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Risk Factors for Spontaneous Preterm Labour

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Research Article
Risk Factors for Spontaneous
Preterm Labour with Intact
Membrane: A Case Control
Study of Malay Ethnic Group in
Hospital Serdang, Malaysia
Niu J. Tan1, Karuppiah Thilakavathy1,2, Norhafizah Mohtarrudin3
and Amilia A.M Jamil4*
1
Medical Genetics Unit, Department of Biomedical Sciences, Faculty of
Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM
Serdang, Selangor, Malaysia
2
Genetics and Regenerative Medicine Research Centre, Faculty of Medicine
and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang,
Selangor, Malaysia
3
Department of Pathology, Faculty of Medicine and Health Sciences, Universiti
Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
4
Department of Obstetrics and Gynaecology, Faculty of Medicine and Health
Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
*Corresponding author: Amilia Afzan Binti Mohd Jamil,
Email: amilia@upm.edu.my
Received: 29 March 2017; Accepted: 21 June 2017; Published: 28 June
2017
Abstract
Objective: Perinatal morbidity and mortality were well-associated
with preterm births. Spontaneous preterm births as a single entity or
preterm births in general were commonly used in identification of risk
factors. These factors, however, are lacking due to absence of subtype-
specific aetiologies. In this investigation, risk factors linked with
spontaneous preterm births with intact membrane were investigated.
Methods: This case-control study using secondary data was
conducted at the Department of Obstetrics and Gynaecology, Hospital
Serdang, Malaysia over the course of three years. A total of 1,559
Malay pregnant women were involved. It consisted of subjects
with spontaneous preterm labours with intact membrane, and the
controls consisted of matched pregnant women with term delivery.
Information in terms of socio-demographic factors, history of prior
pregnancies, maternal health during pregnancy, foetal characteristics,
and biophysical profile were taken from the patients’ medical records
and collected using a set data collection sheet. Any associations with
spontaneous preterm labour with intact membrane were determined
and analysed by employing both chi square bivariate and multivariable
logistic regression via SPSS software.
Results: Incidence rate of spontaneous preterm labour with
intact membrane peaked during the late preterm stage of gestation.
Risk factors, in order of decreasing odds ratios (OR), preeclampsia
(OR=31.92, 95% confidence interval (CI):12.57-81.09), placenta
previa (OR=11.14, 95% CI: 5.19-23.92), history of preterm delivery
(OR=5.43, 95% CI: 3.15-9.36), young mother (OR=5.14, 95%
CI:2.68-9.848), unmarried mother (OR=3.81, 95% CI:1.78-8.13),
systemic infection (OR=4.04, 95% CI:1.96-8.30), urinary tract
infection (OR=3.21, 95% CI:1.73-5.93), absence of antenatal follow-
up (OR=2.62, 95% CI:1.14-5.99), grand multiparity (OR=2.59, 95%
CI:1.01-6.86), hypertension (OR=2.40, 95% CI:1.36-4.26), pregnancy
induced hypertension (OR=2.28, 95% CI:1.17-4.46), oligohydramnios
(OR=1.94, 95% CI:1.14-3.29), vaginal tract infection (OR=1.76, 95%
CI:1.17-2.65) and poor/low socioeconomic status (OR=1.31, 95%
CI:1.02-1.67). This was suggested by the final multivariable model.
Conclusion: Variables identified as risk factors for spontaneous
preterm labour with intact membrane are family income, no utilization
Journal of Gynecology & Obstetrics
Open Access
of prenatal care, marital status, maternal age, history of prematurity,
preeclampsia, placenta previa, infection (systemic, urinary tract and
vaginal tract), hypertension, pregnancy induced hypertension, grand
multiparity, and oligohydramnios. Therefore, women with these risk
factors require more attention through careful antenatal care.
Keywords: Preterm labour; Risk factor; Case-control study;
Pregnancy complications; Malaysia
Introduction
Despite advancements in perinatal medicine and major prevention
efforts, preterm birth (PTB) remains one of the most serious issues
faced by obstetricians. Approximately 15 million babies were born
preterm [1] in both developed and developing countries. It was reported
that there was over 1 million fatalities due to complications in the first
month of gestation. Meanwhile, the remaining millions were affected
with lifetime impairments [2,3] including retarded neurodevelopment,
epilepsy, visual impairment, and respiratory complications. This further
stressed the global negative impact of PTB, which was often overlooked
and masked by other health issues.4 Furthermore, it was known that the
risk of PTB is high in both poor and the rich countries, thereby widening
the survival gap of preterm foetuses in certain parts of the world [4].
PTB is defined as delivery prior to 37 weeks of complete gestation.
It is a multifactorial syndrome which can be generally classified into
two subtypes: (1) spontaneous PTBs, which are deliveries occurring
after spontaneous premature labour or spontaneous rupture of the
membranes, and (2) provider-initiated PTBs, which are the adverse
maternal or foetal diagnoses that warrant an early delivery [5].
According to previous literatures, majority of PTBs were due to the
former, of which 40–45% were related to spontaneous onset of labour
[6,7].
In accordance to the Millennium Development Goals, deaths
under-five years of age were projected to be reduced by two-third in
2015 [8]. Unfortunately, the goal was not achieved even until today
though advances in neonatal care have proven successful reduction of
recent PTB cases. This was believed due to the changes in frequency of
multiple births or limited obstetric interventions, where lack of effective
intervention has been obvious, putting majority of pregnant women
on risk [3,9]. Hence, the long-term consequences of PTB must not be
neglected as it is a rising prenatal health problem in various part of the
world [10] and in Malaysia.
As an attempt to unveil the factors of PTB, various epidemiologic
studies examined the risk factors associated with PTB covering either
all PTBs in a population, or they are focused solely on spontaneous
PTBs without dividing it into its sub-type [11,12]. The latter included
young or advanced maternal age, short interval between pregnancies,
low maternal body mass index [13,14], and cervical insufficiency [15].
Consequently, infection plays an important role in PTB as urinary tract
infections, malaria, bacterial vaginosis, human immunodeficiency virus,
and syphilis are well-associated with the increased risk of PTB [16]. On
the other hand, lifestyle related factors that contribute to spontaneous
PTB include stress, excessive physical work [14], smoking, and
excessive alcohol consumption [16]. There were also studies focused
on spontaneous PTB sub-types which reported socio-economic, genetic,
constitutional, obstetric, multi gravity, and the history of abortion as
factors associated with preterm labour as well. However, prevalence of
these factors varied among populations [17,18].
During the past two decades, we have come closer to understanding
the aetiology of spontaneous PTB; however, better specific risk
factor markers against the specific sub-type of spontaneous PTBs are
Copyright © 2017 The Authors. Published by Scientific Open Access
Journals LLC.
Tan et al. Volume 1, Issue 3 J Gynec Obstet 2017; 1:017

