As this review suggested, while earlier studies showed
protective effect of folic acid on reduced risk of PE, some
recent studies failed to find such an effect. The problem in
recent studies was that nonsupplementation was rare (less
than 5% in most recent studies) so that selection bias/confounding
becomes difficult to control. That is why an RCT
is needed to sort things out. Another issue from studies by
Bodnar et al. [15] and Catov et al. [17] was that they found
a beneficial effect of folic acid in lean women or normalweight
women only. We believe that this is caused by a dose
issue: in the Bodnar and Catov studies most women had
supplementation of 0.4 mg per day, and we proposed a dose
of 4mg per day in our FACT trial. Because of the potential
genetic and metabolic defects, women with increased risk
may need a higher dose.Arecent study byKeating et al. found
that folate uptake was decreased by amphetamine, atenolol,
ethanol, ecstasy, glucose, labetalol, nicotine, and tetrahydrocannabinol
[24]. Moreover, many of these drugs/substances
were cytotoxic, and they differentially modulated the mRNA
expression of folate placental transport systems. In our birth
cohort study, we observed a dose-response relationship in
high risk women (Table 1).