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Women and Birth 28 (2015) 1620

Contents lists available at ScienceDirect

Women and Birth


journal homepage: www.elsevier.com/locate/wombi

Original Research Quantitative

Risk factors for severe perineal trauma during vaginal childbirth:


A Western Australian retrospective cohort study
Yvonne L. Hauck a,b,1,*, Lucy Lewis a,b, Elizabeth A. Nathan c, Christine White b,
Dorota A. Doherty c,d
a

School of Nursing and Midwifery, Curtin University, Australia


King Edward Memorial Hospital, Australia
Women and Infants Research Foundation, Australia
d
School of Womens and Infants Health, The University of Western Australia, Australia
b
c

A R T I C L E I N F O

Article history:
Received 19 August 2014
Received in revised form 23 October 2014
Accepted 25 October 2014
Keywords:
Obstetric risk factors
Perineal trauma
Third degree tear
Fourth degree tear
Incidence

A B S T R A C T

Aim: To determine rates and risk factors for third and fourth degree perineal tears (severe perineal
trauma) in a Western Australian context.
Design and setting: A retrospective hospital-based cohort study was performed using computerised data
for 10,408 singleton vaginal deliveries from 28 weeks gestation.
Methods: Women with severe perineal trauma were compared to those without. Logistic regression
analysis, stratied by parity, was used to assess demographic and obstetric factors associated with
perineal trauma.
Results: Severe perineal trauma incidence was 3% (338/10408), 5.4% (239/4405) for primiparas and 1.7%
(99/5990) for multiparas (p < 0.001). Adjusted risk factors associated with trauma and common across
parity included Asian or Indian ethnicity, shoulder dystocia and assisted delivery. Epidural analgesia (OR
0.72, 95% CI 0.540.96), preterm birth (OR 0.40, 95% CI 0.230.72) and episiotomy (OR 0.54, 95% CI 0.39
0.74) were protective in primiparas, while episiotomy was associated with increased risk in multiparas
(OR 2.01, 95% CI 1.183.45). Additional factors among primiparas were occipito posterior (OP) delivery
(OR 3.35, 95% CI 1.756.41) and prolonged second stage (OR 1.98, 95% CI 1.462.68), and among
multiparas included gestational diabetes (OR 1.78, 95% CI 1.043.03) and birth weight >4000 g (OR 1.86,
95% CI 1.103.15).
Conclusion: Parity differences in risk factors such as episiotomy, infant weight, OP delivery, gestational
diabetes and prolonged second stage warrant investigation into clinical management. Although rates
differ internationally, and replication evidence has conrmed consistency for certain demographic and
obstetric factors, the development of internationally endorsed clinical guidelines and further research
around interventions to protect the perineum are recommended.
2014 Australian College of Midwives. Published by Elsevier Australia (a division of Reed International
Books Australia Pty Ltd). All rights reserved.

1. Introduction
Severe perineal trauma during childbirth involves a third or
fourth degree tear.1 The incidence of severe perineal trauma

* Corresponding author at: School of Nursing and Midwifery, Curtin University,


Perth, WA 6845, Australia. Tel.: +61 8 9340 1672; fax: +61 8 9388 7003.
E-mail addresses: y.hauck@curtin.edu.au, yvonne.hauck@health.wa.gov.au
(Y.L. Hauck), lucy.lewis@health.wa.gov.au, lucy.lewis@curtin.edu.au (L. Lewis),
liz.nathan@uwa.edu.au (E.A. Nathan), christine.white@health.wa.gov.au (C. White),
dorota.doherty@uwa.edu.au (D.A. Doherty).
1
Address: King Edward Memorial Hospital, Bagot Road, Subiaco, WA 6008,
Australia.

reported internationally varies, with rates from 0.1%2 to 0.25% in


Israel3; 1.58% in the United Kingdom4; 1.9%5, 2.0%6 and 2.9%7 in
Australia; and 2.9%8 to 10.2%9 in the United States. Severe perineal
trauma contributes to maternal morbidity including perineal pain,
urinary problems, faecal incontinence and dyspareunia.10 In
addition, primiparas who experience severe perineal trauma have
been found to be at increased risk of requiring a related surgical
procedure within 12 months following birth and were also less
likely to have a subsequent baby.11 Psychological consequences
remain under explored and do require urgent attention by
researchers.11
A systematic review highlighted risk factors for severe perineal
trauma as including: instrumental delivery; a prolonged second

http://dx.doi.org/10.1016/j.wombi.2014.10.007

1871-5192/ 2014 Australian College of Midwives. Published by Elsevier Australia (a division of Reed International Books Australia Pty Ltd). All rights reserved.

