Time trends in the prevalence of birth defects in Texas 1999–2007: Real or artifactual?

BACKGROUND: Few studies have reported time trends for total birth defects or for a comprehensive range of phenotypes. METHODS: We examined data from the Texas Birth Defects Registry (TBDR) from 1999 through 2007. Poisson regression was used to fit trend lines to birth prevalence over time for total birth defects (each infant/fetus counted once), for every birth defect collected by the TBDR, and for subsets of cases or defects grouped various ways. RESULTS: From 1999 through 2007, birth prevalence of total birth defects in Texas increased 3.6% per year. Increases were observed in all population groups, persisted after adjustment for demographic characteristics, and were strongest in regions of Texas that were more urban. There was a wide variety of different defects showing significant increases. The trends of several defects were driven by their mild cases. Perhaps the most compelling finding was that larger upward trends were observed in defects that had been rated as more susceptible to diagnostic variation. One notable exception to that was gastroschisis, which showed an average increase of over 5% per year, the total birth defects rate in TBDR increased at 3.6% per year, similar to 3.7% per year in birth certificate check boxes. CONCLUSIONS: In our opinion, the weight of evidence in our study suggests that the observed increase over time in total birth defects and in many specific birth defects is artifactual. This likely reflects increased awareness, referral, detection, or documentation in health care facilities visited by TBDR staff, resulting in more complete ascertainment by the registry, rather than a true change over time in the occurrence of most birth defects. Birth Defects Research (Part A), 2011. © 2011 Wiley‐Liss, Inc.     

Ascertainment of pregnancies terminated because of birth defects: effect on completeness of adding a new source of data

BACKGROUND: When evaluating preventive programs such as folate promotion and rubella vaccination, it is critically important to include terminations of pregnancy for neural tube defects and congenital rubella syndrome. Data from birth defects registries are often used for this purpose. The Western Australian Birth Defects Registry ascertains cases of birth defects in livebirths, stillbirths, and terminations of pregnancy for fetal abnormality, using multiple sources of ascertainment. METHODS: Data on terminations of pregnancy for fetal abnormality from the Western Australian Hospital Morbidity Data System 1980-1997 (not previously available to the Registry) were used to estimate the completeness of ascertainment of such cases by the Registry. Ascertainment-adjusted prevalences were calculated using capture-recapture methods. RESULTS: A total of 702 terminations with birth defects were identified among hospital discharges, most of which were already known to the Registry (87.9%). Of the 85 new cases, seven had a neural tube defect, 23 had a chromosomal defect, and 12 had confirmed maternal rubella infection during pregnancy. The ascertainment-adjusted prevalence was not importantly [corrected] different for birth defects overall or for these individual conditions, although the 95% confidence intervals for all birth defects, and for all chromosomal defects, did not include the prevalence based on registered cases only. CONCLUSIONS: The Western Australian Birth Defects Registry ascertains a high proportion of pregnancies terminated for fetal abnormality, and should therefore be a reliable source of data with which to assist in monitoring the effectiveness of preventive programs.     

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.     

Feasibility of using the national hospital discharge survey to estimate the prevalence of selected birth defects

BACKGROUND: Nationally representative data on the prevalence of certain birth defects are largely unavailable. We evaluated the feasibility of using data from the National Hospital Discharge Survey (NHDS) to describe the prevalence of selected birth defects. METHODS: All live births recorded in the NHDS during 1999-2001 were included. The prevalence for selected birth defects was calculated using weighted ratio estimators. Prevalence ratios comparing the NHDS estimates to published national estimates from the National Birth Defects Prevention Network (NBDPN) were calculated. RESULTS: With the exception of common truncus, the NHDS prevalence for the selected defects was consistently lower than the NBDPN estimates. The prevalence ratios ranged from 0.38 for trisomy 18 and anopthalmia/micropthalmia to 1.16 for common truncus. The NHDS prevalence estimates for spina bifida without anencephaly (PR 0.89, 95% CI: 0.57-1.22) and gastroschisis/omphalocele (PR 0.94, 95% CF: 0.48-1.40) most closely approximated the NBDPN estimates. CONCLUSIONS: NHDS data underestimate the prevalence of most birth defects. Additional research is needed to determine whether NHDS estimates may be useful for evaluating trends in certain conditions. Surveillance systems employing active case-finding continue to provide more accurate estimates of birth defects prevalence.     

