.62; 95% CI: 2.84, 4.62), perinatal mortality (RR: 2.35; 95% CI: 1.12, 4.91), cesarean delivery (RR: 2.16; 95% CI: 2.02, 2.32) and preterm birth (RR: 3.52; 95% CI: 3.17, 3.91). Women with SLE also had higher risk for preterm delivery (RR: 2.90; 95% CI: 2.42, 3.48) and RDS (RR:2.99; 95% CI: 1.99, 4.51) as did women with Crohn's (cesarean delivery RR:1.31, 95% CI: 1.08, 1.60; preterm delivery RR: 1.84, 95% CI: 1.37, 2.49. RA increased risk for SGA (RR:1.66; 95% CI: 1.08, 2.55).

Conclusion(s): Despite the heterogeneity in autoimmune diseases, we observed elevated preterm birth risk for most women with autoimmune disease. SLE and T1DM appeared to confer increased risk for a wide range of adverse outcomes.
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http://dx.doi.org/10.1016/j.jaut.2019.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708459PMC
September 2019

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Eunice Kennedy Shriver National Institute of Child Health and Human Development, Division of Intramural Population Health Research, Epidemiology Branch, Bethesda, MD, USA.

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http://dx.doi.org/10.1016/S2542-5196(19)30073-7DOI Listing
May 2019