doi:10.1111/jog.13484 J. Obstet. Gynaecol. Res.

Platelet indices in preterm premature rupture of membranes

and their relation with adverse neonatal outcomes

Betul Dundar1, Burcu Dincgez Cakmak1 , Gulten Ozgen1, Fatma Nurgul Tasgoz1,
Tugberk Guclu1 and Gokhan Ocakoglu2
1
Department of Obstetrics and Gynecology, Bursa Yuksek Ihtisas Research and Training Hospital and 2Department of
Biostatistics, Uludag University Medical Faculty, Bursa, Turkey

Abstract
Aim: Preterm premature rupture of membranes (PPROM) is not only the most common distinguishable
cause of preterm delivery, but is also associated with adverse neonatal outcomes. We determined the platelet
indices in PPROM cases and evaluated their relationship to adverse neonatal outcomes.
Methods: Fifty patients with PPROM and 50 patients who experienced spontaneous preterm labor at <
37 gestational weeks were evaluated. Complete blood counts, birth weights, Apgar scores, presence of sepsis
and respiratory distress syndrome (RDS) and neonatal intensive care unit admission were recorded.
Results: Patients with PPROM had increased mean platelet volumes (9.40 vs 10; P = 0.01), plateletcrit (0.19
vs 0.21; P = 0.03) and a higher frequency of neonatal sepsis (18% vs 38%; P = 0.02). Platelet indices in the
patient group were compared according to the development of RDS. Plateletcrit values were higher in the
RDS positive group (0.23  0.05 vs. 0.21  0.04; P = 0.04). The cut-off value for plateletcrit was determined
as > 0.22, and the probability of RDS increased 5.86 times when plateletcrit values exceeded 0.22 (odds ratio
5.86, 95% confidence interval 1.01–32.01; P = 0.04). A one-unit increase in platelet distribution width resulted
in a 1.33-fold increase in the risk of RDS (odds ratio 1.33, 95% confidence interval 1.01–1.77; P = 0.04).
Conclusion: Mean platelet volumes and plateletcrit significantly increased and plateletcrit had a predictive
value for RDS in PPROM cases. Monitoring plateletcrit may be promising for predicting the development of
RDS, one of the most common and serious complications of PPROM rupture.
Key words: adverse neonatal outcome, platelet indices, preterm premature rupture of membranes, respira-
tory distress syndrome, sepsis.

Introduction nearly 60% of cases are term pregnancies.2,3 PPROM

Premature rupture of membranes is one of the most
common and controversial issues in daily obstetrics
practice. It refers to rupture of chorioamniotic mem-
branes before labor begins. If it occurs before 37 weeks
of gestation, it is called preterm premature rupture of
membranes (PPROM) and after 37 weeks, term pre-
mature rupture of membranes.1 Premature rupture of
membranes occur in 5–10% of all pregnancies and
accompanies 2–3% of all pregnancies.4 It usually
occurs as a result of a physiological process, such as
uterine contractions, fetal movements, biochemical
changes and decreasing collagen in the chorioamnio-
tic membranes, which in turn weaken the chorioam-
niotic membranes.5 The management of PPROM
should be carefully considered to reduce associated
adverse maternal and neonatal outcomes, because
PPROM is not only the most common distinguishable

Received: February 19 2017.

Accepted: July 23 2017.
Correspondence: Dr Burcu Dincgez Cakmak, Bursa Yuksek Ihtisas Research and Training Hospital, Obstetrics and Gynecology
Department, Bursa, Turkey Mimar Sinan Mah. Emniyet Cad. No:35 Yıldırım/BURSA. Email: burcumavis@gmail.com
This study was accepted as a poster presentation in the 11th Turkish German Gynecology Congress, May 11–15, 2016, Antalya,
Turkey.

