Direct potable reuse and birth defects prevalence in Texas: An augmented synthetic control method analysis of data from a population-based birth defects registry.

Background: Direct potable reuse (DPR) involves adding purified wastewater that has not passed through an environmental buffer into a water distribution system. DPR may help address water shortages and is approved or is under consideration as a source of drinking water for several water-stressed population centers in the United States, however, there are no studies of health outcomes in populations who receive DPR drinking water. Our objective was to determine whether the introduction of DPR for certain public water systems in Texas was associated with changes in birth defect prevalence. Methods: We obtained data on maternal characteristics for all live births and birth defects cases regardless of pregnancy outcome in Texas from 2003 to 2017 from the Texas Birth Defects Registry and birth and fetal death records. The ridge augmented synthetic control method was used to model changes in birth defect prevalence (per 10,000 live births) following the adoption of DPR by four Texas counties in mid-2013, with county-level data on maternal age, percent women without a high school diploma, percent who identified as Hispanic/Latina or non-Hispanic/Latina Black, and rural-urban continuum code as covariates. Results: There were nonstatistically significant increases in prevalence of all birth defects collectively (average treatment effect in the treated = 53.6) and congenital heart disease (average treatment effect in the treated = 287.3) since June 2013. The estimated prevalence of neural tube defects was unchanged. Conclusions: We estimated nonstatistically significant increases in birth defect prevalence following the implementation of DPR in four West Texas counties. Further research is warranted to inform water policy decisions.

An epidemiologic study of penoscrotal transposition by maternal characteristics using data from the Texas birth defects registry.

BACKGROUND: Penoscrotal transposition (PST) is an uncommon urogenital malformation in which the penis is mal-positioned to be inferior to the scrotum. The purpose of this study was to explore PST risk by maternal characteristics and to describe co-occurring congenital abnormalities in the Texas Birth Defects Registry (TBDR). METHODS: We conducted a population-based descriptive study examining occurrence of PST in the TBDR between 1999 and 2019. The primary outcome variable was PST diagnosis during infancy. Descriptive variables included maternal age, education, and race/ethnicity. Prevalence ratios (PRs) were calculated within each maternal variable category using Poisson regression. Counts and percentages of cases with select co-occurring congenital abnormalities were also calculated. RESULTS: Overall, 251 infants had PST, providing a prevalence of 0.61/10,000 live male births (95% CI: 0.53-0.68). PST prevalence was significantly lower among infants of mothers who had lower educational attainment (high school), who were younger (<25 vs. 25-34), and who were Hispanic (vs. non-Hispanic White) and was significantly higher among older mothers (35+ vs. 25-39). Hypospadias was the most common co-occurring genitourinary anomaly, affecting close to 70% of cases. CONCLUSIONS: To our knowledge, this is the first investigation exploring the prevalence of PST in a population-based birth defects registry. Our findings help to understand the risk for PST among select maternal demographic characteristics and may assist in generating hypotheses about the underlying etiology of this condition for future work.

Pediatric cancer incidence among individuals with overgrowth syndromes and overgrowth features: A population-based assessment in seven million children.

BACKGROUND: Overgrowth syndromes (e.g., Beckwith-Wiedemann) are associated with an increased risk of pediatric cancer, although there are few population-based estimates of risk. There are also limited studies describing associations between other overgrowth features (e.g., hepatosplenomegaly) and pediatric cancer. Therefore, cancer risk among children with these conditions was evaluated with data from a large, diverse population-based registry linkage study. METHODS: This study includes all live births in Texas during the years 1999-2017. Children with overgrowth features and syndromes were identified from the Texas Birth Defects Registry; children with cancer were identified by linkage to the Texas Cancer Registry. Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between each overgrowth syndrome/feature and cancer, which were adjusted for infant sex and maternal age. RESULTS: In the total birth cohort (n = 6,997,422), 21,207 children were identified as having an overgrowth syndrome or feature. Children with Beckwith-Wiedemann syndrome were 42 times more likely to develop pediatric cancer (95% CI, 24.20-71.83), with hepatoblastoma being the most common, followed by Wilms tumor. The presence of any isolated overgrowth feature was associated with increased cancer risk (HR, 4.70; 95% CI, 3.83-5.77); associations were strongest for hepatosplenomegaly (HR, 23.04; 95% CI, 13.37-39.69) and macroglossia (HR, 11.18; 95% CI, 6.35-19.70). CONCLUSIONS: This population-based assessment confirmed prior findings that children with either overgrowth syndromes or features were significantly more likely to develop cancer. Overall, this study supports recommendations for cancer surveillance in children with these conditions and may also inform future research into cancer etiology.