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.     

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.     

Sex differences in the prevalence of human birth defects: a population-based study.

BACKGROUND: Sex differences in the prevalence of several human birth defects have often been reported in the literature, but the extent of sex differences for most birth defects is unknown. To determine the full extent of sex differences in birth defects in a population, we examined population-based data from the Metropolitan Atlanta Congenital Defects Program (MACDP). METHODS: MACDP records were analyzed for 1968 through 1995. We determined the sex-specific prevalence of all major birth defects, using the total number of live births by sex during these years as the denominator. For each specific defect, we calculated a relative risk with regard to sex on the basis of the ratio of prevalence among males to prevalence among females. Male-female relative risks were also determined for total major birth defects and for several broad categories of defects. RESULTS: The overall prevalence of major defects at birth was 3.9% among males and 2.8% among females. All but two of the major categories of birth defects (nervous system defects and endocrine system defects) had a higher prevalence among males. Defects of the sex organs were eight and one-half times more prevalent among males and accounted for about half of the increased risk of birth defects among males relative to females. Urinary tract defects were 62% more prevalent among males, and gastrointestinal tract defects were 55% more prevalent among males. Among specific defect types, twofold or greater differences in prevalence by sex were common. CONCLUSIONS: Our data indicate that sex differences in the prevalence of specific human birth defects are common, and male infants are at greater risk for birth defects than female infants. Several mechanisms have been proposed to account for these differences.     

Are birth defects among Hispanics related to maternal nativity or number of years lived in the United States?

BACKGROUND: Literature on the risk of birth defects among foreign‐ versus U.S.–born Hispanics is limited or inconsistent. We examined the association between country of birth, immigration patterns, and birth defects among Hispanic mothers. METHODS: We used data from the National Birth Defects Prevention Study and calculated odds ratios (ORs) and 95% confidence intervals and assessed the relationship between mothers' country of birth, years lived in the United States, and birth defects among 575 foreign‐born compared to 539 U.S.–born Hispanic mothers. RESULTS: Hispanic mothers born in Mexico/Central America were more likely to deliver babies with spina bifida (OR = 1.53) than their U.S.–born counterparts. Also, mothers born in Mexico/Central America or who were recent United States immigrants (≤5 years) were less likely to deliver babies with all atrial septal defects combined, all septal defects combined, or atrial septal defect, secundum type. However, Hispanic foreign‐born mothers who lived in the United States for >5 years were more likely to deliver babies with all neural tube defects combined (OR = 1.42), spina bifida (OR = 1.89), and longitudinal limb defects (OR = 2.34). Foreign‐born mothers, regardless of their number of years lived in the United States, were more likely to deliver babies with anotia or microtia. CONCLUSIONS: Depending on the type of birth defect, foreign‐born Hispanic mothers might be at higher or lower risk of delivering babies with the defects. The differences might reflect variations in predisposition, cultural norms, behavioral characteristics, and/or ascertainment of the birth defects. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

Association of paternal age with prevalence of selected birth defects

BACKGROUND: Unlike maternal age, the effect of paternal age on birth defect prevalence has not been well examined. We used cases from the Texas birth defect registry, born during 1996-2002, to evaluate the association of paternal age with the prevalence of selected structural birth defects. METHODS: Poisson regression was used to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs) associated with paternal age for each birth defect, adjusting for maternal age, race/ethnicity, and parity. RESULTS: Relative to fathers ages 25-29 years, fathers 20-24 years of age were more likely to have offspring with gastroschisis (PR 1.47, 95% CI: 1.12-1.94), and fathers 40+ years old were less likely to have offspring with trisomy 13 (PR 0.40, 95% CI: 0.16-0.96). No association was seen between paternal age and prevalence of anencephaly and encephalocele. A selection bias was observed for the other birth defects in which cases of younger fathers were more often excluded from study. CONCLUSIONS: In studies of birth defect risk and paternal age, the source of information may affect the validity of findings.     

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.     

