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Journal of Obstetrics and Gynaecology

ISSN: 0144-3615 (Print) 1364-6893 (Online) Journal homepage: http://www.tandfonline.com/loi/ijog20

Effect of maintenance tocolysis with nifedipine


in established preterm labour on pregnancy
prolongation and neonatal outcome

Ajay Aggarwal, Rashmi Bagga, Bhavana Girish, Jaswinder Kalra & Praveen
Kumar

To cite this article: Ajay Aggarwal, Rashmi Bagga, Bhavana Girish, Jaswinder Kalra & Praveen
Kumar (2017): Effect of maintenance tocolysis with nifedipine in established preterm labour on
pregnancy prolongation and neonatal outcome, Journal of Obstetrics and Gynaecology, DOI:
10.1080/01443615.2017.1331340

To link to this article: http://dx.doi.org/10.1080/01443615.2017.1331340

Published online: 08 Aug 2017.

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Download by: [University of Florida] Date: 08 August 2017, At: 13:49


JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 2017
https://doi.org/10.1080/01443615.2017.1331340

ORIGINAL ARTICLE

Effect of maintenance tocolysis with nifedipine in established preterm labour on


pregnancy prolongation and neonatal outcome
Ajay Aggarwala, Rashmi Baggaa, Bhavana Girisha, Jaswinder Kalraa and Praveen Kumarb
a
Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Education and Research, Chandigarh, India; bDepartment of
Paediatrics (Neonatology Division), Post Graduate Institute of Medical Education and Research, Chandigarh, India

ABSTRACT KEYWORDS
Fifty women with singleton pregnancies between 26þ0/7 and 33þ6/7 weeks of gestation and arrested Maintenance tocolysis;
preterm labour (PTL) after acute tocolysis were randomised by a computer generated randomisation preterm birth; preterm
table into an intervention group (n ¼ 25) who received maintenance tocolysis with tablet nifedipine for labour
12 days or up to 34 weeks of gestation, whichever was later and a control group (n ¼ 25). The primary
outcome was achievement of term gestation and the secondary outcomes were the number of days
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gained till delivery and neonatal mortality and morbidity. The mean gestation at admission, cervical
dilatation and effacement were similar in the two groups (30 þ weeks, 2.5 cm, 60%). In the intervention
group, 7/25 (28%) and in the control group, 2/25 (8%) delivered at term (p ¼ .066) and pregnancy pro-
longation of 20 days (IQR 2.5–51) and 14 days (IQR 1–27.5) were achieved, respectively (p ¼ .269).
Maintenance tocolysis was given for a median of 14 days (range 3–25.5). Kaplan–Meier analysis showed
no statistically significant difference in prolongation of pregnancy between the control and the inter-
vention groups (p ¼ .077). The median number of days of neonatal hospital stay were reduced with
maintenance tocolysis, but the difference was not significant (4.0 vs 5.5; p ¼ .608). The mean birth
weight was significantly higher in the intervention group (2266 vs 1880 g, p ¼ .044). Among women at
a high risk for preterm birth (PTB) due to established PTL as evidenced by a mean cervical dilatation of
2.5 cm and a PTB rate of 92% in the control group, maintenance tocolysis did not prolong the preg-
nancy or reduce the neonatal hospital stay significantly.

