Clinton J. Alverson

Maternal Smoking and Congenital Heart Defects in the Baltimore-Washington Infant Study

OBJECTIVE: We investigated associations between maternal cigarette smoking during the first trimester and the risk of congenital heart defects (CHDs) among the infants. METHODS: The Baltimore-Washington Infant Study was the first population-based case-control study of CHDs conducted in the United States. Case and control infants were enrolled during the period 1981–1989. We excluded mothers with overt pregestational diabetes and case mothers whose infants had noncardiac anomalies (with the exception of atrioventricular septal defects with Down syndrome) from the analysis, which resulted in 2525 case and 3435 control infants. Self-reported first-trimester maternal cigarette consumption was ascertained via an in-person interview after delivery. Associations for 26 different groups of CHDs with maternal cigarette consumption were estimated by using logistic regression models. Odds ratios (ORs) corresponded to a 20-cigarette-per-day increase in consumption. RESULTS: We observed statistically significant positive associations between self-reported first-trimester maternal cigarette consumption and the risk of secundum-type atrial septal defects (OR: 1.36 [95% confidence interval (CI): 1.04–1.78]), right ventricular outflow tract defects (OR: 1.32 [95% CI: 1.06–1.65]), pulmonary valve stenosis (OR: 1.35 [95% CI: 1.05–1.74]), truncus arteriosus (OR: 1.90 [95% CI: 1.04–3.45]), and levo-transposition of the great arteries (OR: 1.79 [95% CI: 1.04–3.10]). A suggestive association was observed for atrioventricular septal defects among infants without Down syndrome (OR: 1.50 [95% CI: 0.99–2.29]). CONCLUSIONS: These findings add to the existing body of evidence that implicates first-trimester maternal cigarette smoking as a modest risk factor for select CHD phenotypes.

Are Encephaloceles Neural Tube Defects

OBJECTIVE. Encephalocele is classified as a neural tube defect, but questions have been raised regarding whether its epidemiological characteristics are similar to those of other neural tube defects. DESIGN. We compared characteristics of temporal trends in, and the impact of folic acid grain fortification on, the prevalence of encephalocele, spina bifida, and anencephaly using data from the Metropolitan Atlanta Congenital Defects Program, a population-based birth defects surveillance system. Prevalences of encephalocele, spina bifida, and anencephaly were compared by maternal age, gender, race, birth weight, ascertainment period (1968–1981, 1982–1993, or 1994–2002), and fortification period (1994–1996 [prefortification] and 1998–2002 [postfortification]) using prevalence ratios with 95% confidence intervals. Temporal trends were assessed using Poisson and negative binomial regression models. RESULTS. Prevalence rates of encephalocele (n = 167), spina bifida (n = 650), and anencephaly (n = 431) were 1.4, 5.5, and 3.7 per 10 000 live births, respectively. Encephalocele was similar to anencephaly in showing an increased prevalence among girls and multiple gestation pregnancies and to spina bifida and anencephaly in an annual prevalence decrease between 1968 and 2002 (−1.2% for encephalocele, −4.2% for spina bifida, and −3.6% for anencephaly). With fortification, prevalence decreased for spina bifida but not significantly for encephalocele or anencephaly. CONCLUSIONS. Encephalocele shows more similarities to spina bifida or anencephaly than it shows differences with respect to characteristics, temporal trend, and impact of fortification. Additional studies should be done to explore the etiologic heterogeneity of encephalocele using better markers of folate status and a wider range of risk factors.

Selected birth defects data from population-based birth defects surveillance programs in the United States, 2006 to 2010: Featuring trisomy conditions

The annual National Birth Defects Prevention Network (NBDPN) Congenital Malformations Surveillance Report includes state-level data on major birth defects (i.e., conditions present at birth that cause adverse structural changes in one or more parts of the body) and a directory of population-based birth defects surveillance systems in the United States. Beginning in 2012, these annually updated data and directory information are available in an electronic format accompanied by a data brief. This year’s report includes data from 41 population-based birth defects surveillance programs and a data brief highlighting the more common trisomy conditions (i.e., disorders characterized by an additional chromosome): trisomy 21 (commonly referred to as Down syndrome), trisomy 18, and trisomy 13. State-Specific Data Collection and Presentation for Selected Birth Defects Data collection The NBDPN Data Committee, in collaboration with the Centers for Disease Control and Prevention (CDC), invited population-based birth defects surveillance programs in the United States to submit data on major birth defects affecting central nervous, eye, ear, cardiovascular, orofacial, gastrointestinal, genitourinary, and musculoskeletal systems, as well as trisomies, amniotic bands, and fetal alcohol syndrome. Table 1 lists these 47 conditions and their diagnostic codes (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM]; and Centers for Disease Control and Prevention/British Pediatric Association Classification of Diseases [CDC/BPA]). Table 1 ICD-9-CM and CDC/BPA Codes for 47 Birth Defects Reported in the NBDPN Annual Report Participating state birth defects programs provided counts of all cases of the birth defects listed in Table 1 as well as counts of live births and male live births in their catchment areas for births occurring from January 1, 2006 through December 31, 2010. The cases for all defects were reported by maternal census race/ethnic categories: White non-Hispanic, Black/African-American non-Hispanic, Hispanic, Asian/Pacific Islander non-Hispanic, American Indian/Alaska Native non-Hispanic. Additionally, trisomy cases were provided by six categories of maternal age at delivery: less than 20 years, 20 to 24 years, 25 to 29 years, 30 to 34 years, 35 to 39 years, and 40+ years.

