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Threatened abortion: A risk factor for poor pregnancy outcome

Article  in  Acta medica Iranica · August 2008

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 RESEARCH REPORT

THREATENED ABORTION: A RISK FACTOR FOR POOR

PREGNANCY OUTCOME
F. Davari-Tanha*, M. Shariat, M. Kaveh, M. Ebrahimi and S. Jalalvand

Department of Obstetrics and Gynecology, Mirza Kochak-Khan Hospital, Tehran University of

Medical Sciences, Tehran, Iran

Abstract- The scientific literature regarding threatened abortion is relatively limited on the subject of
outcomes and viability at term. To investigate prospectively the risk of adverse pregnancy outcome in
women presenting with first-trimester threatened miscarriage, a prospective case control study was
performed on 600 subjects, 150 women presenting with bleeding in the first trimester and 450
asymptomatic age-matched controls. Main outcome measures included gestational age and weight at
delivery as well as incidence of adverse pregnancy outcome such as preterm labor, preterm prelabor
rupture of membranes (PPROM), placental abruption, and low birth weight (LBW). The first-trimester
miscarriage rate in the threatened miscarriage group was 42.7%. Compared with controls, women
presenting with threatened miscarriage were more likely to deliver prematurely, 14.7% compared with
52.9%, respectively (relative risk 3.6, 95% confidence interval [CI] 2.4-4.8). They were also more
likely to have PPROM, 6.4% compared with 27.5%, respectively (relative risk 4.2, 95% CI 2.6-6.9);
placental abruption, 5.7% compared with 1.5%, respectively (relative risk 3.6, 95% CI 1.2-11.3); LBW,
14.9% compared with 7.1%, respectively (relative risk 2.1, 95% CI 1.1-3.8) and low lying placenta,
1.1% compared with 18.2%, respectively. birth weight 2866 ± 523.3 g compared with 312.45± 591.4
respectively, gestational age 35.71 ± 4.3 compared with 38.07 ± 3.2 respectively. First-trimester vaginal
bleeding is an independent risk factor for adverse obstetric outcome and this risk factor should be taken
into consideration when deciding upon antenatal surveillance and management of their pregnancies.
© 2008 Tehran University of Medical Sciences. All rights reserved.
Acta Medica Iranica 2008; 46(4): 314-320.

Key words: Threatened abortion, spontaneous pregnancy loss, preterm delivery, preterm premature rupture
of membranes

INTRODUCTION have bleeding, it may cause stress and anxiety for the
mother-to-be about the outcome of pregnancy. So, it
Threatened miscarriage, defined as vaginal bleeding is necessary to be diagnosed and managed to prevent
before 24 weeks of gestation, is a common maternal or fetal mortalities and morbidities (1).
complication affecting about 20% of pregnancies. It The scientific literature regarding threatened
has been shown to be associated with an increased abortion is relatively limited on the subject of
risk of poor obstetric outcomes such as preterm outcomes and viability at term. Small number of
labor, low birth weight, and premature rupture of patients and significantly biased data collection have
membranes. Moreover, when pregnant women limited previous studies of pregnancies that were
Received: 2 Dec. 2007, Revised: 17 Feb. 2007, Accepted: 7 Apr. 2007 complicated by threatened abortion (2-4). Many
* Corresponding Author: studies suggest that first-trimester vaginal bleeding
Fatemeh Davari-Tanha, Department of Obstetrics and Gynecology, is associated with a worse outcome (2-9). However,
Mirza Kochak-Khan Hospital, Tehran University of Medical
Sciences, Tehran, Iran there have been few studies that evaluated outcomes
Tel: +98 21 88313955 other than viability at term, after the documentation
Fax: +98 21 88313955
Email: fatedavari@yahoo.com of a living embryo. In general, the incidence of
 F. Davari-Tanha et al.

