Very High Birth Weight of Offspring Is Associated with an Increased Risk of Leukemia in Their Mothers; Results of a Population-Based Cohort Study.
Authors: Paltiel Ora , Yanetz Rebecca , Calderon Ronit , Manor Orly , Harlap Susan , Friedlander Yehiel 
Published: October 2019

Abstract
High birth weight (HBW) is related to maternal diabetes, height, BMI and weight gain during pregnancy. Many previous studies have shown an association between HBW and childhood leukemia. Postulated mechanisms have included exposure to growth factors involved in somatic growth and leukemogenesis (e.g. IGF-1), common genetic mechanisms or higher cell number in larger individuals providing increased opportunity for genetic errors. It is not known to what extent the association is due to heritable factors, intra-uterine factors or both. To our knowledge, the association between offspring’s birth weight and leukemia risk in the parents has not been addressed.
Methods: We utilized data from the Jerusalem Perinatal Study, a population-based research cohort including all births in West Jerusalem between 1964 and 1976. The database contains information on birth characteristics of the newborns, obstetric complications and birth outcomes as well as demographic data on the parents. After excluding the parents of twins and offspring with congenital malformations, we linked 39,336 mothers and 38,031 fathers of live-born infants through their unique identification numbers to the Israel Cancer Registry. We examined the association between leukemia and the average birth weight of all offspring of the same mother or father, as a categorical and continuous variable, as well as the effect of having at least one offspring weighing ≥4500 gm. Fewer than 2% of parents had offspring weighing 4500 gm or more.
Results: Leukemias developed in 57 mothers and 132 fathers. Controlling for maternal age, having at least 1 child weighing ≥4500 gm at birth was associated with a 3-fold increase in the risk of leukemia (hazard ratio -HR 3.4, 95% confidence interval (CI) 1.06–10.91, p=0.04), compared to having no children at the extremes of birth weight. This result was unchanged after multivariate adjustment. Furthermore having an average birth weight among all offspring of ≥4500 gm increased the risk of leukemia in mothers more than 8 fold (HR 8.3, 95% CI: 2.5–27.7, p=0.0006), after controlling for maternal age and diabetes, compared to an average birth weight of 2500–3999 gm. This result was strengthened after further multivariate adjustment for family size and socioeconomic status (HR 8.99, 95%CI: 2.8–29.27, p=0.001). In a subgroup for which these data were available (∼13,000 mothers), results were unchanged after adjusting for maternal height. Birth weight assessed as a continuous variable was not related to mother’s leukemia. Specific subgroups of leukemia in the mother which were associated with HBW were CLL (HR 11.04, p=0.002) and CML (7.84, p=0.05) but these analyses were severely limited by small numbers. There was no association between HBW and father’s risk of leukemia.
Conclusions: HBW is associated with leukemia not only in infants and children, but appears to confer an increased risk among their mothers. Whether this is due to a common exposure (eg pelvic irradiation), shared genes, or epigenetic phenomena bears exploring, after confirmation of these results in other cohorts.