ESPE Abstracts (2014) 82 FC1.5

Antenatal Glucocorticoid Treatment and Polymorphisms in Glucocorticoid and Mineralocorticoid Receptor Genes are Associated with Long-Term Neurodevelopmental Outcomes in Preterm Survivors

Bibian van der Voorna, Sylvia van der Palb, Jan Witc, Ingrid Meulenbeltc, Eline Slagboomc, Joost Rotteveela & Martijn Finkena

aVU University Medical Center, Amsterdam, The Netherlands; bTNO Prevention and Health, Leiden, The Netherlands; cLeiden University Medical Center, Leiden, The Netherlands

Background: Preterm survivors are found to exhibit deficits in several neurodevelopmental domains. It is unknown whether this could be explained by antenatal glucocorticoid treatment.

Objective and Hypotheses: We studied whether antenatal glucocorticoid treatment is associated with behaviour and IQ in young adults born preterm. In addition, we studied whether these associations could be modified by the R23K and N363S polymorphisms in the glucocorticoid receptor (GR) gene and by the −2G/C and I180V polymorphisms in the mineralocorticoid receptor (MR) gene.

Method: 344 19-year-old with a gestational age of 30±1.5 weeks and a birth weight of 1328±336 g were drawn from the project on preterm and small-for-gestational-age birth cohort. Behaviour was assessed by the Young Adult Self-Report and the Young Adult Behaviour Checklist for parents, and IQ by the digital Multicultural Capacity Test–Intermediate Level.

Results: Antenatal glucocorticoid treatment was associated with higher scores on both self-reported and parent-reported internalizing behaviour and with a higher score on parent-reported externalizing behaviour. Independent of glucocorticoid treatment, carriage of the MR I180V variant was associated with a lower score on internalizing behaviour. Glucocorticoid treatment was not associated with IQ score. Independent of glucocorticoid treatment, carriage of the GR R23K variant was associated with a 9.3 (95% CI 3.4–15.1) points higher IQ score and carriage of the MR −2G/C ‘CC’ variant with a 6.2 (95% CI 1.9–10.5) points lower IQ score. Interaction between glucocorticoid treatment and GR N3633 carriage on IQ score was observed, with treated variant allele carriers showing a reduction in IQ score of 16.4 (95% CI 1.2–34.0) points.

Conclusion: Antenatal glucocorticoid treatment and polymorphisms in GR and MR genes have long-lasting effects on behaviour and IQ in preterm survivors. Replication in independent samples is warranted.

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