Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 58 Records) |
Query Trace: Nembhard R [original query] |
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National population-based estimates for major birth defects, 2016-2020
Stallings EB , Isenburg JL , Rutkowski RE , Kirby RS , Nembhard WN , Sandidge T , Villavicencio S , Nguyen HH , McMahon DM , Nestoridi E , Pabst LJ . Birth Defects Res 2024 116 (1) e2301 BACKGROUND: We provide updated crude and adjusted prevalence estimates of major birth defects in the United States for the period 2016-2020. METHODS: Data were collected from 13 US population-based surveillance programs that used active or a combination of active and passive case ascertainment methods to collect all birth outcomes. These data were used to calculate pooled prevalence estimates and national prevalence estimates adjusted for maternal race/ethnicity for all conditions, and maternal age for trisomies and gastroschisis. Prevalence was compared to previously published national estimates from 1999 to 2014. RESULTS: Adjusted national prevalence estimates per 10,000 live births ranged from 0.63 for common truncus to 18.65 for clubfoot. Temporal changes were observed for several birth defects, including increases in the prevalence of atrioventricular septal defect, tetralogy of Fallot, omphalocele, trisomy 18, and trisomy 21 (Down syndrome) and decreases in the prevalence of anencephaly, common truncus, transposition of the great arteries, and cleft lip with and without cleft palate. CONCLUSION: This study provides updated national estimates of selected major birth defects in the United States. These data can be used for continued temporal monitoring of birth defects prevalence. Increases and decreases in prevalence since 1999 observed in this study warrant further investigation. |
Fever and antibiotic use in maternal urinary tract infections during pregnancy and risk of congenital heart defects: Findings from the National Birth Defects Prevention Study
Patel J , Politis MD , Howley MM , Browne ML , Bolin EH , Ailes EC , Johnson CY , Magann E , Nembhard WN . Birth Defects Res 2023 BACKGROUND: Previous studies report an association between prenatal maternal urinary tract infections (UTI) and specific congenital heart defects (CHDs); however, the role of fever and antibiotic use on this association is poorly understood. Using data from the National Birth Defects Prevention Study, we examined whether the relationship between maternal UTIs during the periconceptional period and occurrence of CHDs is modified by the presence of fever due to UTI and corresponding antibiotic use among 11,704 CHD case infants and 11,636 live-born control infants. METHODS: Information on UTIs, fever associated with UTI and antibiotic use (sulfonamides, nitrofurantoin, cephalosporins, penicillin, macrolides, and quinolones) during pregnancy were obtained using a computer-assisted telephone interview. Using unconditional multivariable logistic regression, we calculated adjusted odds ratios (ORs) to determine the association between maternal UTIs and subtypes of CHDs. Analyses were stratified by the presence of fever and medication use associated with UTI. RESULTS: The prevalence of UTIs during the periconceptional period was 7.6% in control mothers, and 8.7% in case mothers. In the absence of fever, UTI was associated with secundum atrial septal defects (ASD) (OR 1.3; 95% confidence interval [CI] 1.1-1.5) and in the absence of antibiotics, UTI was associated with conotruncal defects as a group and for four specific CHDs. When fever and UTI occurred concomitantly, no significantly elevated odds ratios were noticed for any subtypes of CHD. Among women with UTIs who used antibiotics, an elevated but statistically non-significant estimate was observed for secundum ASD (OR 1.4; 95% CI 1.0-2.0). CONCLUSION: Findings in the present study suggest that fever due to UTI and corresponding maternal antibiotic use do not substantially modify the association between maternal UTIs and specific CHDs in offspring. Further studies with larger sample sizes are warranted to guide clinical management of UTIs during the periconceptional period. |
Is gastroschisis associated with county-level socio-environmental quality during pregnancy?
Krajewski AK , Patel A , Gray CL , Messer LC , Keeler CY , Langlois PH , Reefhuis J , Gilboa SM , Werler MM , Shaw GM , Carmichael SL , Nembhard WN , Insaf TZ , Feldkamp ML , Conway KM , Lobdell DT , Desrosiers TA . Birth Defects Res 2023 115 (18) 1758-1769 BACKGROUND: Gastroschisis prevalence more than doubled between 1995 and 2012. While there are individual-level risk factors (e.g., young maternal age, low body mass index), the impact of environmental exposures is not well understood. METHODS: We used the U.S. Environmental Protection Agency's Environmental Quality Index (EQI) as a county-level estimate of cumulative environmental exposures for five domains (air, water, land, sociodemographic, and built) and overall from 2006 to 2010. Adjusted odds ratios (aOR) and 95% confidence interval (CI) were estimated from logistic regression models between EQI tertiles (better environmental quality (reference); mid; poorer) and gastroschisis in the National Birth Defects Prevention Study from births delivered between 2006 and 2011. Our analysis included 594 cases with gastroschisis and 4105 infants without a birth defect (controls). RESULTS: Overall EQI was modestly associated with gastroschisis (aOR [95% CI]: 1.29 [0.98, 1.71]) for maternal residence in counties with poorer environmental quality, compared to the reference (better environmental quality). Within domain-specific indices, only the sociodemographic domain (aOR: 1.51 [0.99, 2.29]) was modestly associated with gastroschisis, when comparing poorer to better environmental quality. CONCLUSIONS: Future work could elucidate pathway(s) by which components of the sociodemographic domain or possibly related psychosocial factors like chronic stress potentially contribute to risk of gastroschisis. |
Neighborhood deprivation and neural tube defects
Pruitt Evans S , Ailes EC , Kramer MR , Shumate CJ , Reefhuis J , Insaf TZ , Yazdy MM , Carmichael SL , Romitti PA , Feldkamp ML , Neo DT , Nembhard WN , Shaw GM , Palmi E , Gilboa SM . Epidemiology 2023 34 (6) 774-785 BACKGROUND: Individual measures of socioeconomic status (SES) have been associated with an increased risk of neural tube defects (NTDs); however, the association between neighborhood SES and NTD risk is unknown. Using data from the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we investigated the association between measures of census tract SES and NTD risk. METHODS: The study population included 10,028 controls and 1829 NTD cases. We linked maternal addresses to census tract SES measures and used these measures to calculate the neighborhood deprivation index. We used generalized estimating equations to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) estimating the impact of quartiles of census tract deprivation on NTDs adjusting for maternal race-ethnicity, maternal education, and maternal age at delivery. RESULTS: Quartiles of higher neighborhood deprivation were associated with NTDs when compared with the least deprived quartile (Q2: aOR = 1.2; 95% CI = 1.0, 1.4; Q3: aOR = 1.3, 95% CI = 1.1, 1.5; Q4 (highest): aOR = 1.2; 95% CI = 1.0, 1.4). Results for spina bifida were similar; however, estimates for anencephaly and encephalocele were attenuated. Associations differed by maternal race-ethnicity. CONCLUSIONS: Our findings suggest that residing in a census tract with more socioeconomic deprivation is associated with an increased risk for NTDs, specifically spina bifida. |
