Infant Growth and Child Cognition at 3 Years of Age

PATIENTS AND METHODS

RESULTS

Table 1 lists participant characteristics. The mean (SD) PPVT-III score at 3 years of age was 104.2 points (14.4 points), similar to the standardized test mean of 100 points and SD of 15 points. The range of PPVT-III scores was 64 to 148 points. The total WRAVMA standard score is the sum of the WRAVMA drawing, matching, and pegboard test scores, standardized to a mean of 100 and SD of 15 points. In our sample, the mean (SD) total WRAVMA standard score was 102.8 (11.2), and the range was 57 to 151. The mean (SD) weight z score at birth was 0.21 (0.94) and at 6 months was 0.39 (0.96). Mean (SD) breastfeeding duration was 6.7 months (4.5 months).

Compared with the 1579 mother-child pairs who were eligible for the 3-year follow-up, mothers in this analysis were more likely to be of white race (76% vs 69%), better educated (73% vs 68% with college or graduate degree), and more likely to have an annual household income exceeding $70 000 (67% vs 62%) but were of similar age (32.6 vs 32.1 years). Children in this analysis had similar mean birth weight (3.58 vs 3.55 kg) and gestational age (39.9 vs 39.8 weeks) compared with all of the eligible children.

In unadjusted linear regression analyses (Table 2), we found that, for each z score increment in birth weight, the PPVT-III score was 2.3 points higher (95% confidence interval [CI]: 1.3 to 3.3 points), and the total WRAVMA standard score was minimally higher (0.6 points [95% CI: −0.2 to 1.5 points]). Similarly, for each z score increment in birth weight for gestational age (a measure of fetal growth), the PPVT-III score was 2.4 points higher (95% CI: 1.4 to 3.5 points), and the total WRAVMA standard score was 0.7 points higher (95% CI: −0.1 to 1.6 points). There was no association of infant weight z score at 6 months with PPVT-III score (−0.1 points per z score increment [95% CI: −1.1 to 0.9 points]) or total WRAVMA standard score (−0.4 points per z score increment [95% CI: −1.2 to 0.5 points]). There was also no association of infant weight-for-length z score at birth or 6 months with the outcomes.

Table 3 shows the results of our multivariable linear regression models. Weight z score at 6 months adjusted for birth weight z score represents infant weight gain from birth to 6 months. For each z score increment in infant weight gain, the PPVT-III score was 1.1 points lower (95% CI: −2.2 to 0.0 points), and the total WRAVMA standard score was 0.9 points lower (95% CI: −1.7 to 0.0 points). Adjustment for gestational age (model 2) minimally affected these estimates, whereas additional adjustment for breastfeeding duration (model 3) attenuated the association of infant weight gain with PPVT-III score to −0.4 points (95% CI: −1.5 to 0.7 points). Adjustment for parental and child covariates (model 4) minimally affected the association of infant weight gain with the cognitive test scores. In our fully adjusted model (model 4), the association of breastfeeding duration with the cognitive outcomes was 0.3 PPVT-III points per month breastfed (95% CI: 0.1 to 0.5 points) and 0.0 total standard WRAVMA points per month breastfed (95% CI: −0.2 to 0.2 points).

We performed secondary analyses examining infant growth in weight for length, a measure of adiposity. After adjustment for the same covariates as in model 4, associations of infant growth in weight for length with PPVT-III and WRAVMA scores were similar to associations of infant weight gain with PPVT-III and WRAVMA scores (data not shown).

In another secondary analysis, we divided our cohort into gender-specific deciles of infant weight gain and estimated the mean PPVT-III score in each decile (Fig⇓). Adjusting for the same covariates as in model 4, we found that mean PPVT-III scores were 104.0 and 101.3 points in the lowest and highest deciles of weight gain, respectively.

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FIGURE

Estimated Peabody Picture Vocabulary Test III ( PPVT-III) score (standard error) within deciles of infant weight z-score at 6 months (A) and 8 weeks (B). Range of 6 month weight z-scores within deciles for boys: D1(−2.1, −0.9), D3(−0.5, − 0.2), D5(0.0, 0.3), D7(0.5, 0.8), D9(1.1, 1.4), D10 (1.4, 3.2); and for girls D1(−2.6, −0.8), D3(−0.4, −0.1), D5(−0.2, 0.4), D7(0.7, 1.0), D9(1.4, 1.8), D10(1.8, 3.6). Range of 8 week weight z-scores within deciles for boys: D1(−2.2, −0.5), D3(−0.1, 0.1), D5(0.4, 0.6), D7(0.9, 1.1), D9(1.5, 1.8), D10(1.8, 4.3); and for girls D1(−2.1, −0.5), D3(−0.1, 0.1), D5(0.4, 0.6), D7(0.8, 1.1), D9(1.4, 1.8), D10(1.8, 3.1). Estimates are adjusted for child birth weight z score, sex, age at cognitive assessment, gestational age, breastfeeding duration, race/ethnicity, and English as a second language status; maternal age, parity, smoking status, and PPVT-III score; parental educational levels; and annual household income.

To allow comparison with another study,¹² we examined infant weight gain in 2 separate intervals: from birth to 8 weeks and from 8 weeks to 6 months of age. Unlike the other study, we did not find that faster weight gain from birth to 8 weeks predicted higher 3-year PPVT-III scores (Table 4). In fact, the adjusted PPVT-III score in the lowest decile was slightly higher, at 104.5 points, than in the highest decile, at 102.7 points. Likewise, we found no association of weight gain from 8 weeks to 6 months with PPVT-III score (Table 4).

