The overwhelming majority of studies reviewed support an association between preterm SGA and lower neurodevelopment in the longer term. Consistent with the studies on term SGA, many of the studies on preterm SGA did not properly control for key perinatal (e.g., asphyxia), socioeconomic, parental, and home environment confounders (e.g., maternal-child interactions). In addition, although some studies included term births as reference groups (Calame et al., 1983; Silva et al., 1984; Holwerda-Kuipers, 1987; Litt et al., 1995, 2005; Hack et al., 1998; Brandt et al., 2003; Kilbride et al., 2004; Paavonen et al., 2007; Leonard et al., 2008; Strang-Karlsson et al., 2008a, 2008b), others used preterm subgroups as comparison groups (McCarton et al., 1996; Hutton et al., 1997; Casey et al., 2006; Kono et al., 2007). Because of these study design limitations, the effect size or the proportion of the variance in neurodevelopmental outcomes that can be attributed to being born premature per se or to the combination of prematurity and SGA still needs to be determined.

In summary, as was the case with infant mortality, one must link GWG to being born preterm or small- or large-for-gestational age and, from there, to neurodevelopmental outcomes. This sequence is biologically plausible and it is possible that it is causal, but the evidence to establish causality is not available.

Apgar score The Apgar score (see Glossary in Appendix A) assessments are usually conducted 1 and 5 minutes after birth, and scores can range from 0 to 10. However, Apgar scores in term infants, even at 5 minutes, have important limitations, as they are not adequate predictors of longer term morbidity and mortality and do not correlate well with neurological outcomes (ACOG, 2006) although very low scores (0-3) associated with low birth weight do predict neonatal mortality. The AHRQ review (Viswanthan et al., 2008) identified five studies examining the influence of GWG on a newborn’s Apgar score (Stevens-Simon and McAnarney, 1992; Nixon et al., 1998; Cedergren et al., 2006, Stotland et al., 2006; Wataba et al., 2006). Taken together, these studies provide only modest evidence that excessive GWG is associated with low Apgar score, and one study suggested that low GWG in nulliparous women also predicts low Apgar score.

Childhood cognition No published studies directly examine the link between GWG and neurocognitive development in infants and children. However, as discussed in Chapter 3, weight loss or failure to gain during pregnancy due to dietary caloric insufficiency may possibly induce maternal hormonal and metabolic responses, which may, in turn, have subsequent consequences for the intellectual development of the child. Because of the obligatory weight gain in maternal tissues (uterus, breast, blood) and the fetal-placental unit, a weight gain less than ~7.5-8.5 kg would likely result

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