Effect of maternal sleep on embryonic development

Abstract

The concept of developmental origin of health and disease has ignited a search for mechanisms and health factors influencing normal intrauterine development. Sleep is a basic health factor with substantial individual variation, but its implication for early prenatal development remains unclear. During the embryonic period, the yolk sac is involved in embryonic nutrition, growth, hematopoiesis, and likely in fetal programming. Maternal body measures seem to influence its size in human female embryos. In this prospective, longitudinal observational study of 190 healthy women recruited before natural conception, we assessed the effect of prepregnant sleep duration (actigraphy) on the fetal crown-rump-length (CRL) and yolk sac size (ultrasound). All women gave birth to a live child. The prepregnancy daily sleep duration had an effect on the male yolk sac and CRL at the earliest measurement only (7 weeks). I.e., the yolk sac diameter decreased with increasing sleep duration (0.22 mm·h^-1d^-1, 95%CI [0.35-0.09], P < 0.01), and CRL increased (0.92 mm·h^-1d^-1, 95%CI [1.77-0.08], P = 0.03). Since there was no association at the second measurement (10 weeks), and in the group of female fetuses at any measure point, we suggest a sex- and time-dependent embryonic adaptation to sleep generated differences in the intrauterine environment in normal pregnancies.

Figure 1

(a) Flowchart of the study population with the participant exclusions—*other: 1 twin pregnancy, 2 abortions > 18 weeks (fetal anomaly), and 1 irregular menstrual cycle; **missing data: Pregnancies with incomplete entry data (N = 54) and pregnant < 13 weeks at time of data extraction (N = 8). (b) Timing of measurements and recordings.

Figure 2

(a) First and second yolk sac measurements (total N = 358), and (b) the three serial crown-rump-length (CRL) measurements (total N = 559), presented with predicted mean (mixed model with random intercept) and 95% prediction band. Gestational age was based on last menstrual period.

Figure 3

Effect of daily total sleeping time before pregnancy (a), and effect of the daily total sleeping time at 13 weeks (b) on the first (upper row) and second yolk sac measurement (lower row) in naturally conceived healthy pregnancies presented with regression line and its 95% confidence interval. The first column represents the total dataset and the second and third the analysis according to embryonic sex.

Figure 4

Raw-data-descriptive-inferential-statistics plot of the yolk sac size at week 7 (N = 166) grouped according to prepregnant sleep duration quartiles: Low sleep duration range (4 h 30 min–6 h 28 min); middle sleep duration range (6 h 29 min–7 h 40 min); high sleep duration range (7 h 42 min–9 h 19 min)—^* Kruskal–Wallis test (p = 0.03; ^§ Post-hoc-test (Dunn’s test), p = 0.038.