required because the causatives of this syndrome are highly variable Case Control
[19]. Subsequently, identification of such risk factors will provide
• Delivery after 42 weeks
more useful information in suggesting hypotheses on its aetiology.
Therefore, this study aimed to determine risk factors of spontaneous • Delivery before 22 weeks POA
preterm labour with intact membrane (SPTL-IM) among Malays that period of amenorrhea (POA) • Patients of PPROM
potentially leads to elaboration of public health policies for monitoring
preterm labour prevention strategies. • Patients of PPROM • Iatrogenic delivery
• Iatrogenic delivery • Intra-uterine foetal death
Materials and Methods
• Intra-uterine foetal death • Eclampsia
Patient population • Eclampsia • Cervical cerclage
A hospital-based case-controlled study using secondary data was • Cervical cerclage • Major congenital anomaly
conducted on Malay pregnant women who experienced SPTL-IM over
a period of 3 years (from Jan 2013 to Dec 2015) at the Department of • Major congenital anomaly • Multiple gestational
Obstetrics and Gynaecology, Hospital Serdang, Malaysia. Case and • Multiple gestational • Birth of newborn with
control groups were selected according to the inclusion and exclusion
• Birth of newborn with malformation
criteria. Ethical and data collection sheet approval were permitted by
the ethics board of National Medical Research Committee as well as malformation • Severe obstetric bleeding;
the University Putra Malaysia’s ethics committee. This study was • Severe obstetric bleeding; abruptio placenta
conducted on 1,559 women subjects (537 cases and 1,022 controls).
Case subjects were defined as women who delivered a live singleton abruptio placenta • Chinese, Indian and other
newborn between 22 and 36+6 weeks of gestation which was defined • Chinese, Indian and other ethnic groups
as SPTL-IM. Controls were subjects who delivered after spontaneous ethnic groups • Intrauterine growth
labour between 37 and 42 weeks of gestation according to standards
implemented by the Department of Obstetrics and Gynaecology, • Intrauterine growth restriction restriction
Serdang Hospital, Malaysia. Both case and control subjects were • Malay pregnant women with • Malay pregnant women
matched in terms of delivery date.
incomplete medical records with incomplete medical
Two controls were selected by simple random selection for every
was excluded from the study records was excluded from
case record that met the inclusion and exclusion criteria. This is to
ensure that the controls are comparable with the cases. The simple the study
random selection was done by randomly choosing two pregnant Gestational age was determined by the age of last monthly period
women who delivered nearest to the case’s delivery date that meet the and was confirmed by first-trimester obstetric ultrasound.
inclusion and exclusion criteria.
Subjects with the above mentioned criteria were excluded in order to
Sampling obtain an etiologically homogeneous sample. However, the pathogenic
Inclusion criteria for the study group consisted of: pathways may be multiple in this group of subjects.
Studies performed
Case Control
• Pregnant women who were • Pregnant women who were The research instrument is a secondary data resulting from patients’
medical records and prenatal medical records of pregnant women
admitted and delivered in admitted and delivered in registered in labour and delivery unit in Hospital Serdang from 2013-
Hospital Serdang due to Hospital Serdang due to 2015. All live births during these three years that met the inclusion and
SPTL-IM (regular uterine spontaneous term labour exclusion criteria were included in this study.

