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Meconium-stained amniotic fluid: a risk factor for

postpartum hemorrhage
This article was published in the following Dove Press journal:
Therapeutics and Clinical Risk Management

Carlo Bouchè 1 Background/aim: Clinical data with respect to the impact of meconium on the risk of maternal
Uri Wiesenfeld 1 hemorrhage are scarce. Therefore, in this study, we aimed to determine whether meconium-
Luca Ronfani 1 stained amniotic fluid (MSAF) represents a risk factor for postpartum hemorrhage (PPH) after
Roberto Simeone 2 vaginal delivery in a large unselected population.
Paolo Bogatti 1 Patients and methods: A retrospective cohort study evaluated 78,542 consecutive women
who had a vaginal delivery between 24th and 44th weeks of gestation. The women who had
Kristina Skerk 1
undergone cesarean section were excluded to avoid possible bias. Postpartum blood loss was
Giuseppe Ricci 1,2
measured with graduated blood sack. Postpartum blood loss between 1,000 and 2,000 mL and
1
Institute for Maternal and Child 2,000 mL were classified as moderate and severe PPH, respectively.
Health, IRCCS Burlo Garofolo, Trieste,
Italy; 2Department of Medicine, Results: A total of 74,144 patients were available for analysis. According to the color of
Surgery and Health Sciences, amniotic fluid (AF), two groups of patients were identified: MSAF (n=10,997) and clear AF
University of Trieste, Trieste, Italy
(n=63,147). The rates of severe and massive PPH were found to be significantly higher in the
MSAF group than that of clear AF group (OR=1.3, 95% CI: 1.2–1.5, p0.001 and OR=2.5,
95% CI: 1.5–4.2, p0.001). Operative vaginal delivery rate was found to be higher in the MSAF
group than that of clear AF group, but the difference was only borderline significant (OR=1.5,
95% CI: 1.0–2.2, p=0.05). There were no significant differences between the MSAF and the
clear AF groups with respect to episiotomies, second- or third-degree perineal tears, vaginal–
perineal thrombus, cervical lacerations, vaginal births after cesarean section, twin deliveries,
and placental retention rates.
Conclusion: To the best of our knowledge, this is the first clinical study that has investigated
the role of MSAF as a risk factor for PPH after vaginal delivery in an unselected population.
Our results suggest that MSAF is significantly associated with higher risk of moderate and
severe PPH than clear AF.
Keywords: amniotic fluid, delivery complications, meconium, postpartum hemorrhage

Introduction
Postpartum hemorrhage (PPH) is one of the leading causes of maternal mortality.1
Several recent population-based studies have observed an increasing trend in the
incidence of PPH over time.2,3 Several factors, such as maternal age, obesity, grand
multiparity, uterine fibroids, previous cesarean delivery, multiple pregnancy, placenta
previa or abruption, preeclampsia/eclampsia, amnionitis, fetal macrosomia, labor induc-
Correspondence: Giuseppe Ricci tion, instrumental vaginal delivery, cesarean delivery, cervical laceration, and uterine
Institute for Maternal and Child Health,
IRCCS Burlo Garofolo, Via dell’Istria rupture have been associated with high risk of major PPH.3–8 Moreover, recently, new
65/1, Trieste 34137, Italy risk factors have been identified, including index of multiple deprivation (education,
Tel +39 40 378 5351
Fax +39 40 76 1266
skills, and training), multiparity without cesarean section, and antenatal administra-
Email [email protected] tion of steroids.9

