Tunu A. Ramadhani

Control Selection and Participation in an Ongoing, Population-based, Case-Control Study of Birth Defects The National Birth Defects Prevention Study

To evaluate the representativeness of controls in an ongoing, population-based, case-control study of birth defects in 10 centers across the United States, researchers compared 1997-2003 birth certificate data linked to selected controls (n = 6,681) and control participants (n = 4,395) with those from their base populations (n = 2,468,697). Researchers analyzed differences in population characteristics (e.g., percentage of births at > or =2,500 g) for each group. Compared with their base populations, control participants did not differ in distributions of maternal or paternal age, previous livebirths, maternal smoking, or diabetes, but they did differ in other maternal (i.e., race/ethnicity, education, entry into prenatal care) and infant (i.e., birth weight, gestational age, and plurality) characteristics. Differences in distributions of maternal, but not infant, characteristics were associated with participation by selected controls. Absolute differences in infant characteristics for the base population versus control participants were < or =1.3 percentage points. Differences in infant characteristics were greater at centers that selected controls from hospitals compared with centers that selected controls from electronic birth certificates. These findings suggest that control participants in the National Birth Defects Prevention Study generally are representative of their base populations. Hospital-based control selection may slightly underascertain infants affected by certain adverse birth outcomes.

The prevalence and predictors of anencephaly and spina bifida in Texas

Texas shares a 1255-mile border with Mexico and encompasses a variety of ecosystems, industries and other potential environmental exposures. The Texas Birth Defects Registry is an active surveillance system which covers all pregnancy outcomes (livebirths, fetal deaths and elective pregnancy terminations). This study describes the occurrence and the predictors of neural tube defects (anencephaly and spina bifida) in Texas between 1999 and 2003. Birth prevalence, crude and adjusted prevalence ratios and 95% confidence intervals were calculated using Poisson regression, for each defect, by fetal/infant sex, delivery year and maternal sociodemographic characteristics. Among approximately 1.8 million livebirths, a total of 1157 neural tube defects cases were ascertained by the Registry, resulting in an overall prevalence of 6.33 cases per 10 000 livebirths. The prevalences of anencephaly and spina bifida were 2.81 and 3.52 per 10 000 livebirths respectively. Prevalences of both defects were highest in Hispanics, among mothers living along the border with Mexico, among women of higher parity and among mothers who were 40+ years of age. In addition, the prevalence of each defect was higher among women with no record of prenatal care and among women with less than 7 years of education. Hispanic ethnicity was an important predictor for anencephaly, along with sex, maternal age, parity and border residence. However, only border residence and delivery year were significant predictors for spina bifida.

Use of Oral Contraceptives in Pregnancy and Major Structural Birth Defects in Offspring

Background: Oral contraceptives (OCs) are the most commonly used reversible contraceptive method among US women. Although the majority of previous studies have reported no association between OC use during pregnancy and birth defects, some studies have reported increased occurrence of neural tube defects, limb reduction defects, and urinary tract anomalies. Methods: We assessed OC use among mothers who participated in the multisite, case-control, National Birth Defects Prevention Study. Mothers of 9986 infants with 32 types of birth defects and 4000 infants without birth defects were included. Results: Maternal OC use during the first 3 months of pregnancy was associated with an increased odds ratio for 2 of 32 birth defects: hypoplastic left heart syndrome (adjusted odds ratio = 2.3 [95% confidence interval = 1.3–4.3) and gastroschisis (1.8 [1.3–2.7]). Conclusion: Previous reports of associations between OC use and specific types of anomalies were not corroborated. Given that associations were assessed for 32 types of birth defects, our findings of 2 increased associations between OC use and gastroschisis and hypoplastic left heart syndrome should be interpreted as hypotheses until they can be evaluated further. Overall, our findings are consistent with the majority of previous studies that found women who use OCs during early pregnancy have no increased risk for most types of major congenital malformations.

Spina bifida subtypes and sub‐phenotypes by maternal race/ethnicity in the National Birth Defects Prevention Study