Rare variants in CAPN2 increase risk for isolated hypoplastic left heart syndrome
Blue EE , White JJ , Dush MK , Gordon WW , Wyatt BH , White P , Marvin CT , Helle E , Ojala T , Priest JR , Jenkins MM , Almli LM , Reefhuis J , Pangilinan F , Brody LC , McBride KL , Garg V , Shaw GM , Romitti PA , Nembhard WN , Browne ML , Werler MM , Kay DM , Mital S , Chong JX , Nascone-Yoder NM , Bamshad MJ . HGG Adv 2023 4 (4) 100232 Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect (CHD) characterized by hypoplasia of the left ventricle and aorta along with stenosis or atresia of the aortic and mitral valves. HLHS represents only ∼4%-8% of all CHDs but accounts for ∼25% of deaths. HLHS is an isolated defect (i.e., iHLHS) in 70% of families, the vast majority of which are simplex. Despite intense investigation, the genetic basis of iHLHS remains largely unknown. We performed exome sequencing on 331 families with iHLHS aggregated from four independent cohorts. A Mendelian-model-based analysis demonstrated that iHLHS was not due to single, large-effect alleles in genes previously reported to underlie iHLHS or CHD in >90% of families in this cohort. Gene-based association testing identified increased risk for iHLHS associated with variation in CAPN2 (p = 1.8 × 10(-5)), encoding a protein involved in functional adhesion. Functional validation studies in a vertebrate animal model (Xenopus laevis) confirmed CAPN2 is essential for cardiac ventricle morphogenesis and that in vivo loss of calpain function causes hypoplastic ventricle phenotypes and suggest that human CAPN2(707C>T) and CAPN2(1112C>T) variants, each found in multiple individuals with iHLHS, are hypomorphic alleles. Collectively, our findings show that iHLHS is typically not a Mendelian condition, demonstrate that CAPN2 variants increase risk of iHLHS, and identify a novel pathway involved in HLHS pathogenesis. |
Neighborhood social deprivation and healthcare utilization, disability, and comorbidities among young adults with congenital heart defects: Congenital heart survey to recognize outcomes, needs, and well-being 2016-2019
Judge A , Kramer M , Downing KF , Andrews J , Oster ME , Benavides A , Nembhard WN , Farr SL . Birth Defects Res 2023 115 (17) 1608-1618 BACKGROUND: Research on the association between neighborhood social deprivation and health among adults with congenital heart defects (CHD) is sparse. METHODS: We evaluated the associations between neighborhood social deprivation and health care utilization, disability, and comorbidities using the population-based 2016-2019 Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG (CH STRONG) of young adults. Participants were identified from active birth defect surveillance systems in three U.S. sites and born with CHD between 1980 and 1997. We linked census tract-level 2017 American Community Survey information on median household income, percent of ≥25-year-old with greater than a high school degree, percent of ≥16-year-olds who are unemployed, and percent of families with children <18 years old living in poverty to survey data and used these variables to calculate a summary neighborhood social deprivation z-score, divided into tertiles. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) derived from a log-linear regression model with a Poisson distribution estimated the association between tertile of neighborhood social deprivation and healthcare utilization in previous year (no encounters, 1 and ≥2 emergency room [ER] visits, and hospital admission), ≥1 disability, and ≥1 comorbidities. We accounted for age, place of birth, sex at birth, presence of chromosomal anomalies, and CHD severity in all models, and, additionally educational attainment and work status in all models except disability. RESULTS: Of the 1435 adults with CHD, 43.8% were 19-24 years old, 54.4% were female, 69.8% were non-Hispanic White, and 33.7% had a severe CHD. Compared to the least deprived tertile, respondents in the most deprived tertile were more likely to have no healthcare visit (aPR: 1.5 [95% CI: 1.1, 2.1]), ≥2 ER visits (1.6 [1.1, 2.3]), or hospitalization (1.6 [1.1, 2.3]) in the previous 12 months, a disability (1.2 [1.0, 1.5]), and ≥1 cardiac comorbidities (1.8 [1.2, 2.7]). CONCLUSIONS: Neighborhood social deprivation may be a useful metric to identify patients needing additional resources and referrals. |
Scientific impact of the National Birth Defects Prevention Network multistate collaborative publications
Bascom JT , Stephens SB , Lupo PJ , Canfield MA , Kirby RS , Nestoridi E , Salemi JL , Mai CT , Nembhard WN , Forestieri NE , Romitti PA , St Louis AM , Agopian AJ . Birth Defects Res 2023 BACKGROUND: Given the lack of a national, population-based birth defects surveillance program in the United States, the National Birth Defects Prevention Network (NBDPN) has facilitated important studies on surveillance, research, and prevention of major birth defects. We sought to summarize NBDPN peer-reviewed publications and their impact. METHODS: We obtained and reviewed a curated list of 49 NBDPN multistate collaborative publications during 2000-2022, as of December 31, 2022. Each publication was reviewed and classified by type (e.g., risk factor association analysis). Key characteristics of study populations and analytic approaches used, along with publication impact (e.g., number of citations), were tabulated. RESULTS: NBDPN publications focused on prevalence estimates (N = 17), surveillance methods (N = 11), risk factor associations (N = 10), mortality and other outcomes among affected individuals (N = 6), and descriptive epidemiology of various birth defects (N = 5). The most cited publications were those that reported on prevalence estimates for a spectrum of defects and those that assessed changes in neural tube defects (NTD) prevalence following mandatory folic acid fortification in the United States. CONCLUSIONS: Results from multistate NBDPN publications have provided critical information not available through other sources, including US prevalence estimates of major birth defects, folic acid fortification and NTD prevention, and improved understanding of defect trends and surveillance efforts. Until a national birth defects surveillance program is established in the United States, NBDPN collaborative publications remain an important resource for investigating birth defects and informing decisions related to health services planning of secondary disabilities prevention and care. |
Healthcare and socioeconomic outcomes among young adults with congenital heart defects and functional cognitive disabilities, CH STRONG 2016 to 2019
