Larry D. Edmonds

The National Birth Defects Prevention Study.

The National Birth Defects Prevention Study was designed to identify infants with major birth defects and evaluate genetic and environmental factors associated with the occurrence of birth defects. The ongoing case-control study covers an annual birth population of 482,000 and includes cases identified from birth defect surveillance registries in eight states. Infants used as controls are randomly selected from birth certificates or birth hospital records. Mothers of case and control infants are interviewed and parents are asked to collect buccal cells from themselves and their infants for DNA testing. Information gathered from the interviews and the DNA specimens will be used to study independent genetic and environmental factors and gene-environment interactions for a broad range of birth defects. As of December 2000, 7470 cases and 3821 controls had been ascertained in the eight states. Interviews had been completed with 70% of the eligible case and control mothers, buccal cell collection had begun in all of the study sites, and researchers were developing analysis plans for the compiled data. This study is the largest and broadest collaborative effort ever conducted among the nations leading birth defect researchers. The unprecedented statistical power that will result from this study will enable scientists to study the epidemiology of some rare birth defects for the first time. The compiled interview data and banked DNA of approximately 35 categories of birth defects will facilitate future research as new hypotheses and improved technologies emerge.

Decline in the Prevalence of Spina Bifida and Anencephaly by Race/Ethnicity: 1995–2002

Objective. In an effort to reduce the occurrence of neural tube defects (NTDs), folic acid fortification of US enriched grain products was authorized by the Food and Drug Administration in March 1996 and required by January 1998. Fortification has been shown to result in an important decline in the prevalence of spina bifida and anencephaly in the general US population; however, fortifications impact on specific racial/ethnic groups has not been well described. We sought to characterize the decline in the prevalence of spina bifida and anencephaly among specific racial/ethnic groups during the transition to mandatory folic acid fortification in the United States. Methods. Data from 21 population-based birth defects surveillance systems were used to examine trends in prevalence of spina bifida and anencephaly for specific racial/ethnic groups for the years 1995–2002. These years were divided into 3 periods: prefortification, optional fortification, and mandatory fortification. Race/ethnicity was defined as Hispanic, non-Hispanic white, and non-Hispanic black. Prevalence ratios were calculated for each racial/ethnic group by dividing the prevalence from the mandatory fortification period by the prevalence in the prefortification period. Results. The study included data on 4468 cases of spina bifida and 2625 cases of anencephaly. The prevalence of spina bifida and anencephaly was highest among Hispanic births, followed by non-Hispanic white births, with the lowest prevalence among non-Hispanic black births. Significant declines in spina bifida and anencephaly were observed among Hispanic births and non-Hispanic white births. The prevalence ratio for non-Hispanic black births was of borderline significance for spina bifida and was not significant for anencephaly. Conclusions. The results of this study suggest that folic acid fortification is associated with significant decreases in the prevalence of spina bifida and anencephaly among non-Hispanic white and Hispanic births. The magnitude of the reduction was similar between these 2 groups and was more pronounced for spina bifida than for anencephaly. The decline in the prevalence of spina bifida and anencephaly among non-Hispanic black births did not reach statistical significance. Efforts to increase folic acid consumption for the prevention of NTDs in pregnancies among women of all races/ethnicities should be continued, and studies to identify and elucidate other risk factors for NTDs are warranted.

Review of four cases of childhood hepatic angiosarcoma--elevated environmental arsenic exposure in one case.

Four cases of childhood hepatic angiosarcoma (HAS), representing the malignant form of infantile hemangioendothelioma, are described. The morphologic appearance of childhood HAS differs from the adult form in the following features: the associated presence of benign infantile hemangioendothelioma; the presence of dysontogenetic features; and an altered appearance of the angiosarcoma itself. It is postulated for these cases that the benign infantile hemangioendothelioma progressed to the malignant angiosarcoma. One of the four cases had exposure to elevated levels of arsenic in the environment that may have contributed to this progression. This latter case adds to published reports associating arsenic exposure with increased risk for hepatic angiosarcoma.

