bleeding folowing pregnancy loss before 6 weeks gestation

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Human Reproduction Vol.22, No.3 pp. 853857, 2007 doi:10.1093/humrep/del417

Advance Access publication October 27, 2006.

The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. 85For Permissions, please email: journals. [email protected]

Bleeding following pregnancy loss before 6 weeks gestation

J.H.E.Promislow 1,4 , D.D.Baird 2, A.J.Wilcox 2 and C.R.Weinberg 3

1

Social and Scientific Systems,2

Epidemiology Branch and3

Biostatistics Branch, National Institute of Environmental Health Sciences,Durham, NC, USA4To whom correspondence should be addressed at: Social and Scientific Systems, 1009 Slater Road, Suite 120, Durham, NC 27703, USA.E-mail: [email protected]

BACKGROUND: Pregnancy loss before 6 weeks gestation is common, but little has been reported about the associatedbleeding. We compared womens bleeding following a pregnancy loss before 6 weeks gestation with their typicalmenstruation. METHODS: Women provided daily urine samples while trying to become pregnant and recorded thenumber of pads and tampons used each day. Thirty-six women had complete bleed data for a loss before 6 weeksgestation and one or more non-pregnant cycles. RESULTS: Mean bleed length following a pregnancy loss was 0.4days longer than the womans average menstrual bleed ( P = 0.01), primarily because of more days of light bleeding.Although there was no overall increase in the total number of pads plus tampons used, women with losses bled less

than their typical menses following pregnancies of very short duration and more than usual for the pregnancies last-ing the longest. CONCLUSIONS: Overall, the bleeding associated with pregnancy loss before 6 weeks gestation issimilar to menstrual bleeding and unlikely to be recognized as pregnancy loss. The intriguing finding that pregnanciesof very short duration were associated with less bleeding than the womans typical menses might reflect endometrialfactors associated with loss.

Key words : pregnancy loss/menses/bleed length/spontaneous abortion

Introduction

Studies of women seeking medical care for miscarriage havereported that the bleeding that accompanies miscarriage is heav-

ier and more prolonged than typical menses (Haines et al ., 1994;Nielsen and Hahlin, 1995; Chung et al ., 1998; Nielsen et al .,1999; Bagratee et al ., 2004). However, most of these clinicallyreported miscarriages occurred after 6 weeks gestation; thebleeding that accompanies earlier pregnancy loss has not beencarefully described. Such early losses are common: approxi-mately a quarter of all pregnancies end before 6 weeks gesta-tion, often before the pregnancy has received any medicalattention or even become apparent to the woman (Wilcox et al .,1990; Zinaman et al ., 1996; Wang et al ., 2003). Using data froma prospective study of women who were attempting pregnancy,we describe in detail the bleeding that accompanies pregnancyloss before 6 weeks gestation, and we compare those patterns of

bleeding with the womens ordinary menstrual bleeding.

Materials and methodsStudy participants were members of the North Carolina Early Preg-nancy Study, a prospective cohort study conducted from 1982 to 1985involving 221 women who were attempting pregnancy (Wilcox et al .,1988). These women had no known fertility problems or majorchronic disease. Participation began when women discontinued con-traception and continued until 8 weeks past their last menstrual periodif they became pregnant or for 6 months if they did not. During this

time, participants collected daily first-morning urine specimens andkept daily diary records of their menstrual bleeding (number of padsand tampons). The study was approved by the Institutional ReviewBoard of the National Institute of Environmental Health Sciences, andparticipating women provided informed consent.

Ovulation was identified using measurements of estrogen andprogesterone metabolites in urine (Baird et al ., 1991). Pregnancy wasdetected using a highly sensitive and specific polyclonal radioimmu-noassay for urinary HCG (Armstrong et al ., 1984). This assay measuredintact HCG and -HCG with 0.025 ng/ml was the criterion for pregnancy.This criterion ensured high specificity and was determined from a par-allel study of urinary HCG levels in women who had undergone atubal ligation. Pregnancy loss was detected by a subsequent fall in uri-nary HCG. We restricted our study to pregnancies that ended


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addition to blood (5080% of the total discharge); we refer to this dis-charge simply as bleeding, as is customary (Oats and Abraham, 2005).

We used the number of pads and tampons per day as a measure of bleeding quantity, focusing on comparisons within women. Womencan differ from one another in their use of pads and tampons for rea-sons related more to personal habits than to volume of menstrual dis-charge. Because this variability between women is controlled in awithin-woman analysis, it is more informative to conduct within-woman analyses of bleeding (comparing an early loss with the same

womans regular menses) than to make comparisons across women.In support of this, studies comparing pad and tampon counts withquantitative measurement of blood loss across women have reportedconsiderably higher correlation coefficients when the studies includedmultiple cycles per woman [0.61 (Higham and Shaw, 1999) and 0.74(Higham et al ., 1990)] than when they did not [0.14 (Fraser et al .,1981) and 0.30 (Warner et al ., 2004)].

Women may also differ in their patterns of use of pads versustampons. However, women in this study were fairly consistent fromone period to the next in their use of pads versus tampons. The meanpercentage of tampons used per period [100 tampons/(pads + tam-pons)] was 62%, and the mean within-woman SD in the percentage of tampons used per period was 9%.