Y.L. Hauck et al. / Women and Birth 28 (2015) 1620

stage; birth weight >4000 g; delivery in an occipital posterior (OP)


position and episiotomy.12 International population based studies
undertaken to identify risk factors for severe perineal trauma have
produced varying results. Risk factors for Finish primiparas
included: assisted delivery; birth weight >4000 g; OP position;
and prolonged active second stage.13 Swedish results supported
assisted delivery and birth weight >4000 g, adding that women
from Africa and Asia had pronounced risk.14 However, British
research found that being primipara and having an instrumental
delivery for OP position were the only signicant factors.4 One
Israeli study added mediolateral episiotomy as an independent risk
factor2 and another suggested Asian ethnicity and vacuum
delivery, but not forceps delivery, as signicant.3 However, a
Greek study found no difference between vacuum and forceps
deliveries in terms of sustaining a third degree tear.15 Finally, a
recent Australian study found primiparity, being born in China or
Vietnam, having an assisted delivery, birthing in a private hospital
and having a male infant were at higher risk of severe perineal
trauma compared to women with no or minor perineal trauma.5
Only having a male infant remained signicant when women with
severe perineal trauma were compared to those without in the
adjusted analysis.5
Differing severe perineal trauma rates and inconsistencies
across international evidence around risk factors suggest that
further investigation is warranted to compare rates and conrm
consistency of demographic and obstetric risk factors. Reported
severe perineal trauma rates for Australian women only include
data from one eastern state. Therefore the aim of this study was to
determine rates and risk factors for severe perineal trauma in the
sole tertiary public maternity hospital in Western Australia (WA).
2. Methods
A retrospective hospital-based cohort study was performed
using computerised perinatal data collected by the Obstetrics and
Gynaecology Clinical Care Unit at the tertiary public hospital in
Perth, WA. This computerised perinatal data collection system
allows for recording of episiotomy alone or episiotomy in addition
to 1st, 2nd, 3rd, or 4th degree tears enabling the accurate recording
the extensions of an episiotomy. The study was approved by the
hospital Human Ethics Committee (No. 316QK).
At the time of this study the hospital provided a variety of care
models ranging from Family Birth Centre care, shared care, routine
midwifery care, team midwifery, or medical care depending upon
the womans assessed risk. The Birth Centre accepts a limited
number of low risk women within the Perth metropolitan area.
However, other women with a low risk pregnancy wanting care
from this hospital must live within the local area. Being the largest
maternity hospital in Western Australia and the only tertiary
referral centre means many women with high risk complex
pregnancies attend the hospital. As such, specialist services include
a Maternal Foetal Medicine Department and variety of antenatal
clinics which target: adolescents; women with alcohol and drug
dependency; women with a mental illness; women with diabetes;
and women who have experienced a previous caesarean.
Midwifery services for women of any risk include parent education
classes, the Breastfeeding Centre, and the early discharge
programme supported by the Visiting Midwifery Service.
A cohort of 10,408 singleton vaginal deliveries from 28 weeks
gestation between January 2009 and December 2011 attending
the hospital for intrapartum care were included. Women were
grouped according to their perineal status; those who had severe
perineal trauma and those who did not. Demographic factors
included ethnicity, age and parity. Asian ethnicity comprised South
East Asian countries such as China, Vietnam and Thailand, whereas
women of Indian ethnicity were from the country of India.

