• K J Sapra, G M Buck Louis, R Sundaram, K S Joseph, L M Bates, S Galea, and C V Ananth.
• Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA Department of Epidemiology, Joseph L. Mailman School of Public Health, Columbia University, New York, NY, USA saprakj@mail.nih.gov.
• Hum. Reprod. 2016 Apr 1; 31 (4): 887-96.

Study QuestionWhat is the relationship between signs and symptoms of early pregnancy and pregnancy loss <20 weeks' gestation?Summary AnswerVaginal bleeding is associated with increased incidence of early pregnancy loss, with more severe bleeding and bleeding accompanied by lower abdominal cramping associated with greater incidence of loss; conversely, vomiting is associated with decreased incidence of early pregnancy loss, even in the setting of vaginal bleeding, while nausea alone is not.What Is Known AlreadyTwo previous cohort studies with preconception enrollment suggested that bleeding is associated with loss while nausea is inversely associated with loss though these studies were limited by small study size and reporting after loss ascertainment. No prior preconception cohort study has examined multiple signs and symptoms in relation to pregnancy loss.Study Design, Size, DurationPopulation-based preconception cohort of 501 couples discontinuing contraception to try for pregnancy in 16 counties in Michigan and Texas, USA. Participants were followed daily until positive home pregnancy test or 12 months of trying without an hCG pregnancy; women who became pregnant were followed daily from 2 to 7 weeks post-conception.Participants, Setting, MethodsThree hundred and forty-seven women had a positive home pregnancy test denoting hCG pregnancy. Three hundred and forty-one women remained after excluding ineligible pregnancies. Women recorded daily from 2 to 7 weeks post-conception their signs and symptoms, including vaginal bleeding (none, spotting, light, moderate and heavy), lower abdominal cramping, nausea and vomiting. Pregnancy losses were ascertained by a subsequent negative home pregnancy test, clinical confirmation or onset of menses, depending on gestational age at loss; time-to-loss was measured in days post-conception. Cumulative incidence functions and 95% confidence intervals (CIs) were constructed for each sign or symptom, and hazard ratios (HRs) and 95% CIs for presence compared with absence of signs or symptoms were estimated using Cox proportional hazard models.Main Results And The Role Of ChanceWomen experienced lower abdominal cramping (85%), nausea (48%), vomiting (46%) and light/moderate/heavy vaginal bleeding (24%) during early pregnancy. Ninety-five (28%) women experienced a loss. Cumulative incidence of pregnancy loss varied by symptomatology: 19% for vomiting, 27% for lower abdominal cramping, 35% for nausea only, 52% for vaginal bleeding, 81% for vaginal bleeding with lower abdominal cramping. Incidence of pregnancy loss was increased among women with vaginal bleeding (HR: 3.62, 95% CI: 2.29-5.74) and among women with vaginal bleeding and lower abdominal cramping (HR: 5.03, 95% CI: 2.07-12.20). Incidence of pregnancy loss was decreased for women with vomiting (HR: 0.51, 95% CI: 0.30-0.86). In the setting of vaginal bleeding with lower abdominal cramping, vomiting reduced the incidence of pregnancy loss (HR: 0.24, 95% CI: 0.11-0.56).Limitations, Reasons For CautionThere were few losses beyond 14 weeks gestation; thus, the precision of our findings related to losses occurring after the first trimester is limited.Wider Implications Of The FindingsBy using sensitive home pregnancy tests, we are able to document and characterize the cumulative incidence of the earliest pregnancy losses, which constitute the majority of losses. The use of daily, prospective capture of signs and symptoms relative to ascertainment of pregnancy loss minimizes potential biases associated with reporting after rather than before a loss, which could potentially distort the relationship between signs and symptoms and pregnancy loss. The findings of our study suggest that it may be useful to develop prognostic models for pregnancy loss based on signs and symptoms.Study Funding/Competing InterestsThis study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract numbers N01-HD-3-3355; N01-HD-3-3356; N01-HD-3-3358). The authors have no conflict of interest to declare.Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

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