spontaneous abortion after first-trimester bleeding is MATERIALS AND METHODS

quoted to be 50% before sonographic evaluation for
fetal viability (5, 6). If a viable fetus is noted at A prospective case-control study was preformed in
ultrasound examination after first-trimester vaginal 150 women presenting with bleeding in the first
bleeding, 95% to 98% of such pregnancies will still trimester and 450 age-matched control subjects who
continue beyond 20 weeks of gestation (5, 10). attended for routine dating or delivery at MKH
The diagnosis of threatened miscarriage is Hospital of Tehran University Medical Sciences
frequently made in clinical practice as a result of from October 2004 to November 2006. The
taking a history of vaginal spotting and the finding of study was approved by Ethics Committee of
a closed cervix at subsequent vaginal examination. A Tehran University of Medical Sciences and written
definitive diagnosis of threatened miscarriage should informed consent was obtained from all
be made following ultrasonographic examination, subjects.
confirming the presence of fetal heart activity in an Baseline data were recorded by questionnaire and
intrauterine pregnancy (11). patient interview. Subjects were divided into two
Because bleeding originates from the placenta in groups: 1) no bleeding, 2) bleeding (defined as
most cases of threatened abortion, we hypothesized spotting or as similar to menses). Post delivery
that pregnancies complicated by a first-trimester follow-up was performed by telephone interview or
threatened abortion could be at increased risk for medical record review by the research coordinator at
other “placental related” complications. To evaluate each site.
this risk of first-trimester bleeding, we evaluated a Any incident of preeclampsia, IUGR, intrauterine
variety of outcomes that included pregnancy loss, fetal distress (IUFD), low birth weight (LBW), low
preterm delivery, intrauterine growth restriction lying placenta, placenta previa or low lying placenta,
(IUGR), preeclampsia, preterm premature rupture of birth weight and neonatal sex were recorded.
membranes (PPROM), placental abruption, placenta Potential confounding factors were identified and
previa, and Cesarean delivery (12). adjustment was made in the statistical models. These
First-trimester vaginal bleeding is common, factors included: maternal age, gravidity and
occurring in 15-20% of all viable pregnancies. previous recurrent abortion. The following
Despite its common occurrence, the risk of adverse pregnancy outcomes between the two groups were
outcome for pregnancies with first-trimester compared: abortion, low lying placenta, IUGR,
threatened abortion and a living embryo has been IUFD, PPROM, LBW, preeclampsia, neonate
defined incompletely (13). However, unexplained gender, anomalies, maternal anemia and postpartum
prenatal haemorrhage, similar to threatened infection, type of delivery.
miscarriage, probably exerts an indirect effect (as The following adverse pregnancy outcomes
they were not independent risk factors for early among the two groups were then compared: IUGR
neonatal death) on perinatal outcome through the (estimated fetal weight by ultrasound examination of
increased risk of preterm delivery. This suggests that <10th percentile or birth weight of <10th percentile
a threatened miscarriage is possibly related to for gestational age), gestational hypertension (blood
uteroplacental dysfunction. This assumption is pressure >140/90 mm Hg on at least two occasions
supported by the fact that threatened miscarriage was >6 hours apart without evidence of chronic
associated independently with the risk of placental hypertension), preeclampsia (criteria for gestational
abruption and unexplained antenatal haemorrhage. hypertension and significant proteinuria), preterm
The former remained a risk factor even in term labor (labor <37 weeks of gestation), PPROM
pregnancies and contributed independently to early (membrane rupture <37 weeks of gestation),
neonatal deaths (1, 14). placental abruption (premature separation of a
The current study was conducted on patients with normally implanted placenta), placenta previa
first-trimester threatened abortion to evaluate the (placenta completely or partially covering the
outcome. internal os), low lying placenta (placenta edge

Acta Medica Iranica, Vol. 46, No. 4 (2008) 315

Threatened abortion and pregnancy outcome

actually does not reach the internal os but is in close Table 2. Demographic characteristic of neonate*
proximity to it) and Cesarean delivery. Outcome Control Case P value
The outcomes were established and analyzed with Anomaly 8(1.7%) 2(2.3%) 0.742
SPSS 13. Univariate and multivariable logistic Apgar score† 9 8 0.633
regression analyses were used to evaluate the Male 214(47.87%) 50(58.1%) 0.081
association among the two groups with regards to Female 233(52.12%) 36(41.86%) 0.081
specific pregnancy outcomes. Patients without first- *Data are given as number (percent) unless specified otherwise.
†Mean.
trimester vaginal bleeding were used as the control
group. P < 0.05 was considered statistically two groups: control, 3123.45 g ± 591.4; case group,
significant. 2866.25 ± 130.3 g (P < 0.001). The mean gestational
age at delivery for patients in control group and
RESULTS vaginal bleeding group was 38.07 ± 3.2 weeks and
35.71 ± 4.3 weeks, respectively (P = 0.001).
A total of 600 records with complete antenatal, birth, The obstetric outcomes for patients with first-
and pediatric outcome were available for review. trimester bleeding compared with patients without
The control group consisted of 450 (75%) patients bleeding are described in Table 3. No significant
and the bleeding group consisted of 150 patients difference in the incidence of IUGR (P= 0.808),
(25%). preeclampsia (P= 0.121), gender (P= 0.081), type of
The demographic characteristics of the two delivery (P= 0.453), IUFD (P= 0.474) or placenta
groups are summarized in Table 1. Statistically previa between the control group and subjects with
significant differences were noted among the groups first-trimester vaginal spotting was noted.
for age and parity and previous recurrent Statistically significant differences were noted in
miscarriage. In case group, 18% had low-lying these complications: preterm delivery, 14.7% in
placenta in sonography. controls compared with 52.9% in case group (P <
All subjects who were included in this 0.001, relative risk 3.6, 95% confidence interval 2.4-
investigation had a viable pregnancy confirmed by 4.8); PPROM, 6.4% compared with 27.5%, (P <
ultrasound examination at the time of trial 0.001, relative risk 4.2, 95% confidence interval 2.6-
enrolment. Compared with the control group, 6.9); placental abruption, 5.7% compared with 1.5%
patients with vaginal bleeding were significantly (P= 0.015, relative risk 3.6, 95% confidence interval
more likely to have a spontaneous loss (42.7%). 1.2-11.3); LBW, 14.9% compared with 7.1% (P=
Demographic characteristics of neonates are 0.016, relative risk 2.1, 95% confidence interval 1.1-
shown in Table 2. After an adjustment was made for 3.8); and low lying placenta, 1.1% compared with
the potential confounding factors that included 18.2%, respectively, were significantly more
gestational age at delivery, a statistically significant common in patients with vaginal bleeding compared
difference was noted in mean birth weight among the with control patients.