Downing KF , Klewer SE , Nembhard WN , Goudie A , Oster ME , Farr SL . Am J Cardiol 2023 201 229-231 Cognitive disability is the most prevalent disability type among young adults with congenital heart defects (CHD), reported by more than a quarter of young adults with CHD in CH STRONG (Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG).1 However, the long-term outcomes of adults with CHD and cognitive disabilities are not well understood. Therefore, we compared the socioeconomic and healthcare outcomes among adults (aged 19 to 38 years) with CHD with and without cognitive disabilities in CH STRONG and described the socioeconomic characteristics associated with the receipt of disability benefits among adults with CHD and cognitive disabilities. |
Survival from birth until young adulthood among individuals with congenital heart defects: CH STRONG
Downing KF , Nembhard WN , Rose CE , Andrews JG , Goudie A , Klewer SE , Oster ME , Farr SL . Circulation 2023 148 (7) 575-588 BACKGROUND: Limited population-based information is available on long-term survival of US individuals with congenital heart defects (CHDs). Therefore, we assessed patterns in survival from birth until young adulthood (ie, 35 years of age) and associated factors among a population-based sample of US individuals with CHDs. METHODS: Individuals born between 1980 and 1997 with CHDs identified in 3 US birth defect surveillance systems were linked to death records through 2015 to identify those deceased and the year of their death. Kaplan-Meier survival curves, adjusted risk ratios (aRRs) for infant mortality (ie, death during the first year of life), and Cox proportional hazard ratios for survival after the first year of life (aHRs) were used to estimate the probability of survival and associated factors. Standardized mortality ratios compared infant mortality, >1-year mortality, >10-year mortality, and >20-year mortality among individuals with CHDs with general population estimates. RESULTS: Among 11 695 individuals with CHDs, the probability of survival to 35 years of age was 81.4% overall, 86.5% among those without co-occurring noncardiac anomalies, and 92.8% among those who survived the first year of life. Characteristics associated with both infant mortality and reduced survival after the first year of life, respectively, included severe CHDs (aRR=4.08; aHR=3.18), genetic syndromes (aRR=1.83; aHR=3.06) or other noncardiac anomalies (aRR=1.54; aHR=2.53), low birth weight (aRR=1.70; aHR=1.29), and Hispanic (aRR=1.27; aHR=1.42) or non-Hispanic Black (aRR=1.43; aHR=1.80) maternal race and ethnicity. Individuals with CHDs had higher infant mortality (standardized mortality ratio=10.17), >1-year mortality (standardized mortality ratio=3.29), and >10-year and >20-year mortality (both standardized mortality ratios ≈1.5) than the general population; however, after excluding those with noncardiac anomalies, >1-year mortality for those with nonsevere CHDs and >10-year and >20-year mortality for those with any CHD were similar to the general population. CONCLUSIONS: Eight in 10 individuals with CHDs born between1980 and 1997 survived to 35 years of age, with disparities by CHD severity, noncardiac anomalies, birth weight, and maternal race and ethnicity. Among individuals without noncardiac anomalies, those with nonsevere CHDs experienced mortality between 1 and 35 years of age, similar to the general population, and those with any CHD experienced mortality between 10 and 35 years of age, similar to the general population. |
Reproductive health counseling and concerns among women with congenital heart defects with and without disabilities
Farr SL , Galindo M , Downing KF , Nembhard WN , Klewer SE , Judge AS , Bolin EH , Benavides A , Oster ME . J Womens Health (Larchmt) 2023 32 (7) 740-746 Background: Women with disabilities are less likely to receive reproductive health counseling than women without disabilities. Yet, little is known about reproductive health counseling and concerns among women with congenital heart defects (CHD) and disabilities. Methods: We used population-based survey data from 778 women aged 19 to 38 years with CHD to examine contraceptive and pregnancy counseling and pregnancy concerns and experiences by disability status, based on six validated questions on vision, hearing, mobility, cognition, self-care, and living independently. Multivariable Poisson regression was used to examine adjusted prevalence ratios between disability status and each outcome, adjusted for CHD severity, age, race/ethnicity, place of birth (Arkansas, Arizona, Georgia), and insurance type. Results: Women with disabilities (n = 323) were 1.4 and 2.3 times more likely than women without disabilities (n = 455) to receive clinician counseling on safe contraceptive methods and avoiding pregnancy because of their CHD. Women with CHD and disabilities, compared to those without disabilities, were more likely to be concerned about their ability to have children (aPR = 1.2) and to have delayed or avoided pregnancy (aPR = 2.2); they were less likely to have ever been pregnant (aPR = 0.7). Associations differed slightly across specific disability types. All associations remained after excluding 71 women with chromosomal anomalies. Conclusion: Among women with CHD, reproductive counseling, concerns, and experiences differ by disability status. |
Cardiology care and loss to follow-up among adults with congenital heart defects in CH STRONG
Andrews JG , Strah D , Downing KF , Kern MC , Oster ME , Seckeler MD , Goudie A , Nembhard WN , Farr SL , Klewer SE . Am J Cardiol 2023 197 42-45 Many of the estimated 1.4 million adults with congenital heart defects (CHDs) in the United States are lost to follow-up (LTF) despite recommendations for ongoing cardiology care. Using 2016 to 2019 CH STRONG (Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG) data, we describe cardiac care among community-based adults with CHD, born in 1980 to 1997, identified through state birth defects registries. Our estimates of LTF were standardized to the CH STRONG eligible population and likely more generalizable to adults with CHD than clinic-based data. Half of our sample were LTF and more than 45% had not received cardiology care in over 5 years. Of those who received care, only 1 in 3 saw an adult CHD physician at their last encounter. Not knowing they needed to see a cardiologist, being told they no longer needed cardiology care, and feeling "well" were the top reasons for LTF, and only half of respondents report doctors discussing the need for cardiac follow-up. |
A multi-program analysis of cleft lip with cleft palate prevalence and mortality using data from 22 International Clearinghouse for Birth Defects Surveillance and Research programs, 19742014
