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Background: Global efforts are needed to elucidate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the underlying cause of coronavirus disease 2019 (COVID-19), including seroprevalence, risk factors, and long-term sequelae, as well as immune responses after vaccination across populations and the social dimensions of prevention and treatment strategies., Methods: In the United States, the National Cancer Institute in partnership with the National Institute of Allergy and Infectious Diseases, established the SARS-CoV-2 Serological Sciences Network (SeroNet) as the nation's largest coordinated effort to study coronavirus disease 2019. The network comprises multidisciplinary researchers bridging gaps and fostering collaborations among immunologists, epidemiologists, virologists, clinicians and clinical laboratories, social and behavioral scientists, policymakers, data scientists, and community members. In total, 49 institutions form the SeroNet consortium to study individuals with cancer, autoimmune disease, inflammatory bowel diseases, cardiovascular diseases, human immunodeficiency virus, transplant recipients, as well as otherwise healthy pregnant women, children, college students, and high-risk occupational workers (including healthcare workers and first responders)., Results: Several studies focus on underrepresented populations, including ethnic minorities and rural communities. To support integrative data analyses across SeroNet studies, efforts are underway to define common data elements for standardized serology measurements, cellular and molecular assays, self-reported data, treatment, and clinical outcomes., Conclusions: In this paper, we discuss the overarching framework for SeroNet epidemiology studies, critical research questions under investigation, and data accessibility for the worldwide scientific community. Lessons learned will help inform preparedness and responsiveness to future emerging diseases., (© The Author(s) 2022.. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background/objective: Research suggests gestational exposure to particulate matter ≤2.5 μm (PM 2.5 ) and extreme heat may independently increase risk of birth defects. We investigated whether duration of gestational extreme heat exposure modifies associations between PM 2.5 exposure and specific congenital heart defects (CHDs). We also explored nonlinear exposure-outcome relationships., Methods: We identified CHD case children (n = 2824) and non-malformed live-birth control children (n = 4033) from pregnancies ending between 1999 and 2007 in the National Birth Defects Prevention Study, a U.S. population-based multicenter case-control study. We assigned mothers 6-week averages of PM 2.5 exposure during the cardiac critical period (postconceptional weeks 3-8) using the closest monitor within 50 km of maternal residence. We assigned a count of extreme heat days (EHDs, days above the 90th percentile of daily maximum temperature for year, season, and weather station) during this period using the closest weather station. Using generalized additive models, we explored logit-nonlinear exposure-outcome relationships, concluding logistic models were reasonable. We estimated joint effects of PM 2.5 and EHDs on six CHDs using logistic regression models adjusted for mean dewpoint and maternal age, education, and race/ethnicity. We assessed multiplicative and additive effect modification., Results: Conditional on the highest observed EHD count (15) and at least one critical period day during spring/summer, each 5 μg/m 3 increase in average PM 2.5 exposure was significantly associated with perimembranous ventricular septal defects (VSDpm; OR: 1.54 [95% CI: 1.01, 2.41]). High EHD counts (8+) in the same population were positively, but non-significantly, associated with both overall septal defects and VSDpm. Null or inverse associations were observed for lower EHD counts. Multiplicative and additive effect modification estimates were consistently positive in all septal models., Conclusions: Results provide limited evidence that duration of extreme heat exposure modifies the PM 2.5 -septal defects relationship. Future research with enhanced exposure assessment and modeling techniques could clarify these relationships., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: This study determined the prevalence, mortality, and time trends of children with congenital diaphragmatic hernia (CDH)., Methods: Twenty-five hospital- and population-based surveillance programs in 19 International Clearinghouse for Birth Defects Surveillance and Research member countries provided birth defects mortality data between 1974 and 2015. CDH cases included live births, stillbirths, or elective termination of pregnancy for fetal anomalies. Prevalence, cumulative mortality rates, and 95% confidence intervals (CIs) were calculated using Poisson regression and a Kaplan-Meier product-limit method. Joinpoint regression analyses were conducted to assess time trends., Results: The prevalence of CDH was 2.6 per 10,000 total births (95% CI: 2.5-2.7), slightly increasing between 2001 and 2012 (average annual percent change = 0.5%; 95% CI:-0.6 to 1.6). The total percent mortality of CDH was 37.7%, with hospital-based registries having more deaths among live births than population-based registries (45.1% vs. 33.8%). Mortality rates decreased over time (average annual percent change = -2.4%; 95% CI: -3.8 to 1.1). Most deaths due to CDH occurred among 2- to 6-day-old infants for both registry types (36.3%, hospital-based; 12.1%, population-based)., Conclusions: The mortality of CDH has decreased over time. Mortality remains high during the first week and varied by registry type., (Copyright © 2020 Elsevier Inc. All rights reserved.)