17

Antenatal factors considered included body mass index (BMI) at


booking, presence of gestational diabetes mellitus (GDM) and
antenatal complications (including: pre-eclampsia; antepartum
haemorrhage; threatened preterm labour; premature rupture of
membranes, oligohydramnios; placenta praevia; and urinary tract
infection).
Intrapartum and delivery data included: epidural analgesia;
delayed progress; foetal compromise (including thick meconium,
abnormal cardiotocograph and abnormal foetal blood gas); length
of second stage; birthing position; episiotomy; shoulder dystocia;
delivery in an OP position; and assisted delivery. Primary
accoucheur and time of delivery (midnight to 8 a.m., 8 a.m. to
4 p.m. or 4 p.m. to midnight) were examined for their contribution
to severe perineal trauma prediction. The primary accoucheur
recorded can be a midwife, student, obstetrician, other medical
ofcer or self/no attendant. Perinatal outcomes included gestation
at delivery and birth weight.
Categorical data were summarised using frequency distributions and comparisons between women with and without severe
perineal trauma were made using Chi square tests. The risk of
severe perineal trauma differed signicantly between primiparous
and multiparous women on many demographic, labour and birth
characteristics, subsequently; the analysis was stratied by parity
status. All characteristics with p-values <0.1 in univariable logistic
regression analyses were considered as candidate predictors, and
entered into the multivariable regression analysis along with
known risk factors and interactions. The effects of risk factors on
the likelihood of severe perineal trauma were summarised using
odds ratios (OR) and their 95% condence intervals (CI). IBM SPPS
Version 20.0 statistical software (Armonk, NY) was used for data
analysis. All hypothesis tests were two-sided, and p-values <0.05
were considered statistically signicant. A p-value <0.1 was
assigned as a cut off value in the univariate analysis of risk factors
to ensure potential risk factors that approached signicance
(0.05 < p < 0.1) were further investigated in multivariable analysis. A p-value <0.1 is commonly used when investigating potential
risk factors univariately, as the signicance level can change once
other factors are accounted for in multivariable modelling.
3. Results
The incidence of severe perineal trauma in this cohort of WA
women was 3% (338/10408); 5.4% (239/4405) among primiparas
and 1.7% (99/5990) among multiparas (p < 0.001). There were
117 women in the severe perineal trauma group who had an
episiotomy and severe perineal trauma. Compared with women
who did not sustain severe perineal trauma, those who did have
severe perineal trauma were more likely to: report Asian or Indian
ethnicity; have birthed in lithotomy position; experience labour
complications such as delayed progress; have a second stage
exceeding 1 h; experience shoulder dystocia and undergo an
assisted delivery (Table 1). Obstetricians and registrars were more
likely to be the primary accoucheur during deliveries with severe
perineal trauma compared to other clinicians such as midwives or
students (56% vs. 32%, p < 0.001). Preterm birth reduced the
likelihood of severe perineal trauma. Due to 13 missing values for
parity, maternal age and BMI, analysis was conducted on 10,395
women.
Primiparas >20 years and those who experienced OP deliveries
had a higher incidence of severe perineal trauma, while multiparas
with GDM, obstruction caused by malposition of foetus, foetal
compromise, episiotomy and birth weight greater than 4000 g had
a higher incidence of severe perineal trauma. Body mass index,
epidural analgesia and time of delivery (midnight to 8 a.m., 8 a.m.
to 4 p.m. or 4 p.m. to midnight) were not univariately associated
with severe perineal trauma.

Y.L. Hauck et al. / Women and Birth 28 (2015) 1620

18

Table 1
Maternal characteristics of women who sustained severe perineal trauma and those who did not, stratied by parity status.
Primiparas

Characteristics

Maternal age (years)


<20
2034
35
Ethnicity
Asian/Indian
Other
Not specied
BMIa 30
Gestational diabetes
Birthing position
Semi recumbent
Lithotomy
Other
Epidural analgesia
Delayed progress
Malposition of foetus
Foetal compromise
Second stage >1 h
Episiotomy
Occipital posterior delivery
Shoulder dystocia
Assisted delivery
Birth weight >4000 g
Preterm birth
a

Multiparas

SPT
N = 239
n (%)

No SPT
N = 4166
n (%)

18 (7.5)
196 (82)
25 (10.5)

597 (14.3)
3148 (75.6)
421 (10.1)

80
130
29
39
22

(33.5)
(54.4)
(12.1)
(16.8)
(9.2)

727
2978
461
813
360

(17.5)
(71.5)
(11.1)
(20.4)
(8.6)

<0.001

65
137
37
132
79
3
57
161
89
13
13
131
20
13

(27.2)
(57.3)
(15.5)
(55.2)
(33.1)
(1.3)
(23.8)
(67.4)
(37.2)
(5.4)
(5.4)
(54.8)
(8.4)
(5.4)

