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Free access

Christiaan L Meuwese, Anne M Euser, Bart E Ballieux, Huib A van Vliet, Martijn J J Finken, Frans J Walther, Friedo W Dekker, and Jan M Wit

Background

The long-term effects of perinatal growth and corticosteroid exposure on adrenal steroid concentrations in adults born very preterm are uncertain.

Objectives

To examine the effect of birth weight, early postnatal growth, and pre- and postnatal corticosteroid administration on serum adrenal steroids in 19-year-old subjects born very preterm.

Design and methods

Subjects born before 32 weeks of gestation in The Netherlands participating in the Project on Preterm and Small for Gestational Age Infants (POPS) were investigated at 19 years of age. Serum cortisol, DHEA sulfate (DHEAS), and androstenedione (Adione) concentrations were measured in 393 out of 676 eligible subjects, compared with controls, and associated with perinatal growth and pre- and postnatal corticosteroids administration using multiple linear regression analyses.

Results

Serum DHEAS and Adione in men and women were higher than in controls. In the multiple regression analyses, birth weight SDS showed a statistically significant negative association with serum DHEAS concentrations in women (β: −0.865, 95% confidence interval (CI): −1.254 to −0.476) and in men (β: −0.758, 95% CI: −1.247 to −0.268) and with serum Adione concentrations in women (β: −0.337, 95% CI: −0.593 to −0.082). Early postnatal weight gain showed no association with any of measured adrenal markers. In women, serum Adione was associated with postnatal dexamethasone exposure (β: 0.932, 95% CI: 0.022 – 1.843).

Conclusions

Young adults born very preterm show elevated adrenal androgens, particularly when born small for gestational age. Postnatal corticosteroid administration is positively associated with serum Adione in young women.

Free access

Anna M E Noten, Eva M Loomans, Tanja G M Vrijkotte, Peter M van de Ven, A S Paul van Trotsenburg, Joost Rotteveel, Manon van Eijsden, and Martijn J J Finken

Objective

Overt hypothyroidism in pregnant women is associated with a lower intelligence quotient in their children. More recently, subtle decreases in maternal thyroid function have also been associated with neurodevelopmental impairment in offspring. We tested the effect of hypothyroxinaemia during early pregnancy on school performance.

Design

This was a longitudinal study that included the data of 1196 mother-child pairs from the Amsterdam Born Children and Their Development study.

Methods

Maternal serum free thyroxine (T4) and TSH were obtained at a median gestational age of 12.9 (interquartile range: 11.9–14.3) weeks. School performance was assessed at age 5 years and based on scores obtained in arithmetic and language tests from the national monitoring and evaluation system. Poor school performance was defined as a test result <25th percentile and subnormal school performance as a result <50th percentile of the norm population. To estimate the impact of possible non-response bias, we conducted inverse-probability weighted analyses.

Results

Maternal hypothyroxinaemia (i.e., a maternal free T4 in the lowest 10% of distribution) was associated with a 1.61 (95% CI: 1.05–2.47) -fold increased odds of subnormal arithmetic performance after adjustment for confounders (P=0.03). However, the odds ratio dropped to 1.48 (95% CI: 0.94–2.32) after inverse-probability weighting (P=0.09). No such relations were found with TSH.

Conclusions

Maternal hypothyroxinaemia at the end of the first trimester was associated with reduced performance in an arithmetic test, but not in a language test, in 5-year-old offspring. However, our results should be interpreted carefully because of possible non-response bias.

Restricted access

Nienke van Welie, Maite Portela, Kim Dreyer, Linda J Schoonmade, Madelon van Wely, Ben Willem J Mol, Adrianus S P van Trotsenburg, Cornelis B Lambalk, Velja Mijatovic, and Martijn J J Finken

Objective

Thyroid dysfunction is a known side effect of iodinated contrast media. There is some evidence to suggest that iodinated contrast media administered to pregnant women may cause thyroid dysfunction not only in themselves but also in their offspring. Here, we systematically evaluated literature on the use of iodinated contrast media prior to or during pregnancy on the offspring’s thyroid function.