© 2017 Japan Society of Obstetrics and Gynecology 1

B. Dundar et al.
cause of preterm deliveries, but is also associated with
a number of complications, such as maternal and neo-
natal infections.4,6 Recent studies have shown that the
risk of maternal and neonatal infections increases as
the time required until delivery increases.6–8 The risk
of neonatal asphyxia and jaundice also increases in
the presence of chorioamnionitis.9,10 However, there
is no useful predictive biomarker of adverse maternal
and neonatal outcomes in PPROM.
Platelet (PLT) indices, mean platelet volume
(MPV), platelet distribution width (PDW) and plate-
letcrit (PCT), are determinants of PLT functions sim-
ply assessed by complete blood count (CBC).
Currently they are frequently being investigated in a
wide variety of clinical conditions. Changes in PLT
indices are usually associated with PLT consump-
tion, which is generally a result of an inflammatory
process. Disturbed PLT functions are implied in
hypertension; diabetes; myocardial infarction; cere-
brovascular disease; and some inflammatory dis-
eases, such as systemic lupus erythematosus,
inflammatory bowel disease and rheumatoid arthri-
tis.11 In addition to these, the association between
disturbed PLT indices and obstetric conditions, such
as recurrent pregnancy loss, first trimester miscar-
riage, pre-eclampsia, gestational diabetes and pre-
term labor, have been investigated.12–16 We propose
that PLT indices could be useful biomarkers in
PPROM cases.
Increased PLT activation and production most com-
monly develop as a result of increased PLT consump-
tion, which causes a hypercoagulable state and,
consequently, microcirculatory defects and vascular
reactivity in the placental bed, resulting in placental
insufficiency that is considered to be related to
adverse neonatal outcomes.13,17
The aim of this study was to determine the levels of
MPV, PDW and PCT in PPROM patients and evalu-
ate the association between PLT indices and adverse
neonatal outcomes, such as low birth weight, Apgar
scores < 7 at 1 and 5 min, requirement of neonatal
intensive care unit (NICU) admission and the devel-
opment of neonatal sepsis and respiratory distress
syndrome (RDS) in PPROM patients.
Methods
This was a retrospective case–control study, con-
ducted in a university affiliated tertiary hospital
between June and December 2015. Fifty women
2 © 2017 Japan Society of Obstetrics and Gynecology
admitted to hospital as a result of PPROM (study
group) and 50 women who experienced spontaneous
preterm labor before 37 weeks of gestation (control
group) were enrolled. Fifty cases were selected a
priori as the sample size as this size was judged by
the authors to be reasonable and convenient. PPROM
is defined as rupture of the membranes at < 37 weeks
of gestation. Patients between 24–37 weeks of gesta-
tion who were confirmed to have PPROM by one of
the following methods were included in the study:
nitrazine paper test positivity, observation of pooling
of amniotic fluid in posterior fornix of vagina or
active leakage of amniotic fluid from cervix and pres-
ence of placental alpha-microglobulin-1 (AmniSure
Test) in vaginal fluid.
Exclusion criteria were as follows: multiple gesta-
tions; previous history of hematopoietic system disor-
ders, malignancies, gestational diabetes, pre-
eclampsia and any other systemic diseases; infections
of urinary, respiratory or gastrointestinal tracts; and
any acute or chronic infectious conditions. In addi-
tion, patients who had fetuses with intrauterine
growth restriction; structural or chromosomal
abnormalities; who underwent invasive diagnostic or
therapeutic procedures, such as amniocentesis and
cervical cerclage; or any other surgical procedures,
were also excluded.
In our hospital, patients with PPROM are assessed
by clinical signs and symptoms together with one of
the following tests: white blood cell count in CBC, C-
reactive protein and fetal heart rate monitoring to
diagnose the presence of intrauterine infection.
PPROM has been managed in our hospital since we
started data collection as follows:
• Labor is induced in pregnancies complicated with
PPROM at and after 34 weeks of gestation.
• An oral dosage of 6 g/24 h of penicillin is pre-
scribed as antibiotic prophylaxis for a maximum of
10 days or until labor starts spontaneously.
• If infection is suspected, labor is induced.
• Intravenous magnesium sulfate treatment with a
bolus dosage of 4 g/20 min and a following infu-
sion dosage of 1 g/h for 24 h is administered
between 24 and 34 weeks of gestation for neuro-
protective effect if the patients are expected to give
birth within 24 h.
• A single course of betametazon treatment is rou-
tinely used between 24 and 34 weeks of gestation.
A single repeat dose is administered if the first
course of betametazon was completed 14 days