Spina bifida refers to a collection of neural tube defects, including myelomeningocele, meningocele, and myelocele (SBM), as well as lipomyelomeningocele and lipomeningocele (SBL). Maternal race/ethnicity has been associated with an increased risk for spina bifida among offspring. To better understand this relationship, we evaluated different spina bifida subtypes (SBM vs. SBL) and sub‐phenotypes (anatomic level or presence of additional malformations) by maternal race/ethnicity using data from the National Birth Defects Prevention Study. This study is a large, multisite, population‐based study of nonsyndromic birth defects. Prevalence estimates were obtained using data from spina bifida cases (live births, fetal deaths, and elective terminations) and total live births in the study regions. From October 1997 through December 2005, 1,046 infants/fetuses with spina bifida were delivered, yielding a prevalence of 3.06 per 10,000 live births. Differences in the prevalences of SBM vs. SBL, isolated versus non‐isolated SBM, and lesion level in isolated SBM among case offspring were observed by maternal race/ethnicity. Compared to non‐Hispanic (NH) White mothers, offspring of Hispanic mothers had higher prevalences of each subtype and most sub‐phenotypes, while offspring of NH Black mothers generally had lower prevalences. Furthermore, differences in race/ethnicity among those with isolated SBM were more pronounced by sex. For instance, among male offspring, the prevalence of isolated SBM was significantly higher for those with Hispanic mothers compared to NH White mothers [prevalence ratio (PR): 1.55, 95% confidence interval: 1.23–1.95]. These findings provide evidence that certain spina bifida subtypes and sub‐phenotypes may be etiologically distinct.

Maternal use of hot tub and major structural birth defects

BACKGROUND Previous studies on the associations between hot tub use during early pregnancy and birth defects have found an increased risk of neural tube defects, but no increase in risk of cardiac defects. No previous studies have assessed the association between maternal hot tub use and other types of noncardiac birth defects. METHODS We included mothers of infants with birth defects (n = 10,825) and mothers of infants without birth defects (n = 6795) who participated in the multisite National Birth Defects Prevention Study between 1997 and 2005. Odds ratios were adjusted for maternal ethnicity and education. RESULTS Analysis of 17 birth defects revealed that mothers of infants with gastroschisis and anencephaly were significantly more likely to report any use of a hot tub in early pregnancy: adjusted odd ratios were 1.54 (95% confidence interval [CI], 1.10-2.17) and 1.68 (95% CI, 1.05-2.70), respectively. Among the mothers who reported using a hot tub more than once in the exposure period and remaining in it for more than 30 min, we found significantly elevated odds ratios (≥2.0) for esophageal atresia, omphalocele, and gastroschisis and a nonsignificant elevation (≥2.0) for spina bifida and anencephaly. CONCLUSIONS These results suggest that women who use hot tubs more than once during early pregnancy and for long periods of time have an increased risk of certain birth defect phenotypes, particularly anencephaly and gastroschisis. Because of multiple statistical tests and small sample sizes, we cannot exclude the possibility that some of these elevated associations may be due to chance.

Maternal smoking, passive tobacco smoke, and neural tube defects.

BACKGROUND Although cigarette smoke is a well-established toxin and harmful to the developing embryo, the evidence for an independent effect on the occurrence of neural tube defects (NTDs) is mixed. In this study, we examined the relation between NTDs and maternal exposures to cigarette smoke, including passive smoke exposure. METHODS We used cases and controls from the large, multistate, population-based National Birth Defects Prevention Study. A total of 1041 NTD cases and 5862 live birth controls, delivered during 1997 to 2004, were available for analyses. Mothers were interviewed by telephone between 6 weeks and 24 months after delivery. Participation rates were 71% for NTD case mothers and 69% for control mothers. RESULTS Compared with nonsmokers (and also not exposed to passive cigarette smoke), mothers exposed only to passive smoke had an increased NTD odds ratio (OR, 1.7; 95% confidence interval [CI], 1.4-2.0), adjusted for race-ethnicity, and study center. There was no increased OR for mothers who actively smoked 24 or fewer cigarettes per day. Mothers who smoked 25 or more cigarettes per day had an elevated OR (OR, 1.6; 95% CI, 0.9-3.0), but the OR adjusted for race-ethnicity, and center was compatible with the null. CONCLUSION Results suggest that maternal exposure to passive smoke is associated with NTDs. Women who plan on becoming pregnant should minimize their exposure to passive smoke and refrain from smoking.

Epidemiology of nonsyndromic conotruncal heart defects in Texas, 1999–2004

INTRODUCTION Congenital heart defects (CHDs) are the most common structural birth defects, yet their etiology is poorly understood. As there is heterogeneity within the group of CHDs, epidemiologic studies often focus on subgroups, of conditions, such as conotruncal heart defects (CTDs). However, even within these subgroups there may be etiologic heterogeneity. The aim of the present study was to identify and compare maternal and infant characteristics associated with three CTDs: truncus arteriosus (TA), dextro-transposition of the great arteries (d-TGA), and tetralogy of Fallot (TOF). METHODS Data for cases with nonsyndromic TA (n = 78), d-TGA (n = 438), and TOF (n = 529) from the Texas Birth Defects Registry, 1999-2004, were used to estimate crude and adjusted prevalence ratios, separately for each condition, using Poisson regression. Polytomous logistic regression was used to determine whether the observed associations were similar across the two largest case groups (d-TGA and TOF). RESULTS In Texas, 1999-2004, the prevalence of nonsyndromic TA, d-TGA, and TOF was 0.35, 1.98, and 2.40 per 10,000 live births, respectively. There was evidence of a significant linear increase in the risk of each condition with advancing maternal age (p < 0.01). Significant associations were observed for TA and maternal residence on the Texas-Mexico border; d-TGA and infant sex, maternal race/ethnicity, history of previous live birth, and birth year; and TOF and maternal race/ethnicity and education. Further, the associations with some, but not all, of the study variables were significantly different for d-TGA and TOF. CONCLUSION These findings add to our limited understanding of the epidemiology of CTDs.