Mc Goldrick N , Revie G , Groisman B , Hurtado-Villa P , Sipek A , Khoshnood B , Rissmann A , Dastgiri S , Landau D , Tagliabue G , Pierini A , Gatt M , Mutchinick OM , Martínez L , de Walle HEK , Szabova E , Lopez Camelo J , Källén K , Morgan M , Wertelecki W , Nance A , Stallings EB , Nembhard WN , Mossey P . Birth Defects Res 2023 115 (10) 980-997 Background: Cleft lip with cleft palate (CLP) is a congenital condition that affects both the oral cavity and the lips. This study estimated the prevalence and mortality of CLP using surveillance data collected from birth defect registries around the world. Methods: Data from 22 population- and hospital-based surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) in 18 countries on live births (LB), stillbirths (SB), and elective terminations of pregnancy for fetal anomaly (ETOPFA) for CLP from 1974 to 2014 were analyzed. Prevalence and survival (survival for LB only) estimates were calculated for total and subclassifications of CLP and by pregnancy outcome. Results: The pooled prevalence of total CLP cases was 6.4 CLP per 10,000 births. The prevalence of CLP and all of the pregnancy outcomes varied across programs. Higher ETOPFA rates were recorded in most European programs compared to programs in other continents. In programs reporting low ETOPFA rates or where there was no ascertainment of ETOPFA, the rate of CLP among LB and SB was higher compared to those where ETOPFA rates were ascertained. Overall survival for total CLP was 91%. For isolated CLP, the survival was 97.7%. CLP associated with multiple congenital anomalies had an overall survival of 77.1%, and for CLP associated with genetic/chromosomal syndromes, overall survival was 40.9%. Conclusions: Total CLP prevalence reported in this study is lower than estimates from prior studies, with variation by pregnancy outcomes between programs. Survival was lower when CLP was associated with other congenital anomalies or syndromes compared to isolated CLP. © 2023 The Authors. Birth Defects Research published by Wiley Periodicals LLC. |
Racial and ethnic disparities in socio-economic status, access to care, and healthcare utilisation among children with heart conditions, National Survey of Children's Health 2016-2019
Judge AS , Downing KF , Nembhard WN , Oster ME , Farr SL . Cardiol Young 2023 33 (12) 1-9 Among children with and without heart conditions of different race/ethnicities, upstream social determinants of health, such as socio-economic status, access to care, and healthcare utilisation, may vary. Using caregiver-reported data from the 2016-19 National Survey of Children's Health, we calculated the prevalence of caregiver employment and education, child's health insurance, usual place of medical care in the past 12 months, problems paying for child's care, ≥2 emergency room visits, and unmet healthcare needs by heart condition status and race/ethnicity (Hispanic, non-Hispanic Black, and non-Hispanic White). For each outcome, we used multivariable logistic regression to generate adjusted prevalence ratios controlling for child's age and sex. Of 2632 children with heart conditions and 104,841 without, 65.4% and 58.0% were non-Hispanic White and 52.0% and 51.1% were male, respectively. Children with heart conditions, compared to those without, were 1.7-2.6 times more likely to have problems paying for healthcare, have ≥2 emergency room visits, and have unmet healthcare needs. Hispanic and non-Hispanic Black children with heart conditions, compared to non-Hispanic White, were 1.5-3.2 times as likely to have caregivers employed <50 weeks in the past year and caregivers with ≤ high school education, public or no health insurance, no usual place of care, and ≥2 emergency room visits. Children with heart conditions, compared to those without, may have greater healthcare needs that more commonly go unmet. Among children with heart conditions, Hispanic and non-Hispanic Black children may experience lower socio-economic status and greater barriers to healthcare than non-Hispanic White children. |
Exome-wide assessment of isolated biliary atresia: A report from the National Birth Defects Prevention Study using child-parent trios and a case-control design to identify novel rare variants.
Sok P , Sabo A , Almli LM , Jenkins MM , Nembhard WN , Agopian AJ , Bamshad MJ , Blue EE , Brody LC , Brown AL , Browne ML , Canfield MA , Carmichael SL , Chong JX , Dugan-Perez S , Feldkamp ML , Finnell RH , Gibbs RA , Kay DM , Lei Y , Meng Q , Moore CA , Mullikin JC , Muzny D , Olshan AF , Pangilinan F , Reefhuis J , Romitti PA , Schraw JM , Shaw GM , Werler MM , Harpavat S , Lupo PJ . Am J Med Genet A 2023 191 (6) 1546-1556 The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child-parent trios, one child-mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA. We performed (1) a trio-based analysis to identify rare de novo, homozygous, and compound heterozygous PAVs and (2) a case-control analysis using a sequence kernel-based association test to identify genes enriched with rare PAVs. While we replicated previous findings on PKD1L1, our results do not suggest that recurrent de novo PAVs play important roles in BA susceptibility. In fact, our finding in NOTCH2, a disease gene associated with Alagille syndrome, highlights the difficulty in BA diagnosis. Notably, IFRD2 has been implicated in other gastrointestinal conditions and warrants additional study. Overall, our findings strengthen the hypothesis that the etiology of BA is complex. |
Maternal cyclobenzaprine exposure and risk of birth defects in the National Birth Defects Prevention Study (1997-2011) and Birth Defects Study to Evaluate Pregnancy Exposures (2014-2018)
Fisher SC , Howley MM , Tran EL , Ailes EC , Papadopoulos EA , Nembhard WN , Browne ML . Pharmacoepidemiol Drug Saf 2023 32 (8) 855-862 PURPOSE: Cyclobenzaprine is a muscle relaxant indicated for acute pain. Little is known about cyclobenzaprine's safety during pregnancy. We explored the association between maternal cyclobenzaprine exposure and risk of birth defects among offspring. METHODS: We combined data from two large, multi-site, population-based case-control studies in the US. Cases were identified from birth defects registries across 10 states; controls were liveborn infants without birth defects randomly selected from the same catchment areas. Participants reported cyclobenzaprine use during the month before conception through the third month of pregnancy ("periconception") via computer-assisted telephone interview. We used logistic regression to assess associations between periconceptional cyclobenzaprine exposure and selected structural birth defects. We calculated crude odds ratios (OR) with corresponding 95% confidence intervals (CI). RESULTS: Our study included 33,615 cases and 13,110 controls. Overall, 51 case (0.15%) and 9 control (0.07%) participants reported periconceptional cyclobenzaprine use. We observed increased risk for all seven defects with >3 exposed cases: cleft palate (OR=4.79, 95% CI 1.71-13.44), cleft lip (OR=2.50, 95% CI 0.89-7.02), anorectal atresia/stenosis (OR=6.91, 95% CI 1.67, 28.65), d-transposition of the great arteries (OR=6.97, 95% CI 2.17-22.36), coarctation of the aorta (OR=5.58, 95% CI 1.88-16.58), pulmonary valve stenosis (OR=4.55, 95% CI 1.10-18.87), and secundum atrial septal defect (OR=3.08, 95% CI 0.83-11.45). CONCLUSIONS: Even in our large sample, cyclobenzaprine use was rare. Our estimates are unadjusted and imprecise so should be interpreted cautiously. These hypothesis-generating results warrant confirmation and further research to explore possible mechanisms. |
Prevalence and descriptive epidemiology of Turner syndrome in the United States, 2000-2017: A report from the National Birth Defects Prevention Network.
