1 Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, 275997435, 2 Epidemiology Branch and 3 Biostatistics Branch, National Institute of Environmental Health Sciences, Durham, NC 27709, USA
4 To whom correspondence should be addressed. e-mail: ewh{at}unc.edu
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Abstract |
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Key words: bleeding/first trimester/implantation/spontaneous abortion
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Introduction |
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Because of its timing, bleeding during early pregnancy might be mistaken for menses. Such bleeding has been conjectured to account for errors in gestational age estimation using the last menstrual period (LMP) method (Gjessing et al., 1999), especially among pregnancies that end in miscarriage (Iffy et al., 1972
). Vaginal bleeding has also been thought in some cases to accompany implantation (Speert and Guttmacher, 1954
). We carried out an analysis of data from a prospective study of 151 naturally-conceived pregnancies in order to explore these issues in more detail.
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Material and methods |
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Urine samples were assayed for hCG using an extremely sensitive immunoradiometric assay (Canfield et al., 1987). The sensitivity of this assay was sufficient to provide an estimate of the day of implantation. Implantation of the blastocyst is not observable directly, and the best indirect marker of implantation is hCG (Hearn et al., 1991
). We used a highly sensitive radioimmunoassay for hCG in first-morning urine samples to identify the earliest day of pregnancy on which hCG concentration reached 0.15 ng/ml. Initial detection was typically followed by a steady exponential rise of hCG (Wilcox et al., 1999
). Radioimmunoassays of daily urine samples were performed for the major metabolic products of estradiol and progesterone. The ratio of these metabolites changes in characteristic ways with the approach and occurrence of ovulation, providing a reliable means to identify day of ovulation (Baird et al., 1995
). The validity of this measure of ovulation has been confirmed in subsequent studies (Dunson et al., 2001
; Ecochard et al., 2001
).
We defined clinical pregnancy as a pregnancy that lasted at least 6 weeks beyond the LMP. There were 151 women who conceived a clinical pregnancy during the study. We defined early bleeding as 1 day of vaginal bleeding between conception and the end of follow-up. In nearly all cases, follow-up was through the week 8 after LMP. One woman who collected data through her week 9 experienced spotting in week 9; those data are included here. We included bleeding only if it was distinct from the bleeding that accompanied the expulsion of an embryo or fetus. No woman contributed more than one clinical pregnancy to the study.
2-tests were used for analyses of categorical variables. When cell counts were small, Pearson tests were used. t-tests were used for analyses of continuous variables.
Information on the womans medical history, medications, smoking and other factors was collected by in-person interview at the time that woman was enrolled. The protocol was approved by the National Institute of Environmental Health Sciences internal review board, and informed consent was obtained.
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Results |
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Of pregnancies with bleeding, 14% miscarried (2/14), compared with 9% of those without bleeding (13/137). The relative risk of miscarriage after bleeding was 1.5, with broad confidence limits (0.46.0). While these numbers are too small for formal analysis, it is notable that both miscarriages among the bleeders had bleeding within 30 days after LMP (I and K in Figure 1). These were also the only two pregnancies for which bleeding stopped and then resumed. None of the pregnancies with a single uninterrupted bleeding episode miscarried. Conversely, the great majority of pregnancies that eventually miscarried (13/15) had no bleeding in early pregnancy.
We could identify no particular characteristics that predisposed women to bleeding during early pregnancy (Table II). Some characteristics were more common among women with bleeding, but we cannot be sure that these associations were not due to chance. Multiple comparisons were made on a small amount of data, and none of the associations reached statistical significance at = 0.05. Women whose usual periods were heavy were not at increased risk of bleeding in pregnancy; if anything, their risk was lower. Similarly, a history of irregular periods did not predict bleeding in pregnancy. Nulliparous women had a lower risk of bleeding in early pregnancy than parous women (5 versus 13%, P = 0.11); there is no obvious explanation for such a pattern. None of the women with bleeding smoked at the time of the interview. There appeared to be a slight association between Marijuana smoking and bleeding (20% of current marijuana smokers reporting bleeding versus 8% of non-smokers; P = 0.09). However, there was no association with previous tobacco use, and no clear physiologic explanation for a higher risk among marijuana users.
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Conclusions |
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A total of 9% of women with clinical pregnancies reported bleeding during the first 8 weeks of pregnancy. These data suggest that a few days of bleeding in early pregnancy is not a rare event, and furthermore that such bleeding has little relevance to the ultimate success of the pregnancy. Bleeding that stops and then resumes may be more ominousboth such episodes in our study ended in miscarriage several weeks later.
Some authors have speculated that bleeding in early pregnancy might be mistaken for menses, leading to errors in the LMP as a basis for gestational age estimation (Iffy et al., 1972; Gjessing et al., 1999
). This is not supported by our data. Only one of the 136 successful pregnancies in our study had a bleeding episode of a length and intensity that was similar to usual menses. Certainly the majority of women with spontaneous abortions did not have an apparent menstrual period after conception, as has been inferred from other data (Iffy et al., 1972
). Only two of the fifteen miscarriages in our study had bleeding in the earliest stages of pregnancy, and even these bleeding events were too light to be mistaken for menses. We found no data to suggest that early bleeding contributes substantially to errors in LMP-based gestational age.
The mechanisms of bleeding in early pregnancy remain unclear. Implantation has been discussed as one mechanism (Speert and Guttmacher, 1954). However, we found no evidence to support this. Only one episode of bleeding occurred at implantation; most bleeding began at least 5 days after implantation (Figure 1). Similarly, there was no evidence that intercourse in early pregnancy increased the likelihood of vaginal bleeding.
In conclusion, bleeding during the first 8 weeks of naturally-conceived pregnancies seems to occur without clear physiologic cause. Most pregnancies with very early bleeding proceeded to a normal delivery and a healthy live birth.
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Acknowledgement |
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References |
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Submitted on February 7, 2003; accepted on May 29, 2003.