Predictive value of minor anomalies. I. Association with major malformations

doi:10.1016/S0022-3476(87)80543-7

The Journal of Pediatrics

Volume 110, Issue 4, April 1987, Pages 531-537

https://doi.org/10.1016/S0022-3476(87)80543-7 Get rights and content

We examined 4305 white newborn infants for 114 minor physical features and major malformations to evaluate the hypothesis that the presence of three or more minor anomalies is highly predictive of a major malformation. We confirmed that the infant with three or more minor anomalies is at increased risk for a major malformation. However, this risk (19.6%) was much lower than the risk of 90% popularized by Smith and based on the study of Marden et al. (J Pediatr 1964;64:357). Analysis of the findings in the two studies showed that the lower predictive value was probably related to differences in study design. Nevertheless, some minor anomalies remain essential to the early recognition of several serious malformation syndromes.

References (14)

MardenPM et al.
Congenital anomalies in the newborn infant, including minor variations
J Pediatr
(1964)
AlperJC et al.
Birth marks with serious medical significance: nevocellular nevi, sebaceous nevi, and multiple cafe-au-lait spots
J Pediatr
(1979)
MehesK et al.
Minor malformations in the neonate
Helv Pediatr Acta
(1973)
MehesK
Minor malformations in the neonate
(1983)
WaldropMF et al.
Newborn minor physical anomalies predict short attention span, peer aggression, and impulsivity at age 3
Science
(1978)
SmithDW
Recognizable patterns of human malformation
HolmesLB et al.
Mental retardation: an atlas of diseases with associated physical abnormalities
(1972)

There are more references available in the full text version of this article.

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Citation Excerpt :
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⁺: Supported in part by grants from the Developmental Disabilities Council of the Commonwealth of Massachusetts, by Grant 10910 from the National Institutes of Health, and by a grant from Merrell Dow Pharmaceuticals, Inc.

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Original articlePredictive value of minor anomalies. I. Association with major malformations+

J Pediatr

J Pediatr

Minor malformations in the neonate

Helv Pediatr Acta

Minor malformations in the neonate

Newborn minor physical anomalies predict short attention span, peer aggression, and impulsivity at age 3

Science

Recognizable patterns of human malformation

Mental retardation: an atlas of diseases with associated physical abnormalities

Original article
Predictive value of minor anomalies. I. Association with major malformations+