Prevalence of down syndrome among children and adolescents in metropolitan Atlanta

BACKGROUND: Down syndrome (DS) prevalence estimates beyond infancy are needed to assess health service needs among those with DS. METHODS: Children with DS born in metropolitan Atlanta from 1979 through 2003 were ascertained from a population-based birth defects registry. Vital status through 2003 was obtained using case records, vital records, and the National Death Index. Prevalence was calculated by dividing the children surviving with DS by the population derived from U.S. Census estimates. Variations in DS prevalence by race, heart defects, age, birth cohort, and time period were examined using Poisson regression. RESULTS: In metropolitan Atlanta in 2003, there were 67 livebirths with DS (13.0 per 10,000 livebirths) and 738 0- to 19-year-olds surviving with DS (8.3 per 10,000 population). Over time, births to mothers 35 years and older and DS birth prevalence increased. Birth prevalence was higher among Whites, did not vary by sex, and was higher for infants without heart defects. DS prevalence among 0- to 14-year-olds increased over time (p < .05). Within each 5 year birth cohort, prevalence decreased with age: this decrease was greater among Blacks than among Whites and among children with heart defects than among children without heart defects. CONCLUSIONS: DS prevalence increased among livebirths and among young children. Further studies are warranted to determine whether health services are meeting the needs of an increasing number of children with DS.     

High rates of neural tube defects in Ukraine

BACKGROUND: Oral consumption of synthetic folic acid can prevent neural tube defects (NTDs), which are some of the most severe congenital anomalies. The prevalence of NTDs in Ukraine and other countries of the former U.S.S.R. has not been well studied. We determined the prevalence of NTD-affected pregnancies in Northwestern Ukraine as background for policy decisions related to flour fortification in this country. METHODS: The Ukrainian-American Birth Defects Program was established in 1999 and conducts population- based surveillance of birth defects in several oblasts (states) of Ukraine. We determined the prevalence of NTDs in the Volyn and Rivne oblasts of Northwestern Ukraine for three years, 2000-2002. RESULTS: There were 75,928 births in the two oblasts in 2000-2002. There were 159 cases of NTDs among live births, stillbirths, and induced abortions. The prevalence of NTDs in the two oblasts in Northwestern Ukraine is 2.1 per 1000 births. CONCLUSIONS: The prevalence of NTD-affected pregnancies we found in Northwestern Ukraine is almost four times what it should be. This prevalence suggests that population folate deficiency is widespread in Ukraine. Universal folic acid fortification of flour milled in Ukraine is urgently needed to end this epidemic of birth defects. Such fortification would be expected to prevent folate deficiency anemia, heart attacks, and strokes.     

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.     

Linking teratogen information service and birth defects registry databases to improve knowledge of birth defect status

BACKGROUND: Although teratogen information services (TISs) obtain maternal exposure information from their callers, such services often do not know if the pregnancies were affected by a birth defect. This study attempted to improve the completeness of this information for Texas Teratogen Information Service (TTIS) callers by linking their records with the Texas Birth Defects Registry (TBDR) and Texas birth certificates (TBCs). METHODS: A total of 344 expectant mothers called TTIS with expected dates of delivery between 1 January 2000 and 31 December 2001. These pregnancies were linked with TBDR and TBC data. The percentages of pregnancies with known birth defect information both before and after the linkage were compared. RESULTS: The TTIS originally collected birth defect status information for 101 of the 344 callers (29.4%) and 0.6% of all 344 callers or 2.0% of callers with birth defect status information had a pregnancy affected by a birth defect. Linking TTIS records with TBDR and TBC data helped to raise the percentage of callers with birth defect status information from 29.4% to 71.5%. Among those callers, the percentage known to have birth defects increased from 2.0% to 4.1%. The sensitivity of TTIS follow-up calls in identifying birth defects was 50%, and the specificity was 100%. CONCLUSIONS: Linking TTIS caller records with TBDR and TBC data significantly increased both the percentage of pregnancies with birth defect status information and the percentage of pregnancies identified as affected by birth defects. Such linkage may be a good approach by which TISs can increase the completeness of their birth defect status information.     

