Sex differences in birth defects: a study of opposite-sex twins

BACKGROUND: Sex differences in structural birth defects are often confounded by environmental risk factors. Opposite-sex twins provide a unique model for detecting sex differences in birth defects while maximally controlling environmental risk factors in a natural setting. METHODS: Population data from the Florida Birth Defects Registry were analyzed. A total of 4,768 pairs of twins who were discordant for sex and born between 1996 and 2001 were analyzed. The McNemar test was used to compare the differences between a male twin and his twin sister for the risk of developing specific defects and organ-system defects. RESULTS: Of 4,768 twin pairs, 225 males (4.72%) and 175 females (3.67%) had birth defects. Among opposite-sex twin pairs, males had a 29% higher risk for birth defects than their twin sisters. Compared to their twin sisters, males had a 5.4 times higher risk for pyloric stenosis and a 2.4 times higher risk for obstructive genitourinary defect, but only one-tenth the risk for congenital hip dislocation. CONCLUSIONS: Sex differences in birth defects exist between opposite-sex twins.     

Congenital malformation in twins.

Data from the population-based Metropolitan Atlanta Congenital Defects Program (MACDP) show that the overall rate of malformed infants, as well as the incidence of several specific defects, is higher for twins than for singletons. This elevated risk appears limited to same sex twins and, hence, is probably related to monozygosity. In addition to an 18-fold increase in risk of fetal death compared to singletons, twins have almost a 50% greater likelihood of congenital malformation.     

Cocaine and single ventricle: a population study.

A recent case report by Shepard et al. (Teratology 43:113-117, 1991) suggested that single ventricle may result from maternal cocaine ingestion by inducing coronary occlusion in the developing fetal heart. We used data from the Atlanta Birth Defects Case-Control Study and the Metropolitan Atlanta Congenital Defects Program (MACDP) to investigate the role of maternal cocaine ingestion in the induction of single ventricles. We identified through the MACDP 58 case infants with a single ventricle, 27 who were study subjects in the Atlanta Birth Defects Case-Control Study, and 31 who were not. We conducted a case-control study with the 27 Atlanta Birth Defects Case Control Study infants, frequency-matched to control infants by race, hospital of birth, and calendar quarter of birth. None of the 27 case infants were exposed to cocaine during early pregnancy, but 7 (0.43%) of the control infants were exposed during early pregnancy. Using MACDP data, we conducted an analysis of trends for prevalence of single ventricle in the metropolitan area. No upward trend in single ventricle was detected for 1968 through 1990. Our data suggest that even if maternal cocaine ingestion during pregnancy is a cause of single ventricle, most cases appear to be unrelated to this exposure.     

Sex differences in the prevalence of congenital anomalies: a population-based study

BACKGROUND: Limited data is available concerning the sex distribution of various congenital anomaly subtypes. This study investigated sex differences in the prevalence of congenital anomalies, overall and by subtype, using high quality population‐based data from the North of England. METHODS: Information on congenital anomalies occurring among singleton pregnancies during 1985–2003 were extracted from the Northern Congenital Abnormality Survey (NorCAS). Anomalies were categorized by groups, subtypes, and syndromes according to the European Surveillance of Congenital Anomalies guidelines. Relative risks (RRs) comparing the prevalences in males to that in females were calculated for a range of congenital anomaly subtypes. RESULTS: A total of 12,795 eligible cases of congenital anomaly were identified during the study period, including 7019 (54.9%) males and 5776 (45.1%) females. Overall, male fetuses were significantly more prevalent in pregnancies affected by a congenital anomaly than female fetuses (RR, male vs. female = 1.15; 95% confidence interval [CI], 1.11–1.19), but there was significant heterogeneity between subtypes (p < 0.001). Forty‐four of 110 (40%) unique subtypes were at least 40% more prevalent in males than females, with affected subtypes occurring across all major anomaly groups. Thirteen of 110 (12%) unique subtypes were at least 40% more prevalent in females than males, but the female‐biased RR of a neural tube defect was less pronounced than previously reported (RR = 0.84; 95% CI, 0.73–0.95). CONCLUSION:This study adds to the growing evidence of sex‐specific differences in the prevalence of a wide range of congenital anomaly subtypes. Birth Defects Research (Part A), 2011. © 2011 Wiley‐Liss, Inc.     