contractions occurring at a
frequency of at least 4 in 20
minutes or 8 in 60 minutes
synchronizing with pain
with cervical change on
presentation)
• No prior history of preterm
premature rupture of the
membranes (PPROM)
• Malay ethnic group
Exclusion criteria for the study group consisted of:
with intact membrane
(regular uterine contractions
occurring at a frequency of
at least 4 in 20 minutes or 8
in 60 minutes synchronizing
with pain with cervical
change on presentation)
• No prior history of preterm
PPROM
• Malay ethnic group
Since there are some missing data in the secondary data, we
calculated the sample size required based on a guideline established by
Green (1991) in order to reduce bias and to reach valid conclusions for
the target ethnic group [20]. 20 explanatory variables with two potential
categories were included in the model. An additional 25% of cases were
added for improved accuracy. It was estimated that the sample size of
this study consisted of 500 cases and 1,000 controls. A collection of 3
years data was necessary to achieve meaningful statistical analysis after
the missing data was taken into consideration.
Variables and definition
Information regarding sociodemographic factors (maternal age
at delivery; marital status; socioeconomic status, with family who
earn lower than the minimum wages [21] was consider poor to low
income group; antenatal follow-up), history of prior pregnancy (parity,
history of miscarriages and history of PTB), lifestyle (illicit drugs,
alcohol use), maternal health during pregnancy (anaemia, defined as
haemoglobin level <10mg/dl; preeclampsia; chronic hypertension,
defined as blood pressure >140/90mm Hg at <20 weeks; pregnancy
induced hypertension, defined as blood pressure >140/90mm Hg at
>20 weeks, without the presence of proteinuria; diabetes mellitus;
gestational diabetes; heart disease, defined as the presence of all other