Table 1. Demographic characteristics of the two study groups*

Characteristic Controls (n = 450) Cases (n = 150) P value
Age (years) 26.5±4.52 27.13±4.76 0.014
Low lying placenta† 5(1.1%) 16(18.2%) 0.001
Birth weight (g) 3123.45±591.4 2866.25±523.3 0.001
Gestational age at birth (wk) 38.07±3.2 35.71±4.3 0.001
Previous recurrent miscarriage† 3(0.7%) 9(6%) 0.205
Gravid 2 ±1.1 2.17 ±1.3 0.145
*Data are given as mean ± SD unless specified otherwise.
† Number (percent).

316 Acta Medica Iranica, Vol. 46, No. 4 (2008)

 F. Davari-Tanha et al.

Table 3. Obstetric complications by amount of vaginal bleeding

Outcome Controls (n=450) Cases (n=150) P value Adjusted OR (95% CI)
IUGR 18 (4%) 3 (3.4%) 0.088
LBW 32 (7.1%) 13 (14.9%) 0.016 2.1
Preterm delivery 66 (14.7%) 46 (52.9%) 0.001 3.6
IUFD 6 (1.3%) 14 (14.1%) 0.747
Preeclampsia 44 (9.8%) 4 (4.6%) 0.121
Anemia 139 (30.8%) 34 (22.7%) 0.054
PPROM 29 (6.4%) 24 (27.5%) 0.001 4.2
Placental abruption 7 (1.5%) 5 (5.7%) 0.015 3.6
Placenta previa 3 (0.6%) 1 (0.6%) 1
Cesarean delivery 237 (52.7%) 42 (42.8%) 0.453
Abbreviations: IUGR, intrauterine growth restriction; LBW, low birth weight; IUFD, intrauterine fetal distress; PPROM, preterm premature rupture
of membranes.

DISCUSSION placental abruption, and Cesarean delivery. With the

exception of Cesarean delivery (OR, <2.0) these
These data show that threatened miscarriage is not associations appear to be both statistically and
only associated with miscarriage but also with clinically significant (16, 18). In our study increased
adverse pregnancy outcome. Results from this study risk of preterm delivery (rr= 3.6), PPROM (rr= 4.2),
confirm findings from other authors, that threatened placental abruption (rr= 3.6) and LBW (rr= 2.1) was
abortion is associated with an increased risk of occurred.
certain pregnancy-related complications, namely In 1993, Verma et al. reported that pregnancy-
placental abruption, preterm labour, delivery of low induced hypertension was significantly more
birth weight infants and PPROM (15, 16). Generally, common in subjects with threatened abortion and a
high incidence of abortion and complications in viable pregnancy compared with subjects without
threatened miscarriage indicate the necessity of vaginal bleeding (6% vs. 4.7%, respectively; P <
proper programming in care and also educating high 0.05) (2). However, their study was limited by a total
risk women. A potential limitation of this study is of only 113 subjects. Another study did not find an
that the severity of vaginal bleeding was based on a association between first-trimester vaginal bleeding
subjective description by the patient. However, the and gestational hypertension but did find that
ultimate assessment of vaginal bleeding is based on patients with light bleeding were statistically more
patient report. Therefore, we believe the results of likely to have preeclampsia (16). This association
this study can be applied to clinical practice. carried a low OR of < 2.0. Similarly, we don’t find
Results of this study support other evidence that, significant association between vaginal bleeding and
in some patients, first-trimester vaginal bleeding preeclampsia.
may indicate underlying placental dysfunction, Preterm delivery before 37 week’s gestation
which may be manifest in later pregnancy by a occurs in 7-11% of pregnancies, but is responsible
variety of adverse outcomes that have also been for 85% deaths of normally formed infants. Despite
related to placental dysfunction (17). In one study, significant advances in perinatal medicine, the
an increased risk of preeclampsia, preterm delivery, incidence of preterm delivery has remained
placental abruption, and Cesarean delivery was unchanged. The prediction of preterm delivery from
observed for patients who reported light bleeding, currently available methods is unreliable, therefore,
although these risks were low with an OR of < 2.0 associated risk factors remain an important measure
(16). For patients who reported heavy vaginal of identifying at-risk pregnancies (19, 20). This is
bleeding during the first trimester, they observed especially evident by the significantly increased rate
increased risks of IUGR, preterm delivery, PPROM, of early neonatal death rate in infants born from