The Association Between Race/Ethnicity and Major Birth Defects in the United States, 1999–2007

OBJECTIVES We investigated the relationship between race/ethnicity and 27 major birth defects. METHODS We pooled data from 12 population-based birth defects surveillance systems in the United States that included 13.5 million live births (1 of 3 of US births) from 1999 to 2007. Using Poisson regression, we calculated prevalence estimates for each birth defect and 13 racial/ethnic groupings, along with crude and adjusted prevalence ratios (aPRs). Non-Hispanic Whites served as the referent group. RESULTS American Indians/Alaska Natives had a significantly higher and 50% or greater prevalence for 7 conditions (aPR = 3.97; 95% confidence interval [CI] = 2.89, 5.44 for anotia or microtia); aPRs of 1.5 to 2.1 for cleft lip, trisomy 18, and encephalocele, and lower, upper, and any limb deficiency). Cubans and Asians, especially Chinese and Asian Indians, had either significantly lower or similar prevalences of these defects compared with non-Hispanic Whites, with the exception of anotia or microtia among Chinese (aPR = 2.08; 95% CI = 1.30, 3.33) and Filipinos (aPR = 1.90; 95% CI = 1.10, 3.30) and tetralogy of Fallot among Vietnamese (aPR = 1.60; 95% CI = 1.11, 2.32). CONCLUSIONS This is the largest population-based study to our knowledge to systematically examine the prevalence of a range of major birth defects across many racial/ethnic groups, including Asian and Hispanic subgroups. The relatively high prevalence of birth defects in American Indians/Alaska Natives warrants further attention.

Congenital Heart Defects and Major Structural Noncardiac Anomalies, Atlanta, Georgia, 1968 to 2005

OBJECTIVE To identify the proportion of major structural noncardiac anomalies identified with congenital heart defects (CHDs). STUDY DESIGN Records of infants with CHDs in the Metropolitan Atlanta Congenital Defects Program who were born during the period 1968 through 2005 were classified as having isolated, syndromic, multiple CHD (ie, having an unrecognized pattern of multiple congenital anomalies or a recognized pattern of multiple congenital anomalies of unknown etiology), or laterality defects. Frequencies of associated noncardiac anomalies were obtained. RESULTS We identified 7984 live-born and stillborn infants and fetuses with CHDs. Among them, 5695 (71.3%) had isolated, 1080 (13.5%) had multiple, 1048 (13.1%) had syndromic, and 161 (2.0%) had laterality defects. The percentage of multiple congenital anomalies was highest for case with atrial septal defects (18.5%), cardiac looping defects (17.2%), and conotruncal defects (16.0%), and cases with atrioventricular septal defects represented the highest percentages of those with syndromic CHDs (66.7%). CONCLUSIONS Including those with syndromes and laterality defects, 28.7% of case infants with CHDs had associated major noncardiac malformations. Thus, infants with CHDs warrant careful examination for the presence of noncardiac anomalies.

Racial/ethnic variations in the prevalence of selected major birth defects, metropolitan Atlanta, 1994-2005.

Objectives. Birth defects are the leading cause of infant mortality and are responsible for substantial child and adult morbidity. Documenting the variation in prevalence of birth defects among racial/ethnic subpopulations is critical for assessing possible variations in diagnosis, case ascertainment, or risk factors among such groups. Methods. We used data from the Metropolitan Atlanta Congenital Defects Program, a population-based birth defects registry with active case ascertainment. We estimated the racial/ethnic variation in prevalence of 46 selected major birth defects among live births, stillbirths, and pregnancy terminations at >20 weeks gestation among mothers residing in the five central counties of metropolitan Atlanta between 1994 and 2005, adjusting for infant sex, maternal age, gravidity, and socioeconomic status (SES). We also explored SES as a potential effect measure modifier. Results. Compared with births to non-Hispanic white women, births to non-Hispanic black women had a significantly higher prevalence of five birth defects and a significantly lower prevalence of 10 birth defects, while births to Hispanic women had a significantly higher prevalence of four birth defects and a significantly lower prevalence of six birth defects. The racial/ethnic disparities in the prevalence of some defects varied by SES, but no clear pattern emerged. Conclusions. Racial/ethnic disparities were suggested in 57% of included birth defects. Disparities in the prevalence of birth defects may result from different underlying genetic susceptibilities; exposure to risk factors; or variability in case diagnosis, ascertainment, or reporting among the subpopulations examined. Policies that improve early diagnosis of birth defects could reduce associated morbidity and mortality.

Use of Spline Regression in an Analysis of Maternal Prepregnancy Body Mass Index and Adverse Birth Outcomes: Does It Tell Us More Than We Already Know?

