Length of human pregnancy and contributors to its natural variation

Abstract

Study question: How variable is the length of human pregnancy, and are early hormonal events related to gestational length?

Summary answer: 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.

What is known already: 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.

Main results and the role of chance: 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.

Wider implications of the findings: 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.

Keywords: corpus luteum; gestational length; implantation; pregnancy; variability.

Figures

Figure 1

Smoothed distribution of length of gestation (accounting for medical interventions that shortened gestation) derived from 125 singleton live births, North Carolina Early Pregnancy Study, 1982–1985. Though the day-specific percents were calculated from all births, the illustrated curves show only gestational ages with sufficient data for meaningful smoothing. Solid line: ovulation-based length of gestation [excludes 5 (4%) births before 245 days]; this line does not go to zero because the last birth in the cohort was a planned Cesarean delivery, i.e. a censored birth. Dashed line: LMP-based length of gestation (excludes 3 (2%) births before Day 253 and 5 (4%) births after 300 days of gestation). Supplementary data, Table SII shows the ovulation-based gestational age data.

Figure 2

Association of the time from ovulation to implantation with the time from implantation to birth, accounting for medical interventions that shortened gestation. Solid line: 6, 7 or 8 days between ovulation and implantation. Dotted line: 9 days. Dashed line: 10, 11 or 12 days. HR for delivery per one-day increase in time from ovulation to implantation (95% CIs): 0.8 (0.6, 1.0), linear trend P = 0.04.

Figure 3

Association of the pattern of CL rescue with ovulation-based length of gestation, accounting for medical interventions that shortened gestation. Solid line: early progesterone rise; dashed line: late progesterone rise; dotted line: maintenance. Late rise versus early rise, HR (95% CI): 3.0 (1.4, 6.5), P = 0.006. Maintenance versus early rise, HR (CI): 1.6 (0.7, 3.8), P = 0.28.