Maternal age and non‐chromosomal birth defects,Atlanta—1968–2000: Teenager or thirty‐something,who is at risk?

OBJECTIVE: This investigation explored the association between maternal age and non-chromosomal birth defects to assess any increased risk associated with maternal age. METHODS: Birth defect cases were ascertained by the Metropolitan Atlanta Congenital Defects Program (MACDP), denominator information was obtained using birth certificate data. Infants with any chromosomal diagnosis were excluded. Effect estimates were calculated using 5-year maternal age categories with 25-29 years as the referent. Multiple logistic regression was used to adjust for maternal race, parity, infant sex, and birth year. RESULTS: A total of 1,050,616 singleton infants, born after > or = 20 weeks gestation in the five counties of metropolitan Atlanta from 1968 through 2000 who did not have a chromosomal abnormality and whose mother was 14 to 40 years old, were included in the analyses, 32,816 of them were identified with birth defects by the MACDP. Young maternal age (14-19 years) was associated with anencephaly (OR = 1.81, 95% CI = 1.30-2.52), hydrocephaly without neural tube defect (OR = 1.56, 95% CI = 1.23-1.96), all ear defects (OR = 1.28, 95% CI = 1.10-1.49), cleft lip (OR = 1.88, 95% CI = 1.30-2.73), female genital defects (OR = 1.57, 95% CI = 1.12-2.19), hydronephrosis (OR = 1.42, 95% CI = 1.11-1.82), polydactyly (OR = 1.29, 95% CI = 1.09-1.52), omphalocele (OR = 2.08, 95% CI = 1.39-3.12), and gastroschisis (OR = 7.18, 95% CI = 4.39-11.75). Advanced maternal age (35-40 years) was associated with all heart defects (OR = 1.12, 95% CI = 1.03-1.22), tricuspid atresia (OR = 1.24, 95% CI = 1.02-1.50), right outflow tract defects (OR = 1.28, 95% CI = 1.10-1.49), hypospadias 2nd degree or higher (OR = 1.85, 95% CI = 1.33-2.58), male genital defects excluding hypospadias (OR = 1.25, 95% CI = 1.08-1.45) and craniosynostosis (OR = 1.65, 95% CI = 1.18-2.30). CONCLUSIONS: Young and advanced maternal ages are associated with different types of birth defects. Underlying causes for these associations are not clear.     

Birth defects prevalence among infants of Persian Gulf War veterans born in Hawaii, 1989-1993

BACKGROUND: Gulf War veterans (GWVs) have expressed concern about possible teratogenic exposures. However, epidemiologic studies on birth defects prevalence among their progeny have been limited to military hospitals, anomalies diagnosed among newborns, or self-reported data. To measure the prevalence of selected birth defects among infants of GWVs and nondeployed veterans (NDVs) in Hawaii, using birth defects surveillance records. METHODS: Personal identifiers of 684,645 GWVs and 1,587,102 NDVs and their families were matched against birth certificate records of 99,545 live births reported to the State of Hawaii Department of Health between 1989 and 1993 to identify births to military personnel. These births were matched with records from the Hawaii Birth Defects Program. RESULTS: A total of 17,182 military infants (3,717 GWV infants and 13,465 NDV infants) were identified. Of these, 367 infants (2.14/100 live births) were identified with one or more of 48 major birth defects diagnoses. The prevalence of the 48 birth defects were similar for GWV and NDV infants during the prewar and postwar periods, and among GWV infants who were conceived before and after the Gulf war. CONCLUSIONS: The results must be interpreted with caution because of the small number of affected infants in each birth defects category. This study demonstrated the feasibility of measuring birth defects prevalence among military infants through multiple data linkage. Further, it included live births to parents who had separated from the military, births in civilian hospitals, and birth defects diagnosed through the first year of life.     