1660
1850
646
2310
966
40
940
2006
1493
52
92
1602
262
626

(39.9)
(44.5)
(15.5)
(55.4)
(23.2)
(1.0)
(22.6)
(48.2)
(35.8)
(1.2)
(2.2)
(38.5)
(6.3)
(15.0)

<0.001

p-value

0.013

0.184
0.763

0.947
<0.001
0.652
0.644
<0.001
0.661
<0.001
0.001
<0.001
0.202
<0.001

SPT
N = 99
n (%)

No SPT
N = 5891
n (%)

p-value

0
69 (69.7)
30 (30.3)

1290 (2.2)
4369 (74.2)
1393 (23.6)

32
55
12
22
19

(32.3)
(55.6)
(12.1)
(22.9)
(19.2)

710
4437
744
1676
524

(12.1)
(75.3)
(12.6)
(30.8)
(8.9)

<0.001

43
32
22
34
16
2
19
28
28
2
9
31
21
5

(44.3)
(33.0)
(22.7)
(34.3)
(16.2)
(2.0)
(19.2)
(28.3)
(28.3)
(2.0)
(9.1)
(31.3)
(21.2)
(5.1)

3619
815
1438
1885
351
30
711
668
475
60
171
502
672
745

(61.3)
(13.9)
(24.5)
(32.0)
(6.0)
(0.5)
(12.1)
(11.3)
(8.1)
(1.0)
(2.9)
(8.5)
(11.4)
(12.6)

<0.001

0.120

0.098
<0.001

0.620
<0.001
0.041
0.032
<0.001
<0.001
0.329
<0.001
<0.001
0.002
0.024

Body mass index.

stage and epidural analgesia were assessed in each parity group


and were not signicant. Maternal age, birthing in lithotomy
position, delayed progress during labour, malposition of the foetus,
foetal compromise and the attendance of obstetricians and
registrars during delivery were not signicantly associated with
severe perineal trauma in the adjusted analysis.

Adjusted risk factors associated with severe perineal trauma


and common to both primiparous and multiparous women
included Asian or Indian ethnicity, shoulder dystocia and assisted
delivery (Table 2). Epidural analgesia (OR 0.72, 95% CI 0.540.96,
p = 0.025), preterm birth (OR 0.40, 95% CI 0.230.72, p = 0.002) and
episiotomy (OR 0.54, 95% CI 0.390.74, p < 0.001) were protective
against severe perineal trauma in primiparas, while episiotomy
was associated with increased risk of severe perineal trauma in
multiparas (OR 2.01, 95% CI 1.183.45, p = 0.011). Additional risk
factors among primiparous women were OP delivery (OR 3.35, 95%
CI 1.756.41, p < 0.001) and second stage of labour exceeding 1 h
(OR 1.98, 95% CI 1.462.68, p < 0.001), and among multiparous
women included GDM (OR 1.78, 95% CI 1.043.03, p = 0.036) and
birth weight greater than 4000 g (OR 1.86, 95% CI 1.103.15,
p = 0.020).
Interactions between episiotomy and assisted delivery, episiotomy and length of second stage of labour, and length of second

4. Discussion
The incidence of severe perineal trauma in our WA cohort was
3% which was comparable or slightly higher than other Australian
reported prevalence rates of 1.6%,16 1.9%,5 2%6 and 2.9%.7 The WA
severe perineal trauma prevalence was higher than Israel (0.25%)3
and the UK (1.58%)4; comparable to one American study reporting
2.9%8 and lower than another American study citing 10.2%.9 The
WA prevalence of 5.4% for primiparas was similar to 5.8% reported

Table 2
Characteristics associated with severe perineal trauma stratied by parity status. Unadjusted and adjusted odds ratios (OR) and 95% CI for each characteristic are shown.
Characteristics

Primipara
N = 4405
n (%)

Ethnicity Asian/Indian
Gestational diabetes
Epidural analgesia
Second stage >1 h
Shoulder dystocia
Occipital posterior delivery
Episiotomy
Assisted delivery
Birth weight >4000 g
Preterm birth

807
382
2442
2167
105
65
1582
1733
282
639

(18.3)
(7.7)
(55.4)
(49.2)
(2.4)
(1.5)
(35.9)
(39.3)
(6.4)
(14.5)

Multipara
N = 5990
Unadjusted OR
(95% CI)

Adjusted ORa
(95% CI)

n (%)

2.38
1.07
0.99
2.22
2.55
4.55
1.06
1.94
1.36
0.33

2.34
NS
0.72
1.98
2.44
3.35
0.54
1.98
NS
0.40

742
543
1919
696
180
62
503
533
693
750

(1.803.15)
(0.681.68)
(0.761.29)
(1.692.93)
(1.404.62)
(2.448.48)
(0.811.39)
(1.492.52)
(0.852.19)
(0.190.57)

NS = not statistically signicant in the adjusted analysis.


a
Each model is adjusted for other associated risk factors within the parity group.

