van der Voorn Bibian, Wit Jan M, van der Pal Sylvia M, Rotteveel Joost, Finken Martijn J J
Department of Pediatrics (B.v.d.V., J.R., M.J.J.F.), VU University Medical Center, 1007 MB Amsterdam, The Netherlands; Department of Pediatrics (J.M.W.), Leiden University Medical Center, 2333 ZA Leiden, Netherlands; and TNO, Child Health (S.M.v.d.P.), 2316 ZL Leiden, The Netherlands.
J Clin Endocrinol Metab. 2015 Feb;100(2):500-7. doi: 10.1210/jc.2014-2843. Epub 2014 Nov 19.
Preterm survivors exhibit neurodevelopmental impairments. Whether this association is influenced by antenatal glucocorticoid treatment and glucocorticoid sensitivity is unknown.
This study aimed to study the effects of antenatal glucocorticoid treatment and glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) polymorphisms on behavior and intelligence quotient (IQ).
This study was part of the 19-year follow-up of the Project On Preterm and Small-for-gestational-age birth cohort.
Multicenter study.
Three hundred forty-four 19-year-olds born very preterm (gestational age < 32 wk), of whom 71 had received betamethasone antenatally.
Single antenatal treatment course of betamethasone.
Behavior (Young Adult Self Report and Young Adult Behavior Checklist for parents) and IQ (digital Multicultural Capacity Test-intermediate level). Data were analyzed by linear regression and presented as regression coefficient (95% confidence interval [CI]).
Sex ratio, GR (R23K; N363S) and MR (-2G/C; I180V) genotypes were equally distributed between treated and nontreated subjects. Independent of treatment, R23K carriers had improved IQ scores (β 9.3; 95% CI, 3.4 to 15.1) and a tendency toward more favorable total problem behavior scores (β -8.5; 95% CI, -17.3 to 0.2) ; -2G/C CC carriers had poorer IQ scores (β -6.2; 95% CI, -10.5 to -1.9); I180V carriers had more favorable internalizing behavior scores (β -2.0; 95% CI, -3.9 to -0.1). Antenatal glucocorticoid treatment was associated with more unfavorable behavior scores, especially internalizing behavior (β 2.4; 95% CI, 0.3 to 4.5). Interaction between GR and MR polymorphisms and antenatal glucocorticoid treatment was observed, with poorer IQ scores for exposed N363S carriers; poorer intellectual subdomain scores for exposed I180V-carriers; more favorable total problem behavior scores for exposed R23K carriers.
Genetic variations in glucocorticoid sensitivity and antenatal glucocorticoid treatment are associated with IQ and behavior in young adult preterm survivors.
早产幸存者存在神经发育障碍。这种关联是否受产前糖皮质激素治疗和糖皮质激素敏感性影响尚不清楚。
本研究旨在探讨产前糖皮质激素治疗以及糖皮质激素受体（GR）和盐皮质激素受体（MR）基因多态性对行为和智商（IQ）的影响。
本研究是早产和小于胎龄儿出生队列项目19年随访的一部分。
多中心研究。
344名19岁的极早产儿（胎龄<32周），其中71名在产前接受过倍他米松治疗。
单次产前倍他米松治疗疗程。
行为（青年成人自评量表和家长用青年成人行为清单）和智商（数字多元文化能力测试中级水平）。数据采用线性回归分析，并以回归系数（95%置信区间[CI]）表示。
治疗组和未治疗组之间的性别比例、GR（R23K；N363S）和MR（-2G/C；I180V）基因型分布均衡。与治疗无关，R23K携带者的智商得分有所提高（β 9.3；95%CI，3.4至15.1），且总问题行为得分有更有利的趋势（β -8.5；95%CI，-17.3至0.2）；-2G/C CC携带者的智商得分较低（β -6.2；95%CI，-10.5至-1.9）；I180V携带者有更有利的内化行为得分（β -2.0；95%CI，-3.9至-0.1）。产前糖皮质激素治疗与更不利的行为得分相关，尤其是内化行为（β 2.4；95%CI，0.3至4.5）。观察到GR和MR基因多态性与产前糖皮质激素治疗之间存在相互作用，暴露的N363S携带者智商得分较低；暴露的I180V携带者智力子领域得分较低；暴露的R23K携带者总问题行为得分更有利。
糖皮质激素敏感性的基因变异和产前糖皮质激素治疗与年轻成人早产幸存者的智商和行为有关。