earlier in patients at imminent risk of delivery
within the next seven days.
The criteria for NICU admission in our hospital are
as follows: transient problems requiring cardiorespira-
tory monitoring, need for peripheral intravenous fluid
therapy, jaundiced infants requiring peripheral intra-
venous fluid therapy and closer monitoring, preterm
under 32 weeks of gestation, RDS, neonatal sepsis,
exchange transfusion and sustained assisted ventila-
tion. A diagnosis of sepsis is made with the presence
of at least three of the following: temperature instabil-
ity, tachypnea (> 70/min), feeding intolerance,
abdominal distension, hepatosplenomegaly, dyspnea,
lethargy, tachycardia (heart rate > 190 bpm) and
bradycardia (heart rate < 90 bpm). Infants with respi-
ratory distress, tachypnea, nasal flaring, grunting and
a grainy shadow, air bronchogram and a white lung
in chest X-ray are diagnosed with RDS.
The medical records of participants were examined
for maternal CBC values at the time of hospitaliza-
tion, birth weights of neonates, 1 and 5 min Apgar
scores, development of neonatal sepsis, development
of neonatal RDS and NICU admission. We analyzed
whether there was any alterations in PLT indices
between the PPROM group and control. Moreover,
we looked for a relationship between PLT indices
measured by CBC and neonatal outcomes in PPROM
cases.
Complete blood count parameters were measured by
an automated blood counter. Nurses took blood sam-
ples by venipuncture, which were collected in tubes
containing tripotassium-ethylenediaminetetraacetic acid
(EDTA) to prevent coagulation. We recorded data of the
following parameters from CBC records: white blood
cell count (WBC), hemoglobin (Hgb), hematocrit (Hct),
red cell distribution width (RDW), PLT count, MPV,
PCT, PDW and neutrophil count (Neu).
Statistical analysis
A Shapiro–Wilk test was used to assess whether the
variables followed normal distribution. Variables
were reported as mean  standard deviation or
median (minimum: maximum) values. According to
the normality test results, independent sample t or
Mann Whitney U tests were used to compare the
groups. Categorical variables were compared by Chi
square test. In order to estimate the sensitivity and
specificity of PCT values for predicting RDS in the
PPROM group, receiver operator characteristic (ROC)
curve analysis was performed. Area under the ROC
© 2017 Japan Society of Obstetrics and Gynecology
Platelet indices in PPROM
curve values with 95% confidence intervals (CIs) were
reported. To determine independent risk factors
affecting RDS development in the PPROM group,
binary logistic regression analysis with a backward
selection procedure was performed. CBC parameters
and Apgar scores were selected as covariates in the
regression models. SPSS version 21.0 and MEDCALC for
Windows, version 12.5 software were used. A P value
of ≤ 0.05 was considered statistically significant.
All procedures in this study were performed in
accordance with the ethical standards of the institu-
tional and/or national research committee. For retro-
spective studies, formal consent is not required in our
country.
Results
The clinical and laboratory characteristics of patients
and the control group are summarized in Table 1.
Compared to controls, patients with PPROM had
higher MPV (9.40 vs 10; P = 0.01) and PCT (0.19 vs
0.21; P = 0.03) values. The neonatal outcomes of
patients and the control group are listed in Table 2.
The frequency of neonatal sepsis was higher in the
PPROM group (38% vs 18%; P = 0.02).
Complete blood count parameters did not differ
significantly between sepsis positive and negative
PPROM groups (P > 0.05). Moreover, they were simi-
lar in NICU admission positive and negative PPROM
groups. Contrary to these results, in the RDS positive
PPROM group, maternal PCT values were signifi-
cantly higher (0.23  0.05 vs 0.21  0.04; P = 0.04).
Receiver operator characteristic curve analysis was
performed to estimate the sensitivity and specificity
of PCT values for predicting RDS in the PPROM
group only, and the cut-off point for PCT was deter-
mined as > 0.22. The area under the curve for PCT
was 0.62 (sensitivity 80, specificity 43.6, 95% CI
0.52–0.72; P = 0.03), showing that a PCT value > 0.22
was significantly related to an increased risk of neona-
tal RDS in PPROM (Fig. 1).
Logistic regression analysis, which was set at
P < 0.001, revealed that the probability of RDS
increased 5.86 times when PCT levels exceeded 0.22
(odds ratio [OR] 5.86, 95% CI 1.01–32.01; P = 0.04] in
PPROM patients, which was statistically significant.
Logistic regression analysis also revealed that a one
unit increase in PDW led to a 1.33-fold increase in the
risk of RDS (OR 1.33, 95% CI 1.01–1.77; P = 0.04),
which was statistically significant (Table 3).
3
B. Dundar et al.

