Congenital heart defects, maternal febrile illness, and multivitamin use: a population-based study.

We assessed the relation between febrile illness during pregnancy and cardiac defects in the offspring in a population-based case-control study in metropolitan Atlanta. Case infants (905) with cardiac defects were actively ascertained from multiple sources. Control infants (3,029) were infants without birth defects who were selected from birth certificates by stratified random sampling. We compared those whose mothers reported febrile illness from 1 month before pregnancy through the third month of pregnancy with those whose mothers reported no illness during the same period. Febrile illness was positively associated with the occurrence of heart defects in the offspring (odds ratio [OR] = 1.8; 95% confidence interval = 1.4-2.4). When influenzalike illness was the reported febrile illness, the OR was 2.1 (95% confidence interval = 0.8-5.5). The association with febrile illness was strongest for tricuspid atresia (OR = 5.2), left obstructive defects (OR = 2.7), transposition of the great arteries (OR = 1.9), and ventricular septal defects (OR = 1.8). These ORs were generally lower among mothers who used multivitamins during the periconceptional period.

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, 7,470 cases and 3,821 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 nation's 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.

Maternal flu, fever, and the risk of neural tube defects: a population-based case-control study.

Results of clinical and epidemiologic studies have shown an increased risk for neural tube defects (NTD) in infants whose mothers were exposed to heat during pregnancy. However, the risk for NTD in infants whose mothers had influenza during pregnancy has not been well studied. This population-based case-control study of infants born in metropolitan Atlanta, Georgia, from 1968 through 1980 included 385 infants with NTD, 3,647 infants with other birth defects, and 2,676 infants without birth defects. Of the 385 mothers of case infants, 31 reported having a 2-day or longer episode of flu with fever from 1 month before through 3 months after conception (odds ratio (OR) = 3.0; 95% confidence interval (CI) 1.9-4.7). Infants of mothers who took medications for their episodes of flu with fever had an even higher risk for NTD (OR = 4.3, 95% CI 2.6-7.1). When mothers of infants with birth defects other than NTD were used as controls, an increased risk of NTD remained for flu with fever (OR = 1.7, 95% CI 1.1-2.5). There was no increased risk for NTD among the infants of mothers who reported fever from causes other than flu. Because of the heterogeneity of maternal flu, the individual contributions of infection, fever, and medications remain difficult to disentangle.

Congenital yellow fever virus infection after immunization in pregnancy.

To determine whether yellow fever (YF) vaccine administered in pregnancy causes fetal infection, women who were vaccinated during unrecognized pregnancy in a mass campaign in Trinidad were studied retrospectively. Maternal and cord or infant blood were tested for IgM and neutralizing antibodies to YF and dengue viruses. One of 41 infants had IgM and elevated neutralizing antibodies to YF virus, indicating congenital infection. The infant, the first reported case of YF virus infection after immunization in pregnancy, was delivered after an uncomplicated full-term pregnancy and appeared normal. Congenital dengue 1 infection may have occurred in another case. The frequency of fetal infection and adverse events after such exposure could not be estimated; however, the neurotropism of YF virus for the developing nervous system and the now documented possibility of transplacental infection underscores the admonition that YF vaccination in pregnancy should be avoided.

Congenital yellow fever virus infection after immunization in pregnancy

To determine whether yellow fever (YF) vaccine administered in pregnancy causes fetal infection, women who were vaccinated during unrecognized pregnancy in a mass campaign in Trinidad were studied retrospectively. Maternal and cord or infant blood were tested for IgM and neutralizing antibodies to YF virus, indicating congenital infection. The infant, the first repotred case of YF virus infection after immunization in prgnancy, was delivered after an uncomplicated full-term pregnancy and appeared normal. Congenital dengue 1 infection may have occurred in another case. The frequency of fetal infection and adverse events after such exposure could not be estimated; however, the neurotropism of YF virus for the developing nervous system and the now documented possibility of trans-placental infection underscores the admonition that YF vaccination in pregnancy should be avoided (AU)

Interaction between epidemiology and laboratory sciences in the study of birth defects: design of birth defects risk factor surveillance in metropolitan Atlanta.