Martin-Giacalone BA , Lin AE , Rasmussen SA , Kirby RS , Nestoridi E , Liberman RF , Agopian AJ , Carey JC , Cragan JD , Forestieri N , Leedom V , Boyce A , Nembhard WN , Piccardi M , Sandidge T , Shan X , Shumate CJ , Stallings EB , Stevenson R , Lupo PJ . Am J Med Genet A 2023 191 (5) 1339-1349 The lack of United States population-based data on Turner syndrome limits assessments of prevalence and associated characteristics for this sex chromosome abnormality. Therefore, we collated 2000-2017 data from seven birth defects surveillance programs within the National Birth Defects Prevention Network. We estimated the prevalence of karyotype-confirmed Turner syndrome diagnosed within the first year of life. We also calculated the proportion of cases with commonly ascertained birth defects, assessed associations with maternal and infant characteristics using prevalence ratios (PR) with 95% confidence intervals (CI), and estimated survival probability. The prevalence of Turner syndrome of any pregnancy outcome was 3.2 per 10,000 female live births (95% CI = 3.0-3.3, program range: 1.0-10.4), and 1.9 for live birth and stillbirth (≥20 weeks gestation) cases (95% CI = 1.8-2.1, program range: 0.2-3.9). Prevalence was lowest among cases born to non-Hispanic Black women compared to non-Hispanic White women (PR = 0.5, 95% CI = 0.4-0.6). Coarctation of the aorta was the most common defect (11.6% of cases), and across the cohort, individuals without hypoplastic left heart had a five-year survival probability of 94.6%. The findings from this population-based study may inform surveillance practices, prenatal counseling, and diagnosis. We also identified racial and ethnic disparities in prevalence, an observation that warrants further investigation. |
Health insurance status and access to healthcare among young adults with congenital heart disease: From the congenital heart survey to recognize outcomes, needs and well-being (ch strong), 2016-2019
Bolin EH , Ali MM , Farr SL , Oster ME , Klewer SE , Thomas RC 2nd , Seckeler MD , Nembhard WN . Pediatr Cardiol 2023 Having health insurance is associated with better access to healthcare and lower rates of comorbidity in the general population, but data are limited on insurance's impact on adults with congenital heart disease (ACHD). The Congenital Heart Survey To Recognize Outcomes, Needs and well-beinG (CH STRONG) was conducted among ACHD in three locations from 2016 to 2019. We performed multivariable logistic regression to determine the associations between health insurance and both access to healthcare and presence of comorbidities. We also compared health insurance and comorbidities among ACHD to similarly-aged individuals in the Behavioral Risk Factor Surveillance System (BRFSS) as a proxy for the general population. Of 1354 CH STRONG respondents, the majority were ≤ 30 years old (83.5%), and 8.8% were uninsured versus 17.7% in the BRFSS (p < 0.01). Compared to insured ACHD, uninsured were less likely to report regular medical care (adjusted odds ratio [aOR] 0.2, 95% confidence interval [CI] 0.1-0.3) and visited an emergency room more often (aOR 1.6, CI 1.0-2.3). Among all ACHD reporting disability, uninsured individuals less frequently received benefits (aOR 0.1, CI 0.0-0.3). Depression was common among uninsured ACHD (22.5%), but insured ACHD had lower rates of depression than insured in the BRFSS (13.3% vs. 22.5%, p < 0.01). In conclusion, rates of insurance were higher among ACHD compared to the general population. Nonetheless, uninsured ACHD inconsistently accessed healthcare and benefits. Further studies are needed to determine if insurance ameliorates the risk of morbidity as ACHD age. |
Prevalence and mortality among children with anorectal malformation: A multi-country analysis.
Kancherla V , Sundar M , Tandaki L , Lux A , Bakker MK , Bergman JE , Bermejo-Sánchez E , Canfield MA , Dastgiri S , Feldkamp ML , Gatt M , Groisman B , Hurtado-Villa P , Kallen K , Landau D , Lelong N , Lopez-Camelo J , Martinez LE , Mastroiacovo P , Morgan M , Mutchinick OM , Nance AE , Nembhard WN , Pierini A , Sipek A , Stallings EB , Szabova E , Tagliabue G , Wertelecki W , Zarante I , Rissmann A . Birth Defects Res 2022 115 (3) 390-404 We examined the total prevalence, trends in prevalence, and age-specific mortality among individuals with anorectal malformation (ARM) METHODS: We conducted a retrospective cohort study using data from 24 population- and hospital-based birth defects surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) from 18 countries and for births from 1974 to 2014. We estimated pooled and program-specific total prevalence per 10,000 total births. Poisson regression was used to assess time trends in prevalence from 2001 to 2012 when most programs contributed data. We calculated selected age-specific proportions of deaths, stratified by case status RESULTS: The pooled total prevalence of ARM was 3.26 per 10,000 total births (95% Confidence Interval = 3.19, 3.32) for birth years 1974-2014. About 60% of cases were multiple or syndromic. Prevalence of multiple, syndromic, and stillborn cases decreased from 2001 to 2012. The first week mortality proportion was 12.5%, 3.2%, 28.3%, and 18.2% among all, isolated, multiple, and syndromic cases, respectively CONCLUSIONS: ARM is relatively rare, with multiple and syndromic cases showing decreasing prevalence during the study period. Mortality is a concern during the first week of life, and especially among multiple and syndromic cases. Our descriptive epidemiological findings increase our understanding of geographic variation in the prevalence of ARM and can be used to plan needed clinical services. Exploring factors influencing prevalence and mortality among individuals with ARM could inform future studies. |
Assessing associations between residential proximity to greenspace and birth defects in the National Birth Defects Prevention Study
Weber KA , Yang W , Carmichael SL , Collins RT2nd , Luben TJ , Desrosiers TA , Insaf TZ , Le MT , Evans SP , Romitti PA , Yazdy MM , Nembhard WN , Shaw GM . Environ Res 2022 216 114760 BACKGROUND: Residential proximity to greenspace is associated with various health outcomes. OBJECTIVES: We estimated associations between maternal residential proximity to greenspace (based on an index of vegetation) and selected structural birth defects, including effect modification by neighborhood-level factors. METHODS: Data were from the National Birth Defects Prevention Study (1997-2011) and included 19,065 infants with at least one eligible birth defect (cases) and 8925 without birth defects (controls) from eight Centers throughout the United States. Maternal participants reported their addresses throughout pregnancy. Each address was systematically geocoded and residences around conception were linked to greenspace, US Census, and US Department of Agriculture data. Greenspace was estimated using the normalized difference vegetation index (NDVI); average maximum NDVI was estimated within 100m and 500m concentric buffers surrounding geocoded addresses to estimate residential NDVI. