Nausea, Vomiting Linked to Reduced Risk for Pregnancy Loss

Diana Phillips

September 27, 2016

Nausea alone or with vomiting was associated with a 50% to 75% reduction in the risk for pregnancy loss, according to a secondary analysis of a prospective preconception cohort study.

The findings "may provide reassurance to women experiencing these difficult symptoms in pregnancy," write Stefanie N. Hinkle, PhD, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, and colleagues in an article published online September 26 in JAMA Internal Medicine.

Although previous studies have demonstrated a protective association between nausea and vomiting in early pregnancy and the risk for pregnancy loss, they have been limited by analytic and design considerations the current study overcomes, the authors write. The current findings "represent the most definitive data available, to our knowledge," they state.

The researchers analyzed data from the multicenter, randomized controlled Effects of Aspirin in Gestation and Reproduction (EAGER) Trial, in which women with a history of one or two pregnancy losses and who were seeking pregnancy were randomly assigned to receive aspirin or placebo.

All the EAGER study participants provided daily urine samples, making the identification of pregnancy early in the gestation period possible and enabling investigators to definitively quantify pregnancy losses that occurred before ultrasound confirmation of pregnancy at gestational week 6 or 7, the authors note.

The current analysis included a cohort of 797 women (mean age, 28.7 years) who conceived and recorded daily nausea and vomiting symptoms from conception through week 8 and monthly thereafter.

Each of the participants had experienced at least one prior pregnancy loss, and 34.3% had two prior pregnancy losses. Nearly one quarter (n = 188; 23.6%) of the pregnancies being followed in the prospective study ended in a loss, including 55 preimplantation losses and 133 clinically recognized losses. Of the pregnancy losses, 176 (93.6%) occurred during the first trimester.

Most of the women (87%) adhered to recording nausea and vomiting status daily from conception (gestational week 2) to gestational week 7. Of 409 women who submitted diaries at gestational week 2, 73 (17.8%) reported nausea without vomiting and 11 (2.7%) reported nausea with vomiting. The respective proportions increased by week 8 to 254 (57.3%) of 443 women and 118 (26.6%) of 443 women, the authors report.

Monthly pregnancy questionnaires, which were completed by at least 93% of the women in a given month, showed that at week 12, 516 (86.0%) of 597 women had nausea and 207 (35.0%) of 597 had nausea with vomiting at least once per week in the preceding 4 weeks. Seven women (0.9%) were hospitalized at least once for vomiting or hyperemesis.

Women younger than 25 years were more likely than older women to experience nausea or vomiting, the authors note.

Compared with women who did not report nausea or vomiting, women who experienced either or both symptoms during a given week were half as likely to experience pregnancy loss during that week, with a hazard ratio of 0.50 (95% confidence interval [CI], 0.32 - 0.80) for nausea alone and 0.25 (95% CI, 0.12 - 0.51) for nausea with vomiting. A similar but not statistically significant association was observed in an analysis of peri-implantation pregnancy losses only (hazard ratio, 0.59 [95% CI, 0.29 - 1.20] and hazard ratio, 0.51 [95% CI, 0.11 - 2.25], respectively).

Excluding women with peri-implantation pregnancy loss, the hazard ratios for clinical pregnancy loss associated with nausea only and with nausea with vomiting were 0.44 (95% CI, 0.26 - 0.74) and 0.20 (95% CI, 0.09 - 0.44), respectively, each week compared with women with neither symptom, the authors report.

"These findings persist even after accounting for rarely measured lifestyle and fetal factors," the authors write, including smoking, alcohol intake, caffeine intake, maternal stress, fetal sex, multiple-fetal gestation, and karyotype.

"Our study confirms prior research that nausea and vomiting appear to be more than a sign of still being pregnant and instead may be associated with a lower risk for pregnancy loss," the authors write.

In addition, compared with most previous studies, the systematic, prospective collection of data from preconception "allowed for unique assessment of the association of nausea symptoms with peri-implantation pregnancy loss," the authors write. "An additional advantage was our accounting for the fact that women's symptoms were not continuous every week and could wax and wane with intermittent weeks."

"This study's contribution to the existing literature is valuable for several reasons," Siripanth Nippita, MD, and Laura E. Dodge, ScD, MPH, from the Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center write in an accompanying commentary. "It builds on a prior cohort study by Sapra et al and similarly enrolled a large sample of women before conception," they write. "The investigators were able to compare the incidence of nausea and vomiting symptoms among women who experienced an early pregnancy loss [including preimplantation pregnancy loss] with those whose pregnancies continued."

They continue, "The widespread availability of sensitive urine hCG tests coupled with real-time electronic data capture using mobile phone apps or similar technology has the potential to improve data quality and eliminate recall bias. Given these methodologic advantages over previous investigations, we hope that such studies can further deepen our understanding of the underlying causes of [nausea and vomiting in pregnancy]."

Although the knowledge that nausea and vomiting are a good sign in early pregnancy may be reassuring, pregnant women "should not be discouraged from seeking treatment for a condition that can have a considerable negative effect on their quality of life," the commenters stress. The American College of Gynecology guidelines for the treatment of pregnancy nausea and vomiting were reported by Medscape Medical News.

The study authors and invited commenters have disclosed no relevant financial relationships.

JAMA Intern Med. Published online September 26, 2016. Article full text, Invited commentary extract

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