Causes of death and case fatality rates among infants with down syndrome in metropolitan Atlanta

BACKGROUND: There is limited population-based information on the extent of underreporting of congenital heart defects (CHD) as a cause of death among infants with Down syndrome (DS) and on the variation in case fatality by presence of CHD and age at death. METHODS: Using data from the Metropolitan Atlanta Congenital Defects Program (MACDP), we identified infants with DS born 1979-2003. We used data from Georgia death certificates and the National Death Index to determine vital status and identify causes of death. Using MACDP records as a reference, we calculated the sensitivity and positive predictive value of reports of CHD as any cause of death or contributing condition in death certificates. We calculated race-specific case fatality rate by infant's age at death and presence of CHD. RESULTS: CHD was the most frequently reported cause of death from death certificates; however, a review of causes of death and birth defects data indicated a potentially greater impact of CHD among DS infant deaths than could be determined from the reported cause of death. The case fatality rate among infants with DS was significantly higher among blacks than whites, with the greatest racial disparity observed among infants without CHD who died in the post-neonatal period. CONCLUSIONS: Efforts are needed to improve reporting of causes of death related to CHD among infants with DS that would allow for a clearer assessment of determinants of case fatality among DS infants and identification of possible ways to reduce the racial disparities.     

Etiologic heterogeneity of neural tube defects. II. Clues from family studies.

We previously reported that among neural tube defects (NTDs) with no known causes the ones that occur alone (singles) have different epidemiologic characteristics from those that occur in combination with other defects (multiples), suggesting an underlying causal heterogeneity. In this study, we compared family histories of 223 single NTD cases and 66 multiple cases ascertained through the Metropolitan Atlanta Congenital Defects Program (MACDP) between 1970 and 1979. Compared with siblings of multiples, siblings of singles had a higher precurrence rate for NTDs (2.0% vs. 0.0%) and for birth defects in general (10.9% vs. 3.0%). Furthermore, siblings of singles that were born within 2 years before the birth of the index case had a higher precurrence rate for NTDs (8.0% vs. 1.1%) and for major birth defects (20.0% vs. 2.9%) than had those born earlier. These results further suggest that NTDs are etiologically heterogeneous, depending on the presence of associated defects, and point to important environmental influences in the increased risk for birth defects among siblings of singles. Larger studies are needed to confirm these data and show that single and multiple NTDs have different recurrence rates, not only for NTDs but also for other birth defects.     

Epidemiology of congenital heart disease in Louisiana: an association between race and sex and the prevalence of specific cardiac malformations.

We hypothesized that susceptibility to the genetic and environmental factors that disrupt cardiac development is associated with race and sex. To evaluate this hypothesis, we asked whether the prevalence of specific cardiac malformations differs by race and sex. We attempted to include all infants born alive in the State of Louisiana from January 1, 1988, through December 31, 1989, and diagnosed by echocardiography, catheterization and/or autopsy within a year of birth as having one of ten specific cardiac malformations. The prevalence of atrioventricular canal defects (AVCD) per 1,000 live births was significantly higher for black females (.744) compared to black males (.198) and for white females (.414) compared to white males (.116). Complete transposition of the great arteries (TGA) was significantly higher for white males (.559) compared to white females (.122); in contrast, TGA was not significantly different for black males (.198) and black females (.169). Obstructive left heart syndrome (OLHS)--aortic stenosis and/or coarctation of the aorta--was significantly higher for white males (.652) compared to white females (.317); in contrast, OLHS was not significantly different for black males (.264) and black females (.169). Single ventricle (SV) was significantly higher for whites (.202) compared to blacks (.067). We did not find that race and sex were associated with differences in the prevalence of tetralogy of Fallot and hypoplastic left heart syndrome. The numbers of infants with anomalous pulmonary venous return, tricuspid atresia, double outlet right ventricle, or truncus arteriosus were too small to measure an association with race and sex. These results demonstrate that the prevalence of a subset of cardiac malformations differs by race and sex.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relation between small size for gestational age and the sex ratio of children with birth defects