An estimated 1.4 million adults in the United States live with congenital heart defects (CHDs), yet their health outcomes are not well understood (1). Using self-reported, cross-sectional data from 1,482 respondents in the 2016-2019 Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG (CH STRONG) (2), CDC and academic partners estimated the prevalence of comorbidities among adults with CHDs aged 20-38 years born in Arizona (AZ), Arkansas (AR), and metropolitan Atlanta, Georgia (GA) compared with the general population (aged 20-38 years) from the National Health and Nutrition Examination Survey (NHANES) during 2015-2018 (3) and the AZ, AR, and GA Behavioral Risk Factor Surveillance Systems (BRFSS) during 2016-2018 (4). Adults with CHDs were more likely than those in the general population to report cardiovascular comorbidities, such as a history of congestive heart failure (4.3% versus 0.2%) and stroke (1.4% versus 0.3%), particularly those with severe CHDs (2). Adults with CHDs were more likely to report current depressive symptoms (15.1% versus 8.5%), but less likely to report previous diagnoses of depression (14.2% versus 22.6%), asthma (12.7% versus 16.9%), or rheumatologic disease (3.2% versus 8.0%). Prevalence of noncardiovascular comorbidities was similar between adults whose CHD was considered severe and those with nonsevere CHDs. Public health practitioners and clinicians can encourage young adults with CHDs to seek appropriate medical care to help them live as healthy a life as possible., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Wendy N. Nembhard reports grants from the March of Dimes during conduct of the study. No other potential conflicts of interest were disclosed.

Objectives: To evaluate the statewide experience in mode of delivery for pregnancies complicated by stillbirth by annual delivery volume and presence of graduate medical education programs., Methods: This is a descriptive study of all stillbirths without known congenital anomalies or aneuploidy born in our state from July 1, 2015 to June 30, 2019. Stillbirths were ascertained by the State Reproductive Health Monitoring System, a population-based surveillance system. Stillbirths were identified by the State Reproductive Health Monitoring System from medical facilities and fetal death certificates; trained staff abstracted records. All of the stillbirths with a gestational age of >20 weeks or a birth weight of >500 g if birth weight was unknown and without congenital anomalies or aneuploidy were eligible for this study., Results: There were 861 stillbirths from July 2015 through June 2019, 75 (8.7%) of which were delivered by cesarean section. Low-volume hospitals (<1000 deliveries) experienced a higher proportion of their stillbirths delivered by cesarean compared with high-volume hospitals (>1000 deliveries; 13.4% vs 5.5%; P < 0.0001). Before adjusting for maternal characteristics, stillbirths delivered at high-volume hospitals had a 59% lower risk of delivery by cesarean section compared with those delivered at low-volume hospitals (relative risk [RR] 0.41, 95% confidence interval 0.20-0.86, P = 0.02). The cesarean cohort had a higher proportion of Black mothers (44% vs 31.3%, P = 0.025), greater parity ( P < 0.0001), and greater gravidity ( P < 0.0001) compared with the vaginal group. The gestational age at delivery for stillbirths delivered by cesarean was much higher compared with those who were delivered vaginally (34.8 weeks vs 28.6 weeks; P < 0.0001). The RR of the cesarean delivery of a stillbirth at teaching institutions compared with nonteaching institutions was significantly reduced (RR 0.45, 95% confidence interval 0.28-0.73, P = 0.0011)., Conclusions: Annual hospital delivery volumes and residency teaching programs in obstetrics influence the mode of delivery in the management of stillbirth. Advancing gestational age, Black race, and parity are associated with an increased risk of cesarean delivery after stillbirth.

