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.     

Pilot test of prenatal surveillance for birth defects in South Texas

BACKGROUND: The Texas Birth Defects Registry (TBDR) does not access prenatal diagnostic facilities to ascertain cases. Objectives of the study were to determine how many cases may be missing from the registry as a result, and to assess the feasibility and utility of prenatal surveillance for birth defects, through a pilot test in one region of Texas. METHODS: A trained abstractor reviewed medical records of all patients with abnormal ultrasound findings during 2004 in all prenatal diagnostic facilities in Texas Health Region 11 (n = 6 facilities). When birth defects were prenatally detected, demographic and diagnostic data were abstracted. Prenatal abstractions were matched to cases in the TBDR. Those that did not match to registry cases were matched to vital records to determine where and when the pregnancy ended; delivery hospital medical records were reviewed for these cases. RESULTS: Approximately 760 patient charts were reviewed at prenatal diagnostic facilities and 365 were abstracted. Of these, 165 (45%) matched to cases in the TBDR. Delivery medical records were located and reviewed for 177 prenatal abstractions, with 170 (47%) indicating at delivery no defects monitored by the registry. Delivery records for one (0.3%) prenatal abstraction were not found by the hospital. Date and place of delivery were unknown for 22 (6%) prenatal abstractions. Only eight additional infants and fetuses (one twin pair) eligible for the registry were identified. CONCLUSIONS: For Texas Health Service Region 11, it is not necessary to conduct surveillance in prenatal diagnostic facilities, and to do so would be very labor-intensive.     

Pregnancy outcomes following systemic prenatal acyclovir exposure: Conclusions from the international acyclovir pregnancy registry, 1984-1999

BACKGROUND: Oral acyclovir is commonly used for genital herpes and other herpesvirus infections. Data on potential fetal risk are extremely limited. From 1984 to 1998, the Acyclovir in Pregnancy Registry monitored birth outcomes of women exposed to oral or intravenous acyclovir during pregnancy. This report describes the final results. METHODS: The registry was publicized to health care providers most likely to diagnose pregnancy; providers called the registry telephone number, then mailed in a brief questionnaire. Pregnancy outcomes were categorized either as outcomes with birth defects or outcomes without birth defects, subcategorized as live births, spontaneous pregnancy losses (including stillbirths), and induced abortions. Birth defects were defined using a modification of the CDC definition for birth defects surveillance systems. Observed rates were compared to the rate (3.2%) of birth defects expected in the general population. RESULTS: Between June 1, 1984 and June 30, 1998, 1695 pregnancies exposed to oral or IV acyclovir were registered; 461 (27%) were lost to follow-up. A total of 1234 pregnancies in 24 countries were followed, with a total of 1246 outcomes. Among 1246 pregnancy outcomes, 756 involved acyclovir exposure in the first trimester, 197 in the second trimester, and 291 in the third trimester. Among live births with first trimester acyclovir exposure, risk of birth defects was 19 of 596 (3.2%; 95% CI, 2.0-5.0%). No unusual defects or pattern of defects were apparent. CONCLUSIONS: The observed rates and types of birth defects for pregnancies exposed to acyclovir did not differ significantly from those in the general population. Birth Defects Research (Part A), 2004. Published 2004 Wiley-Liss, Inc.     

Epidemiology of noncomplex left ventricular outflow tract obstruction malformations (aortic valve stenosis, coarctation of the aorta, hypoplastic left heart syndrome) in Texas, 1999-2001

BACKGROUND: The left ventricular outflow tract (LVOT) malformations aortic valve stenosis (AVS), coarctation of the aorta (CoA), and hypoplastic left heart syndrome (HLHS) contribute significantly to infant mortality due to birth defects. Previous epidemiology data showed rate differences between male and female and white and black ethnic groups. The Texas Birth Defects Registry, an active surveillance program, enables study in a large, diverse population including Hispanics. METHODS: Records of children up to 1 year old with AVS, CoA, and HLHS born in Texas from 1999 to 2001, were collected from the registry. Those including additional heart defects or a chromosomal anomaly were excluded. Multivariate analysis included: infant sex; United States-Mexico border county residence; and maternal age, race/ethnicity, birthplace, and education. RESULTS: There were 910 cases among 1.08 million live births, of which 499 met inclusion criteria. Multivariate modeling of all LVOT malformations combined demonstrated lower prevalence rate ratios (PRRs) for black males (0.26) and Hispanic males (0.70). Similar results were found for CoA but not AVS or HLHS. Higher PRRs were noted for increased maternal age for LVOT (1.3 for 24-34 years; 1.7 for >34 years), AVS, and HLHS, but not CoA, and higher PRRs across all diagnoses for males (LVOT PRR, 2.4) were noted. CoA PRRs were higher in border county vs. non-border county residents (PRR, 2.1). Maternal education and birthplace were not significant factors. CONCLUSIONS: There are rate differences for males among all 3 ethnic groups. Sex and ethnic differences suggest genetic etiologies, where the ethnic differences could be used to find susceptibility loci with mapping by admixture linkage disequilibrium. Increased CoA rates along the U.S.-Mexico border suggest environmental causes that will require further monitoring.     

