Renata H. Benjamin

Background: The preterm birth rate among infants with trisomy 21 is more than twice the rate among the general population. Maternal hypertension and diabetes are established risk factors for preterm birth in the general population; however, their impact on pregnancies of infants with trisomy 21 is unknown. This study aimed to evaluate the association between maternal hypertensive disorders/diabetes and preterm birth among infants with trisomy 21. Methods: We utilized data from the Texas Birth Defects Registry for deliveries between 1999 and 2018 ( n = 9355). We conducted Poisson regression to estimate crude and adjusted risk ratios for preterm birth associated with any maternal hypertension and any diabetes, and their subtypes (pregestational, gestational). We also evaluated the risk associated with exposure to both (co‐occurring) conditions compared to neither. Stratified analyses were conducted by racial/ethnic subgroups, preterm subtypes (< 32 weeks and 32–36 weeks), and presence/absence of congenital heart defects as part of secondary analyses. Results: We found that maternal hypertension and diabetes were associated with 50% and 21% higher risk for preterm birth, respectively, while the presence of both conditions versus neither was associated with a 71% higher risk. The association with hypertension was much stronger for delivery at < 32 weeks aRR 2.60 (95% CI 1.83, 3.70) than for delivery at 32–36 weeks aRR 1.46 (95% CI 1.28, 1.66). Conclusions: Our findings shed light on the role of maternal hypertension and diabetes in preterm birth risk among infants with trisomy 21, particularly when both conditions co‐occur and for extremely to very preterm birth.

Background: Epidemiologic data on the association between maternal fish intake and birth defects are sparse. Our objective was to assess associations between maternal fish intake and 52 different birth defects, most of which have not been assessed previously. Methods: Using logistic regression, data was analyzed for 29,242 mothers of infants with birth defects and 10,973 mothers of control infants who participated in the National Birth Defects Prevention Study (NBDPS) and delivered between 1997 and 2011. We focused on associations between mothers who reported high fish intake of 2 or more servings of fish per week for the year prior to conception versus those who reported little or no fish intake and 52 birth defects. Each birth defect was analyzed separately. Results: Among control mothers, 13.9% reported high fish intake and 31.3% reported eating very little or no fish. High fish intake was associated with lower odds of 9 birth defects (isolated heterotaxia, double outlet right ventricle transposition of the great arteries, total anomalous pulmonary venous return, Dandy Walker syndrome, holoprosencephaly, choanal atresia, cleft palate, craniosynostosis, and gastroschisis) with adjusted odds ratios (aORs) ranging from 0.32 to 0.83. An elevated association with high fish intake was observed for one birth defect (tricuspid atresia, aOR = 1.76; 95% CI 1.07, 2.89). Conclusion: Based on our findings, consumption of 2 or more servings of fish per week may help to prevent certain types of birth defects. This conclusion is similar to the existing FDA (Food and Drug Administration) recommendation that women who are or can become pregnant should consume 2–3 servings of low mercury seafood per week. A large majority of pregnant women in this US (United States) based study did not meet the FDA recommendations for fish intake, suggesting that many of them may have benefited from increasing their consumption of seafood.

Background: Residing in socioeconomically vulnerable areas is known to be associated with increased preterm birth (PTB) risk in the general population. However, the relationship between social vulnerability and PTB remains unexplored among infants with trisomy 21, who experience more than twice the PTB rate of the general population. Objectives: The primary objective was to examine the association between maternal socioeconomic vulnerability, as measured by the SVI, and PTB among infants with trisomy 21. Methods: We conducted a retrospective cohort study among infants with trisomy 21 born in Texas (1999–2018). We examined the association between neighbourhood vulnerability, measured by Social Vulnerability Index (SVI) quartiles, and PTB utilising data from the Texas Birth Defects Registry. Using Poisson regression, we estimated crude and adjusted risk ratios (RRs) and 95% confidence intervals (CIs), accounting for maternal demographic characteristics and health factors. Results: Of the 8823 eligible infants included in the analysis, 2269 (25.7%) were born preterm. Maternal residence in the highest vulnerability quartile was associated with an increased risk of PTB (RR 1.17, 95% CI 1.04, 1.32) and moderate to late PTB (RR 1.19, 95% CI 1.05, 1.35), compared to the least vulnerable quartile. In secondary analyses stratified by race/ethnicity, the association with high vulnerability was particularly strong among non‐Hispanic Black women (RR 1.44, 95% CI 1.00, 2.07). Conclusions: These findings underscore the importance of neighbourhood social vulnerability in influencing perinatal health risks, particularly PTB among infants with trisomy 21.