Background: Few studies have evaluated associations between birth defects and risk of pediatric cancers by age of attainment. Therefore, we assessed the risk of cancer among children with and without birth defects by age at attainment., Methods: We examined cancer risk in children ≤14 years with and without birth defects born between 1996 and 2011 by linking data from the Arkansas Reproductive Health Monitoring System, Arkansas Central Cancer Registry, and birth certificates. Age of attainment for cancer was calculated as person-years from birth to cancer diagnosis, death, or end of study period, whichever occurred first. Using Cox proportional hazards models, we evaluated associations by attained age groups (<1, 1-4, 5-9, and 10-14 years) between: (1) groups of birth defects (any, chromosomal, and non-chromosomal) and any cancer; (2) non-chromosomal birth defects by organ system and any cancer; and (3) non-chromosomal birth defects and subtypes of cancer., Results: In the cohort of 629,086 children, 23,341 (3.7%) children had birth defects and 1,037 (0.2%) children had cancer. For children with non-chromosomal birth defects, specifically cardiovascular and genitourinary, highest risk of any cancer was observed in first year of life (Hazard Ratio [HR] 18.5; 95% confidence interval [CI] 10.1-33.8). For children with chromosomal birth defects, increased cancer risk was observed among those 1-4 years-old (HR 20.0; 95% CI 8.3-48.4)., Conclusion: Overall, cancer risk among children with birth defects was highest among those <5 years-old. Our findings, consistent with previous studies, may inform surveillance strategies for children with birth defects., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Hypospadias is a common birth defect where the urethral opening forms on the ventral side of the penis. We performed integrative methylomic, genomic, and transcriptomic analyses to characterize sites of DNA methylation that influence genital development. In case-control and case-only epigenome-wide association studies (EWAS) of preputial tissue we identified 25 CpGs associated with hypospadias characteristics and used one-sample two stage least squares Mendelian randomization (2SLS MR) to show a causal relationship for 21 of the CpGs. The largest difference was 15.7% lower beta-value at cg14436889 among hypospadias cases than controls (EWAS P = 5.4e-7) and is likely causal (2SLS MR P = 9.8e-15). Integrative annotation using two-sample Mendelian randomization of these methylation regions highlight potentially causal roles of genes involved in germ layer differentiation (WDHD1, DNM1L, TULP3), beta-catenin signaling (PKP2, UBE2R2, TNKS), androgens (CYP4A11, CYP4A22, CYP4B1, CYP4X1, CYP4Z2P, EPHX1, CD33/SIGLEC3, SIGLEC5, SIGLEC7, KLK5, KLK7, KLK10, KLK13, KLK14), and reproductive traits (ACAA1, PLCD1, EFCAB4B, GMCL1, MKRN2, DNM1L, TEAD4, TSPAN9, KLK family). This study identified CpGs that remained differentially methylated after urogenital development and used the most relevant tissue sample available to study hypospadias. We identified multiple methylation sites and candidate genes that can be further evaluated for their roles in regulating urogenital development.