Measurements of birth defect prevalence: Which is most useful as a comparator group for pharmaceutical pregnancy registries?

Pharmaceutical pregnancy registries document birth defects and other complications reported in pregnancies exposed to specific medications or diseases. A baseline estimate of birth defect prevalence is necessary for comparison. To identify potential teratogenic signals, the pregnancy registry must have a comparator that most closely matches the exposed population and data collection methodology, which are characteristics that vary among the multiplicity of birth defect surveillance systems. The system that yields the most accurate prevalence data may be different from that most closely matching the pregnancy registry methods. State public health programs have highly accurate and precise statistics, but their populations are broader than those of a pharmaceutical pregnancy registry. Large collaborative databases may have a more useful covered population, but there are secondary problems related to data precision. Health care databases enroll large numbers of patients and have good information about exposures and health problems, but the data can be difficult to access and lack useful detail. Exposure‐related databases are closer in population definition and collection methods, though the presence of different diseases and exposures can be problematic. Internal comparators are likely to be most useful in formal statistical analysis, but added cost and management burden and may require significantly increased registry enrollment. There is no ideal comparator, and this must be taken into account when planning a single‐exposure or single‐disease pregnancy registry. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

Collection, use, and protection of population-based birth defects surveillance data in the united states

Birth defects surveillance systems collect population-based birth defects data from multiple sources to track trends in prevalence, identify risk factors, refer affected families to services, and evaluate prevention efforts. Strong state and federal public health and legal mandates are in place to govern the collection and use of these data. Despite the prima facie appeal of "opt-in" and similar strategies to those who view data collection as a threat to privacy, the use of these strategies in lieu of population-based surveillance can severely limit the ability of public health agencies to accurately access the health status of a group within a defined geographical area. With the need for population-based data central to their mission, birth defects programs around the country take their data stewardship role seriously, recognizing both moral and legal obligations to protect the data by employing numerous safeguards. Birth defects surveillance systems are shaped by the needs of the community they are designed to serve, with the goal of preventing birth defects or alleviating the burdens associated with them.     

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.     

Clinician reviewers in birth defects surveillance programs: survey of the National Birth Defects Prevention Network

BACKGROUND: Some birth defects surveillance programs utilize a clinician reviewer ("Clinician") to assist the multidisciplinary staff in the process of case review, coding and classification. The untested assumption is that expertise in the evaluation of individuals with birth defects and genetic syndromes in clinical practice, usually clinical genetics, is useful in reviewing medical records. METHODS: We conducted an exploratory survey of the 50 functioning birth defects surveillance programs that participated in the National Birth Defects Prevention Network in 2004. The survey was mailed electronically to program coordinators and included 10 questions with check-off option replies. Open-ended comments were also solicited. RESULTS: Responses were received from 31 of 50 (62%) programs, 21 (68%) which used a Clinician. In addition to the 9 centers that identified themselves as participants in the National Birth Defects Prevention Study (NBDPS), there were 12 non-NBDPS programs using a Clinician, 2 of whom were not clinical geneticists (1 nurse genetic counselor and 1 primary pediatrician). A total of 86% (18/21) of Clinicians were employed part-time or as consultants; 1 was full-time, and 2 were volunteers. In addition to the core activities of classifying defects and reviewing cases to determine if a syndrome was present, over one-half of the Clinicians participated in education of birth defects surveillance programs staff, research, and program development. Most (86%; 18/21) Clinicians had been trained informally for their roles. Only 1 had received a formal performance review. CONCLUSIONS: Aside from the 9 centers in the NBDPS in which the position of Clinician is funded by the Centers for Disease Control and Prevention (CDC), about one-half of the remaining respondent birth defects surveillance programs used a Clinician. Future research is needed to determine why a birth defects surveillance program hires or refrains from using a Clinician, and whether a Clinician accomplishes the desired goals. This survey reveals a lack of formal training for the Clinicians in their roles in the surveillance programs, and a lack of quality monitors, which might be addressed in the future.     

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. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.     

