In this study, we found that systolic blood pressure at age 3 years was 1.0 mmHg higher for each unit increase in weight-for-length z-score between birth and 6 months. An increase in weight-for-length z-score over time indicates that a child’s weight has increased out of proportion to his or her increase in length, and suggests that the child has experienced an increase in adiposity. As an example of a 1-unit difference in weight-for-length z-score, consider two 6-month old male infants who are of average length (67 cm). The infant with a weight-for-length z-score of 0 would weigh 7.7 kg, whereas the infant with a weight-for-length z-score of 1 would weigh 8.4 kg, a difference of 0.7 kg. Our estimates predict that, after adjusting for weight-for-length z-score at birth, the heavier of these two infants would have 1.0 mmHg higher systolic blood pressure at age 3 years. We also found the highest blood pressure in the children who were in the lowest quartile of weight-for-length at birth, but grew to be in the highest quartile at 6 months. That is, children who were thinnest at birth and had the most rapid weight gain relative to length between birth and 6 months, experienced the highest blood pressure levels at age 3 years.
The results of our study contrast with the only prior study to have examined the relationship between infant growth, using a weight-for-length measure, and later blood pressure. Whereas we found that more rapid relative weight gain in the first 6 months of life was associated with higher blood pressure, Cheung et al11
found, in a Hong Kong cohort born in 1967, that a one unit increase in ponderal index between birth and age 6 months was associated with a 1.4 mmHg decrease
in systolic blood pressure at age 30 years. One possible explanation for our conflicting results is that our study populations reflect different ends of the spectrum of infant growth and nutrition. Children in the Hong Kong cohort, on average, had a decrease in ponderal index between birth and age 6 months, although children in our contemporary cohort, on average, had an increase in weight-for-length z-score from birth to 6 months of age. Although the authors of the Hong Kong study do not present specific data on infant nutrition, they report that living conditions were generally poor in Hong Kong at the time of the study. In contrast, it is reasonable to assume that infants in our study had adequate nutritional resources. Another study of infant growth and blood pressure in the Philippines found that larger gains in weight and length from birth to age 2 were associated with a lower odds of high blood pressure in Filipino adolescents7
. However weight and length gains in that study were large only in relation to the overall study population but were likely not excessive, supported by the fact that fewer than 3% of adolescents in the study are overweight. Our results are likely more relevant to modern, developed countries, whereas the results of the Hong Kong and Filipino studies may be more applicable to children in the developing world.
Three prior studies have examined other measures of infant growth, primarily weight gain, with respect to later blood pressure. Our results are in agreement with those of Forsen et al10
, who found in a rural Finnish cohort born in 1981 – 1982 that weight gain in the first year of life was positively associated with blood pressure at age 7 years. Similarly, in an older Finnish cohort born in 1966, rapid weight gain during the first year of life was associated with higher blood pressure at age 31 years12
. In contrast, there was no appreciable association between weight gain in the first year of life and blood pressure in a cohort of young adults born in the UK3
, though this study examined weight gain over the entire first year, rather than a more narrow time period in the earliest months of life.
Consistent with our finding of an association between a more rapid increase in infant weight-for-length z-score and higher blood pressure later in childhood, animal and human studies have shown links between more rapid weight gain in infancy and other components of the metabolic syndrome, including increased fat mass25
, insulin resistance 27
, and impaired endothelial function28
, in addition to blood pressure.
Some authors have reported that smaller
size during infancy is associated with insulin resistance and coronary heart disease, which themselves are related to blood pressure. In a Finnish cohort born between 1934 and 1944, adult men with coronary heart disease and adults with type 2 diabetes were thinner relative to the rest of the cohort at birth until early childhood, after which their BMI rose progressively, surpassing the average for the cohort by school-age29, 30
. However, there is an apparent upward trend in weight and/or BMI in the earliest months of life. Similarly, Bharghava et al31
found in a cohort of Indian young adults born in the early 1970’s that those with the highest odds of developing insulin resistance were thinner from birth through age 2 years, and had a higher BMI at age 12, compared to the rest of the cohort. However, this study did not examine in detail weight gain in the first months after birth.
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 could limit the generalizability of our findings. A strength of our study is that we used weight-for-length measures which are more likely to represent adiposity than measures of just weight or length. Although we did not have birth length measurements for our entire cohort, our method for measuring length is more accurate than commonly used clinical measures such as the paper-and-pencil method, which tend to overestimate length in young children32
. We also carefully measured child blood pressure and potentially confounding covariates, including maternal blood pressure.
Our results raise the possibility that strategies to moderate excess infant weight gain, particularly among infants who are thin at birth, may contribute to the primary prevention of hypertension. Any intervention to modify infant weight gain, however, must take into account the possible benefits of early growth, such as improved cognition33
, as well as the potential harms to cardiovascular and metabolic health.