(1.753.13)
(0.540.96)
(1.462.68)
(1.324.51)
(1.756.41)
(0.390.74)
(1.432.75)
(0.230.72)

(12.4)
(9.1)
(32.0)
(11.6)
(3.0)
(1.0)
(8.4)
(8.9)
(11.6)
(12.5)

Unadjusted OR
(95% CI)

Adjusted ORa
(95% CI)

3.49
2.43
1.11
3.08
3.35
2.00
4.50
4.89
2.09
0.37

2.85
1.78
NS
NS
2.22
NS
2.01
3.10
1.86
NS

(2.275.35)
(1.464.04)
(0.731.69)
(1.984.81)
(1.666.75)
(0.488.32)
(2.887.03)
(3.177.56)
(1.283.41)
(0.150.91)

(1.814.49)
(1.043.03)

(1.054.70)
(1.183.45)
(1.855.18)
(1.103.15)

Y.L. Hauck et al. / Women and Birth 28 (2015) 1620

by Landys American study8; however, 1.7% for WA multiparas was


higher than the US reported 0.6%.
Risk factors identied in this WA analysis such as: primiparity7,9,12,13,17,18; assisted delivery6,9,1214,17,18; a prolonged second
stage9,12,13; OP position3,13; Asian ethnicity3,7,9; birth weight
>4000 g3,14,17,18 and episiotomy2,9,12 have been identied by
others. The implications of a prolonged second stage have been
researched suggesting an association with increased likelihood of
incontinence at three months following a spontaneous or assisted
vaginal birth,19 whereas, for those with an assisted vaginal birth
the urinary incontinence continued to 18 months.20
An important contribution of these WA results to clinical
practice is greater insight to the complexity of risk factors related
to parity. Younger maternal age and OP delivery were of signicant
risk for primiparas whereas for multiparas women factors included
GDM, foetal malposition, foetal compromise, episiotomy and birth
weight >4000 g. Intrapartum complications such as: foetal
compromise; malposition; a prolonged second stage; and a large
baby highlight the complex sequel that may contribute to
increased intervention, including assisted delivery14,21 and episiotomy12 both associated with severe perineal trauma. The nding
that delivering in lithotomy was associated with severe perineal
trauma was not unexpected given that assisted deliveries tend to
be conducted in this position; however episiotomy was protective
for primipara contrary to being a risk factor for multiparas women.
A Finish study also conrmed that episiotomy was protective for
obstetric anal sphincter rupture for primiparous women but not
for multiparas.13 However, results from an Austrian retrospective
study found that high birth weight and forceps delivery combined
with mediolateral episiotomies were independent risk factors for
severe perineal trauma.22 Up to 35% of American women who have
a forceps delivery experience severe perineal trauma, with delivery
in an OP position found to increase this risk.23 Research utilising
risk clusters found that in the presence of an episiotomy combined
with a forceps delivery and birth weight >3634 g, the rate of severe
perineal trauma was 68.9%.24
The association between Asian ethnicity and severe perineal
trauma has been found internationally4,8 including Australia5,6 and
presents challenges for obstetric management. The reasons for the
racial differences described remain unanswered and are complicated by the fact that racial groups may not necessarily be
homogenous. For example Asian groups may be born overseas or in
their country of residence and have a mixed Asian and Caucasian
heritage. The inuence on clinical management in the presence of
specic risk factors must be recognised as differing practices in
relation to episiotomy have been noted in Vietnamese born
women living in Australia, with their episiotomy rates being 14.8%
higher than Australian born women.25
Similar to results in this study, others have found an association
between severe perineal trauma and birth weight above
4000 g.3,14,17,18 Although, it has been suggested that the absolute
risk that a baby over 4000 g will contribute to severe perineal
trauma is minimal,4 we found GDM was associated with severe
perineal trauma for multiparas imdependently of higher birth
weight. Although Dahlen5 conrmed primiparity as a risk factor,
GDM and birth weight above the 90 centile were not associated
with severe perineal trauma. Other factors hypothesed to have a
subtle effect on severe perineal trauma are the interaction between
increased birth weight and head circumference22 and delivery of a
male infant which could contribute to these two factors.5
Interestingly, a higher incidence of GDM has been found amongst
Australian Chinese and Vietnamese born women.16
The measurement of indicators to determine quality in
obstetrics is recognised as essential2628 and vigilance is recommended as higher severe perineal trauma rates are noted in clinical
settings with comprehensive detection, reporting and treatment