Table 1 Clinical and laboratory characteristics of the study and control groups
PPROM (n = 50) Control (n = 50) P
Age (years) 27 (18:40) 26 (17:41) 0.20†
Gestational age at delivery (weeks) 33 (26:36) 34 (25:35) 0.90†
Gravida (n) 2 (1:6) 2 (1:7) 0.82†
Parity (n) 1 (0:4) 1 (0:5) 0.70†
WBC (×103/mm3) 11.1 (6.5:28.2) 10.5 (6.5:17.7) 0.17†
Neu (×103/mm3) 8.7 (4.3:26.2) 7.9 (3:15.4) 0.12†
Plt (×103/mm3) 217 (136:360) 220 (112:490) 0.90†
Hgb (g/dl) 11.17  1.32 (8.10:14.20) 11.15  1.35 (7.40:13.70) 0.92‡
Hct (%) 35.29  3.82 (26:42.30) 35.30  3.95 (23.50:43.30) 0.99‡
PCT (%) 0.21 (0.13:0.33) 0.19 (0.10:0.28) 0.03†
MPV (fl) 10 (7.40:11.60) 9.40 (0.40:11.60) 0.01†
PDW (%) 16.50 (14.90:19.30) 16.30 (15.40:17.90) 0.30†
RDW (%) 14.20 (12.40:21.30) 14.05 (12.40:17.70) 0.26†
A P value of <0.05 was considered as statistically significant. †Mann Whitney U test; ‡Independent samples t test. Hct, hematocrit; Hgb,
hemoglobin; MPV, mean platelet volume; Neu, neutrophil count; PCT, plateletcrit; PDW, platelet distribution width; Plt, platelet; PPROM,
preterm premature rupture of membranes; RDW, red cell distribution width; WBC, white blood cell count.

Table 2 Neonatal outcomes of study and control groups

PPROM Control P
(n = 50) (n = 50)
Birth weight (g) 2425 (690:3280) 2010 (700:3150) 0.07†
Birth weight
<1500 g 7 (%14) 11 (%22) 0.38‡
1500–2500 g 21 (%42) 23 (%46)
>2500 g 22 (%44) 16 (%32)
Sepsis (+) (n,%) 19 (%38) 9 (%18) 0.02‡
RDS (+) (n,%) 27 (%54) 18 (%36) 0.07‡
NICU(+) (n,%) 29 (%58) 27 (%54) 0.68‡
Apgar < 7 (1 min) (n) 8 (2:9) 8 (0:9) 0.30†
Apgar < 7 (5 min) (n) 9 (3:10) 9 (0:10) 0.41†
A P value of <0.05 was considered as statistically significant. †Mann Whitney U test; ‡Chi-square test. NICU, neonatal intensive care unit;
RDS, respiratory distress syndrome.