Background: We sought to assess the extent to which folic acid supplementation and dietary folate intake are associated with preterm delivery among infants with spina bifida. Methods: We conducted a retrospective population‐based study using the National Birth Defects Prevention Study (NBDPS; 1999–2011) and the Birth Defects Study To Evaluate Pregnancy exposureS (BD‐STEPS; 2014–2019). We utilized robust Poisson regression to calculate the risk ratio (RR) and 95% confidence interval (CI) for the associations between preterm birth (< 37 weeks) and maternal use of folic acid‐containing supplements, dietary folate intake quartile, and a combined variable accounting for supplementation and dietary folate status. Results: Among 1199 infants with spina bifida (1011 in NBDPS, 188 in BD‐STEPS), 217 (18.1%) were born preterm. There were no statistically significant associations between preterm birth and lack of supplementation (RR 1.24, 95% CI: 0.92–1.69) or maternal dietary folate intake quartile (RRs 1.12–1.39). The combination of lack of supplementation and low dietary folate intake had the strongest association with preterm birth (RR 1.73, 95% CI: 1.01–2.96), compared to women who took supplements and had higher dietary folate intake. Conclusions: Our findings suggest a modestly elevated risk of preterm birth among infants with spina bifida born to women with the combination of no supplementation and low dietary folate intake. Future work confirming these findings and further investigating the timing of supplementation could help elucidate whether low folate intake is a risk factor for preterm birth in spina bifida–affected pregnancies.

The rate of preterm birth among infants with trisomy 21 (22%) is around twice that among the general population (10%). We conducted a descriptive epidemiologic study to address the gap in knowledge on what maternal and infant factors are associated with preterm birth among infants with trisomy 21. Singleton infants with trisomy 21 born between 1999 and 2018 were identified from the Texas Birth Defects Registry. We used multivariable logistic regression to assess associations between preterm birth and 14 maternal and infant characteristics. Statistically significant associations were observed between preterm birth and maternal race/ethnicity, maternal age, maternal birthplace, prenatal care, smoking, infant sex, and infant delivery year. For instance, preterm birth was associated with maternal age (adjusted odds ratio [aOR] 1.44, 95% CI: 1.23–1.70 for ≥ 40 vs. 25–29 years) and prenatal care (aOR 1.59, 95% CI: 1.25–2.03 for no care versus any care). Our findings contribute toward a better understanding of the risk profile of preterm birth among infants with trisomy 21 and can guide further research on risk factors and potential interventions for reducing preterm birth rates in this population.

Background: Coloboma is a rare congenital malformation in which part of the tissue that makes up the eye is missing and may cause visual impairment or blindness. Little is known about the epidemiology of this condition. Therefore, we obtained data from the Texas Birth Defects Registry on children identified with coloboma for the period 1999–2014.Methods: Using information on all live births from the same period, prevalence ratios (PRs) for selected demographic and clinical factors were used to estimate associations using Poisson regression among cases with coloboma. Coloboma cases were divided into subgroups to explore patterns of co‐occurring defects and syndromes. All variables significant in unadjusted models (p < 0.05) were included in multivariable models to evaluate adjusted PRs (aPRs).Results: We identified 1587 cases with coloboma, of whom 934 (58.8%) were nonsyndromic, and 474 (29.9%) were isolated. When considering all identified cases, factors associated with significant differences in prevalence included plurality (multiple vs. singleton aPR = 1.4, 95% CI: 1.1–1.8); maternal education (college or greater vs. less than high school aPR = 0.7, 95% CI: 0.6–0.9); maternal race/ethnicity (Hispanic vs. non‐Hispanic White aPR = 0.9, 95% CI: 0.8–1.0); and maternal diabetes (yes vs. no aPR = 1.3, 95% CI: 1.0–1.6). There was a notable increase in the birth prevalence of coloboma during the study period (p‐for‐trend < 0.001). Effect estimates were similar across the different subgroups.Conclusion: In our large population, we identified several factors associated with the prevalence of coloboma. These findings may help define subgroups of women more likely to have children affected by coloboma, which could inform improved screening efforts.

