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



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



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.



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



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.



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.



clinicaltrials.gov Identifier: NCT00467363.
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Stefanie N
SN
Hinkle
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Sunni L
SL
Mumford
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Katherine L
KL
Grantz
Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, School of Medicine, Salt Lake City.
Robert M
RM
Silver
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland3Center for Financing, Access, and Cost Trends, Agency for Healthcare Research and Quality, Rockville, Maryland.
Emily M
EM
Mitchell
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Lindsey A
LA
Sjaarda
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Rose G
RG
Radin
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Neil J
NJ
Perkins
Department of Statistics, University of Haifa, Haifa, Israel.
Noya
N
Galai
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Enrique F
EF
Schisterman
D000022:Abortion, Spontaneous / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D006063:Chorionic Gonadotropin / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007557:Israel; D009325:Nausea / Q000628:therapy*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000628:therapy*; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011446:Prospective Studies; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States; D014839:Vomiting / Q000628:therapy*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D006063:Chorionic Gonadotropin; D001241:Aspirin
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