Citation: Tan NJ, Thilakavathy K, Mohtarrudin N, et al. Risk Factors for Spontaneous Preterm Labour with Intact Membrane: A Case Control
Study of Malay Ethnic Group in Hospital Serdang, Malaysia. J Gynec Obstet 2017; 1:017.
Tan et al. Volume 1, Issue 3
cardiac complications other than preeclampsia and hypertension;
asthma; systemic infection, defined as the presence of other infections
other than vaginal and urinary tract infections; vaginal tract infection,
defined as pregnant women who become symptomatically infected or
positive swab (vaginal) and urinary tract infection, defined as pregnant
women with urinary symptoms or positive urine culture results), foetal
characteristic (placenta previa), and biophysical profile (amniotic
fluid index) for both subject groups were collected from the hospital
patients’ medical records.
Related information from the patients’ medical records were
abstracted directly from the patients’ medical records and prenatal
records and was recorded onto a standardized data collection sheets
by trained investigators. Meanwhile, parameters acquired on neonatal
outcome included gender, Apgar score at 1 min and 5 min, and birth
weight. These risk factors were selected based on association with
spontaneous preterm delivery in general [11,12] and limitations from
the hospital record.
Statistical analysis
Statistical analysis was performed using SPSS statistical software,
version 17.0 for Windows (Chicago, USA). This includes descriptive
statistics and χ2 test (bivariate analysis) in order to compare case-
control differences for categorical variables. P values of <0.05 was
considered statistically significant. A bivariate logistic regression was
performed to study the risk factors associated with SPTL-IM in Malay
ethnic group in Malaysia. SPTL-IM was the dependent variable, while
risk factors were the independent variables. All risk factors obtained
from bivariate analysis was approximated using odds ratio (OR).
Confidence interval (CI) of 95% was also calculated for the OR. P
values of <0.05 was considered statistically significant. All significant
risk factors were evaluated for multicollinearity. Statistically
significant variables in the bivariate analysis were further subjected to
the next multivariate logistic regression model to examine independent
effects. Multivariable logistic regression analyses were performed to
identify the simultaneous effects of several factors while estimating
associations of relevant variables with SPTL-IM.
Results
The study involve 537 cases and 1,022 controls that were collected
from 2013-2015 (Table 1). The highest number of SPTL-IM was late
PTB (35 to 36+6 weeks) constituting about 52.8% (294). This was
followed by moderate PTBs in 27.7% (149) (32-34 weeks). However,
only 17.5% (94) were early PTBs (22-31 weeks) (Table 2). Mean
gestational age of case group subjects ranged from 22 to 36+6 weeks
was 33.8 ± 2.9 week, while controls which ranged from 37 to 42 weeks
was 38.8 ± 1.3 week. Majority of cases gave birth during 33 to 36+6
weeks gestation.
χ2 test of independence showed that there is no association found
between maternal complications during pregnancy such as anaemia,
gestational diabetes and asthma with the occurrence of SPTL-IM (Table
2). However, various risk factors including grand multiparity, history of
miscarriage, hypertension, pregnancy induced hypertension, diabetes
mellitus, heart disease, vaginal tract infection and oligohydramnios
showed significant association with SPTL-IM. In addition, young age,
marital status, socioeconomic status, antenatal follow-up, history of
previous preterm delivery, preeclampsia, systemic infection, urinary
tract infection, and placenta previa were identified to be associated at
high significance with the occurrence of SPTL-IM.
Table 1: Gestational age wise distribution of cases.
Gestational age in weeks Number of cases (%)
22-31 94 (17.5)
32-34 149 (27.7)
35-36+6 294 (54.8)
Citation: Tan NJ, Thilakavathy K, Mohtarrudin N, et al. Risk Factors for Spontaneous Preterm Labour with Intact Membrane: A Case Control
Study of Malay Ethnic Group in Hospital Serdang, Malaysia. J Gynec Obstet 2017; 1:017.
J Gynec Obstet 2017; 1:017
Multicollinearity analysis has been performed to examine the
correlation among the independent variables with significant from
bivariate analysis prior multivariate logistic correlations analysis, and
no multicollinearity was observed (data not shown). Subsequently,
these variables were subjected to multivariate analysis with logistic
regression analysis.
The multivariate analysis suggested a number of risk factors
(Table 3). Overall, preeclampsia (OR=31.92, 95% confidence interval
(CI):12.57-81.09), placenta previa (OR=11.14, 95% CI: 5.19-23.92),
history of preterm delivery (OR=5.43, 95% CI: 3.15-9.36), young
mother (OR=5.14, 95% CI:2.68-9.848), unmarried mother (OR=3.81,
95% CI:1.78-8.13), systemic infection (OR=4.04, 95% CI:1.96-8.30),
urinary tract infection (OR=3.21, 95% CI:1.73-5.93), absence of
antenatal follow-up (OR=2.62, 95% CI:1.14-5.99), grand multiparity
(OR=2.59, 95% CI:1.01-6.86), hypertension (OR=2.40, 95% CI:1.36-
4.26), pregnancy induced hypertension (OR=2.28, 95% CI:1.17-4.46),
oligohydramnios (OR=1.94, 95% CI:1.14-3.29), vaginal tract infection
(OR=1.76, 95% CI:1.17-2.65) and poor/low socioeconomic status
(OR=1.31, 95% CI:1.02-1.67), remained significantly associated with
SPTL-IM among the Malay population.
When compared to the infants born in-term, as expected, preterm
infants had a lower birth weight with lower Apgar scores at 1 and 5
minutes (Table 4). From our study, 0.4% of the preterm babies had birth
weights of ≥4.0kgs, of which 27.9% being 2.5-3.999kgs, 50.1% being
1.5-2.499kgs, while the remaining 21.6% being <1.5kgs. On the other
hand, 2.4% of the term babies had birth weights of ≥4.0kgs, in which
89.5% fell in the range of 2.5-3.999kgs and 8.1% being 1.5-2.499kgs.
Discussion
PTB is a heterogeneous condition with multiple aetiologies; here,
studies on its associated risk factors were lacking, especially in Malaysia
because most available literatures were conferred on Caucasian women
[19]. In this study, we focused on identifying risk factors for SPTL-IM
among Malay pregnant women in Malaysia. Thus, this was the first-of-
its-kind study.
SPTL-IM represented a substantial portion of all live births in this
study (approximately 6.5% on year 2015) [22]. According to Das et al.
[23], spontaneous preterm delivery occurs at a rate of 8% (equivalent
to 5.7% SPTL-IM) among pregnancies. It is responsible for 85% of
neonatal deaths among infants without any congenital anomalies.
However, these rates presented a need and challenge for prevention
efforts with the fact that relative proportion of PTBs related to SPTL-
IM may be increasing in some populations.
This study has several limitations that should be considered when
interpreting the results: (1) The case control study only discusses on risk
factors of SPTL-IM in Hospital Serdang. The findings do not represent
risk factors of SPTL-IM in other hospitals in Malaysia. (2) Multiple tests
of significance both collectively and in subgroups need to be performed
to determine the risk factors association between several variables and
SPTL-IM. Hence, type I error could occur. (3) This study was carried
out on Malay ethnic group; therefore known risk factors may not likely
to be generalizable in the other ethnic groups as well as the general
population of pregnant women of Malaysia. (4) Since this study was
conducted using secondary data, the accuracy of the information is not
known, especially information obtained from the pregnant women’s
self-report who attend the hospital only during delivery without any
previous antenatal follow-up. (5) Risk factors that showed statistically
associated with SPTL-IM does not mean that one factor is necessary to
result to the other. Moreover, this study lacks the ability to determine
the attributed risk. However, the risk factors obtained in this study are
very useful in contributing to the ongoing research in the field of SPTL-
IM in Malay ethnic group.
It was observed that the highest number of SPTL-IM occurred in
Tan et al. Volume 1, Issue 3 J Gynec Obstet 2017; 1:017