Characteristics that predict locating and interviewing mothers identified by a state birth defects registry and vital records

BACKGROUND: State vital records are often used to select population-based controls in record-linkage studies of birth defects. However, locating and contacting individuals based on these data sources to collect additional data can be a challenge. METHODS: A large case-control study of air quality and birth defects was conducted in 7 Texas counties in which cases were selected from the Texas Birth Defects Registry and controls from state vital records. In 2004, data from these sources were used to trace mothers of cases and controls who delivered babies in the year 2000 (n=2477) for participation in a computer-assisted telephone interview. A number of factors that predicted whether an individual would be located and interviewed were identified. RESULTS: Between March and August 2004, 38% of the mothers were located, and 38% of the located mothers were interviewed. Case mothers were more likely than control mothers to be located (44 vs. 30%) and, if located, to be interviewed (43 vs. 31%). We compared the characteristics of mothers who were not located (case n=760; control n=777), mothers who were located but not interviewed (case n=344; control n=236), and mothers who were interviewed (case n=256; control n=104). Among both cases and controls, older mothers (>or=30 years) were more likely than younger mothers to be located, and non-Hispanic black mothers were least likely to be located and interviewed. CONCLUSIONS: Despite the utility of vital records as a source of population-based controls in record-linkage analyses, the poor response rate discourages the use of these data sources to contact individuals for a follow-up study 4 years after delivery.     

Integration of DNA sample collection into a multi-site birth defects case-control study

BACKGROUND: Advances in quantitative analysis and molecular genotyping have provided unprecedented opportunities to add biological sampling and genetic information to epidemiologic studies. The purpose of this article is to describe the incorporation of DNA sample collection into the National Birth Defects Prevention Study (NBDPS), an ongoing case-control study in an eight-state consortium with a primary goal to identify risk factors for birth defects. METHODS: Babies with birth defects are identified through birth defects surveillance systems in the eight participating centers. Cases are infants with one or more of over 30 major birth defects. Controls are infants without defects from the same geographic area. Epidemiologic information is collected through an hour-long interview with mothers of both cases and controls. We added the collection of buccal cytobrush DNA samples for case-infants, control-infants, and their parents to this study. RESULTS: We describe here the methods by which the samples have been collected and processed, establishment of a centralized resource for DNA banking, and quality control, database management, access, informed consent, and confidentiality issues. CONCLUSIONS: Biological sampling and genetic analyses are important components to epidemiologic studies of birth defects aimed at identifying risk factors. The DNA specimens collected in this study can be used for detection of mutations, study of polymorphic variants that confer differential susceptibility to teratogens, and examination of interactions among genetic risk factors. Information on the methods used and issues faced by the NBDPS may be of value to others considering the addition of DNA sampling to epidemiologic studies.     

Visualization and interpretation of birth defects data using linked micromap plots

BACKGROUND: Many states have implemented birth defects surveillance systems to monitor and disseminate information regarding birth defects. However, many of these states rely on tabular methods to disseminate statistical birth defects summaries. An innovative presentation technique for birth defect data that portrays the information in a joint geographical and statistical context is the linked micromap (LM) plot. METHODS: LM plots were generated for oral cleft data at two geographical resolutions—USA states and counties of Utah. The LM plots also included demographic and behavioral risk data. RESULTS: A LM plot for the USA reveals spatial patterns indicating higher oral cleft occurrence in the southwest and the midwest and lower occurrence in the east. The LM plot also indicates relationships between oral cleft occurrence and maternal smoking rates and the proportion of American Indians and Alaskan Natives. In particular, the five states with the highest oral cleft occurrence had a higher proportion of American Indians and Alaskan Natives. Among the 15 states with the highest oral cleft occurrence, nine had a smoking rate of 16% or higher while among the 15 states with the lowest oral cleft occurrence only one state had a smoking rate greater than 16%. The LM plot for the state of Utah shows no clear geographic pattern, due perhaps to a relatively small number of cases in a limited geographic area. CONCLUSIONS: LM plots are effective in representing complex and large volume birth defects data. Integration to birth defects surveillance systems will improve both presentation and interpretation. Birth Defects Research (Part A), 2008. © 2007 Wiley‐Liss, Inc.     

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.     

Nutrient intakes in women and risks of anophthalmia and microphthalmia in their offspring

BACKGROUND: There is a paucity of information about risk factors for the human eye anomalies anophthalmia and microphthalmia. In this population-based case-control study we investigated whether periconceptional intakes of supplemental folic acid, dietary folate, vitamin A, and several other nutrients were associated with these eye defects. METHODS: This study included data on deliveries that had estimated due dates from 1997-2002 and were part of the National Birth Defects Prevention Study (the National Birth Defects Prevention Study is a population-based case-control study of a wide spectrum of birth defects, incorporating data from 10 birth defects surveillance systems in the United States [Arkansas, California, Georgia/Centers for Disease Control and Prevention, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, and Utah]). Cases were those infants or fetuses born with either anophthalmia or microphthalmia. Liveborn infants without major malformations were eligible as controls. Maternal interviews were conducted, primarily by telephone, in English or Spanish. Participation in the interview was 71% among case mothers and 68% among control mothers. Interviews were completed with 89 case mothers and 4,143 control mothers. A shortened version of the food frequency questionnaire from the Nurse's Health Study was used to assess frequency of intake of 58 food items during the year before pregnancy. RESULTS: Our results did not indicate reduced risks for these eye malformations associated with maternal intake of vitamin supplements containing folic acid. The data did not show an association between malformation risk and higher or lower intakes of vitamin A. We also did not observe strong evidence that an abundance or a lack of dietary intake of any other nutrient was associated with increased risk of the studied eye malformations. CONCLUSIONS: Our observations contribute to a limited body of findings on these rare eye defects.     

