Minor anomalies in stillborn and second trimester miscarried fetuses

In 1964, the landmark paper of Marden, Smith, and McDonald established that multiple minor anomalies in newborn infants are associated with an increased risk for major malformations. There were until now no comparable studies in stillbirths. The Wisconsin Stillbirth Service Program (WiSSP) has data regarding nearly 3,000 stillbirths and second trimester losses that have been analyzed for major anomalies and cause of death. One dysmorphologist retrospectively reviewed all 2,397 with usable photographs. Minor anomalies were identified in 1,413 (59%) with 575 of these (41%) having at least one major anomaly. Probability of a major anomaly increased from 7% with no minor anomalies to 15%, 36%, 67%, and 89% with 1, 2, 3, and >33 minor anomalies, respectively. Frequency of minor anomalies was less with lower resolution photographs, but did not show significant differences with maceration or gestational age. The most frequent minor anomalies were infraorbital creases/folds, lowset/posteriorly angulated ears, nuchal edema, flat face, equinovarus foot, camptodactyly, upslanted palpebral fissures, ear antihelix abnormalities (combined), micrognathia/retrognathia, and single transverse palmar crease. Except for infraorbital creases/folds each of these minor anomalies was strongly correlated with major anomalies (P < 0.0001). Infraorbital folds were the only anomaly which increased with placental cause of death, and reanalysis with placental causes excluded showed the expected relationship to major anomalies, suggesting that infraorbital folds may be markers for oligohydramnios due to various causes including placental hypoperfusion. Minor anomalies correlate with presence of major anomalies in stillborn fetuses, regardless of gestational age and maceration, and can provide information to guide decisions regarding laboratory testing and other evaluations.