DISCUSSION

We found that, in our cohort of generally healthy, term-born children, slower infant weight gain in the first 6 months of life was not associated with lower cognitive or visual-motor test scores at 3 years of age. We also found no evidence that children with the slowest weight gain had poorer test scores than children with the fastest weight gain.

Most investigations of infant weight gain and later cognition in developed countries have focused on children with and without FTT⁷ and have generally found that the children with FTT have lower IQ and other cognitive and achievement test scores. However, most of those studies draw cases of FTT from inpatient wards, specialty clinics, or primary care clinics serving predominantly poor children, so the results are not generalizable to the general population of infants. Some population-based studies^27–29 of FTT and later cognition focus exclusively on economically deprived communities and are also limited because they do not account adequately for factors such as the infant's gestational age, breastfeeding status, or for maternal cognition. These factors may be important predictors of postnatal weight gain and childhood neurodevelopment even within the range of “normal” birth weights^30–33 and, thus, potential confounders of the relationship between infant weight gain and later cognition.

The results of our study are similar to 2 others^11,12 from the United Kingdom that, like ours, examined child neurodevelopment across a spectrum of infant weight gain in a generally healthy population, rather than exclusively in children with and without FTT. In 1 of those studies,¹¹ cognitive and school achievement test scores (standardized test mean: 50 points [SD 10 points]) at 10 years of age were 0.3 to 0.7 points lower for each SD score of slower infant weight gain; and in the other,¹² adjusted IQ at 8 years of age was 0.2 points lower per SD score of slower weight gain from birth to 9 months. These effect sizes and our own are too small to support an effect of infant weight gain on neurodevelopment in a healthy population that is of clinical or public health significance.

One of the United Kingdom studies¹² also examined weight gain separately from birth to 8 weeks and from 8 weeks to 9 months of age. In contrast to our findings, those authors found a small, linear association of weight gain from birth to 8 weeks of age with IQ at 8 years of age (0.8 points per SD weight gain [95% CI: 0.4 to 1.3 points]). They also found that the IQ of infants in the slowest weight gain category (less than −1.5 SDs) was ∼3 points lower than the IQ of those in the highest weight gain category (>1.5 SDs). In secondary analyses of our data, we found no association of early weight gain with our cognitive outcome, the PPVT-III score, which is highly correlated with IQ. In addition, in our study, children in the lowest category of weight gain from birth to 8 weeks did not have lower PPVT-III scores than children in the highest category of weight gain. Thus, one must consider the possibility that their findings were attributable to chance.

Also in contrast to our findings, studies of preterm infants^8–10 suggest that slower infant weight gain does lead to poorer cognitive development in that population. One possible explanation for the adverse effect of slower infant weight gain on neurodevelopment in preterm infants is that they experience a degree of undernutrition and energy imbalance in the first months after birth³⁴ that is substantially greater than healthy, term infants in developed countries typically experience. In addition, the preterm brain may be more vulnerable to the effects of poor weight gain.^35,36 Alternatively, there may be shared determinants of poor weight gain and neurodevelopmental impairment in preterm infants, such as perinatal neurologic injury, that lead both to feeding difficulties and to impaired cognitive function.

Mounting evidence suggests that rapid infant weight gain may have harmful consequences, including increasing the risk of obesity,^13–15 high blood pressure,^16,19 and insulin resistance.¹⁷ These disorders are on the rise and seem to have origins early in life.^18,37 Promoting slower infant weight gain may be an effective strategy to prevent these disorders, and our results suggest that, within the range of weight gain that we examined, there do not seem to be harmful effects of slower infant weight gain on cognition at 3 years of age in generally healthy, term-born children. However, other potential adverse effects of slower infant weight gain, such as increased susceptibility to infection³⁸ and decreased adult height,¹⁴ also need to be evaluated in healthy populations of infants.

An important strength of our study is that we carefully measured and controlled for numerous potentially confounding covariates, including gestational age, breastfeeding duration, maternal intelligence, and socioeconomic variables. However, we did not have specific information about infant-caregiver interaction patterns or family functioning, so residual confounding is possible. Our findings should be applied to generally healthy term-born children, not preterm children or children with extremely poor weight gain, such as those with FTT. We confirmed others’ findings in healthy populations that higher birth weight is associated with higher cognitive test scores,^30–33 suggesting that ours is a representative cohort, although generalizability of our findings may be limited by the relatively high socioeconomic status of our participants and the preferential loss to follow-up of participants in lower socioeconomic status and minority racial and ethnic groups. In addition, although we assessed cognition and visual-motor skills using well-validated instruments, our study cannot exclude associations of infant weight gain with other aspects of neurodevelopment, such as executive function and behavior. Finally, although cognitive function at 3 years of age is correlated with later intelligence, testing at ≥5 years of age is likely to yield a more stable measure of intelligence.³⁹ We are currently collecting cognitive data on our cohort at 7 years of age.

CONCLUSIONS

In this study of healthy term-born children, we found that slower infant weight gain is not associated with poorer neurodevelopmental outcomes at 3 years of age. These results should aid in determining optimal growth patterns in infants to balance risks and benefits of health outcomes through the life course.