Results in the context of what is known
The literature on fetal growth and child cognitive development is highly
heterogeneous in terms of how fetal growth restriction is defined
(antenatal and/or postnatal) and how development is assessed (various
measures of IQ and development are used); however, findings are
consistent that infants with fetal growth restriction and/or small size
are more likely to experience developmental challenges. Our finding that
lower estimated fetal weight percentile is associated with greater
developmental challenges is consistent with this literature. However,
our study extends this work to move beyond population-level associations
and evaluate the utility of estimated fetal weight charts as a clinical
prediction tool, by examining measures such as sensitivity, specificity,
positive predictive value, and negative predictive value. Our analyses
highlight that, despite the population-level associations, EFW
percentiles have limited ability as a tool to predict which specific
children will go on to be developmentally vulnerable.
The magnitude of the association between EFW and developmental
vulnerability observed in our study can be contextualized by comparing
it to the effects of other determinants of developmental vulnerability.
The link between low EFW percentile observed in our study (RR= 1.15
[95%CI: 0.65 to 1.86) and 1.49 [95%CI: 1.00 to 2.12] for fetuses
<3rd percentile using the INTERGROWTH and
WHO charts, respectively) are within the range of the magnitudes of
increased risk associated with being born at late preterm gestation:
Guthridge et al. found a two-fold increase of EDI developmental
vulnerability in infants born between 34 and 36 weeks’ gestation (OR=
2.08 [95%CI: 1.27 to 3.39]), while Bentley et al. likewise found
that EDI developmental vulnerability increased as gestational age
decreased: 26% higher risks [95% CI: 1.18 to 1.34] at 34-36 weeks’
gestation compared with those born at 40 weeks.
Guthridge et al. found that a 5 minute Apgar <7 was associated
with an 18% increased risk of developmental vulnerability on the EDI
test [95% CI 0.46 to 3.01] whereas Razaz et al. reported that
infants with 5-minute Apgar scores of 5,6,7, or 8 had increases in risk
of EDI developmental vulnerability ranging from risk ratios of 1.1 to
1.5, compared with those with a 5-minute Apgar score of 10.
With regards to socio-economic factors, Guthridge et al found a two-fold
increase of developmental vulnerability in infants of care-givers with 9
years or less of education [2.16 [95% CI: 1.40-3.33]). Likewise,
Chittleborough et al. found that the most important early-life risks
factors for developmental vulnerability at kindergarten age were
socio-economic in nature (mother’s age, mother’s marital status,
mother’s occupation, father’s occupation, number of previous pregnancies
and smoking in the second half of pregnancy). Thus while risks of
adverse child developmental outcomes are increased with lower EFW
percentiles, they do not appear to be a dominant influence.
Not surprisingly, the association between low EFW percentile and
developmental vulnerability is markedly lower than the association
between low EFW and adverse neonatal outcomes. In previous work from
this cohort of fetuses, we found that fetuses with an EFW less than the
10th centile were 3.1 fold more likely to have
perinatal morbidity/mortality compared with fetuses between the
10th and 90th centile on the IG and
WHO charts. However, this work, as well as that of others, also found
that the charts have a poor ability to predict adverse outcomes at the
individual level (i.e., poor sensitivity, specificity, and low AUC).