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals comparing those in the highest and lowest quartiles of residential NDVI and stratifying by rural/urban residence and neighborhood median income. RESULTS: After multivariable adjustment, for the 500m buffer, inverse associations were observed for tetralogy of Fallot, secundum atrial septal defects, anencephaly, anotia/microtia, cleft lipcleft palate, transverse limb deficiency, and omphalocele, (aORs: 0.54-0.86). Results were similar for 100m buffer analyses and similar patterns were observed for other defects, though results were not significant. Significant heterogeneity was observed after stratification by rural/urban for hypoplastic left heart, coarctation of the aorta, and cleft palate, with inverse associations only among participants residing in rural areas. Stratification by median income showed heterogeneity for atrioventricular and secundum atrial septal defects, anencephaly, and anorectal atresia, with inverse associations only among participants residing in a high-income neighborhood (aORs: 0.45-0.81). DISCUSSION: Our results suggest that perinatal residential proximity to more greenspace may contribute to a reduced risk of certain birth defects, especially among those living in rural or high-income neighborhoods. |
Associations between maternal reports of periconceptional fever from miscellaneous causes and structural birth defects
MohanDass NL , Botto LD , Tinker SC , Canfield MA , Finnell RH , Gallaway MS , Hashmi SS , Hoyt AT , Nembhard WN , Waller DK . Birth Defects Res 2022 114 (15) 885-894 BACKGROUND: Associations between birth defects and fevers attributed to colds, influenza, and urinary tract infections (UTIs) have been observed in previous studies. Our aim was to study associations between birth defects and fevers attributed to other causes. METHODS: We analyzed data from 34,862 participants in the National Birth Defects Prevention Study, a multistate case-control study of major structural birth defects. Using multivariable logistic regression, we assessed the association between maternal report of fever during early pregnancy due to causes other than colds, influenza, or UTI and 36 categories of birth defects. RESULTS: Maternal reports of fever due to other causes were associated with significantly elevated odds ratios ranging from 1.93 to 10.60 for 8 of 36 birth defects, primarily involving the spine, limbs, and heart (spina bifida, intestinal atresia, intercalary limb deficiency, transverse limb deficiency, congenital heart defect with heterotaxy, tetralogy of Fallot, pulmonary atresia and atrial septal defect, not otherwise specified). CONCLUSION: Our data suggests fever itself or other physiologic changes associated with many infections are associated with some birth defects. Women who are pregnant or planning to become pregnant may want to consider speaking with their healthcare provider about the best ways to avoid infections that may cause fever and for guidance on how to treat fevers during pregnancy. |
Exome sequencing identifies genetic variants in anophthalmia and microphthalmia.
Li J , Yang W , Wang YJ , Ma C , Curry CJ , McGoldrick D , Nickerson DA , Chong JX , Blue EE , Mullikin JC , Reefhuis J , Nembhard WN , Romitti PA , Werler MM , Browne ML , Olshan AF , Finnell RH , Feldkamp ML , Pangilinan F , Almli LM , Bamshad MJ , Brody LC , Jenkins MM , Shaw GM . Am J Med Genet A 2022 188 (8) 2376-2388 Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi-center ascertainment of infants affected by A/M. We performed exome sequencing on 67 family trios and identified numerous genes affected by rare deleterious nonsense and missense variants in this cohort, including de novo variants. We identified 9 nonsense changes and 86 missense variants that are absent from the reference human population (Genome Aggregation Database), and we suggest that these are high priority candidate genes for A/M. We also performed literature curation, single cell transcriptome comparisons, and molecular pathway analysis on the candidate genes and performed protein structure modeling to determine the potential pathogenic variant consequences on PAX6 in this disease. |
Analysis of early neonatal case fatality rate among newborns with congenital hydrocephalus, a 2000-2014 multi-country registry-based study.
Gili JA , Lpez-Camelo JS , Nembhard WN , Bakker M , deWalle HEK , Stallings EB , Kancherla V , Contiero P , Dastgiri S , Feldkamp ML , Nance A , Gatt M , Martnez L , Canessa MA , Groisman B , Hurtado-Villa P , Klln K , Landau D , Lelong N , Morgan M , Arteaga-Vzquez J , Pierini A , Rissmann A , Sipek A , Szabova E , Wertelecki W , Zarante I , Canfield MA , Mastroiacovo P . Birth Defects Res 2022 114 (12) 631-644 BACKGROUND: Congenital hydrocephalus (CH) comprises a heterogeneous group of birth anomalies with a wide-ranging prevalence across geographic regions and registry type. The aim of the present study was to analyze the early neonatal case fatality rate (CFR) and total birth prevalence of newborns diagnosed with CH. METHODS: Data were provided by 25 registries from four continents participating in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) on births ascertained between 2000 and 2014. Two CH rates were calculated using a Poisson distribution: early neonatal CFR (death within 7days) per 100 liveborn CH cases (CFR) and total birth prevalence rate (BPR) per 10,000 births (including live births and stillbirths) (BPR). Heterogeneity between registries was calculated using a meta-analysis approach with random effects. Temporal trends in CFR and BPR within registries were evaluated through Poisson regression modeling. RESULTS: A total of 13,112 CH cases among 19,293,280 total births were analyzed. The early neonatal CFR was 5.9 per 100 liveborn cases, 95% confidence interval (CI): 5.4-6.8. The CFR among syndromic cases was 2.7 times (95% CI: 2.2-3.3) higher than among non-syndromic cases (10.4% [95% CI: 9.3-11.7] and 4.4% [95% CI: 3.7-5.2], respectively). The total BPR was 6.8 per 10,000 births (95% CI: 6.7-6.9). Stratified by elective termination of pregnancy for fetal anomalies (ETOPFA), region and system, higher CFR were observed alongside higher BPR rates. The early neonatal CFR and total BPR did not show temporal variation, with the exception of a CFR decrease in one registry. CONCLUSIONS: Findings of early neonatal CFR and total BPR were highly heterogeneous among registries participating in ICBDSR. Most registries with higher CFR also had higher BPR. Differences were attributable to type of registry (hospital-based vs. population-based), ETOPFA (allowed yes or no) and geographical regions. These findings contribute to the understanding of regional differences of CH occurrence and early neonatal deaths. |
A multicountry analysis of prevalence and mortality among neonates and children with bladder exstrophy