Objective: To estimate the risk of stillbirth (fetal death at 20 weeks of gestation or more) associated with specific birth defects., Methods: We identified a population-based retrospective cohort of neonates and fetuses with selected major birth defects and without known or strongly suspected chromosomal or single-gene disorders from active birth defects surveillance programs in nine states. Abstracted medical records were reviewed by clinical geneticists to confirm and classify all birth defects and birth defect patterns. We estimated risks of stillbirth specific to birth defects among pregnancies overall and among those with isolated birth defects; potential bias owing to elective termination was quantified., Results: Of 19,170 eligible neonates and fetuses with birth defects, 17,224 were liveborn, 852 stillborn, and 672 electively terminated. Overall, stillbirth risks ranged from 11 per 1,000 fetuses with bladder exstrophy (95% CI 0-57) to 490 per 1,000 fetuses with limb-body-wall complex (95% CI 368-623). Among those with isolated birth defects not affecting major vital organs, elevated risks (per 1,000 fetuses) were observed for cleft lip with cleft palate (10; 95% CI 7-15), transverse limb deficiencies (26; 95% CI 16-39), longitudinal limb deficiencies (11; 95% CI 3-28), and limb defects due to amniotic bands (110; 95% CI 68-171). Quantified bias analysis suggests that failure to account for terminations may lead to up to fourfold underestimation of the observed risks of stillbirth for sacral agenesis (13/1,000; 95% CI 2-47), isolated spina bifida (24/1,000; 95% CI 17-34), and holoprosencephaly (30/1,000; 95% CI 10-68)., Conclusion: Birth defect-specific stillbirth risk was high compared with the U.S. stillbirth risk (6/1,000 fetuses), even for isolated cases of oral clefts and limb defects; elective termination may appreciably bias some estimates. These data can inform clinical care and counseling after prenatal diagnosis.

Previous research reports associations between air pollution measured during pregnancy and the occurrence of congenital heart defects (CHDs) in offspring. The objective of this research was to assess if exposure to extreme heat events (EHEs) during pregnancy may modify this association., Methods: The study population consisted of 4,033 controls and 2,632 cases with dates of delivery between 1999 and 2007 who participated in the National Birth Defects Prevention Study, a multi-site case-control study in the United States. Daily data from the closest stationary fine particulate matter (PM 2.5 ) monitor within 50 km from the maternal residence were averaged across weeks 3-8 post-conception. EHEs were defined as maximum ambient temperature in the upper 95th percentile for at least 2 consecutive days or the upper 90th percentile for 3 consecutive days. Logistic regression models were adjusted for maternal age, ethnicity, education, and average humidity. Relative excess risks due to interaction (RERI) were calculated., Results: Compared with women with low PM 2.5 exposure and no exposure to an EHE, the odds of a ventricular septal defect in offspring associated with high PM 2.5 exposure was elevated only among women who experienced an EHE (odds ratio [OR] 2.14 95% confidence interval [CI] 1.19, 3.38 vs. OR 0.97 95% CI 0.49, 1.95; RERI 0.82 95% CI -0.39, 2.17). The majority of observed associations and interactions for other heart defects were null and/or inconclusive due to lack of precision., Conclusions: This study provides limited evidence that EHEs may modify the association between prenatal exposure to PM 2.5 and CHD occurrence., (Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Environmental Epidemiology. All rights reserved.)

