Freeman Joshua R, Whitcomb Brian W, Bertone-Johnson Elizabeth R, O'Brien Louise M, Dunietz Galit L, Purdue-Smithe Alexandra C, Kim Keewan, Silver Robert M, Schisterman Enrique F, Mumford Sunni L
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA.
Hum Reprod. 2025 Jul 1;40(7):1366-1376. doi: 10.1093/humrep/deaf074.
Are preconception sleep characteristics associated with pregnancy loss and adverse pregnancy outcomes?
Preconception sleep characteristics were not associated with pregnancy loss, but earlier sleep midpoints were associated with lower risk of adverse pregnancy outcomes, while social jetlag >1 h was associated with greater risk of a composite of adverse pregnancy outcomes.
Short sleep duration in mid-pregnancy has been associated with risk of second-trimester pregnancy loss, preterm birth (PTB), and hypertensive disorders of pregnancy (HDP). The relationships between preconception sleep and pregnancy loss, and adverse pregnancy outcomes have not been well characterized, despite plausible links.
STUDY DESIGN, SIZE, DURATION: This was a secondary analysis of a randomized controlled trial conducted between 2006 and 2012 that prospectively followed 1228 women who were attempting to become pregnant after a history of pregnancy loss. Women were followed for ≤6 cycles while attempting pregnancy, and throughout pregnancy if they conceived. Over the follow-up, 140 women withdrew from the study.
PARTICIPANTS/MATERIALS, SETTING, METHODS: This study evaluated baseline, self-reported preconception sleep duration, sleep latency, sleep midpoint, and social jetlag with risk of pregnancy loss and adverse pregnancy outcomes (e.g. PTB, HDP, and gestational diabetes (GDM)) among 1228 women with a history of pregnancy loss in the EAGeR trial. Pregnancy was documented by hCG tests; 797 women became pregnant over the follow-up. Pregnancy losses were defined as any loss after a positive hCG test; there were 188 pregnancy losses. PTB, HDP, and GDM cases were ascertained via medical record abstraction. PTB (n = 53), HDP (n = 62), and GDM (n = 22) were examined as a composite outcome (n = 118) and PTB and HDP were examined individually in exploratory analyses. GDM was not examined individually due to insufficient numbers. Log-Poisson models were used to estimate relative risks (RR) and 95% CIs for associations between preconception sleep characteristics, and pregnancy loss or adverse pregnancy outcomes with adjustment for age, BMI, lifestyle, and sociodemographic factors. Stabilized inverse probability weights were applied to address potential selection bias from loss to follow-up and from restricting to pregnancy.
Preconception sleep characteristics were not associated with risk of pregnancy loss. Preconception sleep duration and sleep latency were not associated with risk of the composite adverse pregnancy outcome. Early preconception sleep midpoints were associated with a lower risk of the composite adverse pregnancy outcome (first vs second tertile RR; 0.63, 95% CI: 0.40, 0.98) and preconception social jetlag was associated with a higher risk of the composite adverse pregnancy outcome (>1 vs ≤1 h RR; 1.65, 95% CI: 1.11, 2.44).
LIMITATIONS, REASONS FOR CAUTION: Preconception sleep was restricted to baseline self-report, which may be non-differentially misclassified and may underestimate these associations. The EAGeR study did not measure sleep during pregnancy. There were few adverse pregnancy outcomes and thus limited power to evaluate individual outcomes; the findings could be due to chance.
These findings suggest that preconception sleep is not associated with pregnancy loss, but preconception sleep timing may be relevant for risk of adverse pregnancy outcomes. Additional studies on preconception sleep and adverse pregnancy outcomes are needed given the potential impact of poor sleep on pregnancy outcomes.
STUDY FUNDING/COMPETING INTEREST(S): Joshua R. Freeman and this work were supported by the Intramural Research Program Cancer Research Training Award, National Cancer Institute, National Institutes of Health (ZIA CP010197), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract numbers: HHSN267200603423, HHSN267200603424, HHSN267200603426, HHSN275201300023I). Dr Silver received NIH funding through the listed contracts as site-PI for the original EAGeR trial at the University of Utah. Dr O'Brien reports receiving funding from the Star Legacy Foundation (paid to institution); an advisory board role at the Star Legacy Foundation; and receiving travel support from the Star Legacy Foundation. Dr Dunietz reports a role as Associate Editor at Human Reproduction and a role on the Journal Editorial Board of SLEEP. Dr Purdue-Smithe is an employee of Merck & Co. and has received stock compensation as an employee of Merck & Co. in the past 36 months. The work in this manuscript was completed before Dr Purdue-Smithe's employment at Merck & Co. and is unrelated to Dr Purdue-Smithe's work at the company. Dr Silver reports royalties or licenses from BJOG and UpToDate, Inc. in the past 36 months, receiving payment or honoraria for Grand Rounds in the past 36 months, and participating on a Data Safety Monitoring Board or Advisory Board for a National Institutes of Health-funded Apple Trial in the past 36 months. The other authors report there are no competing interests to declare.