Kancherla V , Tandaki L , Sundar M , Lux A , Bakker MK , Bergman JE , Bermejo-Sánchez E , Canfield MA , Feldkamp ML , Groisman B , Hurtado-Villa P , Källén K , Landau D , Lelong N , Lopez-Camelo J , Mastroiacovo P , Morgan M , Mutchinick OM , Nance AE , Nembhard WN , Pierini A , Šípek A , Stallings EB , Szabova E , Wertelecki W , Zarante I , Rissmann A . Am J Perinatol 2022 OBJECTIVE: Bladder exstrophy (BE) is a rare but severe birth defect affecting the lower abdominal wall and genitourinary system. The objective of the study is to examine the total prevalence, trends in prevalence, and age-specific mortality among individuals with BE. STUDY DESIGN: We conducted a retrospective cohort study. Data were analyzed from 20 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research in 16 countries. Live births, stillbirths, and elective terminations of pregnancy for fetal anomaly (ETOPFA) diagnosed with BE from 1974 to 2014. Pooled and program-specific prevalence of BE per 100,000 total births was calculated. The 95% confidence intervals (CI) for prevalence were estimated using Poisson approximation of binomial distribution. Time trends in prevalence of BE from 2000 to 2014 were examined using Poisson regression. Proportion of deaths among BE cases was calculated on the day of birth, day 2 to 6, day 7 to 27, day 28 to 364, 1 to 4 years, and ≥5 years. Mortality analysis was stratified by isolated, multiple, and syndromic case status. RESULTS: The pooled total prevalence of BE was 2.58 per 100,000 total births (95% CI = 2.40, 2.78) for study years 1974 to 2014. Prevalence varied over time with a decreasing trend from 2000 to 2014. The first-week mortality proportion was 3.5, 17.3, and 14.6% among isolated, multiple, and syndromic BE cases, respectively. The majority of first-week mortality occurred on the first day of life among isolated, multiple, and syndromic BE cases. The proportion of first-week deaths was higher among cases reported from programs in Latin America where ETOPFA services were not available. CONCLUSIONS: Prevalence of BE varied by program and showed a decreasing trend from 2000 to -2014. Mortality is a concern among multiple and syndromic cases, and a high proportion of deaths among cases occurred during the first week of life. KEY POINTS: · Total prevalence of BE was 2.58 per 100,000 births.. · Prevalence decreased from 2000 to 2014.. · The first-week mortality was 9.3%.. |
A genome-wide association study of obstructive heart defects among participants in the National Birth Defects Prevention Study.
Rashkin SR , Cleves M , Shaw GM , Nembhard WN , Nestoridi E , Jenkins MM , Romitti PA , Lou XY , Browne ML , Mitchell LE , Olshan AF , Lomangino K , Bhattacharyya S , Witte JS , Hobbs CA . Am J Med Genet A 2022 188 (8) 2303-2314 Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from interplay among maternal exposures, genetic susceptibilities, and epigenetic phenomena. A genome-wide association study was conducted in National Birth Defects Prevention Study participants (N(discovery) = 3978; N(replication) = 2507), investigating the genetic architecture of OHDs using transmission/disequilibrium tests (TDT) in complete case-parental trios (N(discovery_TDT) = 440; N(replication_TDT) = 275) and case-control analyses separately in infants (N(discovery_CCI) = 1635; N(replication_CCI) = 990) and mothers (case status defined by infant; N(discovery_CCM) = 1703; N(replication_CCM) = 1078). In the TDT analysis, the SLC44A2 single nucleotide polymorphism (SNP) rs2360743 was significantly associated with OHD (p(discovery) = 4.08 × 10(-9) ; p(replication) = 2.44 × 10(-4) ). A CAPN11 SNP (rs55877192) was suggestively associated with OHD (p(discovery) = 1.61 × 10(-7) ; p(replication) = 0.0016). Two other SNPs were suggestively associated (p < 1 × 10(-6) ) with OHD in only the discovery sample. In the case-control analyses, no SNPs were genome-wide significant, and, even with relaxed thresholds ( × (discovery) < 1 × 10(-5) and p(replication) < 0.05), only one SNP (rs188255766) in the infant analysis was associated with OHDs (p(discovery) = 1.42 × 10(-6) ; p(replication) = 0.04). Additional SNPs with p(discovery) < 1 × 10(-5) were in loci supporting previous findings but did not replicate. Overall, there was modest evidence of an association between rs2360743 and rs55877192 and OHD and some evidence validating previously published findings. |
Modeling complex effects of exposure to particulate matter and extreme heat during pregnancy on congenital heart defects: A U.S. population-based case-control study in the National Birth Defects Prevention Study.
Simmons W , Lin S , Luben TJ , Sheridan SC , Langlois PH , Shaw GM , Reefhuis J , Romitti PA , Feldkamp ML , Nembhard WN , Desrosiers TA , Browne ML , Stingone JA . Sci Total Environ 2021 808 152150 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. |
Disability Among Young Adults With Congenital Heart Defects: Congenital Heart Survey to Recognize Outcomes, Needs, and Well-Being 2016-2019
Downing KF , Oster ME , Klewer SE , Rose CE , Nembhard WN , Andrews JG , Farr SL . J Am Heart Assoc 2021 10 (21) e022440 Background Disabilities have implications for health, well-being, and health care, yet limited information is available on the percentage of adults with congenital heart defects (CHD) living with disabilities. We evaluated the prevalence of disability and associated characteristics among the 2016-2019 CH STRONG (Congenital Heart Survey to Recognize Outcomes, Needs, and Well-Being) population-based sample of 19- to 38-year-olds with CHD from 3 US locations. Methods and Results Prevalence of disability types (hearing, vision, cognition, mobility, self-care, living independently) were compared with similarly aged adults from the general population as estimated by the American Community Survey and standardized to the CH STRONG eligible population to reduce nonresponse bias and confounding. Health-related quality of life (HRQOL) was measured via Patient-Reported Outcomes Measurement Information System Global Health Scale T-scores standardized to US 18- to 34-year-olds. Separate multivariable regression models assessed associations between disability and HRQOL. Of 1478 participants, 40% reported disabilities, with cognition most prevalent (29%). Of those reporting disability, 45% ever received disability benefits and 46% were unemployed. Prevalence of disability types were 5 to 8 times higher in adults with CHD than the general population. Those with ≥1 disability had greater odds of being female, and of having non-Hispanic Black maternal race and ethnicity, severe CHD, recent cardiac care, and noncardiac congenital anomalies. On average, adults with CHD and cognition, mobility, and self-care disabilities had impaired mental HRQOL and those with any disability type had impaired physical HRQOL. Conclusions Two of 5 adults with CHD may have disabilities, which are associated with impaired HRQOL. These results may inform healthcare needs and services for this growing population. |
Maternal Smoking and Congenital Heart Defects, National Birth Defects Prevention Study, 1997-2011.