Table 2: Univariate analysis of various risk factors of spontaneous preterm labour with intact membrane in singleton live-births, N=1559.
Spontaneous Preterm delivery with intact membrane
Variable Yes n (%) No n (%) χ2 p
N= 537 N= 1022
Socio-demographic factors
Age
<18 years 48 (76.2) 15 (23.8) 50.668 <0.0001*
19-35 years 426 (32.4) 890 (67.6)
>35 years 63 (35.0) 117 (65.0) 0.28 0.868
Marital status
Unmarried 44 (75.9) 14 (24.1)
45.702 <0.0001*
Married 493 (32.9) 1007 (67.1)
Socioeconomic status
Poor-low 273 (39.8) 413 (60.2)
15.533 <0.0001*
Middle-high 264 (30.2) 609 (69.8)
Antenatal follow-up
No 33 (71.7) 13 (28.3)
29.195 <0.0001*
Yes 504 (33.3) 1009 (66.7)
History of prior pregnancies
Parity
>5 14 (63.6) 8 (36.4)
8.421 0.004*
1-5 523 (34.0) 1014 (66.0)
History of preterm delivery
Yes 59 (72.8) 22 (27.2)
55.777 <0.0001*
No 478 (32.3) 1000 (67.7)
History of miscarriage
Yes 29 (50.9) 28 (49.1)
7.075 0.008*
No 508 (33.8) 994 (66.2)
Maternal health during pregnancy
Preeclampsia
Yes 80 (95.2) 4 (4.8)
145.314 <0.0001*
No 457 (31.0) 1018 (69.0)
Anaemia
Yes 102 (31.9) 218 (68.1)
1.178 0.278
No 435 (35.1) 804 (64.9)
Hypertension
Yes 37 (55.2) 30 (44.8)
13.386 <0.001*
No 500 (33.5) 992 (66.5)
Pregnancy induced hypertension
Yes 26 (55.3) 21 (44.7)
9.351 0.002*
No 511 (33.8) 1001 (66.2)
Diabetes mellitus
Yes 29 (51.8) 27 (48.2)
7.735 0.005*
No 508 (33.8) 995 (66.2)
Gestational diabetes
Yes 82 (34.3) 157 (65.7)
0.002 0.962
No 455 (34.5) 865 (65.5)
Heart disease
Yes 15 (55.6) 12 (44.4)
5.423 0.02*
No 522 (34.1) 1010 (65.9)
Asthma
Yes 15 (41.7) 21 (58.3)
0.851 0.356
No 522 (34.3) 1001 (65.7)
Systemic infection
Yes 25 (64.1) 14 (35.9)
15.581 <0.0001*
No 512 (33.7) 1008 (66.3)
Vaginal tract infection
Yes 59 (44.7) 73 (55.3)
6.712 0.01*
No 478 (33.5) 949 (66.5)
Urinary tract infection
Yes 38 (65.5) 20 (34.5)
25.757 <0.0001*
No 499 (33.2) 1002 (66.8)
Foetal characteristic

Citation: Tan NJ, Thilakavathy K, Mohtarrudin N, et al. Risk Factors for Spontaneous Preterm Labour with Intact Membrane: A Case Control
Study of Malay Ethnic Group in Hospital Serdang, Malaysia. J Gynec Obstet 2017; 1:017.
Tan et al. Volume 1, Issue 3 J Gynec Obstet 2017; 1:017

Placenta Previa
Yes 42 (84.0) 8 (16.0)
56.178 <0.0001*
No 495 (32.8) 1014 (67.2)
Biophysical profile
Amniotic fluid index
Oligohydramnios 34 (45.9) 40 (54.1)
4.551 0.044*
Polyhydramnios 3 (42.9) 4 (57.1)
0.220 0.698
Normal 500 (33.8) 978 (66.2)
*statistically significant

Table 3: Multivariate statistical analysis of risk factors and their association with spontaneous preterm labour with intact membrane.
ORa (95% CIb) Adjusted ORa (95% CIb)
<18 years 6.59 (3.654-11.885) 5.14 (2.68-9.848)
Unmarried mother 6.42 (3.49-11.83) 3.81 (1.78-8.13)
Poor-low socioeconomic status* 1.53 (1.24-1.88) 1.31 (1.02-1.67)
No antenatal follow-up 5.08 (2.65-9.74) 2.62 (1.14-5.99)
Grand multiparity# 3.39 (1.41-8.14) 2.59 (1.01-6.86)
History of preterm delivery 5.61 (3.40-9.27) 5.43 (3.15-9.36)
Preeclampsia 44.55 (16.22-122.35) 31.92 (12.57-81.09)
Hypertension 2.45 (1.49-4.01) 2.40 (1.36-4.26)
Pregnancy induced hypertension 2.43 (1.35-4.35) 2.28 (1.17-4.46)
Systemic infectionǂ 3.52 (1.81-6.82) 4.04 (1.96-8.30)
Vaginal tract infectionǂǂ 1.61 (1.12-2.30) 1.76 (1.17-2.65)
Urinary tract infectionǂǂǂ 3.82 (2.20-6.63) 3.21 (1.73-5.93)
Placenta Previa 10.76 (5.01-23.08) 11.14 (5.19-23.92)
Oligohydramniosɛ 1.66 (1.04-2.65) 1.94 (1.14-3.29)
ORa: odd ratio
CIb: confidence interval
*Poor –low socioeconomic status is defined as family who earn lower than RM 1000.0021
#
Grand multiparity is defined as parity of >5 [70]
ǂ
Systemic infection is defined as the presence of other infections identified through symptoms or lab testing other than vaginal and urinary tract
infections [71]
ǂǂ
Vaginal tract infection is defined as pregnant women with vaginal infection symptoms or positive swab [72]
ǂǂǂ
Urinary tract infection is defined as pregnant women with urinary symptoms or positive urine culture results [71]
ɛ
Oligohydramnios is defined as amniotic fluid volume below 2 cm [73]