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Amniotic fluid (AF) contains many coagulation factors PPH was defined as a cumulative postpartum blood
which exert procoagulant, anticoagulant, and fibrinolytic loss 1,000 mL according to the American College of
activities.10–19 A thrombogenic role of amniotic cells has Obstetricians and Gynecologists (ACOG) nomenclature
also been well documented.20 In an animal model, it has consensus conference (reVITALize).29 Postpartum blood loss
been shown that the infusion of AF causes activation of between 1,000 and 2,000 mL and 2,000 mL were classified
coagulation.21 This effect was significantly more pronounced as moderate and severe PPH, respectively.
by injecting AF contaminated with meconium.21 Chi-square test and Fisher’s exact test, when appropriate,
Unfortunately, there are scant clinical data on the impact were used to examine the relationship between the presence
of meconium on the risk of maternal hemorrhage. The only of MSAF and categorical parameters. OR and 95% CIs
published study found no significant differences in the rate were calculated. A p-value 0.05 was considered statisti-
of hemorrhage between the patients with meconium-stained cally significant. Statistical analysis was performed using
amniotic fluid (MSAF) and clear AF.22 However, only GraphPad Prism version 6 (GraphPad Software, Inc., La
patients with preterm delivery were included. Moreover, a Jolla, CA, USA).
very low rate of PPH (0.6%) was observed.22 The study was approved by the Ethical Committee of
In this study, we aimed to determine whether MSAF IRCCS Burlo Garofolo, Trieste, on April 14th 2015 with
represents a risk factor for PPH after vaginal delivery in a protocol Number 759/2015. It was not necessary to obtain
large unselected population. informed consent in this study as the regulatory standards
in Italy do not require consent for a retrospective study;
Patients and methods patients’ data were treated with extreme confidentiality for
The study population consisted of 78,542 consecutive women strictly scientific purposes.
who had a vaginal delivery at IRCCS Burlo Garofolo, Trieste,
Italy, from May 1972 to December 2013, between 24th
and 44th weeks of gestation. Data were collected from the
Results
A total of 78,452 deliveries were evaluated. In about 2.5%
delivery room records.
of the cases, blood loss was considered, but the color of AF
The women who had undergone cesarean section were
was not described. In 0.1% of the cases, AF was absent or
excluded to avoid possible bias. As a matter of fact, blood loss
not reported. In about 3% of the cases, blood loss was not
during the cesarean section can be estimated only with wide
reported. Finally, data of a total of 74,144 patients were
approximation.23 In addition, these cases have a high risk of
available for analysis.
hemorrhage due to surgery3 and the incidence of stained AF
There were 10,997 cases (14.8%) with MSAF and 63,147
could have been much higher, given the significant number
cases (85.2%) with clear AF. The rates of moderate PPH
of fetal distress as indication for cesarean section.24 Finally,
(blood loss between 1,000 and 2,000 mL) and severe PPH
the site of entry of AF is through beant venous vessels in
(blood loss 2,000 mL) were found to be significantly higher
placental site and through venous vessels in delivery channel
in the MSAF group than that of clear AF group (Table 1).
that get lacerated by fetal passage; therefore, we excluded the
MSAF was found to be significantly associated with high risk
potential passage through hysterotomic wound that happens
of moderate PPH (OR=1.3, 95% CI: 1.2–1.5) and severe PPH
in cesarean section. We collected data regarding the color of
(OR=2.5, 95% CI: 1.4–4.2) (Table 1). The operative vaginal
AF and postdelivery blood loss. According to the color of AF,
deliveries with vacuum or forceps were higher in the MSAF
two groups of patients were identified: MSAF and clear AF.
group than that of clear AF group, but the difference was only
MSAF includes any meconium: fresh, old, thick (dark green
borderline significant (OR=1.5, 95% CI: 1.0–2.2, p=0.05).
in color and of pea soup consistency with particulate matter),
There were no statistically significant differences between
or thin (lightly stained yellow or greenish color).25,26
In all patients, postpartum blood loss was measured with
graduated blood sack. Postpartum blood losses were mea- Table 1 Postpartum blood loss in meconium-stained amniotic
sured using graduated blood drape consistently over the entire fluid (MSAF) and clear amniotic fluid (AF) group
41 years. The drape was placed under the buttocks of the Blood loss MSAF, n (%) Clear AF, n (%) OR p-value
woman immediately after delivery and drainage of the AF. (mL) (n=10,997) (n=63,147) (95% CI)
Blood loss was assessed for at least 1 hour after delivery of 1,000 10,670 (97) 61,762 (97.8) 1
the baby. Whenever persistent bleeding occurred, blood loss 1,000–2,000 307 (2.8) 1,338 (2.1) 1.3 (1.2–1.5) 0.001
2,000 20 (0.2) 47 (0.1) 2.5 (1.5–4.2) 0.001
was measured until active bleeding stopped.27,28