PURPOSE Categorical analyses of prepregnancy body mass index (BMI) have shown that maternal overweight and obesity are associated with adverse pregnancy outcomes. It is unclear whether further insight into these associations can be gained from spline regression. METHODS We used spline regression to examine the relations between prepregnancy BMI and five adverse pregnancy outcomes in the Baltimore-Washington Infant Study, a case-control study of congenital cardiac defects. Analyses included 3,226 singleton live-born control infants delivered 1981 through 1989. We modeled BMI using (a) traditional categories of underweight, average weight, overweight, and obese and (b) restricted quadratic splines. RESULTS We confirmed that overweight status and obesity were associated with increased risk of macrosomia and large for gestational age. For these outcomes, splines provided detail about the associations at the ends of the BMI distribution and within the average BMI category. Spline analyses also showed that underweight status was associated with increased risk of preterm delivery. CONCLUSIONS Analyses of traditional categories of BMI provide good understanding of the associations with several adverse birth outcomes. For three outcomes, modeling with splines provided additional insight regarding dose-response relations within categories. Results suggest the need for further analyses of average BMI and adverse pregnancy outcomes.

Neural tube defects in Latin America and the impact of fortification: A literature review

OBJECTIVE Data on the prevalence of birth defects and neural tube defects (NTD) in Latin America are limited. The present review summarizes NTD prevalence and time trends in Latin American countries and compares pre- and post-fortification periods to assess the impact of folic acid fortification in these countries. DESIGN We carried out a literature review of studies and institutional reports published between 1990 and 2010 that contained information on NTD prevalence in Latin America. RESULTS NTD prevalence in Latin American countries varied from 0·2 to 9·6 per 1000 live births and was influenced by methods of ascertainment. Time trends from Bogota, Costa Rica, Dominican Republic, Guatemala City, Mexico and Puerto Rico showed average annual declines of 2·5 % to 21·8 %. Pre- and post-fortification comparisons were available for Argentina, Brazil, Chile, Costa Rica, Puerto Rico and Mexico. The aggregate percentage decline in NTD prevalence ranged from 33 % to 59 %. CONCLUSIONS The present publication is the first to review data on time trends and the impact of folic acid fortification on NTD prevalence in Latin America. Reported NTD prevalence varied markedly by geographic region and in some areas of Latin America was among the lowest in the world, while in other areas it was among the highest. For countries with available information, time trends showed significant declines in NTD prevalence and these declines were greater in countries where folic acid fortification of staples reached the majority of the population at risk, such as Chile and Costa Rica.

Sex Differences in COPD and Lung Cancer Mortality Trends—United States, 1968–1999

PURPOSE Cigarette smoking by U.S. women in the 1940s and 1950s caused large increases in smoking-related lung disease among women. To determine the magnitude of these increases, we compared the mortality trends for males and females in the United States for chronic obstructive pulmonary disease (COPD) and lung cancer for 1968-1999. METHODS We used the national mortality data files compiled by the National Center for Health Statistics of the CDC and U.S. census data to calculate age-adjusted (2000) death rates for COPD, lung cancer, and all causes. RESULTS COPD death rate for females increased by 382% from 1968 through 1999, whereas for males it increased by 27% during the same period. As a result, the COPD death rate for U.S. females is approaching that for males. The lung cancer death rate for females increased by 266% from 1968 to 1999, whereas for males, it increased by 15%. CONCLUSIONS Physicians, women, and groups interested in womens health issues need to be aware of these trends and target prevention strategies toward females.

Population-based microcephaly surveillance in the United States, 2009 to 2013: An analysis of potential sources of variation

BACKGROUND Congenital microcephaly has been linked to maternal Zika virus infection. However, ascertaining infants diagnosed with microcephaly can be challenging. METHODS Thirty birth defects surveillance programs provided data on infants diagnosed with microcephaly born 2009 to 2013. The pooled prevalence of microcephaly per 10,000 live births was estimated overall and by maternal/infant characteristics. Variation in prevalence was examined across case finding methods. Nine programs provided data on head circumference and conditions potentially contributing to microcephaly. RESULTS The pooled prevalence of microcephaly was 8.7 per 10,000 live births. Median prevalence (per 10,000 live births) was similar among programs using active (6.7) and passive (6.6) methods; the interdecile range of prevalence estimates was wider among programs using passive methods for all race/ethnicity categories except Hispanic. Prevalence (per 10,000 live births) was lowest among non-Hispanic Whites (6.5) and highest among non-Hispanic Blacks and Hispanics (11.2 and 11.9, respectively); estimates followed a U-shaped distribution by maternal age with the highest prevalence among mothers <20 years (11.5) and ≥40 years (13.2). For gestational age and birth weight, the highest prevalence was among infants <32 weeks gestation and infants <1500 gm. Case definitions varied; 41.8% of cases had an HC ≥ the 10th percentile for sex and gestational age. CONCLUSION Differences in methods, population distribution of maternal/infant characteristics, and case definitions for microcephaly can contribute to the wide range of observed prevalence estimates across individual birth defects surveillance programs. Addressing these factors in the setting of Zika virus infection can improve the quality of prevalence estimates. Birth Defects Research (Part A) 106:972-982, 2016.