Associations between antenatal prednisone exposure and long-term cortisol and cortisone concentrations in children born to women with rheumatoid arthritis: results from a nationwide prospective cohort study

Abstract

ObjectivesTo identify whether children with antenatal prednisone exposure have chronically elevated cortisol and cortisone concentrations, an altered body composition or higher blood pressure. In addition, to identify whether maternal rheumatoid arthritis disease (RA) activity is associated with these alterations.MethodsIn this prospective study, 56 children (mean age=10.0 years) with and 61 children (mean age=9.6 years) without antenatal prednisone exposure, born to women with RA, were included. Hair cortisol and cortisone were analysed using liquid chromatography–tandem mass spectrometry. Linear regression models were built to analyse differences between the two groups, corrected for relevant covariates. Hair cortisol concentrations were also compared between the study population and an age-matched healthy reference group(n=150 children, mean age=9.8 years).ResultsHair cortisol and cortisone concentrations were similar in children with and without antenatal prednisone exposure (median cortisol 1.14 pg/mg (IQR 0.67–1.75) and 1.15 pg/mg (IQR 0.65–2.21) and median cortisone 6.76 pg/mg (IQR 5.42–8.86) and 7.40 pg/mg (IQR 5.39–10.73), respectively). Antenatal prednisone exposure and maternal RA disease activity were also not associated with body composition or blood pressure. Hair cortisol concentrations were not different in children born to mothers with RA compared with children from the reference group.ConclusionThis, in its kind, large and unique long-term prospective study demonstrates that low-dose antenatal prednisone exposure and maternal RA disease activity are not associated with negative consequences in prepubertal childhood. The findings of this study are reassuring and support the assumption that low-dose maternal prednisone use during pregnancy is safe for the offspring, at least until the age of approximately 10 years.

Body mass index, waist circumference and body fat are positively correlated with hair cortisol in children: A systematic review and meta‐analysis

“…One study examined only the relationship between HCC and waist circumference disaggregated by sex and reported a significant negative relationship ( r = −0.39) between HCC and waist circumference among boys but a nonsignificant positive relationship ( r = 0.22) among girls 39 . One study did not report the correlation direction but found a nonsignificant relationship between HCC and waist circumference 21 . Among the four studies with body fat or fat mass index measurements, three reported a positive relationship between HCC and body fat or fat mass index ( r = 0.05–0.14).…”

“…Thus, 28 articles meeting the inclusion and exclusion criteria were retained for the qualitative synthesis, with a total sample of 11510 children. Among the 28 articles, two lacking adequate data for calculating effect sizes were excluded from the further meta‐analysis after two unsuccessful attempts were made to contact the corresponding authors to obtain more data 21,22 …”

“…Of the 28 studies included in this systematic review (see Table S1), 11 (39.3%) 21–31 were rated as having a high risk of bias, and 17 were rated as having a low risk of bias. For the 11 studies with a high risk of bias, the rating was due to potential confounding: Researchers failed to adjust potential confounders when examining the relationship between HCC and anthropometric factors.…”

“…Table S2 displays a summary of the 28 studies included in the systematic review 21–48 . Of the 28 studies, only four were conducted in the United States, with the remaining ones conducted in Europe ( n = 16; seven in Netherlands, four in Germany, two in Greece, one in Switzerland, one in Belgium and one in Denmark), Australia ( n = 4), China ( n = 2), Canada ( n = 1) or Jordan/Lebanon/Iraq/Syria/Turkey ( n = 1).…”

“…Among the 28 studies that examined the relationship between HCC and BMI/ z ‐score, 19 reported a positive relationship ( r = 0.025–0.91) and four a negative relationship ( r = −0.002 to −0.26). Two studies did not include the correlation direction but reported a nonsignificant relationship between HCC and BMI 21,22 . One study reported no relationship at all between HCC and BMI ( r = 0) 26 .…”