(Meek and Williams, 1997a, b, c), altered morphology of septal neurons (Loy et al., 1991; Williams et al., 1998), and enhanced hippocampal long-term potentiation (Pyapali et al., 1998) and cholinergic neurotransmission (Cermak et al., 1998; Holler et al., 1996). The two periods of sensitivity to extra choline occur during embryonic days 12 to 17 and postnatal days 16 to 30 (Loy et al., 1991; Meek et al., 1988, 1989).

In mammals the placenta transports choline to the fetus (Welsch, 1976); choline concentration in amniotic fluid is 10-fold greater than that in maternal blood (S.Zeisel, University of North Carolina School of Public Health, unpublished observations, 1997). At birth, humans and other mammals have plasma choline concentrations that are much higher than those in adults (Zeisel et al., 1980a). It is not known whether de novo synthesis of choline increases during pregnancy.

The AI for pregnant women is greater than that for the adult by the amount needed for the fetus and placenta. Through the use of published values for the choline concentration of various adult rat tissues (Pomfret et al., 1989) and with the assumption of a body organ weight percentage as estimated by Widdowson (1963) for the human fetus, the fetal choline content can be estimated as approximately 5 mmol/kg (520 mg/kg) fetal weight. Human placental tissue has been estimated to average 1.26 ± 0.24 mmol/kg (mean ± standard error) in a small sample (n = 7) (Welsch, 1976); a value of approximately 2 mmol of choline per kg of placental tissue should cover almost all pregnant women. If it is thus assumed that the average choline content of fetal and placental tissue combined is approximately 3 mmol/kg (312 mg/kg), that there is no extra synthesis during pregnancy, and that there is no contribution of choline by placental or fetal synthesis, the required dietary amount of choline for the 10 kg of tissue that comprises the fetus (3 kg) and organs of pregnancy (7 kg) is 30 mmol, or 3,000 mg (10 kg tissue × 312 mg), which is approximately 11 mg/day (10 µmol/day) of additional dietary choline throughout pregnancy. This amount would be achieved by increasing the AI (after rounding) to 450 mg/day of choline for pregnancy.

The increase in the AI to support pregnancy is based on the fetal and placental accumulation of choline.