Table 4: Infant characteristics of singleton live birth.

Spontaneous Preterm Delivery With Intact Membrane
Characteristic Yes N (%) No N (%) P
N= 537 N= 1022
Infant Gender
Female 248 (33.2) 500 (66.8)
0.303
Male 289 (35.6) 522 (64.4)
Infant Birth Weight
<1.5 116 (100.0) 0 (0.0)
1.5-2.499 269 (76.4) 83 (23.6)
<0.0001*
2.5-3.999 150 (14.1) 915 (85.9)
≥4.0 2 (7.7) 24 (92.3)
Infant APGAR at 1 minutes
≤3 15 (100.0) 0 (0.0)
4-7 86 (82.7) 18 (17.3) <0.0001*
≥8 436 (30.3) 1004 (69.7)
Infant APGAR at 5 minutes
≤3 11 (100.0) 0 (0.0)
4-7 25 (96.2) 1 (3.8) <0.0001*
≥8 501 (32.9) 1021 (67.1)
* Significant (p<0.05)

late preterms which were between 34 to 36+6 weeks of gestation. It worldwide data, where late preterm newborns were reported to
consisted of about 54.8%, followed by moderate (27.7%) and early constitute up to approximately 74% of all stages of PTB and about
(17.5%) preterm cases. This distribution was parallel with available 8% in total births, making it the fastest growing subset of neonates