Prevalence of congenital anomalies according to maternal race and ethnicity, Texas, 1999-2018.

BACKGROUND: Few studies of congenital anomalies provide prevalence estimates stratified by maternal race/ethnicity. We sought to determine whether the prevalence of a broad spectrum of anomalies varies among offspring of women from different race/ethnic groups. METHODS: We obtained information on cases with anomalies from the population-based Texas Birth Defects Registry, and denominator data on livebirths among Texas residents during 1999-2018 from the Texas Center for Health Statistics. We estimated the prevalence ratio (PR) and 95% confidence interval (CI) of N = 145 anomalies among offspring of Hispanic and non-Hispanic Black relative to non-Hispanic White women using Poisson regression, adjusting for maternal age, education, body mass index, and previous livebirths. We performed a two-stage analysis with a Bonferroni-adjusted p < 1.7 × 10-4 in the initial screening phase to identify anomalies with statistically significant variation. RESULTS: There were 7,698,768 livebirths and 1,187,385 anomalies diagnosed in 368,393 cases. The prevalence of any monitored congenital anomaly was similar among offspring of non-Hispanic White (referent), non-Hispanic Black (PR 0.98, CI 0.96-1.00), and Hispanic (PR 0.95, CI 0.93-0.96) women. We observed statistically significant racial/ethnic variation for 42 anomalies. Marked differences were observed when comparing offspring of non-Hispanic Black to non-Hispanic White women with respect to polydactyly (PR 4.38, CI 4.07-4.72), pyloric stenosis (PR 0.34, CI 0.29-0.40), and aortic valve atresia/stenosis (PR 0.51, CI 0.36-0.72). CONCLUSIONS: Birth prevalence of many major congenital anomalies varies by maternal race and ethnicity. While the reasons for these differences are likely multifactorial, a thorough understanding of racial and ethnic disparities is useful to stimulate etiologic research.

Racial and ethnic differences in infant survival for hydrocephaly-Texas, 1999-2017.

BACKGROUND: Congenital hydrocephaly, an abnormal accumulation of fluid within the ventricular spaces at birth, can cause disability or death if untreated. Limited information is available about survival of infants born with hydrocephaly in Texas. Therefore, the purpose of the study was to calculate survival estimates among infants born with hydrocephaly without spina bifida in Texas. METHODS: A cohort of live-born infants delivered during 1999-2017 with congenital hydrocephaly without spina bifida was identified from the Texas Birth Defects Registry. Deaths within 1 year of delivery were identified using vital and medical records. One-year infant survival estimates were generated for multiple descriptive characteristics using the Kaplan-Meier method. Crude hazard ratios (HRs) for one-year survival among infants with congenital hydrocephaly by maternal and infant characteristics and adjusted HRs for maternal race and ethnicity were estimated using Cox proportional hazard models. RESULTS: Among 5709 infants born with congenital hydrocephaly without spina bifida, 4681 (82%) survived the first year. The following characteristics were associated with infant survival: maternal race and ethnicity, clinical classification (e.g., chromosomal or syndromic), preterm birth, birth weight, birth year, and maternal education. In the multivariable Cox proportional hazards model, differences in survival were observed by maternal race and ethnicity after adjustment for other maternal and infant characteristics. Infants of non-Hispanic Black (HR: 1.28, 95% CI: 1.04-1.58) and Hispanic (HR: 1.31, 95% CI: 1.12-1.54) women had increased risk for mortality, compared with infants of non-Hispanic White women. CONCLUSIONS: This study showed infant survival among a Texas cohort differed by maternal race and ethnicity, clinical classification, gestational age, birth weight, birth year, and maternal education in infants with congenital hydrocephaly without spina bifida. Findings confirm that mortality continues to be common among infants with hydrocephaly without spina bifida. Additional research is needed to identify other risk factors of mortality risk.

