Joseph M. Lary

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.

Teratology Society Public Affairs Committee position paper: developmental toxicity of endocrine disruptors to humans.

SUSAN BARLOW,1 ROBERT J. KAVLOCK,2 JOHN A. MOORE,3 SUSAN L. SCHANTZ,4 DANIEL M. SHEEHAN,5 DANA L. SHUEY,6 AND JOSEPH M. LARY7* 1Consultant Toxicologist, Brighton, East Sussex, BN1 6RE United Kingdom 2Reproductive Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711 3Institute for Evaluating Health Risks, Washington, DC 20006 4Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana, Illinois 61802 5Genetic and Reproductive Toxicology Division, National Center for Toxicological Research, Jefferson, Arkansas 72079 6DuPont Pharmaceuticals Company, Stine-Haskell Research Center, Newark, Delaware 19714 7Division of Birth Defects and Pediatric Genetics, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia 30341

The return of thalidomide: can birth defects be prevented?

Thalidomide, the drug that caused a worldwide epidemic of serious birth defects in the late 1950s and early 1960s, was recently approved by the US Food and Drug Administration (FDA) for use in treating the skin disease erythema nodosum leprosum, a complication of leprosy. The drug has also shown promise in the treatment of other serious diseases. If thalidomide is eventually approved for use in the US and other countries for treatment of diseases more prevalent than erythema nodosum leprosum, or if use of the drug for non-approved indications becomes widespread, hundreds of thousands of women with childbearing ability could be treated. If this should happen, can we prevent another epidemic of birth defects?In an effort to prevent fetal exposures to thalidomide, the FDA mandated a comprehensive programme to regulate prescription, dispensing and use of the drug. The programme is designed to require registration of all participating pre-scribers, pharmacies and patients. It also requires use of effective methods of contraception and periodic pregnancy testing of all patients with childbearing ability during treatment. Prescribers are directed to counsel both female and male patients on the risks, benefits and proper use of the drug, as well as on the proper use of contraceptives during treatment. The patient is required to sign an informed consent form before beginning treatment. Prescription and dispensing of thalidomide will be tightly controlled. A thalidomide registry will monitor prescription, dispensing and use of the drug, and will investigate all reported fetal exposures.This mandatory, but untested, programme promises to be effective at preventing fetal exposures to thalidomide, provided that patients, prescribers and pharmacists comply with all of its provisions. However, even if the programme proves to be successful in the US, there is concern that thalidomide may eventually be widely used in countries that may not require such stringent controls. In Brazil, where thalidomide is commercially available for treatment of leprosy patients, 33 cases of thalidomide embryopathy have already been reported in the literature. Even in countries that may tightly regulate the distribution and use of thalidomide, some patients may obtain the drug through black market sources. Should these events occur, many cases of thalidomide-induced birth defects could appear. Therefore, there is a need to develop nonteratogenic analogues of thalidomide that can provide effective treatment for erythema nodosum leprosum and other serious conditions without increasing the potential for another epidemic of thalidomide-related birth defects.

Prevalence of Spina Bifida at Birth — United States, 1983–1990: a Comparison of Two Surveillance Systems†

PROBLEM/CONDITION Spina bifida is a birth defect of the spinal column that is a substantial contributor to serious developmental disabilities in the United States. The risk for spina bifida and other neural tube defects (NTDs) can be reduced if women consume 0.4 mg of folic acid before and during the first trimester of pregnancy. Public health programs are being developed to prevent many NTDs by increasing the consumption of folic acid by women of childbearing age. To assess the national impact of these programs on the prevalence of NTDs at birth, multistate surveillance is needed to monitor secular trends in birth-prevalence rates. This report summarizes a collaborative effort by CDC and state birth defect surveillance programs in 16 states to a) obtain multistate, population-based data concerning the birth prevalence and descriptive epidemiology of spina bifida and b) determine the usefulness of combining state surveillance data to monitor national trends in the birth prevalence of NTDs. REPORTING PERIOD This report presents data from birth defects surveillance systems in 16 states for the period 1983-1990 (specific periods covered varied by state). These findings are compared with CDCs Birth Defects Monitoring Program (BDMP) for the same period. DESCRIPTION OF SYSTEMS Population-based data about live-born and stillborn infants who have spina bifida were analyzed from 16 state programs. These 16 programs differed in size and racial/ethnic composition of the populations, surveillance methods, and completeness of case ascertainment. Hospital-based data about live-born and stillborn infants who have spina bifida also were analyzed from BDMP, a passive case ascertainment surveillance system that obtains data from participating hospitals in 50 states. RESULTS AND INTERPRETATION From 1983 through 1990, the birth-prevalence rate for spina bifida for the 16 states was 4.6 cases per 10,000 births; the BDMP rate was nearly identical (4.4 cases). State-specific rates varied substantially, ranging from 3.0 (Washington) to 7.8 (Arkansas). Both state-based and BDMP rates varied among racial/ethnic groups; in both systems, the rates were highest for Hispanics and lowest for Asians/Pacific Islanders. In both the state-based surveillance systems and BDMP, the annual rate of spina bifida for the total population declined during the period 1983-1990. Much of this decline can be attributed to increased prenatal diagnosis in the 1980s. However, because of decline in the rates of spina bifida and other NTDs in the United States began before the widespread availability of prenatal diagnostic services, an environmental component may have contributed substantially to the etiologies of these defects. The birth-prevalence rate of spina bifida was slightly higher among females than males. The ratio of female-to-male prevalence rates was 1.2 for both the state-based surveillance systems and BDMP. This ratio varied considerably among racial/ethnic groups and among states. The similarities of rates and trends in the birth prevalence of spina bifida between the state-based surveillance data and the BDMP data indicate that both types of surveillance systems can provide reliable information concerning national trends in the birth prevalence of spina bifida. ACTIONS TAKEN CDC and state birth defects surveillance programs will use results from this analysis to monitor national trends in the birth prevalence of spina bifida in the United States. Aggregated state-based surveillance data about spina bifida, anencephaly, and other NTDs will facilitate the monitoring of changes in NTDs after implementation of programs to increase folic acid consumption by women of childbearing age.