Discussion possible in women at ≥ 37 weeks of gestation, how

The primary findings of the present study are that
MPV and PCT values are higher and sepsis is more
common in women with PPROM. Moreover, PCT
values are higher in RDS positive PPROM patients
and a PCT value > 0.22 is significantly related to a
5.86 times increased risk of RDS in patients with
PPROM. The risk of RDS increases 1.33 times with a
one unit increase in PDW.
In PPROM patients, the time interval between
membrane rupture and delivery is a major risk factor
for the development of maternal and neonatal compli-
cations.9 The most common and serious complications
of PPROM are RDS, intraventricular hemorrhage, nec-
rotizing enterocolitis and sepsis.3 There is an inverse
relationship between severity and incidence of these
complications and gestational age. Although it is
quite clear that labor should be induced as soon as
clinical management should be performed at < 37 ges-
tational weeks is controversial.10 According to the
American Collage of Obstetricians and Gynecologists
and the Royal College of Obstetrics and Gynaecology,
in women at ≥ 34 weeks of gestation, delivery should
be considered. Because current guidelines were estab-
lished on limited evidence, whether immediate deliv-
ery is essential for patients with PPROM at ≥
34 weeks of gestation is questionable because of iatro-
genic prematurity.3,18,19 Expectant management is
particularly crucial for pregnancies between 23 and
30 weeks of gestation complicated with PPROM.
Because these fetuses are extremely preterm and
much more prone to neonatal mortality and morbid-
ity, there is broader consensus on expectant manage-
ment for this group of patients.20,21 If expectant
management is preferred, caution is recommended in
regard to infectious complications. Recent studies

