Predictive value of minor anomalies: II. Use in cohort studies to identify teratogens

Abstract

Cohort studies of putative human teratogens can identify the full spectrum of phenotypic effects, including both major malformations and minor anomalies. Cohort studies which include the much more common minor anomalies make it possible to use a relatively small number of exposed and unexposed infants to identify an increase in the frequency of malformations. We evaluated this use of minor anomalies in a cohort study of newborn infants who had been exposed in utero to three putative teratogens: insulin-dependent diabetes mellitus in the mother and the use of the anticonvulsant phenytoin and exogenous sex hormones by the mother. In addition, the reproducibility of identifying minor anomalies was tested by comparing the results of examinations by two independent observers of 444 unexposed infants. The frequency of minor anomalies was increased among infants of diabetic mothers. However, the reproducibility of identifying minor anomalies was poor. We conclude that the examination of teratogen-exposed infants for minor anomalies cannot be used in epidemiologic studies of putative teratogens unless special efforts are made to maximize consistency in the identification of these features.

Inclusion and exclusion criteria for malformations in newborn infants exposed to potential teratogens

“…For example, two examiners of the same 444 infants born at this hospital, using the same definitions and an examination protocol, often did not record the same findings. They had poor agreement for 75% of the features evaluated, good agreement for 19.8%, and excellent agreement for only 5.2% of the features (Holmes et al, 1987).…”

“…This exclusion was based on our previous experience in this project with identifying the presence of minor anomalies and normal variations (Holmes et al, 1987;Leppig et al, 1987), birth marks (Alper and Holmes, 1983), and genetic abnormalities (Nelson and Holmes, 1989;Rasmussen et al, 1996;Holmes et al, 1997;Lin et al, 1998) in systematic study examinations.…”

Birth defects in children with newborn encephalopathy

“…It is important to note that among control children with birth defects the proportion of major defects was similar to that found in children with birth defects and that it was not the severity of birth defects that distinguished between them. The similarity of this distribution also suggests that the children with newborn encephalopathy were not examined more carefully for birth defects than the randomly selected control children which minimizes a possible source of bias in the study (Holmes et al 1987). There was no particular pattern to the birth defects found among infants with encephalopathy, and all systems were represented among the defects.…”

Latent Class Analysis of Complex Sample Survey Data

“…LC and trait models are very useful for summarizing multiple outcomes and has the potential to increase the power to identify effects (Sammel and Ryan 1996; Holmes et al 1987). PDG mention that LC methods are useful tools for data reduction; however, they do not use this attribute to the fullest extent.…”