Purpose: Studies suggest exposure to ambient particulate matter less than 2.5 μg/m 3 in aerodynamic diameter (PM 2.5 ) may be associated with preterm birth (PTB), but few have evaluated how this is modified by ambient temperature. We investigated the relationship between PM 2.5 exposure during pregnancy and PTB in infants without birth defects (1999-2006) and enrolled in the National Birth Defects Prevention Study and how it is modified by concurrent temperature., Methods: PTB was defined as spontaneous or iatrogenic delivery before 37 weeks. Exposure was assigned using inverse distance weighting with up to four monitors within 50 kilometers of maternal residence. To account for state-level variations, a Bayesian two-level hierarchal model was developed., Results: PTB was associated with PM 2.5 during the third and fourth months of pregnancy (range: (odds ratio (95% confidence interval) = 1.00 (0.35, 2.15) to 1.49 (0.82, 2.68) and 1.31 (0.56, 2.91) to 1.62 (0.7, 3.32), respectively); no week of exposure conveyed greater risk. Temperature may modify this relationship; higher local average temperatures during pregnancy yielded stronger positive relationships between PM 2.5 and PTB compared to nonstratified results., Conclusions: Results add to literature on associations between PM 2.5 and PTB, underscoring the importance of considering co-exposures when estimating effects of PM 2.5 exposure during pregnancy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective Despite heterogeneity among Pacific Islanders, most studies aggregate them regardless of origin. Thus, limited information is available about perinatal outcomes among various subgroups of Pacific Islanders in the United States, including immigrants from the Republic of the Marshall Islands. We sought to evaluate perinatal outcomes among Marshallese women. Methods We conducted a cross-sectional study of women with at least one singleton live birth between 1997 and 2013 in two Arkansas counties using birth certificate data from the Arkansas Department of Health. Unadjusted and adjusted prevalence ratios (PR) and 95% confidence intervals (CI) were calculated from modified Poisson regression models. Results Of the 91,662 singleton births in both counties during the study period, 2488 were to Marshallese women. In adjusted analyses, Marshallese women had higher prevalence of "other medical risk factors" (PR = 1.47; 95% CI 1.30, 1.65) than NH White women. Marshallese women had higher rates of precipitous labor and fetal distress during labor compared to NH White women (PR = 2.65; 95% CI 2.22, 3.17 and 1.89; 95% CI 1.62, 2.21, respectively). Marshallese were also more likely to have tocolysis (PR = 1.43; 95% CI 1.16, 1.76), forceps (PR = 1.68; 95% CI 1.16, 2.43) or vacuum (PR = 1.89; 95% CI 1.60, 2.22) used in delivery and cesarean section (PR = 1.13; 95% CI 1.01, 1.27). Marshallese infants had higher rates of anemia (PR = 3.10; 95% CI 2.01, 4.77), birth injury (PR = 2.13; 95% CI 1.50, 3.03), assisted ventilation < 30 min (PR = 2.11; 95% CI 1.64, 2.71), preterm birth (PR = 1.67; 95% CI 1.50, 1.83), and small-for-gestational age (PR = 1.25; 95% CI 1.12, 1.39) than NH White infants. Conclusions Marshallese women and infants had higher rates of adverse perinatal outcomes compared to their NH White counterparts. Additional studies are needed to determine if perinatal outcomes among the Marshallese differed from other Pacific Islander subgroups.

Background: Substance use during pregnancy is a major medical and public health concern. Determination of the most appropriate screening protocol remains a clinical conundrum. Interviews and/or laboratory drug screens may be costly, inaccurate, and are frequently inadequate to identify patterns of substance use for a given population or geographic area. We compared commercially available urine "dip cup" toxicology screens obtained in the clinic to university hospital drug toxicology results., Methods: 267 observed urine samples were collected from pregnant women with known substance use disorders enrolled in a specialized treatment program that included access to buprenorphine medication-assisted treatment. Each urine sample was tested by commercial dip cup with temperature confirmation and then sent to the university hospital laboratory for analyses. The number of substances detected and cost for each screening method were compared., Results: Uniformly, the dip cup had comparable detection of amphetamines, barbiturates, cocaine, methadone, opiates, and tetrahydrocannabinol to the university hospital laboratory with the exception of benzodiazepines. In addition, the dip cup detected use of buprenorphine (a commonly misused opiate receptor ligand not included in the hospital screen) and was significantly less expensive., Conclusions: Commercially available urine dip cups are cost-effective, equally comparable to hospital based screening, and provide 'real time' results germane to clinical care and treatment planning., (Copyright © 2019. Published by Elsevier B.V.)