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Dovepress Meconium-stained amniotic fluid and postpartum hemorrhage

the clear AF group and the MSAF group regarding episioto- thromboelastographic analysis indicated that AF could
mies, second- or third-degree perineal tears, vaginal–perineal initiate the cascade of coagulation. The authors concluded
thrombus, cervical lacerations, vaginal births after cesarean that other factors such as the presence of meconium in AF
section, twin deliveries, and placental retention requiring may be needed to provoke more severe clinical signs.36 Since
manual placental removal. AF cannot be absorbed through vaginal mucosa, it can be
hypothesized that coagulopathy and subsequent hemorrhage
Discussion are caused by the entrance of AF into maternal circulation.
In this study, we examined a very large population of women It has been reported that this event is frequent,37 and several
who had vaginal delivery. We collected data regarding the cases of AF embolism with isolated coagulopathy have been
color of AF and postdelivery blood loss. The incidence of reported.38–44 If AF is contaminated by meconium, the severity
deliveries with MSAF was found to be 14.8%, which is of coagulopathy and hemorrhage might significantly increase.
slightly higher than what is reported by the other authors.30–32 In fact, we have observed that in patients with MSAF, the
However, it may be influenced by the fact that between rates, both of moderate and severe hemorrhages were sig-
1972 and 2004, delivery management was to wait, in most nificantly higher than that of clear AF group.
cases, for spontaneous labor till the 42nd week. Several In this study, we found a higher, although not significant,
studies have reported that MSAF proportionally increases incidence of MSAF in operative deliveries than that of other
with the increase of gestational age.24,33,34 We observed a studies.45–47 This may be due to higher incidence of fetal
significant increase in the risk of moderate and severe PPH in hypoxia in these cases involving a higher risk of meconium
the presence of MSAF. Our results do not agree with those of release during the labor.47 Several other hypotheses have been
the other clinical studies published so far. Mazor et al22 found suggested to explain this finding. Meconium has been asso-
that MSAF was not a risk factor for PPH. However, it should ciated with fetal heart rate abnormalities48 that may induce
be noticed that this study included only preterm delivery and physicians to an aggressive obstetric management. The pres-
that a very low rate of PPH was reported.22 ence of meconium per se may cause physician concern for
We are unable to explain why meconium may increase fetal well-being thus lowering the threshold for intervention.46
the risk of hemorrhage. The coagulation and fibrinolysis in Meconium might negatively influence the regular labor pro-
AF have been extensively investigated. Most proteins of the gression, perhaps through subclinical infection.46 Experimen-
coagulation and fibrinolysis system, and many vasoactive tal studies showed that meconium may inhibit the umbilical
and procoagulant substances, such as platelet activating vessel smooth muscle contractile effect of a thromboxane
factor, cytokines, bradykinin, thromboxane, leukotrienes, A2 analog.49 Finally, it is possible that meconium inhibits
and arachidonic acid have been detected in AF.10–19 uterine smooth muscle contraction and increases the risk of
However, data regarding the effects of MSAF on coagu- labor dystocia and operative delivery.46
lation and fibrinolysis system are scarce; there is no such This study has some advantages. To the best of our
data with respect to human beings, and there are only few knowledge, this is the first clinical, specifically addressed
animal studies on this topic. Petroianu et al21 showed that study that has investigated the role of MASF as risk factor
the infusion of native AF (including meconium) triggered a for PPH in an unselected population of pregnant women.
response similar to disseminated intravascular coagulation It is a single center study and it included data from a very
(DIC). After infusion of centrifuged AF (excluding meco- large number of deliveries, thus reducing the role of potential
nium), in spite of the much higher volumes used, the changes confounding factors. The study also has some limitations.
were less pronounced. The authors concluded that the factor It is, in fact, a retrospective study over a long span of time
(or factors) initiating DIC after infusion of native AF are and assessment of AF characteristics was eye-based, which
unknown and are probably contained in meconium, since may include bias due to subjective evaluation. Moreover,
meconium-free AF is not life-threatening even if very high data were collected from the delivery room records and some
volumes are infused.21 Similar results have been obtained in information regarding antenatal complications of pregnancy
pregnant goats where left ventricular dysfunction and dys- were lacking.
oxia were observed only with the infusion of AF containing
meconium.35 Conclusion
Recently, it has been observed that the injection of Our results suggest that MSAF is significantly associated
autologous AF induced a transient and severe thrombocy- with higher risk of moderate and severe PPH than clear AF.
topenia, but not AF embolism in a rabbit model.35 However, Therefore, in case of MASF, more attention should be paid

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Bouchè et al Dovepress

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