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Original Investigation
November 2016

Association of Nausea and Vomiting During Pregnancy With Pregnancy LossA Secondary Analysis of a Randomized Clinical Trial

Author Affiliations
  • 1Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
  • 2Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, School of Medicine, Salt Lake City
  • 3Center for Financing, Access, and Cost Trends, Agency for Healthcare Research and Quality, Rockville, Maryland
  • 4Department of Statistics, University of Haifa, Haifa, Israel
JAMA Intern Med. 2016;176(11):1621-1627. doi:10.1001/jamainternmed.2016.5641
Key Points

Question  Are nausea and vomiting in pregnancy associated with the risk for pregnancy loss?

Findings  In this prospective preconception cohort of 797 women with a pregnancy confirmed by human chorionic gonadotropin test results, nausea and nausea with vomiting during pregnancy were associated with a substantial reduction in the risk for pregnancy loss.

Meaning  These findings indicate a protective association of maternal nausea and vomiting in early pregnancy with the risk for pregnancy loss and may provide reassurance to women experiencing these difficult symptoms in pregnancy.


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