BACKGROUND: Infants with birth defects are more likely to be born small for gestational age (SGA) than are other infants. This study describes a relation noted between the percentage SGA and the percentage male among children with various defect types. The data source was case records collected by the Metropolitan Atlanta Congenital Defects Program, a population-based, active surveillance system, during 1968 through 1998. METHODS: The study calculated the correlation between the percentage male and the percentage SGA for isolated cases of 44 different defect types for male-dominant and female-dominant defects separately. RESULTS: The correlation coefficient was -0.47 (P < 0.01) for male-dominant defects and 0.20 (P > 0.05) for female-dominant defects. Male-dominant defects were more likely to show less than 15% SGA and more likely to show the strongest risk differences by sex. CONCLUSIONS: These results are consistent with genetic causation of strongly skewed sex ratios, at least among male-dominant defects. Review of the literature suggests that defects with sex ratios closer to 1 are likely to have lower recurrence risks and therefore are less likely to be inherited than are other defects with skewed sex ratios. Sex ratios closer to 1 and a high percentage SGA may be markers of acquired or environmental birth defects.     

Prenatal diagnosis, pregnancy terminations and prevalence of Down syndrome in Atlanta

BACKGROUND: The impact of prenatal diagnosis on the live birth prevalence of Down syndrome (trisomy 21) has been described. This study examines the prevalence of Down syndrome before (1990-1993) and after inclusion of prenatally diagnosed cases (1994-1999) in a population-based registry of birth defects in metropolitan Atlanta. METHODS: We identified infants and spontaneous fetal deaths with Down syndrome (n = 387), and pregnancies electively terminated after a prenatal diagnosis of Down syndrome (n = 139) from 1990 to 1999 among residents of metropolitan Atlanta from a population-based registry of birth defects, the Metropolitan Atlanta Congenital Defects Program (MACDP). Only diagnoses of full trisomy 21 were included. Denominator information on live births was derived from State of Georgia birth certificate data. We compared the prevalence of Down syndrome by calendar period (1990-1993, 1994-1999), maternal age (<35 years, 35+ years), and race/ethnicity (White, Black, other), using chi-square and Fisher's exact tests. RESULTS: During the period when case ascertainment was based only on hospitals (1990-1993), the prevalence of Down syndrome was 8.4 per 10,000 live births when pregnancy terminations were excluded and 8.8 per 10,000 when terminations were included. When case ascertainment also included perinatal offices (1994-1999), the prevalence of Down syndrome was 10.1 per 10,000 when terminations were excluded and 15.3 when terminations were included. During 1990-1993, the prevalence of Down syndrome was 24.7 per 10,000 among offspring to women 35+ years of age compared to 6.8 per 10,000 among offspring to women <35 years of age (rate ratio [RR] = 3.65, 95% confidence interval [CI] = 2.53-5.28). During 1994-1999, the prevalence of Down syndrome was 55.3 per 10,000 among offspring to women 35+ years compared to 8.5 per 10,000 among offspring to women <35 years (RR = 6.55, 95% CI = 5.36-7.99). There was no statistically significant variation in the prevalence of Down syndrome by race/ethnicity within maternal age and period of birth strata. During 1994-1999, the proportion of cases that were electively terminated was greater for women 35+ years compared to women <35 years (RR = 5.10, 95% CI = 3.14-8.28), and lower for Blacks compared to Whites among women 35+ years of age (RR = 0.33, 95% CI = 0.16-0.66). CONCLUSIONS: In recent years, perinatal offices have become an important source of cases of Down syndrome for MACDP, contributing at least 34% of cases among pregnancies in women 35+ years of age. Variation in the prevalence of Down syndrome by race/ethnicity, before or after inclusion of cases ascertained from perinatal offices, was not statistically significant. Among Down syndrome pregnancies in mothers 35+ years we found a lower proportion of elective termination among Black women compared to White women. We suggest that future reports on the prevalence of Down syndrome by race/ethnicity take into account possible variations in the frequency of prenatal diagnosis or elective termination by race/ethnicity.     