Obstructive heart defects (OHDs) are a major health concern worldwide. The platelet-derived growth factor (PDGF) genes are known to have regulatory functions that are essential for proper heart development. In a zebrafish model, Pdgfra was further demonstrated to interact with ethanol during craniofacial development. In this article, we investigated interactions between variants in PDGF genes and periconceptional alcohol exposure on the risk of OHDs by applying log-linear models to 806 OHD case and 995 control families enrolled in the National Birth Defects Prevention Study. The interactions between four variants in PDGFA and maternal binge drinking reached a nominal significance level. The maternal T allele of rs869978 was estimated to increase OHD risk among women who binge drink, while infant genotypes of rs2291591, rs2228230, rs1547904, and rs869978 may reduce the risk. Although none of these associations remain statistically significant after multiple testing adjustment and the estimated maternal effect may be influenced by unknown confounding factors, such as maternal smoking, these findings are consistent with previous animal studies supporting potential interactions between the PDGFRA gene and maternal alcohol exposure. Replication studies with larger sample sizes are needed to further elucidate this potential interplay and its influence on OHD risks.

The association between conotruncal heart defects (CTHDs) and maternal genetic and environmental exposures is well studied. However, little is known about paternal genetic or environmental exposures and risk of CTHDs. We assessed the effect of paternal genetic variants in the folate, homocysteine, and transsulfuration pathways on risk of CTHDs in offspring. We utilized National Birth Defects Prevention Study data to conduct a family-based case only study using 616 live-born infants with CTHDs, born October 1997-August 2008. Maternal, paternal and infant DNA was genotyped using an Illumina® Golden Gate custom single nucleotide polymorphism (SNP) panel. Relative risks (RR) and 95% confidence intervals (CI) from log-linear models determined parent of origin effects for 921 SNPs in 60 candidate genes involved in the folate, homocysteine, and transsulfuration pathways on risk of CTHDs. The risk of CTHD among children who inherited a paternally derived copy of the A allele on GLRX (rs17085159) or the T allele of GLRX (rs12109442) was 0.23 (95%CI: 0.12, 0.42; p = 1.09 × 10 -6 ) and 0.27 (95%CI: 0.14, 0.50; p = 2.06 × 10 -5 ) times the risk among children who inherited a maternal copy of the same allele. The paternally inherited copy of the GSR (rs7818511) A allele had a 0.31 (95%CI: 0.18, 0.53; p = 9.94 × 10 -6 ] risk of CTHD compared to children with the maternal copy of the same allele. The risk of CTHD is less influenced by variants in paternal genes involved in the folate, homocysteine, or transsulfuration pathways than variants in maternal genes in those pathways., (© 2018 Wiley Periodicals, Inc.)

Information on dietary intakes of Jamaican immigrants in the United States is sparse. Understanding factors that influence diet is important since diet is associated with chronic diseases. This study examined the association between acculturation, socio-cultural factors, and dietary pattern among Jamaican immigrants in Florida. Jamaican persons 25-64 years who resided in two South Florida counties were recruited for participation. A health questionnaire that assessed acculturation, dietary pattern, and risk factors for cardiovascular disease was administered to participants. Generalized Estimating Equations were used to determine associations. Acculturation score was not significantly associated with dietary intake pattern (β = - 0.02 p  = 0.07). Age at migration was positively associated with traditional dietary pattern (β = 0.02 p  < 0.01). Persons with 12 or fewer years of education (β = - 0.55 p  < 0.001), divorced (β = - 0.26 p  = 0.001), or engaged in less physical activity (β = - 0.07 p  = 0.01) were more likely to adhere to a traditional diet. Although acculturation was not a statistically significant predictor of dietary intake, findings show the role of demographic and lifestyle characteristics in understanding factors associated with dietary patterns among Jamaicans. Findings point to the need to measure traditional dietary intakes among Jamaicans and other immigrant groups. Accurate assessment of disease risk among immigrant groups will lead to more accurate diet-disease risk assessment and development of effective intervention programs.