IMPACT STATEMENT
 What is already known on this subject: In women with preterm labour (PTL) the role of mainten-
ance tocolysis following acute tocolysis to reduce recurrent PTL is uncertain. Of the six studies using
nifedipine, one reported pregnancy prolongation (26.65 vs 16.14 days, p ¼ .007), but similar peri-
natal outcome (Sayin et al. 2004). Others did not find pregnancy prolongation (Carr et al. 1999;
Lyell et al. 2008; Uma et al. 2012; Roos et al. 2013; Parry et al. 2014). The PTB rate in the control
groups ranged from 38 to 67%. A Cochrane review reported pregnancy prolongation by 5.35 days
but similar neonatal outcome (RR 0.75) (Naik et al. 2013). A meta-analysis including five studies
using progesterone and five using nifedipine concluded that progesterone, but not nifedipine, pro-
longed pregnancy (Ding et al. 2016). Thus, data on maintenance tocolysis is limited and
inconclusive.
 What the results of this study add: In the present randomised study in 50 women with arrested
PTL, 25 received maintenance tocolysis. The mean gestation at admission, cervical dilatation and
effacement were similar in the two groups (30þ weeks, 2.5cm, 60%). In the intervention group,
7/25 (28%) and controls, 2/25 (8%) delivered at term (p ¼ .066) and pregnancy prolongation of 20
days (IQR 2.5–51) and 14 days (IQR 1–27.5) were achieved, respectively (p ¼ .269). Kaplan–Meier ana-
lysis showed no statistically significant difference in prolongation of pregnancy between the control
and the intervention groups (p ¼ .077). The median number of days of neonatal hospital stay were
reduced with maintenance tocolysis but the difference was not significant (4.0 vs 5.5; p ¼ .608).
 What are the implications of these findings for clinical practice and/or future research: The
mean birth weight was higher in the intervention group (2266 vs 1880g, p ¼ .044). Future studies
should take cervical dilatation and the PTB rate in the control group into consideration while assess-
ing the impact of maintenance tocolysis.

Introduction
South Asia and Sub-Saharan Africa (12.8%) with 9.1 million
The estimated worldwide incidence of preterm birth (PTB) in PTBs occurring annually accounting for 60% of the global
2010 was 11.1% and has not decreased despite the efforts to PTBs (Bick 2012). The commonest cause of PTB is spontan-
reduce it (Blencowe et al. 2012). The PTB rate is higher in eous preterm labour (PTL) in 40–50% of the cases

CONTACT Rashmi Bagga rashmibagga@gmail.com Department of Obstetrics and Gynaecology, Post Graduate Institute of Medical Education and Research,
Chandigarh 160012, India
Present address: Consultant, Obstetrics and Gynaecology, Sunrise Hospital, New Delhi, India.
ß 2017 Informa UK Limited, trading as Taylor & Francis Group
2 A. AGGARWAL ET AL.