Despite years of research, the etiology of most birth defects remains largely unknown. Interview instruments have been the major tools in the search for environmental causes of birth defects. Because of respondents' problems with recognition and recall, interviews are limited in their capacity to measure certain exposures. Laboratory scientists can have a major impact on defining markers of environmental exposure and genetic susceptibility. The Centers for Disease Control is starting a case-control study of serious birth defects on the basis of a population-based surveillance system for birth defects diagnosed during the first year of life in metropolitan Atlanta. Each year, 300 infants with selected birth defects (case subjects) and 100 population-based control subjects (infants without birth defects) will be enrolled in an ongoing study that will supplement surveillance. In addition to conducting extensive maternal interviews, we will collect blood and urine specimens from case and control subjects and their mothers for laboratory testing. Eventually, some environmental sampling may be incorporated. Particular areas of emphasis are (1) nutritional factors, specifically measuring maternal folic acid levels and other micronutrients (e.g., zinc) to explore their role in the etiology of neural tube defects, (2) substance use, specifically measuring cocaine metabolites in the blood and urine to explore their role for specific vascular disruption defects, and (3) environmental factors such as pesticides and aflatoxins, to explore their potential relationships with specific defects. In addition, a DNA bank will be maintained to evaluate the role of specific candidate genes in the etiology of birth defects. The development and testing of these methods could be useful to assess the interaction between environmental exposures and genetic susceptibility in the etiology of birth defects.

Leukemia in telephone linemen.

This case-control study examines potential associations between telephone linework and the occurrence of leukemia except chronic lymphocytic leukemia in a primarily retired population of American Telephone and Telegraph Company (AT&T) workers. Cases died between 1975 and 1980. Exposure is defined both by job title and, for workers with complete job histories, by a lifetime exposure score based on industrial hygiene personal monitoring measurements of line and nonline jobs. When the time-weighted average mean for each job is accumulated into a lifetime exposure score, workers with scores above the median for the population show an excess of leukemia 2.5 times higher than workers below the median (95% confidence interval (CI) 0.7-8.6). Those individuals with long duration of employment in jobs with intermittent peak exposures may be at higher risk of leukemia than those with a constant exposure level. Analyses that allow for a latent period suggest the risk is associated with exposures that occurred 10 or more years before death. Workers with peak exposure scores above the median have odds ratios of 2.4 (95% CI 0.7-9.0) and 6.6 (95% CI 0.7-58) for latent periods of 10 and 15 years, respectively. The data suggest an increasing risk with increasing exposure (p for trend = 0.05) when cumulated scores are based on peak exposure scores. Peak exposures tended to occur in cable splicing work and in old telephone switching offices. The numbers in this study are small and observed differences may be due to chance.

Quantitative analysis of associations between birth defects and suspected human teratogens.

Case series of infants with certain birth defect patterns and putative teratogenic exposures should be interpreted with caution since the presence of birth defects and the exposure among the same infants could be entirely due to chance. In the absence of other epidemiologic data, the plausibility for a causal association is strengthened by 1) rarity of the defect pattern, 2) rarity of the exposure in the population, 3) small source population, 4) short time period for the study, and 5) biologic plausibility for the association. These concepts are illustrated using case reports of putative teratogenicity of cocaine and etretinate. In the presence of epidemiologic data, the concept of attributable fraction in exposed (AFE) can be used to evaluate the likelihood that the defect pattern among infants with a particular exposure is attributable to the exposure. This quantity is related to the strength of the epidemiologic association between the defect pattern and the exposure, as measured in terms of relative risk R (or odds ratio), and is equal to (R-1)/R. Even for strong teratogens such as maternal diabetes and isotretinoin, where R is about 7, in more than 14% (1-AFE) of exposed infants with birth defects, the pattern of defects is not attributable to the exposure. Furthermore, AFE can be used to "correct" crude measures of sensitivity (the proportion of exposed malformed infants with a defect pattern attributable to the exposure) and positive predictive value (the proportion of malformed infants who have the exposure and have the defect pattern attributable to the exposure).(ABSTRACT TRUNCATED AT 250 WORDS)

Surveillance of postneonatal mortality, United States, 1980-1987.