Changes in the birth prevalence of selected birth defects after grain fortification with folic acid in the United States: findings from a multi-state population-based study

BACKGROUND: Observational studies and clinical trials have suggested that periconceptional use of folic acid can reduce the risk of birth defects other than neural tube defects (NTDs). Using data reported by states to the National Birth Defects Prevention Network, we examined whether folic acid fortification might have decreased the prevalence of other specific birth defects. METHODS: For each of 16 birth defect categories selected for study, birth prevalence for two time periods was calculated with data submitted from a number of states in 1995-1996 ("pre-fortification") and 1999-2000 ("post-fortification"). Changes in birth prevalence between the two time periods were assessed by calculating prevalence ratios and 95% confidence intervals for each defect, and compared by maternal race/ethnicity and availability of prenatally diagnosed cases. RESULTS: We confirmed previously reported reductions in the birth prevalence of NTDs. In addition, we found modest, yet statistically significant, decreases in the birth prevalence for transposition of the great arteries(12%), cleft palate only (12%), pyloric stenosis (5%), upper limb reduction defects (11%), and omphalocele (21%). More substantial subgroup decreases were observed for renal agenesis among programs that conduct prenatal surveillance (28%), for common truncus among Hispanics (45%), and for upper limb reduction defects among Hispanics (44%). There were modest yet significant increases in the prevalence of obstructive genitourinary defects (12%) and Down syndrome (7%), but not among programs conducting prenatal surveillance for these defects. CONCLUSIONS: These results suggest some modest benefit from the folic acid fortification on the prevalence of a number of non-NTD birth defects.     

Are there ethnic disparities in risk of preterm birth among infants born with congenital heart defects?

BACKGROUND: Birth defects and preterm birth (PTB) are leading causes of infant morbidity and mortality in the United States. Infants with birth defects are more likely to be born preterm (<37 weeks), yet the roles of maternal ethnicity and fetal growth in this relationship are unclear. This study aimed to assess the risk of PTB among non-Hispanic (NH) Black, NH-White, and Hispanic infants with congenital heart defects (CHD), adjusting for fetal growth. METHODS: Florida Birth Defects Registry data were used to conduct a retrospective cohort study on 14,319 live-born infants with CHDs born January 1, 1998 to December 31, 2002. ORs and 95% CIs were computed for each growth category (small-for-gestational age [SGA], appropriate-for-gestational-age [AGA], and large-for-gestational-age [LGA]) by ethnicity and adjusted for maternal and infant covariates using logistic regression. RESULTS: After adjusting for potential confounders, SGA and AGA NH-Black infants with CHDs had increased risk of PTB compared to NH-White infants with CHDs (OR 1.79; 95% CI: 1.40, 2.30 and OR 1.89; 95% CI: 1.68, 2.13, respectively). Hispanic SGA, AGA, and infants with CHDs had no increased risk of PTB compared to NH-White infants. CONCLUSIONS: The increased risk of PTB among SGA and AGA NH-Black infants with CHDs is not explained by the overall disparities in risk of PTB between NH-Blacks and NH-Whites. Additional studies are needed to determine the specific subtypes of CHD for which these relationships are present and if these findings are seen among infants with other birth defects.     