Introduction: Traditional strategies for grouping congenital heart defects (CHDs) using birth defect registry data do not adequately address differences in expected clinical consequences between different combinations of CHDs. We report a lesion‐specific classification system for birth defect registry–based outcome studies.Methods: For Core Cardiac Lesion Outcome Classifications (C‐CLOC) groups, common CHDs expected to have reasonable clinical homogeneity were defined. Criteria based on combinations of Centers for Disease and Control‐modified British Pediatric Association (BPA) codes were defined for each C‐CLOC group. To demonstrate proof of concept and retention of reasonable case counts within C‐CLOC groups, Texas Birth Defect Registry data (1999–2017 deliveries) were used to compare case counts and neonatal mortality between traditional vs. C‐CLOC classification approaches.Results: C‐CLOC defined 59 CHD groups among 62,262 infants with CHDs. Classifying cases into the single, mutually exclusive C‐CLOC group reflecting the highest complexity CHD present reduced case counts among lower complexity lesions (e.g., 86.5% of cases with a common atrium BPA code were reclassified to a higher complexity group for a co‐occurring CHD). As expected, C‐CLOC groups had retained larger sample sizes (i.e., representing presumably better‐powered analytic groups) compared to cases with only one CHD code and no occurring CHDs.Discussion: This new CHD classification system for investigators using birth defect registry data, C‐CLOC, is expected to balance clinical outcome homogeneity in analytic groups while maintaining sufficiently large case counts within categories, thus improving power for CHD‐specific outcome association comparisons. Future outcome studies utilizing C‐CLOC‐based classifications are planned.

Objective: To compare maternal demographics based on occupation coding status and evaluate potential bias by excluding manually coded occupations. Methods: This case-control study assessed cases with clefts obtained from the Texas Birth Defects Registry. The NIOSH Industry and Occupation Computerized Coding System automatically coded occupations, with manual coding for unclassified cases. Maternal demographics were tabulated by occupation coding status (manual vs. automatic). Logistic regression examined associations between major occupation groups and clefts. Results: Automatic coding covered over 90% of all mothers. Building, grounds cleaning, and maintenance occupations, and office and administrative support occupations were significantly associated with cleft lip with or without cleft palate, even after excluding manually coded occupations. Conclusion: We found consistent associations before and after excluding manually coded data for most comparisons, suggesting that machine learning can facilitate occupation-related birth defects research.

Epidemiologic studies of birth defects often conduct separate analyses for cases that have isolated defects (e.g., spina bifida only) and cases that have multiple defects (e.g., spina bifida and a congenital heart defect). However, in some instances, cases with additional defects (e.g., spina bifida and clubfoot) may be more appropriately considered as isolated because the co‐occurring defect (clubfoot) is believed to be developmentally related to the defect of interest. Determining which combinations should be considered isolated can be challenging and potentially resource intensive for registries. Thus, we developed automated classification procedures for differentiating between isolated versus multiple defects, while accounting for developmentally related defects, and applied the approach to data from the Texas Birth Defects Registry (1999–2018 deliveries). Among 235,544 nonsyndromic cases in Texas, 89% of cases were classified as having isolated defects, with proportions ranging from 25% to 92% across 43 specific defects analyzed. A large proportion of isolated cases with spina bifida (44%), lower limb reduction defects (44%), and holoprosencephaly (32%) had developmentally related defects. Overall, our findings strongly support the need to account for isolated versus multiple defects in risk factor association analyses and to account for developmentally related defects when doing so, which has implications for interpreting prior studies.