Survival of neonates, infants, and children with birth defects: a population-based study in Texas, 1999-2018.

Background: Birth defects are a leading cause of neonatal, infant, and childhood mortality, but recent population-based survival estimates for a spectrum in the U.S. are lacking. Methods: Using the statewide Texas Birth Defects Registry (1999-2017 births) and vital records linkage to ascertain deaths, we conducted Kaplan-Meier analyses to estimate survival probabilities at 1, 7, and 28 days, and 1, 5, and 10 years. We evaluated survival in the full cohort of infants with any major defect and for 30 specific conditions. One-year survival analyses were stratified by gestational age, birth year, and case classification. Findings: Among 246,394 live-born infants with any major defect, the estimated survival probabilities were 98.9% at 1 day, 95.0% at 1 year, and 93.9% at 10 years. Ten-year survival varied by condition, ranging from 36.9% for holoprosencephaly to 99.3% for pyloric stenosis. One-year survival was associated with increasing gestational age (e.g., increasing from 46.9% at <28 weeks to 95.8% at ≥37 weeks for spina bifida). One-year survival increased in more recent birth years for several defect categories (e.g., increasing from 86.0% among 1999-2004 births to 93.1% among 2014-2017 births for unilateral renal agenesis/dysgenesis) and was higher among infants with an isolated defect versus those with multiple defects. Interpretation: This study describes short- and long-term survival outcomes from one of the largest population-based birth defect registries in the world and highlights improved survival over time for several conditions. Our results may lend insight into future healthcare initiatives aimed at reducing mortality in this population. Funding: This study was funded in part by a Centers for Disease Control and Prevention (CDC) birth defects surveillance cooperative agreement with the Texas Department of State Health Services and Health Resources and Services Administration (HRSA) Block Grant funds.

Neighborhood Deprivation and Neural Tube Defects.

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.

Are individual-level risk factors for gastroschisis modified by neighborhood-level socioeconomic factors?

BACKGROUND: Two strong risk factors for gastroschisis are young maternal age (<20 years) and low/normal pre-pregnancy body mass index (BMI), yet the reasons remain unknown. We explored whether neighborhood-level socioeconomic position (nSEP) during pregnancy modified these associations. METHODS: We analyzed data from 1269 gastroschisis cases and 10,217 controls in the National Birth Defects Prevention Study (1997-2011). To characterize nSEP, we applied the neighborhood deprivation index and used generalized estimating equations to calculate odds ratios and relative excess risk due to interaction. RESULTS: Elevated odds of gastroschisis were consistently associated with young maternal age and low/normal BMI, regardless of nSEP. High-deprivation neighborhoods modified the association with young maternal age. Infants of young mothers in high-deprivation areas had lower odds of gastroschisis (adjusted odds ratio [aOR]: 3.1, 95% confidence interval [CI]: 2.6, 3.8) than young mothers in low-deprivation areas (aOR: 6.6; 95% CI: 4.6, 9.4). Mothers of low/normal BMI had approximately twice the odds of having an infant with gastroschisis compared to mothers with overweight/obese BMI, regardless of nSEP (aOR range: 1.5-2.3). CONCLUSION: Our findings suggest nSEP modified the association between gastroschisis and maternal age, but not BMI. Further research could clarify whether the modification is due to unidentified biologic and/or non-biologic factors.

Associations between birth defects with neural crest cell origins and pediatric embryonal tumors.

