Does prednisone use in pregnant women with rheumatoid arthritis induce insulin resistance in the offspring?

OBJECTIVES: The use of long-term corticosteroids during pregnancy has been growing over the past decades. 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. Our objective was to investigate whether prednisone use in pregnant women with RA induces insulin resistance in offspring. METHODS: One hundred three children were included after their mother had participated in a prospective cohort study on RA and pregnancy. Forty-two children were in utero exposed to prednisone and 61 were non-exposed. To assess insulin resistance, we measured homeostasis model of assessment insulin resistance (HOMA-IR) and serum adiponectin and lipid levels, corrected for body fat distribution. RESULTS: An average of 6 mg prednisone on a daily use gave no difference in mean HOMA-IR (SD) between the children who were prednisone-exposed in utero (1.10 (0.84)) and those non-exposed (1.09 (0.49)). No difference was found in mean adiponectin level, body fat distribution, or lipid levels such as total cholesterol, fasting triglyceride, or high-density lipoprotein. CONCLUSION: Children who are prednisone-exposed in utero (low dose) have no increased risk for insulin resistance at the age of approximately 7 years. These findings are reassuring because the prednisone use during pregnancy is increasing worldwide. Further research has to be performed to evaluate if the insulin resistance remains absent in the future. Key Points • What is already known on this topic-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. • What this study adds-long-term corticosteroids use in pregnant women with rheumatoid arthritis has no increased risk for insulin resistance in the offspring. • How this study might affect research, practice, or policy-findings are reassuring because prednisone use during pregnancy is increasing worldwide. Further research should evaluate if the insulin resistance remains absent in the future.

Rheumatoid arthritis during pregnancy and postnatal catch-up growth in the offspring.

OBJECTIVE: Active rheumatoid arthritis (RA) during pregnancy and the presence of rheumatoid factor (RF) or anti-citrullinated protein antibodies (ACPAs) are associated with lower birth weight of the child. Moreover, treatment of the mothers with prednisone may shorten the gestational age at birth. Rapid catch-up in weight for length during the first year of life has been related to a worse cardiovascular and metabolic profile in early adulthood. This study was therefore undertaken to assess the influence of RA disease activity, medication use, and presence of RF or ACPAs during pregnancy on the growth of the child in the first year of life. METHODS: Among 180 children born to mothers with RA, the tempo of catch-up in weight during the first year of life was studied. Independent variables were the extent of RA disease activity (according to the Disease Activity Score in 28 joints [DAS28]), medication use, and presence of RF or ACPAs during pregnancy. RESULTS: Of 167 children with available data, 52 (31%) showed catch-up in weight in the first year of life, of whom 90% (47 of 52) showed rapid catch-up. An elevated DAS28 score in the mother was associated with rapid catch-up in weight of the offspring, independent of maternal medication use or the presence of RF or ACPAs during pregnancy (odds ratio 1.44 [95% confidence interval 1.07-1.95] per 1-point increase in the DAS28). Use of medications during pregnancy had no influence on postnatal growth. CONCLUSION: Elevated RA disease activity during pregnancy should be avoided because it is associated with rapid postnatal catch-up in weight, a risk factor for a worse cardiovascular and metabolic profile in adults. Medication for RA during pregnancy, including prednisone, had no effect on growth. Continuation or extension of medication will not only improve maternal health during pregnancy, but could be beneficial for the future health of the unborn child.

Brief report: does medication use or disease activity during pregnancy in patients with rheumatoid arthritis affect bone density in their prepubertal offspring?

OBJECTIVE: Prednisone use and active disease are associated with reduced bone mineral density (BMD) in patients with rheumatoid arthritis (RA). Either or both of these factors may be inevitable during pregnancy in women with RA, but it is unknown whether they variables influence the BMD of the offspring. This study was undertaken to investigate whether medication use or disease activity during pregnancy in RA patients influences the BMD of their prepubertal offspring. METHODS: Mothers (n = 255) participated in a prospective cohort study of RA and pregnancy, and 108 children of these mothers (ages 5-10 years) were included in this followup study. Information on features known to influence BMD in children, i.e., calcium intake, physical activity, serum 25-hydroxyvitamin D level, sex, height, and weight, was collected. In addition, pre- and postnatal variables known to influence BMD, i.e., gestational age, maternal smoking, birth weight, postnatal rate of growth, and type of feeding, were recorded. Independent variables were prednisone use, sulfasalazine use, and RA disease activity during pregnancy. RESULTS: We found no association of BMD in the children with either prednisone use or RA disease activity during pregnancy, even after correcting for all known associated variables. Sulfasalazine use during pregnancy had a positive effect on the total-body BMD of the offspring (difference in standard deviation score 0.53, P = 0.005). CONCLUSION: Our findings indicate that neither medication use nor high RA disease activity during pregnancy is associated with decreased BMD in offspring at age ∼7 years. The maternal benefit of medication use for RA during pregnancy outweighs the effect on BMD in the offspring.

