Marcia L. Feldkamp

Background: Population‐based data on healthcare utilization in adults with congenital heart disease (CHD) are limited. We examined utilization patterns in a multi‐site, population‐based U.S. cohort of adults with CHD. Methods: This retrospective cohort linked health and administrative records from five regions (Colorado, North Carolina, Utah, metropolitan Atlanta, and New York). Adults aged 19–64 years with at least one CHD‐related ICD‐9‐CM code recorded during 2011–2013 were included. We evaluated inpatient, emergency department (ED), outpatient, and cardiology outpatient encounters, as well as cardiac diagnostic/imaging, therapeutic/interventional, and vascular procedures. Multivariable mixed‐effects logistic regression models compared utilization by CHD severity (severe vs. non‐severe), adjusting for sex, race/ethnicity, insurance, comorbidity, and site, and including age group as an effect modifier. Results: Over 3 years, this cohort of 18,877 adults (20.7% severe CHD), 45.9% had at least one hospitalization, 35.1% had an ED visit, 92.1% had an outpatient encounter, and 43.8% had a cardiology outpatient visit. Cardiac diagnostic/imaging procedures occurred in 67.8%, cardiac interventions in 20.3%, and vascular procedures in 10.5%. Severe CHD was associated with higher odds of cardiac procedures but lower odds of ED use than non‐severe CHD. Age modified these associations, and site‐level variation was marked, with cardiology visit rates ranging from 21% to 59%. Conclusions: Adults with CHD had high healthcare utilization, including frequent ED use, yet fewer than half saw a cardiology specialist, particularly at older ages. These findings highlight persistent gaps in lifelong care and substantial geographic variation, underscoring the need to improve access to specialized care for adults with CHD.

Introduction: Small intestinal atresia (SIA) consists of a congenital obstruction of the lumen of the duodenum, jejunum, or ileum with varying severity. The aim of the investigation was to analyze the prevalence and mortality of SIA, using data from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). Methods: Data on SIA cases were collected from 25 ICBDSR members' surveillance programs in 17 countries over 1974–2015. All pregnancy outcomes were included, but terminations of pregnancy were not available for 11 programs. Statistical analysis is descriptive, and the prevalence is established by the total of SIA cases divided by the total of births. The survival time was calculated, and mortality was analyzed individually using the Kaplan–Meier method for comparison. Results: The total prevalence of SIA was 2.1 per 10,000 births. Iran had the highest prevalence with 11.5 per 10,000 total births (95% CI: 9–14.1); on the other hand, the lowest prevalence of SIA was in Mexico‐Nuevo Leon with 0.5 per 10,000 births (95% CI: 0.3–0.8), and Cali‐Colombia had zero cases. In South America, a higher prevalence of SIA was estimated compared to what was reported in 2000. Most deaths occurred between Day 2 and 6, except in Bogotá‐Colombia, Spain, UK‐Wales, and Mexico, where the deaths occurred on Day 1. The mortality in the first year was 4.3%, but the specific causes of death were not determined in this study. Conclusion: The prevalence of SIA was about 2.1 per 10,000 births during a 41‐year period in 25 centers, with variations in prevalence according to geographical locations. Future research is suggested to analyze changes in trends and the impact of early diagnosis and treatment in mortality.

Background: Survival of individuals with congenital heart disease (CHD) has improved, leading to a growing and aging population of adults living with these conditions. Over their lifetime, they often face an array of comorbidities that affect outcomes and complicate medical management. However, population‐based information on such comorbidities is scarce, reducing opportunities for prevention. Methods: This population‐based, cross‐sectional study assessed comorbid conditions in adults with CHD residing in five geographic areas in the United States (in Colorado, Georgia, New York, North Carolina, and Utah). The study included 18,672 adults aged 19 to 64 years who had a healthcare encounter between 2011 and 2013 associated with ≥ 1 CHD‐related diagnosis code. Data were derived from linked clinical and administrative sources, reflecting inpatient, outpatient, and emergency department encounters. Results: Most adults with CHD experienced at least one (88.5%) and usually multiple (76%) comorbidities. Overall, noncardiac comorbidities exceeded cardiac comorbidities. The most frequent noncardiac comorbidities were endocrine/metabolic conditions (e.g., diabetes, hyperlipidemia, hypothyroidism), hypertension, and neuropsychiatric conditions (e.g., anxiety, depression). The presence and number of comorbidities varied in different sociodemographic groups. Men and older individuals experienced higher rates of many comorbidities, cardiac and noncardiac, regardless of CHD type. Conclusions: Preventable and treatable comorbidity and multimorbidity are common in adults with CHD, with patterns shaped by sociodemographic factors and CHD type. Reducing preventable mortality in this growing population will require sustained tracking of health metrics and coordinated, data‐driven, and lifelong care.

