Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, Durham, NC 27709, USA.
Hum Reprod. 2013 Oct;28(10):2848-55. doi: 10.1093/humrep/det297. Epub 2013 Aug 6.
How variable is the length of human pregnancy, and are early hormonal events related to gestational length?
Among natural conceptions where the date of conception (ovulation) is known, the variation in pregnancy length spanned 37 days, even after excluding women with complications or preterm births.
Previous studies of length of gestation have either estimated gestational age by last menstrual period (LMP) or ultrasound (both imperfect measures) or included pregnancies conceived through assisted reproductive technology.
STUDY DESIGN, SIZE, DURATION: The Early Pregnancy Study was a prospective cohort study (1982-85) that followed 130 singleton pregnancies from unassisted conception to birth, with detailed hormonal measurements through the conception cycle; 125 of these pregnancies were included in this analysis.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We calculated the length of gestation beginning at conception (ovulation) in 125 naturally conceived, singleton live births. Ovulation, implantation and corpus luteum (CL) rescue pattern were identified with urinary hormone measurements. We accounted for events that artificially shorten the natural length of gestation (Cesarean delivery or labor induction, i.e. 'censoring') using Kaplan-Meier curves and proportional hazards models. We examined hormonal and other factors in relation to length of gestation. We did not have ultrasound information to compare with our gold standard measure.
The median time from ovulation to birth was 268 days (38 weeks, 2 days). Even after excluding six preterm births, the gestational length range was 37 days. The coefficient of variation was higher when measured by LMP (4.9%) than by ovulation (3.7%), reflecting the variability of time of ovulation. Conceptions that took longer to implant also took longer from implantation to delivery (P = 0.02). CL rescue pattern (reflecting ovarian response to implantation) was predictive (P = 0.006): pregnancies with a rapid progesterone rise were longer than those with delayed rise (a 12-day difference in the median gestational length). Mothers with longer gestations were older (P = 0.02), had longer pregnancies in other births (P < 0.0001) and were heavier at birth (P = 0.01). We did not see an association between the length of gestation and several factors that have been associated with gestational length in previous studies: body mass index, alcohol intake, parity or offspring sex.
LIMITATIONS, REASONS FOR CAUTION: The sample size was small and some exposures were rare, reducing power to detect weak associations.
Human gestational length varies considerably even when measured exactly (from ovulation). An individual woman's deliveries tend to occur at similar gestational ages. Events in the first 2 weeks after conception are predictive of subsequent pregnancy length, and may suggest pathways underlying the timing of delivery.
STUDY FUNDING/COMPETING INTEREST: This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. None of the authors has any conflict of interest to declare.
人类妊娠的长度变化有多大,早期的激素事件与妊娠长度有关吗?
在已知受孕日期(排卵)的自然受孕中,妊娠长度的变化范围为 37 天,即使排除了有并发症或早产的女性。
之前关于妊娠期的研究要么通过末次月经(LMP)或超声(两者都不完美的测量方法)估计妊娠龄,要么包括通过辅助生殖技术受孕的妊娠。
研究设计、大小、持续时间:早期妊娠研究是一项前瞻性队列研究(1982-85 年),对 130 名自然受孕的单胎妊娠从受孕到分娩进行了随访,通过受孕周期的详细激素测量;其中 125 例妊娠纳入本分析。
参与者/材料、地点、方法:我们计算了 125 例自然受孕、单胎活产的妊娠从受孕(排卵)开始的时间。排卵、着床和黄体(CL)挽救模式通过尿激素测量来确定。我们使用 Kaplan-Meier 曲线和比例风险模型来计算剖宫产或引产等人为缩短自然妊娠时间的事件(“删失”)。我们研究了与妊娠时间相关的激素和其他因素。我们没有超声信息来与我们的金标准测量进行比较。
从排卵到分娩的中位时间为 268 天(38 周零 2 天)。即使排除 6 例早产,妊娠时间范围仍为 37 天。通过 LMP 测量的变异系数(4.9%)高于通过排卵(3.7%),反映了排卵时间的可变性。着床时间较长的妊娠,从着床到分娩的时间也较长(P=0.02)。CL 挽救模式(反映卵巢对着床的反应)具有预测性(P=0.006):孕酮快速上升的妊娠比孕酮缓慢上升的妊娠长(中位数妊娠时间相差 12 天)。妊娠时间较长的母亲年龄较大(P=0.02),在其他分娩中妊娠时间较长(P<0.0001),出生时体重较重(P=0.01)。我们没有发现妊娠时间与之前研究中与妊娠时间相关的几个因素之间存在关联:体重指数、饮酒量、产次或后代性别。
局限性、谨慎的原因:样本量小,一些暴露因素罕见,降低了检测弱关联的能力。
即使从排卵开始进行精确测量,人类妊娠的长度也有很大的差异。个体女性的分娩往往发生在相似的妊娠龄。受孕后前 2 周的事件可预测随后的妊娠时间,并可能提示分娩时间的潜在途径。
研究资金/利益冲突:本研究由美国国立卫生研究院(NIH)内部研究计划、国家环境健康科学研究所资助。作者均无利益冲突声明。