Forty-four women had 48 pregnancy losses before 6 weeks gestation

during their study participation. One of these women had a single lossfor which she reported no associated bleeding; because her reportingwas incomplete in other respects, we believed her report of no bleedingcould have been a recording error, and we have excluded her from thisanalysis. Of the remaining women, 36 provided complete data on bleedlength and padtampon use for at least one regular menses in addition toa pregnancy loss bleeding episode. One non-conception cycle wasexcluded because no bleeding was reported. All but one of the 36women were white; most were college-educated (72%). The median agewas 29 years (range 2436 years), and 61% were parous at enrolment.

These 36 women in the analysis sample had 38 pregnancy lossesbefore 6 weeks gestation (two women had two losses). Informationon bleeding after an ovulatory non-conception cycle was available for17 menses per woman (median = 3) for 198 non-conception menses.

Analyses were based on differences between the within-woman aver-ages. For each woman, a value for each bleed characteristic was calcu-lated for both the non-conception and the pregnancy loss bleeds. If awoman had more than one non-conception or pregnancy loss bleed,then the mean value of the bleed characteristic was used. A bleedcharacteristic difference was then computed by subtracting the non-conception bleed value from the pregnancy loss bleed value, and dif-ferences were tested with a Wilcoxon signed rank test. Non-parametriccorrelation statistics and tests for difference were used because of theinherent non-normality of some of the bleed characteristic variables.The 25th and 75th percentile values for the distributions are presented,but means and SEs are also presented for ease of comparison withother published bleed length values. All P -values cited are two-sided,with a significance level of 0.05.

The pregnancy losses represented a range of durations and amountsof HCG production, which we hypothesized might also be related tothe pattern of bleeding. To explore this, we used two markers: max-imum level of HCG obtained during the pregnancy and the length of the failed pregnancy (days from ovulation to onset of bleeding).

Results

The overall pattern of bleeding after a pregnancy loss of


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menses. Overall, we saw no evidence of heavier bleeding afterthe pregnancy loss, either on a given day or over the entirebleeding episode. There was a slight tendency for women tobleed longer following pregnancy loss than they did for theirtypical menses, but this difference was small (0.4 days) andentirely because of light bleeding. The evidence suggests thatmost women would be unlikely to distinguish the bleedingepisode that follows an early pregnancy loss from their ordinarymenses.

Our results are consistent with those from a study of highland Bolivian women. In this study of 189 women, ges-tational age of the pregnancy losses was not reported, butfor the 14 losses that were likely to have happened at veryearly gestational ages, the mean bleed duration of 3.3 daysdid not differ markedly from the study populations meannon-conception menses duration of 3.6 days (Vitzthumet al ., 2001).

Most information on bleeding with pregnancy loss comesfrom studies of expectant management of women seeking med-ical care for miscarriage. Most of these miscarriages occurredin the latter half of the first trimester. Mean length of bleeding

with these miscarriages was in the range of 911 days (Haineset al ., 1994; Nielsen and Hahlin, 1995; Chung et al ., 1998;Nielsen et al ., 1999; Bagratee et al ., 2004). For comparison,the mean duration of menstrual bleeding among a large cohortof predominantly white, college-educated, US women has beenreported to be 5.3 days (Cooper et al ., 1996), virtually the sameas the 5.4 days seen for non-conception cycles in our study(Table I).

Although variations in maximal HCG production andpregnancy duration were unrelated to the length of the bleed-ing associated with the loss in Early Pregnancy Studywomen, they were correlated with intensity of bleeding(compared with usual menses). An increase in bleeding for

longer lasting pregnancies is not surprising; such pregnan-cies will generally have reached a later stage of develop-ment, with more advanced decidualization and trophoblastinvasion (Cunningham et al ., 2005). However, the reductionin bleeding seen with pregnancy losses of shorter durationand lower HCG production was surprising. It may be that amenstrual cycle with poorer endometrial development mayincrease the risk of very early pregnancy loss. A relatedhypothesis is that a hormonally suboptimal cycle predisposesthe woman to both suboptimal endometrial development andvery early pregnancy loss, producing an association of thetwo. Alternatively, impending early loss may produce achange in the endometrium that results in reduced sheddingof tissue.

In conclusion, we found that the bleeding after a preg-nancy loss of


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Warner PE, Critchley HOD, Lumsden M, Campbell-Brown M, Douglas A andMurray GD (2004) Menorrhagia I: Measured blood loss, clinical features,and outcome in women with heavy periods: a survey with follow-up data.Am J Obstet Gynecol 190,12161223.

Wilcox AJ, Weinberg CR, OConnor JF, Baird DD, Schlatterer JP, CanfieldRE, Armstrong EG and Nisula BC (1988) Incidence of early loss of pregnancy. N Engl J Med 319,189194.

Wilcox AJ, Weinberg CR and Baird DD (1990) Risk factors for early preg-nancy loss. Epidemiol 1,382385.

World Health Organization Task Force on Adolescent Reproductive Health(1986) World Health Organziation multicenter study on menstrual and ovu-latory patterns in adolescent girls. J Adolesc Health 7,236244.

Zinaman MJ, Clegg ED, Brown CC, OConnor J and Selevan SG (1996) Esti-mates of human fertility and pregnancy loss. Fertil Steril 65,503509.

Submitted on June 29, 2006; resubmitted on August 22, 2006, September 21,2006; accepted on September 27, 2006

bleeding folowing pregnancy loss before 6 weeks gestation

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