Citation: Tan NJ, Thilakavathy K, Mohtarrudin N, et al. Risk Factors for Spontaneous Preterm Labour with Intact Membrane: A Case Control
Study of Malay Ethnic Group in Hospital Serdang, Malaysia. J Gynec Obstet 2017; 1:017.
Tan et al. Volume 1, Issue 3
[24]. In another study, Merlino et al. [25] reported the increased
likelihood for late PTBs to occur due to SPTL-IM or PPROM, when
compared to iatrogenic PTB. The American College of Obstetricians
and Gynaecologists clinical management guidelines for obstetrician
gynaecologists in preterm labour management suggested that the
relative distribution of aetiologies of PTB ≥ 34 week gestation was
20%, followed by 25% PPROM, and 55% SPTL-IM [26].
Studies also reported a higher risk of PTB among Black ethnicity
who generally paid less medical attention due to lower social income,
when compared to the White ethnicity [27,28]. The same findings were
observed in Malaysia, where premature deliveries were significantly
more common (p=0.004) among the Indian mothers (61.5%) in
comparison to Malays (49.0%), Chinese (37.6%), and others (47.1%)
[29]. However, since we choose to control ethnicity’s variable to the
ease of matching cases and controls, we cannot comment on ethnicity
as risk factors per se in this study. Furthermore, although multiple
gestations has been known to be the major risk factor of PTB [6,13],
this risk factor was not brought into consideration because various
intention was made to study spontaneous preterm labour singleton
deliveries with intact membrane.
In bivariate analysis, one of the risk factor found to be associated
with increased risk of SPTL-IM was pregnancy in young age. Previous
studies confirmed the fact that maternal age affects pregnancy
duration, where subjects below 18 or over 35 years old [30,31] were
directly associated. Hence, these pregnant women were at higher risk.
Moreover, low maternal age has been extensively reported to be one
of the contributing risk factors [32], although it has not been a uniform
finding [33]. However, causes of PTBs in young age were unclear. The
effect of age could simply reflect on other factors related to an adverse
environment or that leads to PTB as a consequence of the biological
immaturity of young women [34,35].
Bivariate analysis also shows that low socio-economic status
has a significant risk factor in SPTL-IM. Other study evaluating the
role of socioeconomic status in preterm deliveries have found similar
association [36]. Moreover, low socio-economic status are more
likely to suffer from malnutrition and reduced ability to seek quality
healthcare [37,38].
Booked or unbooked status was known to significantly associate
with SPTL-IM as well. This finding was in parallel with a study carried
out in United Kingdom where Tucker et al. [39] reported that unbooked
mothers were five times more likely to have PTB (OR = 6.44, 95%, CI:
2.24-18.50). Lack of prenatal care has been demonstrated by studies
to negatively affect pregnancy outcome, such as increased maternal
mortality, complicated maternal emergency, and perinatal mortality
[40]. This can be reduced by providing prenatal care to pregnant
teenagers.
Based on history of pregnancy, a significant association was
seen between parity, mothers’ own history of prematurity and/or
miscarriage, and SPTL-IM. Several studies had successfully linked
multiparity with PTBs, due to a range of side effects accumulated from
previous pregnancies [17,41]. A significantly increased risk of PTB in
subsequent pregnancies was observed from women who experienced
preterm delivery and miscarriage previously; thus, women with three
or more miscarriages had the highest risk amongst all (OR 2.14; 95%CI
1.93-2.38) as reported by Oliver et al. [42]. Besides that, among Thai
women, previous histories of PTB was associated with a 3.64-fold
increased preterm delivery risk (95% CI 1.87, 7.09) [43].
With regard to maternal medical conditions associated with SPTL-
IM, our data reflected strong associations between preeclampsia,
hypertension, pregnancy induced hypertension, diabetes mellitus,
and heart disease with SPTL-IM. This was in parallel with previous
studies, where preeclampsia was reported with a rate of 21.9%, being
the third cause of prematurity [44]. Additionally, in another study [45],
Citation: Tan NJ, Thilakavathy K, Mohtarrudin N, et al. Risk Factors for Spontaneous Preterm Labour with Intact Membrane: A Case Control
Study of Malay Ethnic Group in Hospital Serdang, Malaysia. J Gynec Obstet 2017; 1:017.
J Gynec Obstet 2017; 1:017
cases of preterm neonates in preeclamptic mothers were 7.7 times more
than that of term infants. In addition, Afrakhteh et al. [46] reported
that 17.7% of preterm cases was caused by preeclampsia, and this was
further confirmed by a significant association of preeclampsia with PTB
as reported by Meis et al. [47] Moreover, numerous studies had reported
higher rates of spontaneous preterm delivery among pregnant women
with medical conditions including hypertension, diabetes mellitus [48],
pregnancy induced hypertension, and heart disease [49].
It was found that infected pregnant women were often more
susceptible to spontaneous PTBs. In this study, urinary tract infection,
vaginal tract infection, and systemic infection were determined to be
associated with SPTL-IM. Both symptomatic and asymptomatic urinary
tract infections have been well-associated with an increased risk of
PTB, which was similar to our findings [47].
Microbes, including bacteria vagonosis, trichomonas vaginalis,
group B streptococcus and candidia, has been associated with
increased PTB due to their involvement in vaginal tract infection [50].
Nonetheless, it is rather unlikely for these infections to exert major
effects on the overall rate of PTB, as the prevalence in each category
are relatively low. Therefore, every type of vaginal tract infections
were merged and analysed as a sole parameter in this study. This factor
has been investigated and reported in previous studies, where women
with vaginal tract infection were identified to carry higher risk for
spontaneous PTB [50]. In a large recent meta-analysis which consisted
of over 20,000 women, Leitich et al. [51] reported that a doubled risk
of PTB was observed among bacterial vaginosis patients. Furthermore,
systemic maternal infections, for example malaria and kidney infection,
have also been associated with spontaneous PTB [52].
Other maternal medical condition such as placenta previa was found
to be associated with SPTL-IM. This condition was in concordance
with other studies [1,53]. Besides that, a condition of amniotic fluid
was linked with SPTL-IM as well. This result was reported by previous
study as well, where oligohydramnios was brought into consideration
[46].
In addition, anaemia, gestational diabetes, and asthma were
identified as risk factors for PTB [54,55]. However, there were no
statistical significant associations found between mother’s anaemia,
gestational diabetes, and asthma with SPTL-IM. Although the ORs for
the three outcomes were higher, a significant association was absent.
Multivariate logistic regression analysis revealed statistically
significant association considering the following risk factors: unmarried
mother, poor/low socioeconomic status, absence of antenatal follow-
up, grand multiparity, history of preterm delivery, preeclampsia,
hypertension, pregnancy induced hypertension, systemic infection,
urinary tract infection, vaginal tract infection, placenta previa, young
maternal age and oligohydramnios. Other risk factors including history
of miscarriage, diabetes mellitus, and heart disease had no associations
with SPTL-IM. This might be due to the intercorrelated nature between
these risk factors, which failed to establish a significant relationship
in the multivariate analysis. However, it was worthy to note that these
risk factors can be considered in screening pregnant women with high
risks. This would help in identifying those pregnant women that should
receive more medical attention.
Consequently, this outcome whereby heart disease and diabetes
mellitus were excluded from the model after multivariate analysis was
not surprising. This is due to their collinearity with preeclampsia, which
was considered in the model. Diabetes was known to trigger directly or
indirectly by increasing risk of infection, polyhydramnios, hypertensive
disorders, and severe diabetic nephropathy, and it eventually triggers
preterm delivery [41,56]. Women with early severe preeclampsia,
preeclampsia as multiparas, and especially women with recurrent
preeclampsia were reported to be at greater risk, and they appeared
more prone to cardiovascular disease at earlier stages of life [57].
Tan et al. Volume 1, Issue 3
Microvascular dysfunction has been implicated in pathophysiology of
both preeclampsia and cardiovascular disease in women. Endothelial
dysfunction following preeclamptic pregnancy was demonstrated
by endothelial-mediated brachial artery dilation and stress-induced
forearm blood flow [58,59].
Bivariate analysis reported significant relations between history
of miscarriage and SPTL-IM, but they are not seen in multivariate
analysis. This might be due to the fact that uterine damage can lead to
placenta previa among pregnant women with history of miscarriage.
Therefore, this greatly reduced the strength of this risk factor in the
model. In a study [60], it was reported that women who experienced
one or more previous spontaneous or induced abortions were
30% more likely to suffer from placenta previa in their subsequent
pregnancies. Furthermore, Poorolajal et al. [61] reported a strong
association between abnormal placental status such as placenta previa
and placenta abruptio with miscarriage (OR= 10.44; 95% CI, 0.95-
114.92). All these previous findings had shown the increased likelihood
of placenta complications and preterm labour with increased history of
miscarriage.
Furthermore, several studies have shown that male gender has a
prematurity risk factors in both singleton and twin pregnancies [62,63].
There was no significant association between gender and women
experiencing SPTL-IM, although the proportion of male gender
increases with decreasing gestation. Moreover, the mechanisms
underlying the relationship between gender and PTB are still unclear
[64]. A study performed in Nigeria found that 55% of PTBs are of
female infants and another study showing no association was observed
between the infant gender and PTB [65,66].
Consistent with the findings of others, we have shown that
SPTL-IM infants’ had markedly lower weight and Apgar score when
compared to term infants. Gaiva et al. [67] in their study on 9349
infants, determined the clinical features of prematurity infants with
low birth weight as well as Apgar score less than 7. This finding was
also demonstrated by several other studies [68,69].
Conclusion
SPTL-IM remains high with preeclampsia as the commonest
obstetrical risk factor and young pregnant women as non-obstetrical
risk factor. Significant risk factors for SPTL-IM found in this study
were preeclampsia, placenta previa, history of preterm delivery,
pregnant at young age, unmarried mother, systemic infection, urinary
tract infection, grand multiparity, absence of antenatal follow-up,
hypertension, pregnancy induced hypertension, abnormal amniotic
fluid index, vaginal tract infection, and poor/low socioeconomic
status. Some of these risk factors which were found to be associated
with SPTL-IM are modifiable (pregnant at young age, marital status,
absence of antenatal follow-up and poor/low socioeconomic status).
They should be taken into consideration in the planning of a preventive
programme to reduce the frequency of SPTL-IM. When taken together,
these results can help in reducing the SPTL-IM frequency, and its
complications in Malay ethnic group in Malaysia.
Conflict of Interest
The authors reported no conflict of interest.
Acknowledgement
The authors would like to acknowledge the Fundamental Research
Grant Scheme (FRGS) grant: FRGS/2/2013/SKK09/UPM/02/2, and
My PhD fellowship by the Ministry of Higher Education, Malaysia.
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Citation: Tan NJ, Thilakavathy K, Mohtarrudin N, et al. Risk Factors for Spontaneous Preterm Labour with Intact Membrane: A Case Control
Study of Malay Ethnic Group in Hospital Serdang, Malaysia. J Gynec Obstet 2017; 1:017.
Tan et al. Volume 1, Issue 3 J Gynec Obstet 2017; 1:017