The influence of foetal prednisone exposure on the cortisol levels in the offspring.

OBJECTIVE: Pregnant women suffering from autoimmune disease use glucocorticoids. Glucocorticoids can partly diffuse to the foetus and may influence the development of the foetal hypothalamic-pituitary-adrenal axis, especially in early stage of pregnancy. The objective was to investigate whether prednisone exposure in utero influences the cortisol levels of the prepubertal children. DESIGN: Mothers participated in a prospective cohort study on rheumatoid arthritis (RA) and pregnancy. Children were exposed (n = 44) or nonexposed (n = 65) to prednisone in utero. Salivary cortisol levels were taken from all children during 1 day: at awakening, 30 min after awakening, 1 p.m. and bedtime. Cortisol levels between groups were also analysed using area under the curve (AUC), cortisol awakening response (CAR) and slope. RESULTS: The mean age (SD) of the children was 6·98 (1·23). The difference in mean (SD) cortisol level at '1 p.m.' was 5·42 nm (4·08) in the prednisone-exposed and 3·97 nm (4·00) in the nonexposed (P = 0·03). Prednisone-exposed children had a higher AUC (ß = 13·28; P = 0·02), even after correction for RA disease activity. No differences were found on CAR, slope or blood pressure. The cortisol levels of the nonexposed were more similar to the age-specific references than the prednisone-exposed. CONCLUSION: Prednisone use during pregnancy is associated with a higher daytime cortisol level, in the prepubertal offspring, not yet accompanied with clinical outcomes. This conclusion will have no consequences at this moment, but it does raise questions concerning prednisone exposure in utero and the long-term consequences for the offspring.

Circulating maternal cytokines influence fetal growth in pregnant women with rheumatoid arthritis.

BACKGROUND: High rheumatoid arthritis (RA) disease activity during pregnancy is associated with a lower birth weight. Active RA is characterised by high circulating levels of cytokines, which can mediate placental growth and remodelling. OBJECTIVES: To assess the influence of maternal serum cytokine levels on birth weight in RA pregnancy. METHODS: This study is embedded in the PARA Study, a prospective study on RA and pregnancy. In the present study, 161 pregnant women with RA and 32 healthy pregnant women were studied. The main outcome measures were birth weight SD score (birth weight SDS) in relation to maternal serum levels of interleukin-10 (IL-10), interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα) at three different time points: preconception and during the first and third trimester. Single-nucleotide polymorphisms (SNPs) in the corresponding cytokine genes were also studied. RESULTS: During the first trimester, IL-10 was detectable in 16% of patients with RA, IL-6 in 71%, and TNFα in all patients with RA. Mean birth weight SDS of children born to mothers with RA was higher when IL-10 level was high compared with low (difference=0.75; p=0.04), and lower when IL-6 was high compared with low (difference=0.50; p<0.01) in the first trimester. No correlation was seen at the other time points studied or with TNFα. Cytokine levels were not related to their corresponding SNPs. CONCLUSIONS: Maternal IL-10 and IL-6 levels are associated with fetal growth in RA. In the first trimester, high IL-10 levels are associated with higher birth weight SDS, and high IL-6 levels are associated with lower birth weight SDS, even after correction for disease activity.

Low carriage rate of group B streptococcus in pregnant women in Maputo, Mozambique.

The prevalence of group B streptococcus (GBS) carriage varies strongly with geographical region. A study was done to determine the prevalence of GBS in women in Maputo, Mozambique. The method used was a rectovaginal swab which was taken from women between 35 and 37 weeks of pregnancy who visited the clinic for antenatal consultation. GBS was cultured from 2 out of 113 samples, yielding a prevalence of 1.8% (95% Cl: 0.0-4.0). In conclusion, the prevalence of GBS carriage among pregnant women in Maputo, Mozambique was low.