Fracture risk elevated for children of mothers with prepregnancy or gestational diabetes
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Key takeaways:
- Children have a 7% higher risk for fractures if their mother had type 2 diabetes before pregnancy or developed gestational diabetes.
- The increased risk was mostly due to long-bone upper extremity fractures.
Risk for incident fracture is higher for children born to mothers with type 2 diabetes or gestational diabetes compare with those whose mothers did not have diabetes, according to data published in the Journal of Bone and Mineral Research.
“This was the first study to evaluate an association between maternal diabetes and fracture risk, so these findings were new to us and the scientific societies,” Viral N. Shah, MD, professor of medicine in the division of endocrinology and metabolism and director of diabetes clinical research at the Center for Diabetes and Metabolic Diseases at Indiana University School of Medicine, told Healio. “We did hypothesize that fracture risk would be increased in offspring of mothers with diabetes prior to starting this study, and therefore, we were not surprised to see results of our study.”
Shah and colleagues collected data from all pregnant women who had a child born from April 1980 to March 2020 in the province of Manitoba in Canada. Women who had type 2 diabetes before 20 weeks gestation were defined as having pregestational type 2 diabetes. Diabetes diagnosed at 21 weeks gestation or later was defined as gestational diabetes. The control group consisted of women without diabetes during pregnancy. The study’s primary outcome was any incident fracture occurring in children during follow-up. Fractures were categorized as long bone upper extremity, long bone lower extremity, vertebral and nontraumatic fractures.
There were 585,176 children born during the study, of which 26,397 were born to women with type 2 diabetes or gestational diabetes and 558,779 were born to women without diabetes. A greater percentage of children of mothers with diabetes were large for gestational age (27.7% vs. 12%) and were later diagnosed with diabetes (2.4% vs. 1.2%).
After adjusting for covariates, children of mothers with diabetes had a higher risk for sustaining any incident fracture than children of mothers without diabetes (adjusted HR = 1.07; 95% CI, 1.027-1.115; P = .0012). Children who were large for gestational age (aHR = 1.065; 95% CI, 1.044-1.087), boys (aHR = 1.385; 95% CI, 1.364-1.404), those living in remote communities (aHR = 1.054; 95% CI, 1.018-1.09), children diagnosed with chronic kidney disease (aHR = 1.2; 95% CI, 1.17-1.24) and children of mothers with a history of fractures (aHR = 1.2; 95% CI, 1.13-1.28) had elevated risk for any fracture. Each 1 U increase in parity was also associated with increased risk for fracture among children (aHR = 1.02; 95% CI, 1.014-1.026).
“We don’t know exact mechanisms for adverse bone health in offspring of mothers with diabetes,” Shah said. “We hypothesize that it may be due to glucose (or other intrauterine factors) during pregnancy that may be affecting calcium transfer in the fetus, especially during third trimester; shared genetic factors between mother and offspring as we noticed higher fracture risk in offspring of mothers with previous history of fracture; and the development of type 2 diabetes and CKD in offspring of mothers with gestational diabetes or type 2 diabetes. Both type 2 diabetes and CKD are known factors increasing fracture risk.”
Children of mothers with diabetes had higher risks for long-bone upper extremity fractures (aHR = 1.065; 95% CI, 1.005-1.129; P = .033) and nontraumatic fractures (aHR = 1.067; 95% CI, 1.023-1.113; P = .0026) than children of mothers without diabetes. There were no differences in lower extremity and vertebral fracture risks between the two groups.
Shah said many more studies are needed to better understand the risk for fractures for children of mothers with diabetes.
“Understanding placental pathophysiology and its effect of calcium transfer during pregnancy complicated by diabetes, and prospective studies on infant and children of mothers with diabetes would provide us more information on bone accrual and health among offspring of mothers with diabetes,” Shah said.
For more information:
Viral N. Shah, MD, can be reached at shahvi@iu.edu.
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