No increased risk of insulin resistance in prednisone-exposed fetuses

Children who were exposed to low dose prednisone in utero had no increased risk for insulin resistance in early childhood (from infancy through approximately 7 years). Although the results are reassuring, further research should analyze if insulin resistance remains as children age, according to a study published in Springer.¹

“The use of long-term corticosteroids during pregnancy has been growing over the past decades,” investigators stated. “Corticosteroids can be given when an auto-inflammatory disease like rheumatoid arthritis (RA) is too active. Several studies have shown that long-term corticosteroids use in pregnancy is associated with maternal and fetal adverse outcomes, like preeclampsia, shorter gestational age, lower birth weight, and rapid catch-up growth. These last two outcomes could influence the insulin resistance later in life.”

In total, 103 children were initially included in the study after their mother participated in a prospective cohort study (PARA) evaluating RA and pregnancy. Of these children, 42 (41%) were exposed to prednisone in utero and 61 were non-exposed. Insulin resistance was measured by homeostasis model of assessment insulin resistance (HOMA-IR) and lipid and serum adiponectin levels, which were corrected for body fat distribution. Children, aged 5 years or older, were seen at the Sophia Children’s Hospital in Rotterdam, located in the Netherlands. Participants gave fasting blood samples, anthropometric measurements were performed, and a dual-energy x-ray absorptiometry (DXA-scan) analyzed fat distribution.

Pregnant women in the original study received an average of 6 mg of prednisone (IQR: 1–15 mg) daily during pregnancy. Mean fasting glucose level was 4.87 (0.37) mmol/L in the children exposed to prednisone and 4.94 (0.42) those who were not exposed. Insulin was 4.95 (3.57) µU/mL and 4.92 (2.03) µU/mL, respectively. Dosage made no difference in mean HOMA-IR (SD) between children in the prednisone-exposed cohort (1.10 [0.84]) and those in the non-exposed group (1.09 [0.49]). There were no differences in the mean adiponectin level and lipid levels, such as total cholesterol, high-density lipoprotein, or fasting triglyceride, and body fat distribution.

Prospectively following all pregnancies of patients was a main strength of the study, as well as following medication intake and disease activity throughout pregnancy, which was assessed by the same research assistants. Further, the data were both measured and collected by 1 doctor, thus preserving continuity. Although roughly half of children (54%) participated, there were no statistical differences between those who participated and those who did not. While investigators conducted a nationwide study, all children needed to be evaluated at Sophia’s Children’s Hospital in Rotterdam, which caused 38% of parents to opt out due to the distance of the hospital. The second most prevalent reason parents opted out of the study was due to too much burden for the child (30%). Lastly, investigators did not use a hyperinsulinemic euglycemic clamp (HEC), intravenous, or oral glucose tolerance test (OGTT) to quantify insulin resistance.

“Long-term corticosteroids use in pregnancy is associated with fetal adverse outcomes, like lower birth weight and rapid catch-up growth which can influence the insulin resistance later in life,” investigators concluded. “Findings are reassuring because prednisone use during pregnancy is increasing worldwide. Further research should evaluate if the insulin resistance remains absent in the future.”

Reference

de Steenwinkel FDO, Dolhain RJEM, Hazes JMW, Hokken-Koelega ACS. Does prednisone use in pregnant women with rheumatoid arthritis induce insulin resistance in the offspring? [published online ahead of print, 2022 Aug 30]. Clin Rheumatol. 2022;10.1007/s10067-022-06347-0. doi:10.1007/s10067-022-06347-0