(Pennell et al. 2007). Of the women who present with signs arrested with acute tocolysis. The outcomes assessed were
and symptoms of PTL, 30% show spontaneous resolution achievement of term gestation, pregnancy prolongation and
(King et al. 1988). The current management of PTL includes neonatal outcome.
‘acute tocolysis’ for 48 h to delay the delivery while cortico-
steroids are administered for foetal lung maturation (RCOG
2011). After an episode of arrested PTL, about 60–70% of Materials and methods
women delivered preterm babies (Sayin et al. 2004; Lyell The present randomised open-label study was conducted at a
et al. 2008). After PTL is arrested with acute tocolysis, con- tertiary care hospital in north India. It was approved by the
tinuing a tocolytic agent for some days more to reduce the Institute Ethics Committee and registered in the Clinical Trials
risk of recurrent PTL is called ‘maintenance tocolysis’. Registry (CTRI), India (CTRI/2013/08/003916). Women with a
Ritodrine, terbutaline, indomethacin, nifedipine and mag- singleton pregnancy between 26þ0/7 and 33þ6/7 weeks of ges-
nesium sulphate have been tried for maintenance tocolysis. tation and arrested PTL who fulfilled the inclusion and exclu-
Progesterone has also been used as a maintenance therapy sion criteria and consented to participate were recruited. The
after the inhibition of PTL (Facchinetti et al. 2007; Borna and CONSORT checklist was followed. Regular uterine contractions
Sahabi 2008). Borna and Sahabi (2008) observed that after (4/20 min or 8/60 min) plus either cervical dilatation >2 cm or
successful parenteral tocolysis, use of vaginal progesterone effacement >50% were used to diagnose PTL (Holbrook et al.
suppository resulted in longer latency preceding delivery but 1987). Arrested PTL was defined as uterine quiescence of less
failed to reduce the incidence of re-admission for PTL in 37 than four contractions per hour for 12 h after 48 h of acute
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women who were presented with PTL as compared to con- tocolysis (ACOG practice bulletin no. 31, 2001). Women with
trols (Borna and Sahabi 2008). A Cochrane review found antepartum haemorrhage (APH), foetal malformation or
insufficient evidence to advocate the use of progestational demise, severe foetal growth restriction, advanced PTL (cer-
agents for tocolysis in women with PTL, but limited evidence vical dilatation >4 cm), ruptured membranes, contraindication
suggests that progesterone used as a co-treatment with to nifedipine or any indication necessitating delivery were
another tocolytic agent may reduce PTB (Su et al. 2014). excluded. Gestational age was calculated from last menstrual
Nifedipine is a good choice for the maintenance tocolysis period and confirmed by sonography. Sonography was done
due to ease of administration and less side-effects. to assess foetal biometry, amniotic fluid and biophysical pro-
Maintenance tocolysis with nifedipine is commonly practised file including non-stress test and to rule out placental abrup-
in the United States (Haas et al. 2012). Six randomised studies tion. A speculum examination was done and women with
reported maintenance tocolysis with nifedipine and only one vaginal discharge suggestive of vaginitis were treated with a
reported pregnancy prolongation (26.65 ± 18.89 vs vaginal tablet for six nights (clotrimazole 250 mg, tinidazole
16.14 ± 12.91 days, p ¼ .007) and a higher gestation at delivery 500 mg and lactobacilli 150 million spores; EmceelTM,
(37.03 ± 2.06 vs 35.1 ± 3 weeks, p ¼ .003) with nifedipine, but Meridian Medicare Limited, Bathinda, India), based on the
there was no improvement in the perinatal outcome (Sayin syndromic approach followed in India (WHO 2007; Patel et al.
et al. 2004). The other five studies did not find any prolonga- 2008). Asymptomatic bacteriuria was treated as per culture
tion of pregnancy (Carr et al. 1999; Lyell et al. 2008; Uma and sensitivity. Acute tocolysis was initiated with the tablet
et al. 2012; Roos et al. 2013; Parry et al. 2014). A Cochrane nifedipine (plain) 30 mg orally followed by 10–20 mg
review of six trials (794 women) using maintenance tocolysis 4–6 hourly depending on the uterine contractions, for a
reported no benefit to reduce PTB (RR 0.97; 95%CI 0.87–1.09), maximum of 48 h or for 12 h after uterine quiescence
birth within 48 h (RR 0.46; 95%CI 0.07–3.00) or neonatal mor- was achieved (ACOG practice bulletin no. 31, 2001).
tality or morbidity (RR 0.75; 95%CI 0.05–11.76) as compared Corticosteroids were administered for foetal pulmonary
to placebo or no treatment, though pregnancy was pro- maturity (betamethasone 12 mg intramuscularly two doses,
longed by 5.35 days (95%CI 0.49–10.2) with maintenance 24 h apart). Women with arrested PTL and intact membranes
tocolysis (Naik et al. 2013). An individual patient data analysis were randomised into two groups by a computer generated
of six trials (787 women) found no difference between the randomisation table. The intervention group (n ¼ 25) received
intervention and control groups in pregnancy prolongation maintenance tocolysis with tablet nifedipine (retard) 20 mg
(hazard ratio 0.74; 95%CI 0.55–1.01), incidence of respiratory 8th hourly PO for 12 more days. Women who did not achieve
distress syndrome (RDS) (RR 0.98; 95%CI 0.51–1.85), necrotis- 34 weeks of gestation after 12 days continued to take nifedi-
ing enterocolitis (NEC) (RR 1.15; 95%CI 0.50–2.65), intraven- pine till 34 weeks of gestation. Women in the control group
tricular haemorrhage (IVH)  grade II (RR 0.65; 95%CI (n ¼ 25) did not receive maintenance tocolysis. Women with a
0.16–2.67) or perinatal death (RR 1.36; 95%CI 0.35–5.33) (van repeat episode of PTL (uterine contractions four per 20 min
Vliet et al. 2016). A meta-analysis including five studies using or eight per 60 min) were re-treated with acute tocolysis if
progesterone and five using nifedipine for maintenance tocol- cervical dilatation was <4 cm. Oral maintenance therapy was
ysis concluded that progesterone prolonged the pregnancy restarted after successful repeat acute tocolysis. Similarly,
(standard mean difference or SMD, 1.64; 95%CI, 1.21–2.07; women in the control group were treated with acute tocoly-
p < .00001). However, they did not find a similar benefit with sis in case of recurrent PTL. All women were followed till
nifedipine as compared to placebo or no treatment (SMD, delivery and details of neonatal outcome were noted.
0.31; 95%CI, 0.60–1.22; p ¼ .50) (Ding et al. 2016). The primary outcome was achievement of term gestation;
The present study was carried out to evaluate the main- secondary outcomes were latency in term of number of days
tenance tocolysis with nifedipine after an episode of PTL was gained till delivery and neonatal mortality and morbidity in
JOURNAL OF OBSTETRICS AND GYNAECOLOGY 3