Clinicaltrials.gov NCT00467363.
孕前睡眠特征与妊娠丢失及不良妊娠结局有关吗?
孕前睡眠特征与妊娠丢失无关,但较早的睡眠中点与较低的不良妊娠结局风险相关,而社交时差大于1小时与不良妊娠结局综合风险较高相关。
孕中期睡眠时长较短与孕中期妊娠丢失、早产(PTB)及妊娠高血压疾病(HDP)风险相关。尽管存在合理关联,但孕前睡眠与妊娠丢失及不良妊娠结局之间的关系尚未得到充分阐明。
研究设计、规模、持续时间:这是一项对2006年至2012年间进行的随机对照试验的二次分析,前瞻性随访了1228名有妊娠丢失史且试图怀孕的女性。女性在尝试怀孕期间随访≤6个周期,若怀孕则在整个孕期进行随访。在随访期间,140名女性退出研究。
参与者/材料、设置、方法:本研究评估了1228名EAGeR试验中有妊娠丢失史女性的基线、自我报告的孕前睡眠时长、入睡潜伏期、睡眠中点和社交时差与妊娠丢失及不良妊娠结局(如PTB、HDP和妊娠期糖尿病(GDM))风险的关系。通过hCG检测记录妊娠情况;797名女性在随访期间怀孕。妊娠丢失定义为hCG检测呈阳性后的任何丢失;共有188例妊娠丢失。PTB、HDP和GDM病例通过病历摘要确定。将PTB(n = 53)、HDP(n = 62)和GDM(n = 22)作为一个综合结局(n = 118)进行检查,并在探索性分析中分别检查PTB和HDP。由于数量不足,未单独检查GDM。使用对数泊松模型估计孕前睡眠特征与妊娠丢失或不良妊娠结局之间关联的相对风险(RR)和95%置信区间(CI),并对年龄、体重指数、生活方式和社会人口学因素进行调整。应用稳定的逆概率权重来解决因失访和仅限于妊娠而导致的潜在选择偏倚。
孕前睡眠特征与妊娠丢失风险无关。孕前睡眠时长和入睡潜伏期与综合不良妊娠结局风险无关。较早的孕前睡眠中点与较低的综合不良妊娠结局风险相关(第一三分位数与第二三分位数RR;0.63,95%CI:0.40,0.98),而孕前社交时差与较高的综合不良妊娠结局风险相关(>1小时与≤1小时RR;1.65,95%CI:1.11,2.44)。
局限性、谨慎原因:孕前睡眠仅限于基线自我报告,这可能存在非差异性错误分类,且可能低估这些关联。EAGeR研究未测量孕期睡眠。不良妊娠结局较少,因此评估个体结局的效能有限;这些发现可能是由于机遇所致。
这些发现表明,孕前睡眠与妊娠丢失无关,但孕前睡眠时间可能与不良妊娠结局风险相关。鉴于睡眠不佳对妊娠结局的潜在影响,需要对孕前睡眠和不良妊娠结局进行更多研究。
研究资金/利益冲突:约书亚·R·弗里曼及本研究得到了美国国立卫生研究院国家癌症研究所癌症研究培训奖内部研究项目(ZIA CP010197)以及美国国立卫生研究院尤尼斯·肯尼迪·施莱佛国家儿童健康与人类发展研究所(合同编号:HHSN267200603423、HHSN267200603424、HHSN267200603426、HHSN275201300023I)的支持。西尔弗博士作为犹他大学原EAGeR试验的现场主要研究者,通过所列合同获得美国国立卫生研究院的资金。奥布赖恩博士报告从星之遗产基金会获得资金(支付给机构);在星之遗产基金会担任顾问委员会成员;并获得星之遗产基金会的差旅支持。杜涅茨博士报告担任《人类生殖》副主编以及《睡眠》杂志编辑委员会成员。普渡 - 斯米斯博士是默克公司的员工,在过去36个月内作为默克公司员工获得了股票补偿。本手稿中的工作在普渡 - 斯米斯博士受雇于默克公司之前完成,且与她在该公司的工作无关。西尔弗博士报告在过去36个月内从BJOG和UpToDate公司获得版税或许可,在过去36个月内因大查房获得报酬或酬金,并在过去36个月内参与了美国国立卫生研究院资助的苹果试验的数据安全监测委员会或顾问委员会。其他作者报告无利益冲突声明。
Clinicaltrials.gov NCT00467363