Goldenhar syndrome among infants born in military hospitals to Gulf War veterans

Reports in the popular press described the occurrence of Goldenhar syndrome among children of Persian Gulf War veterans (GWVs). The objective of this investigation was to compare the birth prevalence of Goldenhar syndrome among infants born in military hospitals to GWVs and to military personnel who were not deployed to the Gulf War (NDVs). Computerized hospital discharge data were reviewed for infants conceived after the war and born prior to the 1st of October, 1993, in medical treatment facilities (MTFs) operated by the U.S. Department of Defense. Medical records were evaluated for infants diagnosed at birth with at least one abnormality that might be related to Goldenhar syndrome. Two pediatricians, blinded to the parental Gulf War status of each infant, reviewed records. An estimated 75,414 infants were conceived after the Gulf War and born in MTFs during the study period (34,069 GWV infants and 41,345 NDV infants). Seven infants fulfilled the case criteria (five GWV infants and two NDV infants). All infants had fathers who served in the military at the time of their conception and birth. The birth prevalence was 14.7 per 100,000 live births among GWV infants (95% confidence interval [CI]: 5.4-36.4) and 4.8 per 100,000 live births (95% CI: 0.8-19.5) among NDV infants (relative risk: 3.03; 95% CI: 0.63-20.57; P values: [2-tailed] = 0.26, [1-tailed] = 0.16). The few affected cases and the broad confidence intervals surrounding the relative risk require that these results be interpreted with caution and do not exclude chance as an explanation for these findings.

Airport Noise and Teratogenesis

It has been suggested that exposures to high-noise levels near major airports may cause increased incidence of birth defects in the offspring of parents residing near these airports. Using data gathered in Metropolitan Atlanta during 1970 to 1972, we compared the rates of seventeen categories of defects in high- and low-noise census tracts. No significant differences were observed. However, when we subdivided the category of central nervous system defects into several subcategories of specific defects, we noted a significantly increased incidence of spina bifida without hydrocephalus in the high-noise areas. Because the small number of cases associated with this finding we did a matched case-control study using all cases of central nervous system defects born during the years 1968 to 1976. No significantly increased risk for residents in the high-noise areas was noted in this study. It is our opinion that noise or other factors associated with residence near airports are unlikely to be important environmental teratogens.

State birth defects surveillance programs directory

State health officers provided the information for this directory. Their names can be found under the “Contact” section of each state profile.

Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites. I. birth defects and developmental disorders

Members of the workgroup on birth defects and developmental disorders discussed methods to assess structural anomalies, genetic changes and mutations, fetal and infant mortality, functional deficits, and impaired fetal and neonatal growth. Tier 1 assessments for all five adverse reproductive outcomes consist of questionnaires and reviews of medical records rather than laboratory testing of biologic specimens. The work-group members noted a role for neurodevelopmental testing and for limited genetic studies, such as karyotyping in Tier 2 assessments. Emerging methodologies to identify chromosomal aberrations, DNA adducts, and repair inhibition were reserved for Tier 3.

Role of exposure databases in epidemiology

At present, exposure databases record data primarily for regulatory purposes; they have not focused on serving the needs of epidemiologists or public health. However, the modification of exposure databases could facilitate their use in epidemiology. Characteristics necessary to enhance the use of all databases include easy access by users; documentation of methods, sampling bias, error, and inconsistences; widespread coverage in time and space; and methods and measures for estimating exposure of individuals as well as populations. Also needed are exposure scenarios and models to estimate exposures for geographic areas and time intervals not currently sampled. Multidisciplinary teams are needed to examine current databases, to review strategies for improving data collection, and to suggest and help implement appropriate changes. A long-term goal is to develop and validate data from exposure scenarios and models using data on the relationship of exposure to doses measured in humans.