Patterns and trends of multiple congenital anomalies in birth defects surveillance systems

Infants with multiple congenital anomalies (MCA) can provide important clues in the detection of teratogenic agents. Definition, classification, and ascertainment of MCA vary, however. We present comparative epidemiologic data on MCA from two U.S. surveillance systems: the Metropolitan Atlanta Congenital Defects Program, which ascertains major birth defects during the first year of life, and the Birth Defects Monitoring Program, a nationwide system that relies on newborn hospital-discharge diagnoses. This system has two components: the Commission on Public Hospitals Activities (CPHA) and the McDonnell Douglas Health Information System (MDHIS). Our analyses were based on over 600,000 births occurring in Atlanta, and over 5 million births occurring nationwide. Infants were classified as having MCA if they had two or more major defects from different categories (central nervous system, eye, orofacial, gastrointestinal, cardiovascular, genitourinary, and musculoskeletal). Additional analyses were also done on infants with three or more defects. Compared with the nationwide system, Atlanta showed 1) a much higher rate of MCA (16.2 per 10,000 births vs. 4.9 and 3.8 per 10,000 births in CPHA and MDHIS, respectively) and 2) a higher rate of MCA with chromosomal syndromes (2.0 per 10,000 births vs. 0.6 and 0.3 per 10,000 births in CPHA and MDHIS, respectively). Moreover, in Atlanta, the proportion of MCA with recorded chromosomal syndromes increased substantially during 20 years. These data point to differences in the ascertainment of MCAs in birth defects surveillance systems. More effort is needed to improve the ascertainment and comparability of MCA in surveillance systems, an important step toward better detection of human teratogens.     

Using registry data to suggest which birth defects may be more susceptible to artifactual clusters and trends

BACKGROUND: Some birth defects appear to be more susceptible than others to artifactual prevalence variability over time or geographically. This article uses an empirical approach to try to identify them. METHODS: Assumption: Variation in clinical practice and other artifactual sources of variability impact observed variation in prevalence of mild cases more than severe cases for a given birth defect. Approach: Data were examined from Texas Birth Defects Registry deliveries from 1999-2003. For each of 312 delivery hospitals, birth prevalence for mild cases was calculated for birth defect X. The 5(th) percentile was subtracted from the 95(th) percentile to measure spread in the frequency distribution of all hospitals. That was repeated for severe cases. The ratio of the mild:severe spread was calculated for 49 defects, and the defects ranked into quintiles. That was repeated using birth prevalence based on county, and using isolated cases. The percentages of severe cases were calculated and also ranked into quintiles. A sensitivity analysis and simulation were conducted. RESULTS: Forty-nine birth defects were ranked from those least susceptible to differences in mild:severe prevalence variability (e.g., anencephaly, hypoplastic left heart syndrome) to most susceptible (e.g., atrial septal defect, fetal alcohol syndrome). Resulting quintile ranks based on the three measures were highly correlated, whether based on all cases or isolated cases. CONCLUSIONS: This empirical approach may be helpful for a number of public health applications. Birth defects and other health outcomes more susceptible to prevalence variability may be more likely to exhibit artifactual trends or clusters.     

Risk factors for birth defects: data from the Atlanta Birth Defects Case-Control Study

The Atlanta Birth Defects Case-Control Study data comprises information obtained from interviews with parents of 4,900 babies born with major birth defects and with the parents of 3,000 babies born without defects. The source of cases is the Centers for Disease Control's Metropolitan Atlanta Congenital Defects program; the case-control study is population-based. Birth defects are classified into 92 groups and cross-tabulated by 105 exposure/risk factor variables; data from selected cross-tabulations are presented. The associations of each of the 105 exposure variables with all types of defects combined are presented, as are the associations of each of the 92 defect groups with the specific exposure variable, maternal diabetes. These data can be used to evaluate hypotheses arising from other sources, and for the purpose of "generating" hypotheses. The data describing all 92 x 105 cross-tabulations are available to other investigators on floppy disk; write to Chief, Birth Defects and Genetic Diseases Branch, Centers for Disease Control, Atlanta, Georgia 30333.     

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 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.