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins. METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal tumors included neuroblastoma, nephroblastoma, and hepatoblastoma. Potential HR modification (HRM) was investigated by infant sex, maternal race/ethnicity, maternal age, and maternal education. RESULTS: The risk of embryonal tumors among those with BDNCOs was 0.09% (co-occurring n = 105) compared to 0.03% (95% CI, 0.03%-0.04%) among those without a birth defect. Children with BDNCOs were 4.2 times (95% CI, 3.5-5.1 times) as likely to be diagnosed with an embryonal tumor compared to children born without a birth defect. BDNCOs were strongly associated with hepatoblastoma (HR, 16.1; 95% CI, 11.3-22.9), and the HRs for neuroblastoma (3.1; 95% CI, 2.3-4.2) and nephroblastoma (2.9; 95% CI, 1.9-4.4) were elevated. There was no notable HRM by the aforementioned factors. CONCLUSIONS: Children with BDNCOs are more likely to develop embryonal tumors compared to children without a birth defect. Disruptions of shared developmental pathways may contribute to both phenotypes, which could inform future genomic assessments and cancer surveillance strategies of these conditions.

Sunspot activity and birth defects among Texas births (1999-2016).

BACKGROUND: Building on findings that linked higher levels of sunspot (SS) activity with a range of health and adverse birth outcomes, we sought to understand how SS activity over a 17-year time period may be correlated with the occurrence of birth defects. METHODS: Data from the Texas Birth Defects Registry, vital events from the Texas Center for Health Statistics, and mean monthly numbers of sunspots from the National Oceanic and Atmospheric Administration were utilized. Poisson regression was used to calculate crude/adjusted prevalence ratios (cPRs/aPRs) and 95% confidence intervals for three quartiles (Q) of increasing SS activity (compared to a referent of low activity) and 44 birth defects (31 non-cardiac; 13 cardiac) with estimated dates of conception from 1998 to 2016. RESULTS: We found moderately protective aPRs (range: 0.60-0.89) in a little over half of the case groups examined in our quartiles of higher SS activity (19 non-cardiac; 6 cardiac), after adjusting for maternal age, race/ethnicity, and education. Particularly protective aPRs in the highest SS quartiles (Q3-4) were noted for: anophthalmia, cataract, gastroschisis, trisomy 18, ventricular septal defects, atrial septal defects, and pulmonary valve atresia or stenosis. Conversely, modestly elevated aPRs were noted for two defect groups (agenesis, aplasia, and hypoplasia of the lung and microcephaly [Q2-3]). Following an additional adjustment of year of conception, results remained similar although many of the estimates were attenuated. CONCLUSION: The seemingly protective associations between increasing SS activity may be an artifact of increasing spontaneous abortions that occur following conception during these periods of heightened SS activity.

Prevalence and descriptive epidemiology of Turner syndrome in the United States, 2000-2017: A report from the National Birth Defects Prevention Network.

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.

Neighborhood-level Socioeconomic Position During Early Pregnancy and Risk of Gastroschisis.

BACKGROUND: Neighborhood-level socioeconomic position has been shown to influence birth outcomes, including selected birth defects. This study examines the un derstudied association between neighborhood-level socioeconomic position during early pregnancy and the risk of gastroschisis, an abdominal birth defect of increasing prevalence. METHODS: We conducted a case-control study of 1,269 gastroschisis cases and 10,217 controls using data from the National Birth Defects Prevention Study (1997-2011). To characterize neighborhood-level socioeconomic position, we conducted a principal component analysis to construct two indices-Neighborhood Deprivation Index (NDI) and Neighborhood Socioeconomic Position Index (nSEPI). We created neighborhood-level indices using census socioeconomic indicators corresponding to census tracts associated with addresses where mothers lived the longest during the periconceptional period. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with multiple imputations for missing data and adjustment for maternal race-ethnicity, household income, education, birth year, and duration of residence. RESULTS: Mothers residing in moderate (NDI Tertile 2 aOR = 1.23; 95% CI = 1.03, 1.48 and nSEPI Tertile 2 aOR = 1.24; 95% CI = 1.04, 1.49) or low socioeconomic neighborhoods (NDI Tertile 3 aOR = 1.28; 95% CI = 1.05, 1.55 and nSEPI Tertile 3 aOR = 1.32, 95% CI = 1.09, 1.61) were more likely to deliver an infant with gastroschisis compared with mothers residing in high socioeconomic neighborhoods. CONCLUSIONS: Our findings suggest that lower neighborhood-level socioeconomic position during early pregnancy is associated with elevated odds of gastroschisis. Additional epidemiologic studies may aid in confirming this finding and evaluating potential mechanisms linking neighborhood-level socioeconomic factors and gastroschisis.