Nutrients that regulate methylation processes may modify susceptibility to the effects of air pollutants. Data from the National Birth Defects Prevention Study (United States, 1997-2006) were used to estimate associations between maternal exposure to nitrogen dioxide (NO2), dietary intake of methyl nutrients, and the odds of congenital heart defects in offspring. NO2 concentrations, a marker of traffic-related air pollution, averaged across postconception weeks 2-8, were assigned to 6,160 nondiabetic mothers of cases and controls using inverse distance-squared weighting of air monitors within 50 km of maternal residences. Intakes of choline, folate, methionine, and vitamins B6 and B12 were assessed using a food frequency questionnaire. Hierarchical regression models, which accounted for similarities across defects, were constructed, and relative excess risks due to interaction were calculated. Relative to women with the lowest NO2 exposure and high methionine intake, women with the highest NO2 exposure and lowest methionine intake had the greatest odds of offspring with a perimembranous ventricular septal defect (odds ratio = 3.23, 95% confidence interval: 1.74, 6.01; relative excess risk due to interaction = 2.15, 95% confidence interval: 0.39, 3.92). Considerable departure from additivity was not observed for other defects. These results provide modest evidence of interaction between nutrition and NO2 exposure during pregnancy., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To investigate survival up to early adulthood for children with intellectual disability and compare their risk of mortality with that of children without intellectual disability., Study Design: This was a retrospective cohort study of all live births in Western Australia between January 1, 1983 and December 31, 2010. Children with an intellectual disability (n = 10 593) were identified from the Western Australian Intellectual Disability Exploring Answers Database. Vital status was determined from linkage to the Western Australian Mortality database. Kaplan-Meier product limit estimates and 95% CIs were computed by level of intellectual disability. Hazard ratios (HRs) and 95% CIs were calculated from Cox proportional hazard regression models adjusting for potential confounders., Results: After adjusting for potential confounders, compared with those without intellectual disability, children with intellectual disability had a 6-fold increased risk of mortality at 1-5 years of age (adjusted HR [aHR] = 6.0, 95%CI: 4.8, 7.6), a 12-fold increased risk at 6-10 years of age (aHR = 12.6, 95% CI: 9.0, 17.7) and a 5-fold increased risk at 11-25 years of age (aHR = 4.9, 95% CI: 3.9, 6.1). Children with severe intellectual disability were at even greater risk. No difference in survival was observed for Aboriginal children with intellectual disability compared with non-Aboriginal children with intellectual disability., Conclusions: Although children with intellectual disability experience higher mortality at all ages compared with those without intellectual disability, the greatest burden is for those with severe intellectual disability. However, even children with mild to moderate intellectual disability have increased risk of death compared with unaffected children., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective  To evaluate whether the association between maternal periconceptional use of selective serotonin reuptake inhibitors (SSRIs) and increased risk of congenital heart defects in offspring is modified by maternal or infant genetic variants in folate, homocysteine, or transsulfuration pathways. Design  Population based study. DNA from mothers, fathers, and infants was genotyped with an Illumina GoldenGate custom single nucleotide polymorphism panel. A hybrid design based on a log linear model was used to calculate relative risks and Bayesian false discovery probabilities (BFDP) to identify polymorphisms associated with congenital heart defects modified by SSRI use. Data sources  Data from the US National Birth Defects Prevention Study on 1180 liveborn infants with congenital heart defects and 1644 controls, born 1997-2008. Main outcome measures  Cases included infants with selected congenital heart defects and control infants had no major defects. SSRI use was obtained from telephone interviews with mothers. Results  For women who reported taking SSRIs periconceptionally, maternal SHMT1 (rs9909104) GG and AGgenotypes were associated with a 5.9 and 2.4 increased risk of select congenital heart defects