Surveillance for Anencephaly and Spina Bifida and the Impact of Prenatal Diagnosis—United States, 1985–1994

PROBLEM/CONDITION The reported prevalence of anencephaly and spina bifida in the United States has steadily declined since the late 1960s. During this time, the ability to diagnose these defects prenatally has progressed rapidly. Many U.S. birth defects surveillance systems ascertain defects only among live-born infants or among infants and fetuses beyond a certain gestational age, thus excluding defects among pregnancies prenatally diagnosed as being affected by a neural tube defect (NTD) and electively terminated before the gestational age limit. The impact of prenatal diagnosis and subsequent pregnancy termination on the reported prevalence of anencephaly and spina bifida in the United States has not been well established. However, assessment of this impact is crucial to the use of surveillance data to monitor trends in the occurrence of NTDs and the effectiveness of interventions for these defects (e.g., increased consumption of folic acid). REPORTING PERIOD This report presents data from birth defects surveillance systems in six states over different time periods: Arkansas, 1985-1989; California, 1989-1991; Georgia, 1990-1991; Hawaii, 1988-1994; Iowa, 1985-1990; and South Carolina, 1992-1993. DESCRIPTION OF SYSTEMS Population-based data about a) live-born and stillborn infants with anencephaly and spina bifida and b) pregnancies electively terminated after prenatal diagnosis of these defects were analyzed from the Arkansas Reproductive Health Monitoring System; the California Birth Defects Monitoring Program; CDCs Metropolitan Atlanta Congenital Defects Program; the Iowa Birth Defects Registry, the University of Iowa, and the Iowa Department of Public Health; and the Greenwood Genetic Center in South Carolina. Data also were analyzed from the Hawaii Birth Defects Monitoring Program, which includes data for some women who were not residents of the state. The systems differed in the size and racial/ethnic composition of the populations studied, the surveillance methods used, the completeness of ascertainment, and the availability and utilization of prenatal testing and pregnancy termination. RESULTS AND INTERPRETATION Among all pregnancies ascertained in which the infant or fetus had anencephaly or spina bifida, the percentages that were electively terminated ranged from 9% in Arkansas to 42% in Atlanta and Hawaii, with a corresponding increase in the adjusted prevalence of these defects compared with the prevalence at birth. In each system, pregnancies associated with anencephaly were terminated more frequently than were those associated with spina bifida. These data indicate that the impact of prenatal diagnosis and subsequent pregnancy termination on the prevalence at birth of anencephaly and spina bifida differs among geographic areas and populations. Comprehensive surveillance for these defects requires inclusion of pregnancies that are prenatally diagnosed and then terminated. ACTIONS TAKEN CDC will use these data to promote the inclusion of prenatally diagnosed and terminated pregnancies in estimates of the prevalence of anencephaly and spina bifida generated by birth defects surveillance programs in the United States. Including such pregnancies is crucial to the ability of these programs to monitor trends accurately and to establish the effectiveness of interventions, including the use of folic acid, for these defects.

Registry to Referral: A Promising Means for Identifying and Referring Infants and Toddlers for Early Intervention Services.

Birth defects are the leading cause of death for infants in their first year of life and contribute substantially to childhood morbidity and long-term disability among survivors. Both the Centers for Disease Control and Prevention and the March of Dimes Birth Defects Foundation actively support birth defects monitoring programs across the United States. Currently, 33 states have some type of birth defects monitoring program and 16 more have programs in the planning stages. In general, these surveillance programs track birth defects to describe incidence and identify subpopulations for possible preventive interventions. The importance of early intervention in reducing or preventing secondary disabilities associated with a primary condition has been well documented. A birth defects registry, because of its ability to capture this information earlier than other data collection methods, is a potentially valuable source of information to use in referring families for services. In this paper, we describe the results of a survey to identify programs that are using, or are planning to use, their birth defects surveillance systems as a means of identifying and referring children and families for services. We report the level of interest and experience in developing such referral systems in state birth defect surveillance programs, provide 4 brief case examples, and recommend steps early intervention professionals can take to further discussion about using registries for making referrals.