Patterns of co-occurring birth defects in children with anotia and microtia.

Many infants with anotia or microtia (A/M) have co-occurring birth defects, although few receive syndromic diagnoses in the perinatal period. Evaluation of co-occurring birth defects in children with A/M could identify patterns indicative of undiagnosed/unrecognized syndromes. We obtained information on co-occurring birth defects among infants with A/M for delivery years 1999-2014 from the Texas Birth Defects Registry. We calculated observed-to-expected ratios (OER) to identify birth defect combinations that occurred more often than expected by chance. We excluded children diagnosed with genetic or chromosomal syndromes from analyses. Birth defects and syndromes/associations diagnosed ≤1 year of age were considered. We identified 1310 infants with non-syndromic A/M, of whom 38% (N = 492) were diagnosed with co-occurring major defects. Top combinations included: hydrocephalus, ventricular septal defect, and spinal anomalies (OER 58.4); microphthalmia and anomalies of the aorta (OER 55.4); and cleft lip with or without cleft palate and rib or sternum anomalies (OER 32.8). Some combinations observed in our study may represent undiagnosed/atypical presentations of known A/M associations or syndromes, or novel syndromes yet to be described in the literature. Careful evaluation of infants with multiple birth defects including A/M is warranted to identify individuals with potential genetic or chromosomal syndromes.

Factors associated with nonsyndromic anotia and microtia, Texas, 1999-2014.

BACKGROUND: Few risk factors have been identified for nonsyndromic anotia/microtia (A/M). METHODS: We obtained data on cases and a reference population of all livebirths in Texas for 1999-2014 from the Texas Birth Defects Registry (TBDR) and Texas vital records. We estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) for A/M (any, isolated, nonisolated, unilateral, and bilateral) using Poisson regression. We evaluated trends in prevalence rates using Joinpoint regression. RESULTS: We identified 1,322 cases, of whom 982 (74.3%) had isolated and 1,175 (88.9%) had unilateral A/M. Prevalence was increased among males (PR: 1.3, 95% CI: 1.2-1.4), offspring of women with less than high school education (PR: 1.3, 95% CI: 1.1-1.5), diabetes (PR: 2.0, 95% CI: 1.6-2.4), or age 30-39 versus 20-29 years (PR: 1.2, 95% CI: 1.0-1.3). The prevalence was decreased among offspring of non-Hispanic Black versus White women (PR: 0.6, 95% CI: 0.4-0.8) but increased among offspring of Hispanic women (PR: 2.9, 95% CI: 2.5-3.4) and non-Hispanic women of other races (PR: 1.7, 95% CI: 1.3-2.3). We observed similar results among cases with isolated and unilateral A/M. Sex disparities were not evident for nonisolated or bilateral phenotypes, nor did birth prevalence differ between offspring of non-Hispanic Black and non-Hispanic White women. Maternal diabetes was more strongly associated with nonisolated (PR: 4.5, 95% CI: 3.2-6.4) and bilateral A/M (PR: 5.0, 95% CI: 3.3-7.7). Crude prevalence rates increased throughout the study period (annual percent change: 1.82). CONCLUSION: We identified differences in the prevalence of nonsyndromic A/M by maternal race/ethnicity, education, and age, which may be indicators of unidentified social/environmental risk factors.