Appendix

Multicollinearity Analysis

Multicollinearity analysis was performed to examine the correlation among the independent variables prior
multivariate logistic correlations analysis. None of the variance inflation factor is greater than 5, therefore all
variables are considered to be independent.

Coefficientsa
Model Collinearity Statistics
Tolerance VIF
MARITAL STATUS .649 1.541
LOW INCOME .958 1.044
PRENATAL CARE .672 1.489
HYPERTENSION .955 1.047
DIABETESMILLITUS .959 1.043
PE .946 1.057
PIH .977 1.024
PREMHX .969 1.032
MISCARRIAGE HISTORY .965 1.036
1 SYSTEMIC INFECTION .974 1.026
VAGINAL TRAVT
.970 1.031
INFECTION
URINARY TRACT
.969 1.032
INFECTION
AMNIOTIC FLUID
.993 1.007
INDEX
PLACENTA PREVIA .986 1.014
nparity .963 1.038
NEW AGE .899 1.113
a. Dependent Variable: CASE/CONTROL

Citation: Tan NJ, Thilakavathy K, Mohtarrudin N, et al. Risk Factors for Spontaneous Preterm Labour with Intact Membrane: A Case Control
Study of Malay Ethnic Group in Hospital Serdang, Malaysia. J Gynec Obstet 2017; 1:017.

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