Preterm birth and random plasma insulin levels at birth and in early childhood

Abstract

Importance: Although previous reports have linked preterm birth with insulin resistance in children and adults, it is not known whether altered insulin homeostasis is detectable at birth and tracks from birth through childhood.

Objective: To investigate whether preterm birth is associated with elevated plasma insulin levels at birth and whether this association persists into early childhood.

Design, setting, and participants: A prospective birth cohort of 1358 children recruited at birth from 1998 to 2010 and followed-up with prospectively from 2005 to 2012 at the Boston Medical Center in Massachusetts.

Main outcomes and measures: Random plasma insulin levels were measured at 2 time points: at birth (cord blood) and in early childhood (venous blood). The median age was 1.4 years (interquartile range [IQR], 0.8-3.3) among 4 gestational age groups: full term (≥39 wk), early term (37-38 wk), late preterm (34-36 wk), and early preterm (<34 wk).

Results: The geometric mean of insulin levels at birth were 9.2 µIU/mL (95% CI, 8.4-10.0) for full term; 10.3 µIU/mL (95% CI, 9.3-11.5) for early term; 13.2 µIU/mL (95% CI, 11.8-14.8) for late preterm; and 18.9 µIU/mL (95% CI, 16.6-21.4) for early preterm. In early childhood, these levels were 11.2 µIU/mL (95% CI, 10.3-12.0) for full term; 12.4 µIU/mL (95% CI, 11.3-13.6) for early term; 13.3 µIU/mL (95% CI, 11.9-14.8) for late preterm; and 14.6 µIU/mL (95% CI, 12.6-16.9) for early preterm. Insulin levels at birth were higher by 1.13-fold (95% CI, 0.97-1.28) for early term, 1.45-fold (95% CI, 1.25-1.65) for late preterm, and 2.05-fold (95% CI, 1.69-2.42) for early preterm than for those born full term. In early childhood, random plasma insulin levels were 1.12-fold (95% CI, 0.99-1.25) higher for early term, 1.19-fold (95% CI, 1.02-1.35) for late preterm, and 1.31-fold (95% CI, 1.10-1.52) for early preterm than those born full term. The association was attenuated after adjustment for postnatal weight gain and was not significant after adjustment for insulin levels at birth. Infants ranked in the top insulin tertile at birth were more likely to remain in the top tertile (41.2%) compared with children ranked in the lowest tertile (28.6%) in early childhood.

Conclusions and relevance: There was an inverse association between gestational age and elevated plasma insulin levels at birth and in early childhood. The implications for future development of insulin resistance and type 2 diabetes warrant further investigation.

Figure 1

Flow Chart of Initial Enrollment and Postnatal Follow-up of the Boston Birth Cohort and the Sample Included in the Analysis ^a FT: full term; ET: early term; LP: late preterm; EP: early preterm; Eligible mother-infant pairs were those who delivered a singleton live birth at the Boston Medical Center. Multiple-gestation pregnancies (e.g., twins, triplets) or newborns with major birth defects were excluded. ^b BMC: Boston Medical Center;^c Early childhood: age range: 0.5–6.5 years, median (25tn–75^th percentile): 1.4 (0.8–3.3) years.

Figure 2

Association of plasma insulin levels at birth with gestational age, stratified by birthweight for gestational age category (SGA, AGA, LGA) (n=1117)a ^aY-axis is the mean of logarithmically transformed insulin levels. Birthweight for gestational age was categorized into three groups: small for gestational age (SGA) (birthweight <10^th percentile), large for gestational age (LGA) (birthweight ≥90^th percentile), and appropriate for gestational age (AGA) (birthweight in the 10^th to 90^th percentile) according to the local reference population.

Figure 3

Tracking of plasma insulin levels from birth to early childhood a (n=785) ^aY-axis is the mean of logarithmically transformed insulin levels. Age at insulin measurement was the age when blood sample was obtained for the insulin measurement; Early childhood: age range: 0.5–6.5 years, median (25^th–75^th percentile): 1.4 (0.8–3.3) years; The participants were grouped as low, middle and high tertile based on cord blood insulin levels; the median (interquartile) cord blood insulin levels were 4.8 (2.9–6.9) µU/ml for low tertile; 12.0 (10.4–13.7) µU/ml for middle tertile; and 24.0 (18.6–33.8) µU/ml for high tertile.