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To assess if vitamin A concentration in umbilical cord blood is associated with incidence and severity of respiratory infections in preschool Inuit children from Nunavik (Québec, Canada). The medical charts of 305 children were reviewed from 0 to 5 years of age. The association between vitamin A concentration in umbilical cord plasma and the incidence rates of acute otitis media (AOM), lower respiratory tract infections (LRTIs) and hospitalization rates for LRTIs was evaluated using Poisson regression. Compared to children with vitamin A concentration ≥20 µg/dl, adjusted rate ratios (RR) for children below 20 µg/dl ranged between 1.06-1.62 for AOM, 1.12-1.34 for LRTIs, and 1.09-1.43 for hospitalization for LRTIs. Most RRs were statistically significant for AOM and LRTIs, but not for hospitalization for LRTIs. Neonatal vitamin A deficiency appears to be a significant risk factor for AOM and LRTIs in this population.

DISCUSSION

This study was undertaken in order to document the association between neonatal vitamin a concentration and acute respiratory infections during the first five years of life in inuit children. For the first 5 years of life, a statistically significant association between lower blood vitamin a concentration and higher incidence rate was found for aOM and LRTIs, but not for hospitalization for LRTIs. For aOM, the association showed a dose-response pattern.

Reports of placebo-controlled prospective studies on supplementation are controversial, as some authors found that vitamin a supplementation decreased respiratory infections incidence rates12,15 while some did not.8,16-19 in observational prospective studies, vitamin a deficiency was associated with an increased rate of respiratory infections,9,20 but not with rate of aOM.21 in a cross-sectional, follow-up and interventional trial study performed in thailand in a population with a vitamin a deficiency similar to that of the current study, bloem et al.10 found a dose-response relationship between respiratory diseases incidence rates in children and mild vitamin a deficiency.

It has been discussed by some authors that the effect of a deficient level of vitamin a could better be observed on the severity of infectious episodes rather than on the incidence rate.22 indeed, an association between vitamin a level and severity has been demonstrated in some studies,8,23 but not all.16 to assess the impact of deficient vitamin a level at birth on the severity of infections in our population, we examined the incidence of hospitalization for LRTIs. Although no statistically significant association was found, most RR were above 1.0 and the effect-size in both the categorical and the continuous models was greater when only LRTIs that led to an admission were considered, compared to the total rate of LRTIs. This suggests that not only the rate of LRTIs is increased in children with lower vitamin a levels, but that these episodes were also more severe. Further studies with a greater number of subjects are needed to clarify this issue.

In this study, the vitamin a status of the mother-infant pairs was extrapolated through the umbilical cord blood retinol level. It is well known that a low concentration of retinol in umbilical cord blood correlates with a maternal vitamin adeficient state during pregnancy.24-26 such deficiency will in turn decrease significantly the amount of vitamin a passed to the infant through breastfeeding.24,27 We therefore hypothesized that breastfed infants born to vitamin a-deficient mothers were exposed to insufficient level of vitamin a in utero and would be fed inadequate amounts of vitamin a in the early postnatal period. We also think that, for these children, the daily diet in their first years would likely be low in vitamin a, although we could not assess this aspect in our study. We therefore believe that the association between low retinol level in cord blood and increased infection rates was due to a lack of vitamin a store both in the prenatal and the postnatal period. Whether an insufficient vitamin a concentration during the fetus development impairs the functioning of the immune systems late into childhood remains to be elucidated.

Bottle-feeding, on the other hand, will provide the infant with sufficient amount of vitamin a but can increase infections rate. Bottle-feeding is not common in nunavik as more than 70% of children in the 5-year subgroup were breastfed for more than 3 weeks (data not shown). although breastfeeding duration was not available for all children, its inclusion in the model for the 5-year subgroup did not affect the association between vitamin a and infections rate.

Nutrition status is an important factor that can modulate the immune system. Our preliminary analyses allowed us to find that low socio-economic status and crowding, two factors that could be related to poorer nutrition, did not influence the association between vitamin a and infection rate. Nevertheless, we cannot completely rule out that part of the association between vitamin a and infection rate could be due to other nutriments deficiencies, or to a generally less healthy diet.

The parent's decision of seeking medical attention is related to many cultural and socio-economic factors, which in turn could be associated with dietary habits. A bias could therefore be introduced if the propensity to seek medical attention was associated with maternal vitamin a intakes. if this bias was present in our data, it is likely that it would be insignificant when severe symptoms were present, symptoms for which most parents would go to the clinic. It would also not be present for hospitalization. We cannot, however, exclude the possibility of such a bias, especially for AOM.

This study underlines a possible link between low vitamin a concentration at birth and acute respiratory infections in inuit children from nunavik. Because children from this population are burdened by a high incidence of aOM and LRTIs compared to other north-american populations, the identification of a preventable risk factor such as neonatal vitamin a deficiency is of paramount importance. together with the first phase of this study, these results indicate that a carefully planned supplementation program should be considered in nunavik for both pregnant women and newborns.