Awareness and attitudes regarding prenatal testing among Texas women of childbearing age

Despite increased visibility and availability of prenatal testing procedures, very little is known about the attitudes among the populace toward these procedures. Using a computer assisted telephone interview of pregnant and non-pregnant women of childbearing age we analyze awareness and attitudes regarding prenatal tests among a diverse group of women of childbearing age in Texas. We also examine maternal characteristics associated with awareness and the willingness to undergo these procedures. While 89% were aware that such tests are available, younger, black and less educated women were less likely to know about prenatal tests for birth defects. Seventy-two percent of respondents said they would want their baby tested while Hispanic and black women were significantly more likely to express an interest than non-Hispanic whites. This study demonstrates the variability of knowledge and beliefs and confirms the importance of taking time to understand an individual’s personal beliefs, knowledge and attitudes about prenatal diagnosis.

Importance of including all pregnancy outcomes to reduce bias in epidemiologic studies of neural tube defects—Texas, 1999 to 2005†

BACKGROUND Neural tube defects (NTDs) often result in fetal death or elective termination; therefore, not all cases are captured in typical hospital-based surveillance. We examined sociodemographic differences among pregnancy outcomes to assess sources of bias in NTD surveillance and research. METHODS We used 1999 to 2005 Texas Birth Defects Registry data, a population-based active surveillance system, and calculated crude and adjusted prevalence ratios (aPRs). We then assessed the association of anencephaly and spina bifida with the selected characteristics, stratified by pregnancy outcomes (fetal death, elective termination, or live birth). RESULTS Data were available for 1852 NTD cases (anencephaly, 677; spina bifida, 954; and encephalocele, 221), resulting in 1211 live births, 236 fetal deaths, and 405 elective terminations. For both anencephaly and spina bifida, a significant excess of Hispanic mothers was observed among live-birth cases (aPRs=1.2-2.4), but not among mothers experiencing other pregnancy outcomes. Mothers of anencephaly cases resulting in a non-live birth were more likely to be adolescents (aPRs=2.4-2.7 for ages<20 years old vs. ages 25-29 years old), but this pattern was not observed for live-birth cases. A trend of increasing anencephaly risk with increasing parity was demonstrated only among fetal-death cases. For spina bifida, mothers of fetal-death (but not live-birth) cases were less likely to live along the Texas-Mexico border (aPR=0.30). CONCLUSIONS Demographic differences across NTD pregnancy outcomes exist and are a potential source of bias. Inclusion of all pregnancy outcomes in NTD surveillance is vital in NTD monitoring and research.

Do foreign‐ and U.S.‐born mothers across racial/ethnic groups have a similar risk profile for selected sociodemographic and periconceptional factors?

BACKGROUND We examined differences in selected pregnancy-related risk factors, including maternal sociodemographic characteristics, health-related conditions, and periconceptional behavioral factors, among foreign-born versus U.S.-born control mothers across race/ethnic groups. METHODS We used data from the National Birth Defects Prevention Study, and calculated odds ratios (ORs) and 95% confidence intervals (CIs) of the risk factors, for foreign-born Hispanic, non-Hispanic white, non-Hispanic black, and Asian/Pacific Islander (API) mothers, compared to their U.S.-born counterparts. RESULTS Across all race/ethnic groups, foreign-born mothers were older and had lower odds of obesity compared to their U.S.-born counterparts. With the exception of foreign-born black mothers, foreign-born mothers from other race/ethnic groups had significantly lower odds of binge drinking during the periconceptional period. Compared to U.S.-born, foreign-born Hispanic mothers had twice the odds of gestational diabetes (OR = 2.23; 95% CI = 1.36-3.66). Certain health behaviors were less prevalent in foreign-born black mothers (e.g., folic acid use; OR = 0.54; 95% CI = 0.31-0.96) and foreign-born API mothers (e.g., cigarette smoking; OR = 0.10; 95% CI = 0.02-0.48). CONCLUSIONS Significant differences in pregnancy related risk factors during the periconceptional period and throughout pregnancy were observed between maternal nativity groups and across race/ethnicity. Prevention efforts for both prepregnancy and after conception should be designed and delivered according to maternal nativity for each racial/ethnic group.