4 © 2017 Japan Society of Obstetrics and Gynecology


PCT
100
80
60
Sensititvity
40
20
Sensitivity : 00.0
Specificity : 43.6
Cnteron : 0.22
0 the circulation increase in number and size, migrating
0 20 40 60 80
100-Specificity
Figure 1 Receiver operating characteristic (ROC) curve
for the diagnosis of respiratory distress syndrome
(RDS) using plateletcrit (PCT) in preterm premature
rupture of membranes (PPROM) group only (n = 50;
RDS [+] = 27, RDS [−] = 23).
Table 3 Independent risk factors affecting RDS devel-
opment with the effect of confounding variables of
CBC parameters and Apgar scores in PPROM group
only by binary logistic regression (n = 50; RDS
[+] = 27, RDS [−] = 23)
Factor B OR (95% CI)
PCT (Ref.Cat: 1.74 5.86(1.01:32.01)
PCT ≤ 22)
PDW 0.29 1.33(1.01:1.77)
Significance for final logistic regression model: P < 0.001. CBC,
complete blood count; CI, confidence interval; OR, odds ratio;
PCT, plateletcrit; PDW, platelet distribution width; PPROM,
preterm premature rupture of membranes; RDS, respiratory
distress syndrome; Ref.Cat., reference category.
have shown that neonatal sepsis is more common in
pregnancies complicated with early onset PPROM
and in PPROM cases complicated with histologic
chorioamnionitis.22,23 Similar to these findings, sepsis
was more common in the PPROM patients in our
study. On the other hand, Morris et al. stated in the
PPROMT trial that immediate delivery did not reduce
neonatal sepsis, but did increase the likelihood of
RDS and mechanical ventilator support for the baby
and cesarean section for the mother.24 While an
appropriate waiting time is important to provide a
favorable cervix and neonatal lung maturation, early
intervention will result in failure to induce labor and
© 2017 Japan Society of Obstetrics and Gynecology
Platelet indices in PPROM
an increase in operative delivery and cesarean
section rates.25
Recent improvements have allowed us to better
understand the role of PLTs in immunity, inflamma-
tion and angiogenesis.26 PLTs are disc shaped parti-
cles 1–2 μm in size, with a life cycle of 8–10 days and
are released into circulation during megakaryocyto-
poiesis.27 They are cytoplasmic fragments of megakar-
yocytes and their functional and morphologic
capabilities may be affected by several factors, such as
thrombopoietin, granulocyte-macrophage colony
stimulating factor, interleukin 1,interleukin 6 and
tumor necrosis factor alpha.28 In inflammatory pro-
cesses with an increased risk of thrombosis, PLTs in
100
to the site of infection where they should be heavily
consumed.29 As they migrate, they regulate their own
functions by changing their shapes and releasing bio-
logically active substances.30 This may explain the
possible mechanisms to understand how PLT indices
such as MPV, PDW and PCT are altered in some
cases.
In several studies, a number of diseases, such as
hypertension; diabetes; myocardial infarction; cere-
brovascular disease; and inflammatory diseases, such
as systemic lupus erythematosus, inflammatory bowel
disease and rheumatoid arthritis, PLTs indices were
altered. Gasparyan et al. reviewed data on MPV,
P which may function as a prothrombotic or a proin-
0.04 flammatory agent in different clinical settings. The
data suggested MPV is increasingly used as a marker
0.04 to determine disease activity or the effectiveness of
anti-inflammatory treatment in chronic inflammatory
diseases. In systemic infections, the sizes of PLTs in
the circulation increase as the severity of disease
increases, whereas MPV decreases in cases of high
and low grade infections and during anti-
inflammatory treatment.11 In addition, PLT indices
were reported to be disturbed in some obstetric condi-
tions, such as recurrent pregnancy loss, pre-eclampsia,
gestational diabetes and preterm labor.12–15 Aynioglu
et al. showed that there was a relationship between
recurrent pregnancy loss and altered PLT indices,
such as a higher PLT count and PCT.12 Another study
demonstrated that MPV became higher as the severity
of hypertension in pregnancy increased.13 Sahbaz
et al. evaluated the relationship of gestational diabetes
with different PLT indices and determined a statisti-
cally significant increase in PCT, MPV and PDW
values compared to healthy pregnancies.14 Whether
PLT indices are of value for predicting preterm labor
5
B. Dundar et al.
was also examined and PCT values were found to be
significantly higher in preterm deliveries.15,31 Gioia
et al. investigated the association of MPV and oxygen
metabolic changes in pregnancies affected by altered
umbilical artery maternal-fetal Doppler velocimetry.
They found that MPV was significantly higher in
