Discussion
Based on data from six trials that included more than 4000
women, the Cochrane review showed that balanced proteinenergy
supplementation reduced the overall risk of SGA by
30%.
Most of the trials were conducted in developing countries,
thus the positive effect of this intervention is likely to be
replicable in those settings. In contrast, a trial conducted
among women in New York, U.S., without evidence of undernutrition,
showed that high protein supplementation may
negatively affect fetal growth and neonatal mortality.
Single micronutrient supplementation interventions have
not been shown to affect size at birth, except magnesium
supplementation which reduced the rate of both SGA by
30% in three trials including more than 1700 women.
Methodological concerns about a large magnesium trial in the
review suggest caution in interpreting those results. Calcium
supplementation may reduce low birth weight, although it is
likely to be related to prolonged gestation.
The biological importance of the effect of nutrition
supplementation on other fetal growth parameters besides
birth weight remains to be evaluated. Recently fetal ultrasonography
has been used to evaluate nutrition interventions
during pregnancy and the results from one clinical trial on
maternal zinc supplementation showed a positive effect on
fetal long bone growth despite no observed effect on birth
weight [See Annex Table 1 (10) Trial 81). Focusing on
outcomes other than birth weight may help identify the effects
of nutrition interventions on specific growth components and
suggest mechanistic hypotheses that might be further investigated
in animal and in vitro studies. To acquire public
health relevance, new outcome measures must have strong
biological links with substantive outcomes such as severe
morbidity or postnatal growth. Further research in this area is
warranted, as suggested by recent findings of an inverse
relationship between fetal femur length, assessed by ultrasonography
during pregnancy, and blood pressure at 6 y old (26).
Most studies have relied on assessing gestational age based
on the last menstrual period or postnatal newborn assessment
that have limitations and may decrease their accuracy.