High vitamin A intake in early pregnancy and major malformations: A multicenter prospective controlled study

The European Network of the Teratology Information Services (ENTIS) collect ed and evaluated data on 423 pregnancies exposed during the first 9 weeks o f gestation to a "high" dose of vitamin A (10,000 IU per day or more). Data were collected prospectively; 394 women (93.1%) were followed by telephone interview up to the first few weeks after the expected date of delivery, u sing standardized procedures. The presence of major structural malformation s, excluding chromosomal and genetic diseases, was evaluated in 311 infants exposed to a median daily dose of vitamin A of 50,000 IU per day(range, 10 ,000-300,000 IU per day; interquartile range, 25,000-60,000 IU per day). Th ree infants with a major malformation were reported: pulmonary stenosis, st enotic anus with fistula, and bilateral inguinal hernia. No congenital malf ormations were reported among 120 infants exposed to more than 50,000 IU pe r day of vitamin A. When the birth prevalence rate of major malformations i n the study group was compared with two internal control groups of infants exposed to: 1) "high" vitamin A exposure later in pregnancy, and 2) nontera togenic agent exposures, the rate ratio was, respectively, 0.28 (CI 95% int erval, 0.06, 1.23) and 0.50 (CI 95% interval, 0.14, 1.76). The studied samp le did not provide evidence for an increased risk of major malformations, a ssociated with "high" vitamin A intake during the organogenetic period, hig her than 2.76 above the control reference risk of 1.91% (power 80%, alpha 0 .10). Teratology 59:7-11, 1999. (C) 1999 Wiley-Liss, Inc.