patients with abnormal umbilical artery Doppler velo-
cimetry and an MPV value ≥ 10 fl was significantly
related to adverse neonatal outcomes, such as RDS
and brain damage.17
Predictive values of PLT indices are have generally
been investigated in the literature to determine differ-
ent obstetric conditions. However, their roles in
PPROM and relationships to adverse neonatal out-
comes have not been comprehensively studied. Beyan
et al. reported that MPV may not be useful as a
marker in predicting PPROM.32 Contrary to this
study, Ekin et al. cited that MPV and PLT count at
first trimester of pregnancy can be used for an early
diagnosis of PPROM and revealed that the PLT count
was significantly higher and MPV significantly lower
during the first trimester in women who developed
PPROM in the following weeks.16 In the present
study, we found that MPV and PCT were signifi-
cantly higher in the PPROM group compared to con-
trols. We also evaluated whether there was an
association in patients with PPROM between adverse
neonatal outcomes and MPV, PCT and PDW. Preg-
nancies complicated with PPROM were grouped
according to the development of RDS and it was
observed that PCT was higher in patients who devel-
oped RDS. A PCT value > 0.22 is associated with a
5.86 times increased risk for RDS. Increasing values of
PDW were also associated with an increased risk of
RDS in patients with PPROM.
There were several limitations to the current study.
First, this study had a small sample size from single
center. Second, the retrospective design meant that
potential bias could not be excluded while validating
information from medical records. Finally, as we only
had the CBC results of patients at the time of hospital-
ization, serial CBC evaluation may affect the results.
Further prospective studies with a large sample size
are required to elucidate the role of each PLT index in
predicting neonatal outcomes in PPROM patients.
Conclusion
In conclusion, as the time interval between membrane
rupture and delivery increases, the risk of maternal
6 © 2017 Japan Society of Obstetrics and Gynecology
and neonatal infections also rises. Controversy over
the appropriate management remains. The appropri-
ate time interval for expectant management is impor-
tant to provide a favorable cervix and consequently
decrease operative deliveries, allow neonatal lung
maturation and avoid iatrogenic prematurity. There-
fore, it is critical to decide how long to wait until
labor starts spontaneously or to determine the appro-
priate time to induce labor. Determining the markers
to predict neonatal complications in antenatal surveil-
lance during expectant management are crucial. We
suggest that in cases of PPROM, monitoring PCT may
be promising to predict the development of RDS,
which is one of the most common and serious compli-
cations of PPROM.
Disclosure
The authors declare that they have no conflicts of
interest.
References
1. American College of Obstetrics and Gynecology. Practice
bulletin no. 139: Premature rupture of membranes. Obstet
Gynecol 2013; 122: 918–930.
2. Duff P. Premature rupture of the membranes in term
patients. Semin Perinatol 1996; 20: 401–408.
3. Duff P. Management of premature rupture of membranes in
term patients. Clin Obstet Gynecol 1991; 34: 723–729.
4. Simhan HN, Canavan TP. Preterm premature rupture of
membranes: Diagnosis, evaluation and management strate-
gies. BJOG 2005; 112 (Suppl 1): 32–37.
5. Moore RM, Mansour JM, Redline RW, Mercer BM, Moore JJ.
The physiology of fetal membrane rupture: Insight gained
from the determination of physical properties. Placenta 2006;
27: 1037–1051.
6. Goys M, Bernabeu A, García N et al. Premature rupture of
membranes before 34 weeks managed expectantly: Maternal
and perinatal outcomes in singletons. J Matern Fetal Neonatal
Med 2013; 26: 290–293.
7. Romero R, Ghidini A, Bahado-Singh R. Premature rupture
of the membranes. In: Reece AE, Hobbins JC, Mahoney MJ,
Petrie RH (eds). Medicine of the Fetus and Mother.
Philadelphia, PA: JB Lippincott, 1992; 1430–1468.
8. Liu L, Johnson HL, Cousens S et al. Global, regional, and
national causes of child mortality: An updated systematic
analysis for 2010 with time trends since 2000. (Published
erratum appears in Lancet 2012; 380: 1308). Lancet 2012; 379:
2151–2161.
9. Xia H, Li X, Li X, Liang H, Xu H. The clinical management
and outcome of term premature rupture of membrane in
East China: Results from a retrospective multicenter study.
Int J Clin Exp Med 2015; 8: 6212–6217.
10. Hannah ME, Ohlsson A, Farine D et al. Induction of labor
compared with expectant management for prelabor rupture

