Hypervitaminosis a in early human pregnancy and malformations of the central nervous system

Abstract

A case of malformations of the fetal central nervous system following hypervitaminosis A in early pregnancy is reported. The mother was treated with 150 000 IU vitamin A daily during gestation days 19 to 40. Determination of urinary oestriol carried out in the 42nd week of pregnancy revealed a very low excretion (4.2-6.6) mumol/24 h). Induced delivery resulted in a microcephalic child who died after 18 min. The child had multiple malformations of the central nervous system and very small adrenal glands (1.5 g; normal 11 +/- 4 g). The very low urinary oestriol excretion is well explained by the hypoplastic adrenals, which in turn can be related to insufficient ACTH stimulation, a condition similar to anencephaly. The malformations shown in the present case are considered to be related to the high doses of vitamin A given to the mother, and the authors wish to warn against uncritical use of high doses of vitamin A in whomen of childbearing age.

Epidemiological aspects of prenatal exposure to high doses of vitamin a in Spain

“…However, we still know very little about the effect of vitamin A on human intrauterine development. There are few reports (2, 16,17,19,22,24,25) of human cases which appear to relate excess intake of vitamin A during pregnancy and birth defects (Table 1). These cases do not supply acceptable evidence for human teratogenicity.…”

Vitamins E and A

“…More recent reports of signs of intoxication in fetuses of women consuming large amounts of vitamin A (Muenter, 1974;Strange et al, 1978) contradict the earlier conclusions and suggest that placental transport of the vitamin may be quantitatively more important than was recognized previously. Daily supplementation of pregnant women with 9000 ^g RE significantly increased cord serum concentrations of vitamin A (Venkatachalam et a/., 1962).…”

Impairment of Retinoic Acid Signaling in Cornelia de Lange Syndrome Fibroblasts

“…Possible functions of RA during embryogenesis were first inferred by studying its teratogenic effects, that is, interferences with normal developmental processes, since the first report in 1978 (Stå nge et al, 1978). Experimental studies have been performed in a wide range of species including amphibians, zebrafish, chick, and rodents (e.g., Durston et al, 1989;Avantaggiato et al, 1996), and excess of RA has been shown to affect anteroposterior (AP) and dorsoventral vertebrate embryonic patterning, as reviewed (Rhinn and Dolle, 2012).…”