19

for severe perineal trauma. It has been suggested that documentation and prevalence of severe perineal trauma rates may reect
the quality and rigorous nature of the reporting systems rather
than actual rates.28 Monitoring the quality of maternity care
including severe perineal trauma through public data systems has
been reliably used to evaluate maternity care. Advantages of these
systems include the ability to perform large population based
studies,3,6,11,13,14 compare prevalence between countries18 and
estimate economic impacts of events such as severe perineal
trauma.26 However, a global denition for severe perineal trauma1
must be adhered to as misdiagnosis may contaminate results.18
Indeed this WA population based study benetted from the
avaliability of reliable data collected through the data system at
the tertiary maternity hospital.
Explanation for differences in risk factors concering parity and
episiotomy, birth weight, OP delivery, and prolonged second stage
remain unclear. Results would suggest that clinical management
may need to be considered as a contributing factor affecting severe
perineal trauma rates across parity groups, in the same way clinical
management affects the wide range of caesarean section rates
across the globe.29 Indeed specic practices such as manual
protection of the perinuem and the use of mediolateral or lateral
episiotomy have been recommended to decrease the risk of severe
perineal trauma.1,30 However, a recent cochrane review of eight
clinical trails concluded that hands off versus hands on
demonstrated no effect on severe perineal trauma, with a
signicant effect noted for hands off reducng the episiotomy
rate.10 Massage was found to be more effective in reducing severe
perineal trauma than hands off and the recommendations for use
of warm compresses on the perineum is particularly relevant to
midwives.10 The impact of severe perineal trauma on womens
emotional, psychological and physical wellbeing must also be
considered. The limited qualitative evidence around womens
experience with severe perineal trauma hightlights the importance
of appropriate follow-up using a sensitive, consistence, evidencebased approach, particularly in terms of decision-making for
subsequent births involving a multidciplinary team that includes
midwives.31 (p. 129).
Further research into perineal techniques to prevent perineal
trauma is necessary.10 The Royal Collge of Obstetricians and
Gynaceologists1 emphasise caution that although clinicians must
be aware of risk factors, such factors do not necessarily allow for
prediction or prevention. Given the variability of international
results, further studies are warranted to explore severe perineal
trauma rates within different care models and across practices
between health professionals. Finally the evaluation of the
effectiveness of proposed interventions to prevent severe perineal
trauma in women with recognised risk factors must be a priority
using prospective research designs.
5. Limitations
Input of data into the computerised perinatal data system relies
on accurate input of data by clinical midwives. In addition, this
analysis required exploration of multiple associations between
variables within the available sample size at one tertiary maternity
centre. These two factors must be acknowledged when interpreting the results.
6. Conclusion
Our results add to the existing evidence and may provide
explanation into differences noted in international literature
around severe perineal trauma risk factors associated with parity.
Inconsistencies reported in the international literature around
the affect of parity, episiotomy and birth weight on severe perineal

Y.L. Hauck et al. / Women and Birth 28 (2015) 1620

20

trauma would suggest further research and exploration of clinical


management may be necessary to explain differences.
12.

Authors contribution
All authors of this manuscript have participated sufciently in
the work to take public responsibility of the content. This includes
conception or design, analysis and interpretation of data, drafting
the manuscript and revising it, and approval of the nal version
submitted for review and publication.
Conicts of interest
The authors declare that there are no conicts of interest.

13.

14.

15.

16.

17.

Ethical approval
18.

The study was approved by the King Edward Memorial Hospital


Human Ethics Committee (No. 316QK) on March 28th, 2012.

19.

Acknowledgements
20.

Source of funding support: Women and Infants Research


Foundation and King Edward Memorial Hospital.
21.

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