Association of Nausea and Vomiting During Pregnancy With Pregnancy Loss: A Secondary Analysis of a Randomized Clinical Trial

Abstract

Importance: Nausea and vomiting during pregnancy have been associated with a reduced risk for pregnancy loss. However, most prior studies enrolled women with clinically recognized pregnancies, thereby missing early losses.

Objective: To examine the association of nausea and vomiting during pregnancy with pregnancy loss.

Design, setting, and participants: A randomized clinical trial, Effects of Aspirin in Gestation and Reproduction, enrolled women with 1 or 2 prior pregnancy losses at 4 US clinical centers from June 15, 2007, to July 15, 2011. This secondary analysis was limited to women with a pregnancy confirmed by positive results of a human chorionic gonadotropin (hCG) test. Nausea symptoms were ascertained from daily preconception and pregnancy diaries for gestational weeks 2 to 8. From weeks 12 to 36, participants completed monthly questionnaires summarizing symptoms for the preceding 4 weeks. A week-level variable included nausea only, nausea with vomiting, or neither.

Main outcomes and measures: Peri-implantation (hCG-detected pregnancy without ultrasonographic evidence) and clinically recognized pregnancy losses.

Results: A total of 797 women (mean [SD] age, 28.7 [4.6] years) had an hCG-confirmed pregnancy. Of these, 188 pregnancies (23.6%) ended in loss. At gestational week 2, 73 of 409 women (17.8%) reported nausea without vomiting and 11 of 409 women (2.7%), nausea with vomiting. By week 8, the proportions increased to 254 of 443 women (57.3%) and 118 of 443 women (26.6%), respectively. Hazard ratios (HRs) for nausea (0.50; 95% CI, 0.32-0.80) and nausea with vomiting (0.25; 95% CI, 0.12-0.51) were inversely associated with pregnancy loss. The associations of nausea (HR, 0.59; 95% CI, 0.29-1.20) and nausea with vomiting (HR, 0.51; 95% CI, 0.11-2.25) were similar for peri-implantation losses but were not statistically significant. Nausea (HR, 0.44; 95% CI, 0.26-0.74) and nausea with vomiting (HR, 0.20; 95% CI, 0.09-0.44) were associated with a reduced risk for clinical pregnancy loss.

Conclusions and relevance: Among women with 1 or 2 prior pregnancy losses, nausea and vomiting were common very early in pregnancy and were associated with a reduced risk for pregnancy loss. These findings overcome prior analytic and design limitations and represent the most definitive data available to date indicating the protective association of nausea and vomiting in early pregnancy and the risk for pregnancy loss.

Trial registration: clinicaltrials.gov Identifier: NCT00467363.

Figure 1.. Nausea and Vomiting During Gestational Weeks 2 to 8

Participants rated nausea and vomiting via daily preconception and pregnancy diaries as none, nausea only, vomiting once per day, or vomiting more than once per day. The week-specific sample size depends on active or passive follow-up and on the number of women remaining pregnant at a given week.

Figure 2.. Nausea and Vomiting During Gestational Weeks 9 to 36

From gestational weeks 12 to 36, participants completed monthly questionnaires describing their nausea and vomiting symptoms during the prior 4 weeks as never, rarely (once per month), occasionally (2 or 3 times per month), sometimes (1 or 2 times per week), often (3–6 times per week), or daily. Only participants who remained pregnant at the time of the questionnaire were asked to complete the questionnaire for the preceding 4 weeks, ensuring that all data were prospectively collected before the pregnancy outcome.Week-specific sample size depends on the number of women remaining pregnant at a given week.