Maternal obesity and morbid obesity: The risk for birth defects in the offspring

BACKGROUND : The objective of this study was to assess, in a large data set from Swedish Medical Health Registries, whether maternal obesity and maternal morbid obesity were associated with an increased risk for various structural birth defects. METHODS : The study population consisted of 1,049,582 infants born in Sweden from January 1, 1995, through December 31, 2007, with known maternal weight and height data. Women were grouped in six categories of body mass index (BMI) according to World Health Organization classification. Infants with congenital birth defects were identified from three sources: the Swedish Medical Birth Registry, the Register of Birth Defects, and the National Patient Register. Maternal age, parity, smoking, and year of birth were thought to be potential confounders and were included as covariates in the adjusted odds ratio analyses. RESULTS : Ten percent of the study population was obese. Morbid obesity (BMI ≥ 40) occurred in 0.7%. The prevalence of congenital malformations was 4.7%, and the prevalence of relatively severe malformations was 3.2%. Maternal prepregnancy morbid obesity was associated with neural tube defects OR 4.08 (95% CI 1.87–7.75), cardiac defects OR 1.49 (95% CI 1.24–1.80), and orofacial clefts OR 1.90 (95% CI 1.27–2.86). Maternal obesity (BMI ≥ 30) significantly increased the risk of hydrocephaly, anal atresia, hypospadias, cystic kidney, pes equinovarus, omphalocele, and diaphragmatic hernia. CONCLUSION : The risk for a morbidly obese pregnant woman to have an infant with a congenital birth defect is small, but for society the association is important in the light of the ongoing obesity epidemic. Birth Defects Research (Part A), 2010. © 2009 Wiley‐Liss, Inc.     

Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: a report from the National Down Syndrome Project

BACKGROUND: Maternal folic acid supplementation has been associated with a reduced risk for neural tube defects and may be associated with a reduced risk for congenital heart defects and other birth defects. Individuals with Down syndrome are at high risk for congenital heart defects and have been shown to have abnormal folate metabolism. METHODS: As part of the population‐based case‐control National Down Syndrome Project, 1011 mothers of infants with Down syndrome reported their use of supplements containing folic acid. These data were used to determine whether a lack of periconceptional maternal folic acid supplementation is associated with congenital heart defects in Down syndrome. We used logistic regression to test the relationship between maternal folic acid supplementation and the frequency of specific heart defects correcting for maternal race or ethnicity, proband sex, maternal use of alcohol and cigarettes, and maternal age at conception. RESULTS: Lack of maternal folic acid supplementation was more frequent among infants with Down syndrome and atrioventricular septal defects (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.08–2.63; p = 0.011) or atrial septal defects (OR, 1.69; 95% CI, 1.11–2.58; p = 0.007) than among infants with Down syndrome and no heart defect. Preliminary evidence suggests that the patterns of association differ by race or ethnicity and sex of the proband. There was no statistically significant association with ventricular septal defects (OR, 1.26; 95% CI, 0.85–1.87; p = 0.124). CONCLUSIONS: Our results suggest that lack of maternal folic acid supplementation is associated with septal defects in infants with Down syndrome. Birth Defects Research (Part A), 2011. © 2011 Wiley‐Liss, Inc.     

Laterality patterns in infants with external birth defects.

The lateral distribution of external birth defects has not been reported in a comprehensive way, and patterns in this distribution have not been examined. This study presents the lateral distribution of 6,390 unilateral defects from among 102 defect categories in data collected by the Metropolitan Atlanta Congenital Defects Program. Among all defects, 49% (95% CI 48-51%) were right-sided. Among males and females, 51% (95% CI 50-53%) and 47% (95% CI 46-49%) of the defects, respectively, were right-sided. Of the 102 defect types, 57 had an excess of defects on the right side of the body; 39 had an excess of defects on the left side; and 6 were equally distributed. The excess on the right side was statistically significant for inguinal hernia, incarcerated inguinal hernia, microtia, preauricular sinus, talipes calcaneovalgus, and lambdoidal craniosynostosis. For the left side, the excess was statistically significant for preauricular tags, cleft lip, fused lip and cleft gum, cleft lip with cleft palate, congenital hip dysplasia, unstable hip, absent forearm or hand, anomaly of the knee, and skin tags. The percentage of right-sided defects among case subjects with unilateral defects was correlated with the percentage of males among all case subjects (r = 0.24, P < 0.05). Among male case subjects with unilateral defects, the correlation coefficient was 0.31 (P < 0. 01), and among females with unilateral defects, it was 0.11 (P > 0. 10). Differences in the lateral distribution of specific birth defects may be due to subtle differences in morphogenesis on the left and right sides of the embryo brought about by establishment of left-right asymmetry prior to organogenesis. The fact that more defect categories were right-sided than left-sided may be related to the observation that mitochondrial maturation in rat embryos is delayed on the right side. The right side, therefore, may be more susceptible than the left to defects caused by prenatal hypoxia. The significant correlation between the percentage right-sided and percentage male may then also be related to the observation that male sex hormones lower the mitochondrial respiration rate in rats and increase rat sensitivity to chemical hypoxia. Investigators should consider reporting the laterality of specific defects in both laboratory and epidemiological studies of birth defects. Right- and left-sided defects should perhaps be considered separately in etiologic studies of birth defects. Teratology 60:265-271, 1999. Published 1999 Wiley-Liss, Inc.     

