549 SELECTIVE FETAL MALNUTRITION: A NEW CONCEPT IN THE FETAL ALCOHOL SYNDROME (FAS)

Abstract

Several features of the FAS suggest intrauterine growth retardation. Traditionally, these findings have been ascribed to the direct toxic effects of ethanol (EtOH) or its metabolite, acetaldehyde (AcH). Deprivation of essential fetal nutrients at the placental level (selective fetal malnutrition) has not been considered etiologic. EtOH is known, however, to inhibit membrane transport of amino acids (A-A). We have therefore investigated the effect of EtOH and AcH upon human placental uptake of the actively transported, non-metabolized A-A, α-aminoisobutyric acid (AIB). Term human placental villi were incubated with ¹⁴C-AIB in the presence or absence of EtOH (300 mg/dl). No inhibition of uptake was seen at 30, 90 or 150 min. of incubation. However, after 90 min. of incubation with varying concentrations of AcH (readily achieved in the blood of drinking humans), there was significant (p<0.01) inhibition of AIB uptake. % inhibition (mean ± SEM): 2 uM = 25 ± 8.7%; 5 uM = 34.7 ± 4.0%; 10 uM = 54.6 ± 2.9%; 20 uM = 61.5 ± 7.5%. When villi were pre-incubated with 10 uM AcH for 60 min. and then incubated with ¹⁴C-AIB in the absence of AcH, normal AIB uptake was not totally restored: % inhibition (90 min.) = 25.5 ± 5.6%, p<0.01. CONCLUSION: (1) In vivo metabolism of EtOH to AcH in the chronic alcoholic pregnant human may impair placental transport of essential A-A's, thereby contributing to the pathophysiology of the FAS. (2) The effects of AcH upon placental function may not be totally reversible.

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