In the United States, one-third of all infant deaths (deaths of infants ages 0-364 days) occurs in the postneonatal period (28-364 days). A substantial proportion of these deaths potentially could be prevented. To examine recent trends in postneonatal mortality (PNM) in the United States, the investigators analyzed birth and death certificate data for resident infants for the period from 1980 through 1987. Rates of PNM declined 11% from 3.5 to 3.1/1,000 live births among white infants and declined 16% from 7.3 to 6.1/1,000 live births among black infants. Most of the decline resulted from reduced mortality from infectious diseases and injuries. A decreased mortality attributable to sudden infant death syndrome (SIDS) among black infants additionally accounted for the decline. Autopsy rates for SIDS increased from 82% to 92% but did not differ for black infants and white infants. Birth defects-related PNM declined more among white infants than among black infants. The racial gap in PNM (rate ratio (RR) = approximately 2.0) persisted. However, the largest black/white gap occurred in the Northeast (RR = 2.5), the region with the lowest PNM. Black infants were 2.7 and 2.3 times more likely to die of infections and injuries, respectively, than were white infants. Although PNM rates declined during the 1980s, a greater rate of reduction is needed to achieve the Year 2000 objectives, especially among black infants. Such reductions are possible through improved access to comprehensive pediatric care as well as education and community-oriented prevention programs designed to reduce deaths due to infections and injuries. A better understanding of the etiology of SIDS and birth defects is critical for preventing postneonatal deaths.

Sensitivity, specificity, and positive predictive value of multiple malformations in isotretinoin embryopathy surveillance.

Isotretinoin causes serious birth defects in about 25% of babies exposed in the first trimester of pregnancy. Despite warnings about the drug's teratogenicity, cases of isotretinoin embryopathy continue to occur; more than 80 such cases have been reported since 1982. The true magnitude of the problem is unknown, however, and case estimates range to more than 1,000. The need for isotretinoin embryopathy (IE) surveillance is therefore great. Sixty-one known cases were evaluated to determine the sensitivity (proportion of cases with a given defect pattern) of various defect combinations. Using data from the Metropolitan Atlanta Congenital Defects Program for the period before isotretinoin was available, we evaluated the specificity (proportion of malformed infants without exposure who do not have the pattern of defects) for the various defect combinations. Ear malformations (microtia, anotia, absence or stricture of auditory canal, missing pinnae) have an associated sensitivity of 70.5% and a specificity of 99.5%. Ear defects combined with central nervous system (CNS) defects (microcephalus, hydrocephalus, reduction deformities of the brain) and cardiovascular (CVS) defects (conotruncal defects, aortic arch abnormalities) have an associated sensitivity of 19.7% and a specificity of 100.0%. The case definition of ear defects combined with either CNS or CVS defects maximizes both specificity (99.9%) and sensitivity (45.9%). The investigators are now evaluating the feasibility of using this pattern of defects to monitor for IE within a national monitoring program.

Contribution of birth defects to infant mortality among racial/ethnic minority groups, United States, 1983.

Linked birth/infant death data from the National Center for Health Statistics (NCHS) for the 1983 U.S. birth cohort, the latest year for which linked data were available, were evaluated in order to assess the contribution of birth defects to infant mortality among racial/ethnic groups. Of the 34,566 singleton infant deaths with specified birth weight born to U.S. residents, birth defects were listed as an underlying cause of death for 7,678 (22.2%) infants and as a contributing cause of death for an additional 1,006 (2.9%) infants. Infant mortality rates due to birth defects were highest among American Indians (2.9 deaths/1,000 live births), followed by Asians and Hispanics (2.6), and blacks (2.5). Proportional mortality due to birth defects varied among racial/ethnic groups; it was greatest among Asians (27%), followed by whites (25%), Hispanics (24%), American Indians (18%), and blacks (13%). Also, infant mortality rates due to birth defects were high among minority infants of low birth weight, particularly among those born weighing between 1,500 and 2,499 g. Within this group of infants, proportional mortality due to birth defects ranged from 52% among Asians to 29% among blacks. These data indicated that birth defects were an important contributor to infant mortality among all racial/ethnic groups. Birth-defects surveillance systems should be used to evaluate whether racial/ethnic differences in infant mortality from birth defects are due to differences in incidence and/or survival among minority infants with birth defects.