Do Birth Weight and Weight Gain During Infancy and Early Childhood Explain Variation in Mammographic Density in Women in Midlife? Results From Cohort and Sibling Analyses

Abstract

High birth weight is associated with increased breast cancer risk and, less consistently, with higher mammographic density. In contrast, adolescent body size has been consistently, negatively associated with both MD and breast cancer risk. It is unclear when the direction of these associations changes and whether weight gain in infancy is associated with MD. We evaluated the associations of birth weight and postnatal weight (measured at 4 months, 1 year, and 4 years) by absolute and velocity measures (relative within-cohort percentile changes) with adult mammographic density, assessed using a computer-assisted thresholding program (Cumulus), using linear regression models with generalized estimating equations to account for correlation between siblings in the Early Determinants of Mammographic Density study (1959-2008; n = 700 women with 116 sibling sets; mean age = 44.1 years). Birth weight was positively associated with dense area (per 1-kg increase, β = 3.36, 95% confidence interval (CI): 0.06, 6.66). Weight gains from 0 months to 4 months and 1 year to 4 years were negatively associated with dense area (for 10-unit increase in weight percentile, β = -0.65, 95% CI: -1.23, -0.07, and β = -1.07, 95% CI: -1.98, -0.16, respectively). Findings were similar in the sibling subset. These results support the hypothesis that high birth weight is positively associated with increased breast density and suggest that growth spurts starting in early infancy reduce mammographic dense area in adulthood.

Figure 1.

Associations between early-life weight change and dense area (cm²) according to birth weight category, Early Determinants of Mammographic Density study, United States, 1959–2008. β estimates correspond to a 100-g increase in birth weight or a 10-percentile increase in percentile rank change in weight from 0 months to 4 months, 4 months to 12 months, and 1 year to 4 years. Models adjusted for birth weight, percentile change in rank in previous time periods, age at interview, maternal prepregnancy body mass index, maternal weight gain, maternal age at registration, maternal education, prenatal smoking exposure, race/ethnicity, and adult body mass index. CI, confidence interval.

Figure 2.

Sensitivity analyses for the association between birth weight, rapid weight gain, and dense area (cm²), Early Determinants of Mammographic Density study, United States, 1959–2008. Low birth weight (LBW) was defined as less than 2.5 kg; being small for gestational age (SGA) was defined as below the 10th percentile of within-cohort birth weight/gestational age; and preterm was defined as less than 37 weeks’ gestational age. β estimate for birth weight corresponds to a 1-kg increase. Rapid weight gain was defined as an increase of at least 1 major Centers for Disease Control and Prevention reference percentile (5th, 10th, 25th, 50th, 75th, 95th) relative to stable (staying within 1 major reference percentile). Models adjusted for birth weight, weight gain pattern in previous time periods, maternal prepregnancy body mass index, maternal weight gain, maternal age at registration, maternal education, prenatal smoking exposure, race/ethnicity, and adult body mass index. CI, confidence interval.