in offspring, respectively, versus the AA genotype (BFDP=0.69). Compared with the AA genotype, BHMT (rs492842 and rs542852) GG and AG genotypes were associated with twice the riskof congenital heart defects (BFDP=0.74 and 0.79, respectively). MGST1 (rs2075237) CC and ACgenotypes were associated with an increased risk compared with the GG genotype (8.0 and 2.8, respectively; BFDP=0.79). Single nucleotide polymorphism in infant genes in the folate (MTHFS rs12438477), homocysteine (TRDMT1 rs6602178 and GNMT rs11752813) and transsulfuration (GSTP1 rs7941395 and MGST1 rs7294985) pathways were also associated with an increased risk of congenital heart defects. Conclusions  Common maternal or infant genetic variants in folate, homocysteine, or transsulfuration pathways are associated with an increased risk of certain congenital heart defects among children of women taking SSRIs during cardiogenesis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Introduction: Our objective was to determine the incidence and mortality rates associated with emergency peripartum hysterectomy, factors that lead to uncontrolled hemorrhage and emergency peripartum hysterectomy, and to determine the relationship between cesarean section and risk of emergency peripartum hysterectomy., Materials and Methods: Studies published between January 1, 2000 and December 31, 2012 were identified using PubMed, OVID and Web of Science databases. Studies were included if they reported incidence rates for emergency peripartum hysterectomy, factors that lead to hemorrhage and emergency peripartum hysterectomy, or the association of emergency peripartum hysterectomy with cesarean section in high-income countries., Results: Four hundred and fifty-one studies were identified, and 52 were included. The incidence of emergency peripartum hysterectomy ranged from 0.20 to 5.09 per 1000 deliveries with a median incidence rate of 0.61 per 1000 deliveries. These rates have increased over time. Rates varied by region/country, specifically with the United States reporting higher rates than North American, Asian, Oceania, and European countries. The most common factor leading to emergency peripartum hysterectomy was placental abnormalities. Both cesarean section and prior cesarean section were strong risk factors for emergency peripartum hysterectomy with higher risks conferred for each additional cesarean section. The mean percentage of maternal deaths for EPH survivors was 3.0 %., Conclusion: Given the association of cesarean section with emergency peripartum hysterectomy, the increased risk of emergency peripartum hysterectomy should be factored into the decision of whether to proceed with cesarean delivery, particularly for women who desire more children.

Objectives: To examine racial/ethnic-specific survival of children with major birth defects in the US., Study Design: We pooled data on live births delivered during 1999-2007 with any of 21 birth defects from 12 population-based birth defects surveillance programs. We used the Kaplan-Meier method to calculate cumulative survival probabilities and Cox proportional hazards models to estimate mortality risk., Results: For most birth defects, there were small-to-moderate differences in neonatal (<28 days) survival among racial/ethnic groups. However, compared with children born to non-Hispanic white mothers, postneonatal infant (28 days to <1 year) mortality risk was significantly greater among children born to non-Hispanic black mothers for 13 of 21 defects (hazard ratios [HRs] 1.3-2.8) and among children born to Hispanic mothers for 10 of 21 defects (HRs 1.3-1.7). Compared with children born to non-Hispanic white mothers, a significantly increased childhood (≤ 8 years) mortality risk was found among children born to Asian/Pacific Islander mothers for encephalocele (HR 2.6), tetralogy of Fallot, and atrioventricular septal defect (HRs 1.6-1.8) and among children born to American Indian/Alaska Native mothers for encephalocele (HR 2.8), whereas a significantly decreased childhood mortality risk was found among children born to Asian/Pacific Islander mothers for cleft lip with or without cleft palate (HR 0.6)., Conclusion: Children with birth defects born to non-Hispanic black and Hispanic mothers carry a greater risk of mortality well into childhood, especially children with congenital heart defect. Understanding survival differences among racial/ethnic groups provides important information for policy development and service planning., (Copyright © 2015 Elsevier Inc. All rights reserved.)