National rates of birth defects among hospitalized newborns

BACKGROUND: The Healthcare Cost and Utilization Project (HCUP) family of hospital discharge databases offer an unprecedented opportunity to generate national estimates of newborn infants with birth defects. This report estimates national hospital admissions for newborn infants diagnosed with birth defects computed from HCUP and compares them to pooled prevalence figures computed from state birth defect surveillance systems. METHODS: HCUP-derived rates of 36 birth defects from 1997 through 2001 were compared to rates derived from pooled data reported by 26 state-based surveillance systems stratified by inclusion of elective terminations in case definitions. Rate ratios (RRs) were calculated for each birth defect by dividing the rate derived from HCUP by the rate derived from the relevant surveillance systems. RESULTS: HCUP newborn hospitalization rates for birth defects closely approximate pooled birth defect rates for surveillance systems that do not include elective terminations. HCUP rates were not significantly different for 35 of 36 defects. Overall, 20 HCUP rates were within 10% of state rates, 11 more were within 20% of state rates, and only 1 differed by more than 50%. HCUP rates compared most closely to state rates for cardiovascular (VSD RR = 0.98, ASD = 0.96, pulmonary valve atresia and stenosis = 0.92), orofacial (cleft palate RR = 1.10, cleft lip = 1.06), and genitourinary defects (obstructive genitourinary RR = 1.01, bladder exstrophy = 0.97). HCUP rates compared less favorably to rates derived from surveillance systems that included elective terminations. CONCLUSIONS: HCUP data approximate state-based surveillance system data for defects that are easily recognized in the newborn period and infrequently a cause for elective termination. HCUP data can be used to examine the impact of public health efforts on the number of infants born with birth defects as well as the cost and consequences of variations in the hospital management of birth defects.     

Maternal asthma,asthma medication use,and the risk of congenital heart defects

BACKGROUND: Asthma is a common problem that complicates pregnancy. Several drugs are considered acceptable for use during pregnancy, although none have been classified as safe. Few studies have assessed the health impact of maternal asthma/medication use on the fetus. METHODS: A population‐based case‐control study was conducted in New York State to determine if cardiac congenital malformations in offspring were associated with maternal use of asthma medication and/or maternal asthma. Cases were cardiac anomalies in the New York State Congenital Malformations Registry. Controls were live births without any major birth defects randomly selected from birth certificates and frequency matched by year of birth. Data were collected through a 30 min telephone interview. Exposure was maternal asthma/medication use, maternal asthma/no medication use, no asthma/medication use, and no asthma/no medication use (reference). RESULTS: A total of 502 (59.4%) cases and 1,066 (53.8%) controls participated. A positive association was seen between any heart defect and women with asthma who used medication (OR 2.38; 95% CI: 1.18, 4.82). No significant associations were observed between heart defects and either women with asthma who did not use medication or women without asthma who used asthma medications. When considering types of medication used, offspring of women with asthma who used bronchodilators had an increased risk of any heart defect (OR 2.20; 95%CI: 1.05, 4.61). CONCLUSIONS: These results suggest that both maternal asthma status (controlled vs. uncontrolled; severe vs. mild) and asthma medication use, particularly bronchodilators, may play a role in cardiac malformations in offspring. Birth Defects Research (Part A), 2009. © 2008 Wiley‐Liss, Inc.     

Are selective serotonin reuptake inhibitors cardiac teratogens? Echocardiographic screening of newborns with persistent heart murmur

BACKGROUND : Selective serotonin reuptake inhibitors (SSRIs) have been suspected of cardiac teratogenicity, but reports have been inconsistent. Our aim was to investigate the rate of nonsyndromic congenital heart defects in newborns exposed in utero to SSRIs compared with unexposed controls. METHODS : This prospective study of women who gave birth at our tertiary center from 2000 to 2007 yielded 235 women who reported first‐trimester SSRI use during pregnancy. All newborns born during the study period and found to have a persistent cardiac murmur on day 2 or 3 of life were referred for examination by a pediatric cardiologist and by echocardiography. The findings were compared between the newborns who were exposed to SSRIs and those who were not. RESULTS : Nonsyndromic congenital heart defects were identified by echocardiography in 8 of 235 (3.40%) newborns exposed in utero to SSRIs and in 1083 of 67,636 (1.60%) non‐exposed newborns. The difference in prevalence between the two groups was significant (relative risk, 2.17; 95% confidence interval, 1.07–4.39). The prevalence rates for paroxetine and fluoxetine exposure were 4.3% and 3.0%, respectively. All cardiac defects in the study group were mild: ventricular septal defect (6), bicuspid aortic valve (1) and right superior vena cava to coronary sinus (1). CONCLUSIONS : Newborns exposed in utero to SSRIs, have a twofold higher risk of mild nonsyndromic heart defects than unexposed infants. The data suggest that women who require SSRI treatment during pregnancy can be reassured that the fetal risk is low and possible cardiac malformations will probably be mild. Late‐targeted ultrasound and fetal echocardiography at 22 to 23 weeks' gestation are recommended in this patient group. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.