Background: Gastroschisis is a birth defect with the greatest risk among women n = 53 participated/57, 93%; controls: pregnant women without fetal abnormalities, n = 102 participated/120, 85%). A clinic coordinator consented and interviewed women and obtained a blood sample and prenatal medical records. We evaluated self‐reported maternal characteristics, risk factors, and infections. To assess pathogen seropositivity we used Serimmune's Serum Epitope Repertoire Analysis validated 35 pathogen panels and Chlamydia trachomatis and compared seropositivity to self‐report and prenatal medical record screening to assess sensitivity.Results: Cases were more likely to report a younger age at sexual debut (p = p = 0.02), being unmarried (p < 0.01), changing partners between pregnancies (p = p = 0.02). No differences were observed for self‐report of illicit drug use or periconceptional urinary tract infections. Cases had a higher seropositivity for cytomegalovirus (p = 0.01). No differences were observed for herpes simplex I, II, or Epstein–Barr. Though based on small numbers, C. trachomatis seropositivity was highest in cases (17%) compared to controls (8.8%) with the highest proportion observed in case women C. trachomatis seropositive women, self‐report and prenatal medical record sensitivity was 27.8% and 3%, respectively.Conclusions: Cases were more likely to engage in behaviors that can increase their risk of exposure to sexually transmitted pathogens. Case women C. trachomatis seropositivity and any STI. Prenatal medical records and self‐report were inadequate to identify a recent chlamydial infection whereas, the SERA assay is a novel approach for evaluating subclinical infections that may impact the developing embryo.

Background: The use of chlorine to treat drinking water produces disinfection by‐products (DBPs), which have been associated with congenital heart defects (CHDs) in some studies.Methods: Using National Birth Defects Prevention Study data, we linked geocoded residential addresses to public water supply measurement data for DBPs. Self‐reported water consumption and filtration methods were used to estimate maternal ingestion of DBPs. We estimated adjusted odds ratios and 95% confidence intervals using logistic regression controlling for maternal age, education, body mass index (BMI), race/ethnicity, and study site to examine associations between CHDs and both household DBP level and estimated ingestion of DBPs.Results: Household DBP exposure was assessed for 2717 participants (1495 cases and 1222 controls). We observed a broad range of positive, null, and negative estimates across eight specific CHDs and two summary exposures (trihalomethanes and haloacetic acids) plus nine individual DBP species. Examining ingestion exposure among 2488 participants (1347 cases, 1141 controls) produced similarly inconsistent results.Conclusions: Assessing both household DBP level and estimated ingestion of DBPs, we did not find strong evidence of an association between CHDs and DBPs. Despite a large study population, DBP measurements were available for less than half of participant addresses, limiting study power.

Background: Primary congenital glaucoma (PCG) affects approximately 1 in 10,000 live born infants in the United States (U.S.). PCG has a autosomal recessive inheritance pattern, and variable expressivity and reduced penetrance have been reported. Likely causal variants in the most commonly mutated gene, CYP1B1, are less prevalent in the U.S., suggesting that alternative genes may contribute to the condition. This study utilized exome sequencing to investigate the genetic architecture of PCG in the U.S. and to identify novel genes and variants.Methods: We studied 37 family trios where infants had PCG and were part of the National Birth Defects Prevention Study (births 1997–2011), a U.S. multicenter study of birth defects. Samples underwent exome sequencing and sequence reads were aligned to the human reference sample (NCBI build 37/hg19). Variant filtration was conducted under de novo and Mendelian inheritance models using GEMINI.Results: Among candidate variants, CYP1B1 was most represented (five trios, 13.5%). Twelve probands (32%) had potentially pathogenic variants in other genes not previously linked to PCG but important in eye development and/or to underlie Mendelian conditions with potential phenotypic overlap (e.g., CRYBB2, RXRA, GLI2).Conclusion: Variation in the genes identified in this population‐based study may help to further explain the genetics of PCG.