Design

Systematic review of published literature.

Materials and methods

Relevant studies were identified by PubMed, EMBASE and The Cochrane Library up to June 5, 2020. All study designs, reporting on the foetal or neonatal thyroid function after exposure to iodinated contrast media prior to or during pregnancy, were included. We undertook random effects meta-analysis and pooled the estimates as proportions with 95% CIs.

Results

We identified 402 articles, of which 26 were included. Six studies reported (n = 369) on exposure to iodinated contrast media prior to pregnancy by hysterosalpingography and 20 studies (n = 670) on exposure to these media during pregnancy by amniofetography, urography or CT. There was low to high risk of bias. The proportion of (transient) neonatal thyroid dysfunction was 0.0% (95% CI: 0.0–2.9% based on 3 studies) for hysterosalpingography, 2.25% (95% CI: 0.03–6.55% based on 2 studies) for amniofetography and 0.0% (95% CI: 0.0–0.02% based on 5 studies) for CT. There was a tendency towards an increased risk of thyroid dysfunction with higher amounts of contrast used.

Conclusions

Exposure to iodinated contrast media prior to or during pregnancy may increase the risk of thyroid dysfunction in offspring. We recommend keeping the amount of contrast used as low as possible.

Open access

Irina Bacila, Nicole Freeman, Eleni Daniel, Marija Sandrk, Jillian Bryce, Salma Rashid Ali, Zehra Yavas Abalı, Navoda Atapattu, Tania A Bachega, Antonio Balsamo, Niels Birkebæk, Oliver Blankenstein, Walter Bonfig, Martine Cools, Eduardo Correa Costa, Feyza Darendeliler, Silvia Einaudi, Heba Hassan Elsedfy, Martijn Finken, Evelien Gevers, Hedi L Claahsen-van der Grinten, Tulay Guran, Ayla Güven, Sabine E. Hannema, Claire E Higham, Violeta Iotova, Hetty J. van der Kamp, Marta Korbonits, Ruth E Krone, Corina Lichiardopol, Andrea Luczay, Berenice Bilharinho Mendonca, Tatjana Milenkovic, Mirela C Miranda, Klaus Mohnike, Uta Neumann, Rita Ortolano, Sukran Poyrazoglu, Ajay Thankamony, Jeremy W Tomlinson, Ana Vieites, Liat de Vries, S Faisal Ahmed, Richard J Ross, and Nils P Krone

Objective: Despite published guidelines no unified approach to hormone replacement in congenital adrenal hyperplasia (CAH) exists. We aimed to explore geographical and temporal variations in the treatment with glucocorticoids and mineralocorticoids in CAH.

Design: This retrospective multi-center study, including 31 centers (16 countries), analyzed data from the International-CAH Registry.

Methods: Data was collected from 461 patients aged 0-18 years with classic 21-hydroxylase deficiency (54.9% females) under follow-up between 1982 – 2018. Type, dose and timing of glucocorticoid and mineralocorticoid replacement was analyzed from 4174 patient visits.

Results: The most frequently used glucocorticoid was hydrocortisone (87.6%). Overall, there were significant differences between age groups with regards to daily hydrocortisone-equivalent dose for body surface, with the lowest dose (median with interquartile range) of 12.0 (10.0 – 14.5) mg/ m2/ day at age 1 - 8 years and the highest dose of 14.0 (11.6 - 17.4) mg/ m2/ day at age 12-18 years. Glucocorticoid doses decreased after 2010 in patients 0-8 years (p<0.001) and remained unchanged in patients aged 8-18 years. Fludrocortisone was used in 92% of patients, with relative doses decreasing with age. A wide variation was observed among countries with regards to all aspects of steroid hormone replacement.

Conclusions: Data from the I-CAH Registry suggests international variations in hormone replacement therapy, with a tendency to treatment with high doses in children.