of the membranes at term. TERMPROM Study Group. N
Engl J Med 1996; 334: 1005–1010.
11. Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD.
Mean platelet volume: A link between thrombosis and
inflammation? Curr Pharm Des 2011; 17: 47–58.
12. Aynıoglu O, Isık H, Sahbaz A, Harma MI, Isık M,
Kokturk F. Can plateletcrit be a marker for recurrent preg-
nancy loss? Clin Appl Thromb Hemost 2016; 22: 447–452.
13. Piazze J, Gioia S, Maranghi L, Anceschi M. Mean platelet
and red blood cell volume measurements to estimate the
severity of hypertension in pregnancy. J Perinat Med 2006;
34: 246–247.
14. Sahbaz A, Cicekler H, Aynioglu O, Isik H, Ozmen U. Com-
parison of the predictive value of plateletcrit with various
other blood parameters in gestational diabetes development.
J Obstet Gynaecol 2016; 36: 589–593.
15. Isik H, Aynioglu O, Sahbaz A et al. Can plateletcrit, an
underestimated platelet parameter, be related with preterm
labour? J Obstet Gynaecol 2015; 35: 676–680.
16. Ekin A, Gezer C, Kulhan G, Avcı ME, Taner CE. Can plate-
let count and mean platelet volume during the first trimester
of pregnancy predict preterm premature rupture of mem-
branes? J Obstet Gynaecol Res 2015; 41: 23–28.
17. Gioia S, Piazze J, Anceschi MM et al. Mean platelet volume:
Association with adverse neonatal outcome. Platelets 2007;
18: 284–288.
18. Royal College of Obstetrics and Gynaecology. Green-top
Guideline No. 44: Preterm Prelabour Rupture of Membranes.
London: RCOG, 2010.
19. Teune MJ, Bakhuizen S, Gyamfi-Bannerman C et al. A sys-
tematic review of severe morbidity in infants born late pre-
term. Am J Obstet Gynecol 2011; 205: 374.e1–e9.
20. Buchanan S, Crowther C, Morris J. Preterm prelabour rup-
ture of the membranes: A survey of current practice. Aust N
Z J Obstet Gynaecol 2004; 44: 400–403.
21. Ramsey PS, Nuthalapaty FS, Lu G, Ramin S, Nuthalapaty
ES, Ramin KD. Contemporary management of preterm pre-
mature rupture of membranes (PPROM): A survey of
© 2017 Japan Society of Obstetrics and Gynecology
Platelet indices in PPROM
maternal-fetal medicine providers. Am J Obstet Gynecol 2004;
191: 1497–1502.
22. Manuck TA, Varner MW. Neonatal and early childhood out-
comes following early vs later preterm premature rupture of
membranes. Am J Obstet Gynecol 2014; 211: 308.e1–6.
23. Xie A, Zhang W, Chen M et al. Related factors and adverse
neonatal outcomes in women with preterm premature rup-
ture of membranes complicated by histologic chorioamnioni-
tis. Med Sci Monit 2015; 21: 390–395.
24. Morris JM, Roberts CL, Bowen JR et al. Immediate delivery
compared with expectant management after preterm pre-
labour rupture of the membranes close to term (PPROMT
trial): A randomised controlled trial. Lancet 2015; 387:
444–452.
25. Frederiks F, Lee S, Dekker G. Risk factors for failed induc-
tion in nulliparous women. J Matern Fetal Neonatal Med 2012;
25: 2479–2487.
26. Smyth SS, McEver RP, Weyrich AS et al. Platelet colloquium
participants. Platelet functions beyond hemostasis. J Thromb
Haemost 2009; 7: 1759–1766.
27. Kamath S, Blann AD, Lip GY. Platelet activation: Assess-
ment and quantification. Eur Heart J 2001; 22: 1561–1571.
28. Kaushansky K. The molecular mechanisms that control
throm-bopoiesis. J Clin Investig 2005; 115: 3339–3347.
29. Thompson CB, Jakubowski JA. The pathophysiology and
clinical relevance of platelet heterogeneity. Blood 1998;
72: 1–8.
30. Mete Ural U, Bayo glu Tekin Y, Balik G, Kir Şahin F,
Colak S. Could platelet distribution width be a predictive
marker for unexplained recurrent miscarriage? Arch Gynecol
Obstet 2014; 290: 233–236.
31. Kim MA, Lee BS, Park YW, Seo K. Serum markers for pre-
diction of spontaneous preterm delivery in preterm labour.
Eur J Clin Invest 2011; 41: 773–780.
32. Beyan C, Beyan E. Were the measurements standardized
sufficiently in published studies about mean platelet vol-
ume? Blood Coagul Fibrinolysis 2017; 28: 234–236. https://
doi.org/10.1097/MBC.0000000000000586.
7