Do infants with major congenital anomalies have an excess of macrosomia?

BACKGROUND: Infants that develop congenital anomalies may also have an excess prevalence of macrosomia (birth weight > or =4,000 g). This may indicate that abnormalities of glycemic control play a role in the etiology of birth defects. This study was undertaken to determine whether all infants with congenital anomalies have an excess of macrosomia and whether it is confined to specific types of anomalies. METHODS: A case-control study was conducted, comparing the birth weights of 8,226 infants with congenital anomalies ascertained by the Texas Birth Defects Monitoring Division with those of 965,965 infants without birth defects. Odds ratios were calculated to determine the association between birth weight and congenital anomalies, for 45 specific defects, and for all these defects combined. RESULTS: For all 45 defects combined, a significant association occurred only in the highest birth weight category. Infants with congenital anomalies were more likely than infants without birth defects to have a birth weight > or =4,500 g (OR = 1.65; 95% CI = 1.39-1.96). Infants born with ventricular septal defects, atrial septal defects, ventricular hypertrophy, or anomalies of the great vessels were 1.5-2.5 times more likely to weigh > or =4,000 g than were infants without birth defects. Based on small numbers, a stronger excess of macrosomia was observed for infants with encephalocele, holoprosencephaly, anomalies of the corpus callosum, preaxial polydactyly, and omphalocele. CONCLUSIONS: Our data suggest that infants with specific congenital anomalies are more likely to be macrosomic than are infants without an anomaly. If these findings are confirmed, associations between macrosomia and specific types of birth defects may help to identify birth defects that are caused by alterations in glycemic control.     

National estimates and race/ethnic-specific variation of selected birth defects in the United States, 1999-2001

BACKGROUND: In the United States, birth defects affect approximately 3% of all births, are a leading cause of infant mortality, and contribute substantially to childhood morbidity. METHODS: Population-based data from the National Birth Defects Prevention Network were combined to estimate the prevalence of 21 selected defects for 1999-2001, stratified by surveillance system type. National prevalence was estimated for each defect by pooling data from 11 states with active case-finding, and adjusting for the racial/ethnic distribution of US live births. We also assessed racial/ethnic variation of the selected birth defects. RESULTS: National birth defect prevalence estimates ranged from 0.82 per 10,000 live births for truncus arteriosus to 13.65 per 10,000 live births for Down syndrome. Compared with infants of non-Hispanic (NH) white mothers, infants of NH black mothers had a significantly higher birth prevalence of tetralogy of Fallot, lower limb reduction defects, and trisomy 18, and a significantly lower birth prevalence of cleft palate, cleft lip with or without cleft palate, esophageal atresia/tracheoesophageal fistula, gastroschisis, and Down syndrome. Infants of Hispanic mothers, compared with infants of NH white mothers, had a significantly higher birth prevalence of anencephalus, spina bifida, encephalocele, gastroschisis, and Down syndrome, and a significantly lower birth prevalence of tetralogy of Fallot, hypoplastic left heart syndrome, cleft palate without cleft lip, and esophageal atresia/tracheoesophageal fistula. CONCLUSIONS: This study can be used to evaluate individual state surveillance data, and to help plan for public health care and educational needs. It also provides valuable data on racial/ethnic patterns of selected major birth defects.