St Clair Sophie L, Walters Anthony G B, Crowther Caroline A, Dalziel Stuart R, Eagleton Carl, Gamble Gregory D, McKinlay Christopher J D, Milne Barry J, Harding Jane E
Liggins Institute, The University of Auckland, Auckland, New Zealand.
Department of Pediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand.
Acta Obstet Gynecol Scand. 2024 Dec;103(12):2412-2425. doi: 10.1111/aogs.14984. Epub 2024 Oct 4.
Antenatal corticosteroids are widely used to prevent morbidity and mortality after preterm birth, but there are ongoing concerns about the possible risk of long-term adverse effects, including perturbation of endocrine systems, with potential implications for reproduction. A small number of animal studies have suggested possible adverse effects on reproduction after antenatal exposure to corticosteroids, but there is a paucity of human data.
This is a secondary cohort analysis of the 50-year follow-up of the Auckland Steroid Trial (1969-1974) comparing antenatal exposure to corticosteroids or placebo. Participants whose mothers took part in the placebo-controlled randomized trial of antenatal corticosteroids completed a questionnaire reporting reproductive outcomes at 50 years of age. The main outcome was at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks. Additional outcomes included a number of pregnancies or fathered pregnancies ≥20 weeks, outcomes relating to female reproductive lifespan (including age at menarche and menopause), and outcomes relating to their offspring (including birthweight and gestation).
Of 917 eligible participants, 415 (45% of eligible) completed the questionnaire at a mean (SD) age of 49.3 (1.0) years. The proportion of participants who had experienced at least one pregnancy ≥20 weeks or fathered at least one pregnancy ≥20 weeks was similar in betamethasone and placebo-exposed groups (163/217 [75%] vs. 136/190 [72%]; RR 1.08, (95% CI 0.95 to 1.22); p = 0.23). Participants exposed to betamethasone had a slightly higher number of pregnancies or fathered pregnancies ≥20 weeks compared to those exposed to placebo (mean 1.89 vs. 1.60; marginal mean difference 0.20, (95% CI 0.03-0.37); p = 0.03). Other outcomes, including female reproductive lifespan and offspring-related outcomes, were similar in both randomized groups. There were also no differences in any outcomes between those born preterm and those born at term.
Antenatal exposure to corticosteroids appears to have no clinically important effect on reproductive outcomes to 50 years.
产前使用皮质类固醇广泛用于预防早产相关的发病和死亡，但人们一直担心其可能存在长期不良影响的风险，包括对内分泌系统的干扰，这可能对生殖产生潜在影响。少数动物研究表明，产前接触皮质类固醇可能对生殖产生不良影响，但人类数据匮乏。
这是对奥克兰类固醇试验（1969 - 1974年）50年随访的二次队列分析，比较产前接触皮质类固醇或安慰剂的情况。母亲参与了产前皮质类固醇安慰剂对照随机试验的参与者在50岁时完成了一份报告生殖结局的问卷。主要结局是至少有一次妊娠≥20周或使至少一次妊娠≥20周。其他结局包括妊娠次数或使妊娠≥20周的次数、与女性生殖寿命相关的结局（包括初潮年龄和绝经年龄）以及与后代相关的结局（包括出生体重和孕周）。
在917名符合条件的参与者中，415名（占符合条件者的45%）在平均（标准差）年龄49.3（1.0）岁时完成了问卷。倍他米松组和安慰剂组中经历至少一次妊娠≥20周或使至少一次妊娠≥20周的参与者比例相似（163/217 [75%] 对136/190 [72%]；相对危险度1.08，（95%可信区间0.95至1.22）；p = 0.23）。与安慰剂组相比，倍他米松组妊娠次数或使妊娠≥20周的次数略多（平均1.89对1.60；边际均值差异0.20，（95%可信区间0.03 - 0.37）；p = 0.03）。两个随机分组组中的其他结局，包括女性生殖寿命和与后代相关的结局，相似。早产出生者和足月出生者在任何结局上也没有差异。
产前接触皮质类固醇在50岁时似乎对生殖结局没有临床重要影响。