Acta Medica Iranica, Vol. 46, No. 4 (2008) 317

Threatened abortion and pregnancy outcome

mother who had presented with a threatened rupture (4). Alternatively, the prolonged presence of
miscarriage, probably secondary to the increased rate blood may act as a nidus for intrauterine infection.
of preterm deliveries and placental abruption. The Persistent or recurrent placental haemorrhage could
only potential risk factor found to be associated also stimulate subclinical uterine contractions that
significantly with the risk of preterm delivery in result in cervical change and eventual ruptured
women with a threatened miscarriage was membranes. In our study PPROM was increased in
unexplained antepartum haemorrhage rather than case group (rr = 4.2).
other factors, such as smoking or preterm rupture of Placenta previa is a common cause of obstetric
membranes. In our study, preterm delivery was more vaginal bleeding. It is possible that first-trimester
common in bleeding group (rr= 3.6). bleeding could be a reflection of placenta previa in
The association between vaginal bleeding and some patients. Das et al. reported an increased risk
preterm delivery has also been noted by others (21- for a low-lying placenta among patients with
23). Both Batzofin et al. (4) and Williams et al. (7) threatened abortion but reported no difference in
reported that patients with bleeding had double the placental location compared with control subjects by
risk of preterm delivery compared with patients 36 weeks of gestation (15). Others have found a
without bleeding. The study of Williams et al. was higher rate of placenta previa among patients with
limited to first trimester bleeding (7); Batzofin et al. heavy vaginal bleeding during the first trimester, but
included patients with bleeding up to 20 weeks (4). this association was not statistically significant (14,
Strobino and Pantel-Silverman failed to show an 4). Our data showed that placenta previa was not
association between preterm delivery before 36 increased in case group but presence of low lying
weeks of gestation with light vaginal bleeding in the placenta was increased in case group (P < 0.001).
first or second trimester of pregnancy (24). Another Currently, there is no information in the literature
study found that preterm delivery is increased regarding threatened abortion and Cesarean delivery.
significantly in patients with either light (OR, <2.0) One study suggested that a statistical association is
or heavy (OR, 3.0) first-trimester bleeding (16). present with threatened abortion and risk for
Other studies were reported that patients with cesarean delivery (4). In present study, Caesarean
first-trimester threatened abortion are also at delivery was not higher in case group (P <
increased risk for placental abruption and IUGR (1, 0.455).
25). Placental haemorrhage may recur later in In conclusion, the current study reports that
pregnancy, which results in placental abruption. In patients with first-trimester threatened abortion are at
present study placental abruption was significantly increased risk for spontaneous loss and adverse
more common in case group (rr= 3.6) but no pregnancy outcome. For patients who reported
increase risk for IUGR (rr= 0.088) was found. vaginal bleeding during the first trimester, we
Haddow et al. reported an increased risk for low observed increased risks of LBW, preterm delivery,
birth weight (<2500 g) in pregnancies that were PPROM, placental abruption, and low lying
complicated by vaginal bleeding (26). Infants of placenta. These associations appear to be both
patients with heavy bleeding had nearly a 200 g statistically and clinically significant. Because the
difference in birth weight compared with control overall prognosis is favourable, these results can be
infants after accounting for preterm delivery. In used to help reassure patients with threatened
present study risk of LBW was increased (rr = abortion during the first trimester. At the same time,
2.1). physicians should be aware of the adverse outcomes
Our findings corroborate other studies that that are associated with first-trimester bleeding and
suggested an association between threatened remain alert for signs of these complications.
abortion and PPROM (4-6). Although the cause is
unclear, it is hypothesized that disruption of the Conflict of interests
chorionic-amniotic plane by adjacent haemorrhage The authors declare that they have no competing
may make the membranes more susceptible to interests.

318 Acta Medica Iranica, Vol. 46, No. 4 (2008)

 F. Davari-Tanha et al.

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