Background: Associations between maternal periconceptional exposure to disinfection by‐products (DBPs) in drinking water and neural tube defects (NTDs) in offspring are inconclusive, limited in part by exposure misclassification.Methods: Maternal interview reports of drinking water sources and consumption from the National Birth Defects Prevention Study were linked with DBP concentrations in public water system monitoring data for case children with an NTD and control children delivered during 2000–2005. DBPs analyzed were total trihalomethanes, the five most common haloacetic acids combined, and individual species. Associations were estimated for all NTDs combined and selected subtypes (spina bifida, anencephaly) with maternal periconceptional exposure to DBPs in public water systems and with average daily periconceptional ingestion of DBPs accounting for individual‐level consumption and filtration information. Mixed effects logistic regression models with maternal race/ethnicity and educational attainment at delivery as fixed effects and study site as a random intercept were applied.Results: Overall, 111 case and 649 control children were eligible for analyses. Adjusted odds ratios for maternal exposure to DBPs in public water systems ranged from 0.8–1.5 for all NTDs combined, 0.6–2.0 for spina bifida, and 0.7–1.9 for anencephaly; respective ranges for average daily maternal ingestion of DBPs were 0.7–1.1, 0.5–1.5, and 0.6–1.8. Several positive estimates (≥1.2) were observed, but all confidence intervals included the null.Conclusions: Using community‐ and individual‐level data from a large, US, population‐based, case–control study, we observed statistically nonsignificant associations between maternal periconceptional exposure to total and individual DBP species in drinking water and NTDs and subtypes.

Background: Socioeconomic factors may lead to a disproportionate impact on health care usage and death among individuals with congenital heart defects (CHD) by race, ethnicity, and socioeconomic factors. How neighborhood poverty affects racial and ethnic disparities in health care usage and death among individuals with CHD across the life span is not well described. Methods and Results: Individuals aged 1 to 64 years, with at least 1 CHD‐related International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD‐9‐CM ) code were identified from health care encounters between January 1, 2011, and December 31, 2013, from 4 US sites. Residence was classified into lower‐ or higher‐poverty neighborhoods on the basis of zip code tabulation area from the 2014 American Community Survey 5‐year estimates. Multivariable logistic regression models, adjusting for site, sex, CHD anatomic severity, and insurance‐evaluated associations between race and ethnicity, and health care usage and death, stratified by neighborhood poverty. Of 31 542 individuals, 22.2% were non‐Hispanic Black and 17.0% Hispanic. In high‐poverty neighborhoods, non‐Hispanic Black (44.4%) and Hispanic (47.7%) individuals, respectively, were more likely to be hospitalized (adjusted odds ratio [aOR], 1.2 [95% CI, 1.1–1.3]; and aOR, 1.3 [95% CI, 1.2–1.5]) and have emergency department visits (aOR, 1.3 [95% CI, 1.2–1.5] and aOR, 1.8 [95% CI, 1.5–2.0]) compared with non‐Hispanic White individuals. In high poverty neighborhoods, non‐Hispanic Black individuals with CHD had 1.7 times the odds of death compared with non‐Hispanic White individuals in high‐poverty neighborhoods (95% CI, 1.1–2.7). Racial and ethnic disparities in health care usage were similar in low‐poverty neighborhoods, but disparities in death were attenuated (aOR for non‐Hispanic Black, 1.2 [95% CI=0.9–1.7]). Conclusions: Racial and ethnic disparities in health care usage were found among individuals with CHD in low‐ and high‐poverty neighborhoods, but mortality disparities were larger in high‐poverty neighborhoods. Understanding individual‐ and community‐level social determinants of health, including access to health care, may help address racial and ethnic inequities in health care usage and death among individuals with CHD.

Background: Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population.Methods: We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe^{+ (includes Iran)}, Latin America, North America). Cases were identified using diagnostic codes (i.e., 756.7, 756.71, or Q79.3). We excluded cases of amniotic band syndrome, limb–body wall defect, and ruptured omphalocele. Programs provided annual counts for gastroschisis cases (live births, stillbirths, and legally permitted pregnancy terminations for fetal anomalies) and source population (live births, stillbirths), by maternal age.Results: Overall, gastroschisis occurred in 1 of every 3268 births (3.06 per 10,000 births; 95% confidence intervals [CI]: 3.01, 3.11), with marked regional variation. European⁺ prevalence was 1.49 (95%CI: 1.44, 1.55), Latin American 3.80 (95%CI: 3.69, 3.92) and North American 4.32 (95%CI: 4.22, 4.42). A statistically significant increasing time trend was observed among six European⁺, four Latin American, and four North American programs. Women <20 years of age had the highest prevalence in all programs except the Slovak Republic.Conclusions: Gastroschisis prevalence increased over time in 61% of participating programs, and the highest increase in prevalence was observed among the youngest women. Additional inquiry will help to assess the impact of the changing maternal age proportions in the birth population on gastroschisis prevalence.

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.