Bolin EH , Gokun Y , Romitti PA , Tinker SC , Summers AD , Roberson PK , Hobbs CA , Malik S , Botto LD , Nembhard WN . J Pediatr 2021 240 79-86 e1 OBJECTIVES: To assess associations between maternal smoking and congenital heart defects (CHDs) in offspring. STUDY DESIGN: We performed a retrospective case-control study using data for cases of CHD (n=8,339) and non-malformed controls (n=11,020) children from all years (1997-2011) of the National Birth Defects Prevention Study. Maternal self-reported smoking one month before through three months after conception was evaluated as a binary (none, any) and categorical (light, medium, heavy) exposure. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals. Stratified analyses were performed for septal defects according to maternal age, pre-pregnancy body mass index, and maternal race/ethnicity. RESULTS: Multiple CHDs displayed modest associations with any level of maternal periconceptional smoking independent of potential confounders; the strongest associations were for aggregated septal defects (OR 1.5 [1.3-1.7]), tricuspid atresia (OR 1.7 [1.0-2.7]), and double outlet right ventricle (DORV) (1.5 [1.1-2.1]). TA and DORV also displayed dose-response relationships. Among heavy smokers, the highest odds were again observed for TA (aOR 3.0 [1.5-6.1]) and DORV (aOR 1.5 [1.1-2.2]). Heavy smokers ≥35 years old more frequently had a child with a septal defect when compared with similarly aged non-smokers (aOR 2.3 [1.4-3.9]). CONCLUSIONS: Maternal periconceptional smoking is most strongly associated with septal defects, TA and DORV; the risk for septal defects is modified by maternal age. |
Survival of infants born with esophageal atresia among 24 international birth defects surveillance programs.
Bell JC , Baynam G , Bergman JEH , Bermejo-Sánchez E , Botto LD , Canfield MA , Dastgiri S , Gatt M , Groisman B , Hurtado-Villa P , Kallen K , Khoshnood B , Konrad V , Landau D , Lopez-Camelo JS , Martinez L , Morgan M , Mutchinick OM , Nance AE , Nembhard W , Pierini A , Rissmann A , Shan X , Sipek A , Szabova E , Tagliabue G , Yevtushok LS , Zarante I , Nassar N . Birth Defects Res 2021 113 (12) 945-957 BACKGROUND: Esophageal atresia (EA) affects around 2.3-2.6 per 10,000 births world-wide. Infants born with this condition require surgical correction soon after birth. Most survival studies of infants with EA are locally or regionally based. We aimed to describe survival across multiple world regions. METHODS: We included infants diagnosed with EA between 1980 and 2015 from 24 birth defects surveillance programs that are members of the International Clearinghouse for Birth Defects Surveillance and Research. We calculated survival as the proportion of liveborn infants alive at 1 month, 1- and 5-years, among all infants with EA, those with isolated EA, those with EA and additional anomalies or EA and a chromosomal anomaly or genetic syndrome. We also investigated trends in survival over the decades, 1980s-2010s. RESULTS: We included 6,466 liveborn infants with EA. Survival was 89.4% (95% CI 88.1-90.5) at 1-month, 84.5% (95% CI 83.0-85.9) at 1-year and 82.7% (95% CI 81.2-84.2) at 5-years. One-month survival for infants with isolated EA (97.1%) was higher than for infants with additional anomalies (89.7%) or infants with chromosomal or genetic syndrome diagnoses (57.3%) with little change at 1- and 5-years. Survival at 1 month improved from the 1980s to the 2010s, by 6.5% for infants with isolated EA and by 21.5% for infants with EA and additional anomalies. CONCLUSIONS: Almost all infants with isolated EA survived to 5 years. Mortality was higher for infants with EA and an additional anomaly, including chromosomal or genetic syndromes. Survival improved from the 1980s, particularly for those with additional anomalies. |
Paternal genetic variants and risk of obstructive heart defects: A parent-of-origin approach.
Patel J , Bircan E , Tang X , Orloff M , Hobbs CA , Browne ML , Botto LD , Finnell RH , Jenkins MM , Olshan A , Romitti PA , Shaw GM , Werler MM , Li J , Nembhard WN . PLoS Genet 2021 17 (3) e1009413 Previous research on risk factors for obstructive heart defects (OHDs) focused on maternal and infant genetic variants, prenatal environmental exposures, and their potential interaction effects. Less is known about the role of paternal genetic variants or environmental exposures and risk of OHDs. We examined parent-of-origin effects in transmission of alleles in the folate, homocysteine, or transsulfuration pathway genes on OHD occurrence in offspring. We used data on 569 families of liveborn infants with OHDs born between October 1997 and August 2008 from the National Birth Defects Prevention Study to conduct a family-based case-only study. Maternal, paternal, and infant DNA were genotyped using an Illumina Golden Gate custom single nucleotide polymorphism (SNP) panel. Relative risks (RR), 95% confidence interval (CI), and likelihood ratio tests from log-linear models were used to estimate the parent-of-origin effect of 877 SNPs in 60 candidate genes in the folate, homocysteine, and transsulfuration pathways on the risk of OHDs. Bonferroni correction was applied for multiple testing. We identified 3 SNPs in the transsulfuration pathway and 1 SNP in the folate pathway that were statistically significant after Bonferroni correction. Among infants who inherited paternally-derived copies of the G allele for rs6812588 in the RFC1 gene, the G allele for rs1762430 in the MGMT gene, and the A allele for rs9296695 and rs4712023 in the GSTA3 gene, RRs for OHD were 0.11 (95% CI: 0.04, 0.29, P = 9.16x10-7), 0.30 (95% CI: 0.17, 0.53, P = 9.80x10-6), 0.34 (95% CI: 0.20, 0.57, P = 2.28x10-5), and 0.34 (95% CI: 0.20, 0.58, P = 3.77x10-5), respectively, compared to infants who inherited maternally-derived copies of the same alleles. We observed statistically significant decreased risk of OHDs among infants who inherited paternal gene variants involved in folate and transsulfuration pathways. |
Comorbidities among young adults with congenital heart defects: Results from the Congenital Heart Survey to Recognize Outcomes, Needs, and well-beinG - Arizona, Arkansas, and Metropolitan Atlanta, 2016-2019
Oster ME , Riser AP , Andrews JG , Bolin EH , Galindo MK , Nembhard WN , Rose CE , Farr SL . MMWR Morb Mortal Wkly Rep 2021 70 (6) 197-201 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. |
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