Connecting children with birth defects to health and social service programs: A collaboration between the Texas Birth Defects Registry and agency social workers.

BACKGROUND: Timely referral to services for children born with birth defects can improve health outcomes. Birth defects surveillance registries may be a valuable data source for connecting children to health and social service programs. METHODS: Population-based, state-wide data from the Texas Birth Defects Registry (TBDR) at the Texas Department of State Health Services (DSHS) were used to connect children 9-18 months old, born with select birth defects with DSHS social workers. The social workers reviewed developmental milestones and referred children and their families to various health and social service programs. We tabulated the proportions of children meeting milestones and referral characteristics by referral program type and type of birth defect. RESULTS: Social workers reached 67% (909/1,362) of identified families. Over half of children (54%, 488/909) were not meeting the developmental milestones for their age. Social workers provided over 3,000 program referrals, including referring 21% (194/909) of children to Early Childhood Intervention (ECI) and 28% (257/909) to case management. CONCLUSION: Our results illustrate a method of leveraging a birth defects surveillance system for referral services. Given the large number of referrals made, our findings suggest that birth defects registries can be a valuable source of data for referring children to programs.

Neural Tube Defects in Pregnancies Among Women With Diagnosed HIV Infection - 15 Jurisdictions, 2013-2017.

In May 2018, a study of birth defects in infants born to women with diagnosed human immunodeficiency virus (HIV) infection in Botswana reported an eightfold increased risk for neural tube defects (NTDs) among births with periconceptional exposure to antiretroviral therapy (ART) that included the integrase inhibitor dolutegravir (DTG) compared with other ART regimens (1). The World Health Organization* (WHO) and the U.S. Department of Health and Human Services† (HHS) promptly issued interim guidance limiting the initiation of DTG during early pregnancy and in women of childbearing age with HIV who desire pregnancy or are sexually active and not using effective contraception. On the basis of additional data, WHO now recommends DTG as a preferred treatment option for all populations, including women of childbearing age and pregnant women. Similarly, the U.S. recommendations currently state that DTG is a preferred antiretroviral drug throughout pregnancy (with provider-patient counseling) and as an alternative antiretroviral drug in women who are trying to conceive.§ Since 1981 and 1994, CDC has supported separate surveillance programs for HIV/acquired immunodeficiency syndrome (AIDS) (2) and birth defects (3) in state health departments. These two surveillance programs can inform public health programs and policy, linkage to care, and research activities. Because birth defects surveillance programs do not collect HIV status, and HIV surveillance programs do not routinely collect data on occurrence of birth defects, the related data have not been used by CDC to characterize birth defects in births to women with HIV. Data from these two programs were linked to estimate overall prevalence of NTDs and prevalence of NTDs in HIV-exposed pregnancies during 2013-2017 for 15 participating jurisdictions. Prevalence of NTDs in pregnancies among women with diagnosed HIV infection was 7.0 per 10,000 live births, similar to that among the general population in these 15 jurisdictions, and the U.S. estimate based on data from 24 states. Successful linking of data from birth defects and HIV/AIDS surveillance programs for pregnancies among women with diagnosed HIV infection suggests that similar data linkages might be used to characterize possible associations between maternal diseases or maternal use of medications, such as integrase strand transfer inhibitors used to manage HIV, and pregnancy outcomes. Although no difference in NTD prevalence in HIV-exposed pregnancies was found, data on the use of integrase strand transfer inhibitors in pregnancy are needed to understand the safety and risks of these drugs during pregnancy.

Likelihood of meeting defined VATER/VACTERL phenotype in infants with esophageal atresia with or without tracheoesophageal fistula.

Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is a foregut defect that is a major component of the VATER/VACTERL association. The specific diagnostic criteria for the VATER/VACTERL association phenotype have changed over time. The current definition is presence of at least three of the following: Vertebral defects, Anal atresia, Cardiac defects, TE fistula, or Renal and Limb anomalies in the absence of a specific genetic diagnosis. Using the Texas Birth Defect Registry, 1,175 cases of EA+/-TEF (174 EA; 1,001 EA + TEF) were evaluated against strict definitions of VATER/VACTERL. Nine (5.2%) cases of EA alone and 164 (16.3%) cases of EA + TEF met criteria for a diagnosis of VATER; and 20 (11.5%) and 223 (22.2%), respectively, met criteria for VACTERL. Trisomy 21, Trisomy 18, 22q11 deletion, and CHARGE were the most common syndromic diagnoses. About 88.5% (154) cases of EA and 77.8% (778) cases of EA + TEF were likely not to meet the criteria for VACTERL. EA+/-TEF is more likely to be an isolated defect or part of a multiple malformation syndrome in a pattern other than VACTERL, than be part of the defined association. This study reinforces the need to consider broader evaluation for alternate diagnoses in the presence of these defects.

Understanding how the concentration of neighborhood advantage and disadvantage affects spina bifida risk among births to non-Hispanic white and Hispanic women, Texas, 1999-2014.

BACKGROUND: This is the first study to utilize the index of concentration at the extremes (ICE) to examine risk factors for spina bifida in Texas. The ICE is a useful measure for providing the degree to which residents in a certain area are concentrated into groups at the extremes of disadvantage and privilege. We introduce two novel ICE measures (language and nativity), and three existing ICE measures (race/ethnicity, income, and education), which we applied specifically to Texas residents. METHODS: We used multivariable mixed-model Poisson regression analyses to estimate spina bifida birth prevalence and prevalence ratios among singleton live births in Texas, 1999-2014, for each of our ICE measures. Maternal census tract at delivery was included in the models as a random effect. Analyses were stratified by maternal race/ethnicity (Hispanics and non-Hispanic whites). Live births served as denominators for each category. RESULTS: Among non-Hispanic white women, those in the most disadvantaged versus the advantaged census tract quintile had adjusted relative risk between 1.6 and 8.5 for having a baby affected by spina bifida. However, Hispanic women in the most disadvantaged versus advantaged census tract quintile for four ICE measures had a 33% to 87% lower risk of having an affected pregnancy. CONCLUSIONS: Findings suggest spina bifida risk is associated with neighborhood disadvantage or advantage, and that relationship seems to vary by race-ethnicity. The varied associations between ICE measures and spina bifida by race/ethnicity highlights the importance of using targeted interventions in the prevention of spina bifida.

Pre-Zika descriptive epidemiology of microcephaly in Texas, 2008-2012.

BACKGROUND: There are limited population-based studies on microcephaly. We characterized the epidemiology of microcephaly in Texas during a 5-year period (2008-2012), prior to the Zika epidemic in the Western hemisphere (2015). The associations of suspected risk factors were compared across four clearly defined case groups. METHODS: Data from the Texas Birth Defects Registry were used to calculate the prevalence of congenital microcephaly and crude and adjusted prevalence ratios using Poisson regression. Twelve maternal and infant factors were assessed across case groups, which included total (explained + unexplained), explained (e.g., syndromic), unexplained, and severe unexplained microcephaly (head circumference <3rd percentile). RESULTS: The birth prevalence for total and total severe microcephaly were 14.7 and 4.8 per 10,000 livebirths, respectively. For explained and unexplained cases, significantly elevated risks were noted for mothers who were older (35+), less educated (≤12 years), diabetic (pre-pregnancy or gestational), or had a preterm delivery. Unlike explained cases, however, mothers who were non-White or smoked had an increased risk for unexplained microcephaly. Furthermore, young maternal age (<20), multiparity, and higher BMI reduced the risk for unexplained microcephaly. For severe unexplained cases, the risk profile was similar to that for all unexplained cases-with the exception of null associations noted for diabetes and birth year. CONCLUSIONS: We found that risk patterns for microcephaly varied across case groupings. Risk factors included maternal race/ethnicity, age, and smoking during pregnancy. Among severe unexplained cases, notable positive associations were seen among mothers who were non-Hispanic Black or less educated, while inverse associations were noted for obesity.