terms of RDS, IVH, NEC and neonatal ICU (NICU) admission. hydration and she delivered at 38þ3/7 weeks. The mean ges-
RDS was defined by clinical diagnosis as requiring surfactant tation at delivery was similar in the two groups (intervention
therapy, IVH and NEC were graded according to the classifica- group: 34þ4/7± 3þ2/7 weeks, control group: 33þ3/7 ± 3þ0/7
tion of Papile et al. and Bell et al., respectively (Bell et al. weeks; p ¼ .239, NS). A median prolongation of pregnancy of
1978; Papile et al. 1983). A sample size of 58 was calculated 20 days (IQR 2.5–51) vs 14 days (IQR 1–27.5) was achieved for
on the basis of expecting a term delivery rate of 70% in the the study and control groups, respectively (p ¼ .269, NS).
control group with a 50% reduction in PTB in the interven- Kaplan–Meier analysis (Figure 2) showed no statistically sig-
tion group giving a power of 80% with a one-tailed alpha of nificant difference in prolongation of pregnancy between the
0.05. Measurable data were tested for normality using the control and the intervention groups (p ¼ .077). The mean
‘Kolmogorov–Smirnov’ Test. Normally distributed variables birth weight of babies born to women in the intervention
were compared for their means using ‘Student’s t-test’. Non- group was significantly higher than that of babies in the con-
normal data was expressed as median and inter-quartile trol group (2266 g vs 1880 g, p ¼ .044). There was no signifi-
range (IQR) and their distribution was compared using cant difference in the 1, 5 and 10 minute Apgar scores in the
Mann–Whitney U Test. The association of various Categorical/ two groups (Table 3). The total duration of hospital stay was
Classified data was analysed using Chi-square Test. A ‘p’ value longer for babies in the control group, however, the differ-
of <.05 was considered as significant in all statistical tests. ence was not significant (intervention group: 4 days, IQR 2–10
Kaplan–Meier analysis was used to assess pregnancy pro- and control group 5.5 days, IQR 2.25–12; p ¼ .608, NS). An
longation in the intervention group. Statistical analysis was equal number of babies required surfactant (2/25, 8% in each
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conducted on IBM SPSS V21. group). A total of 16/25 (64%) babies in the intervention
group and 15/25 (60%) babies in the control group required
phototherapy (p ¼ .922, NS). The total number of babies
Results
requiring neonatal ICU care (intervention group ¼ 8; control
Over a period of 18 months (July 2011–December 2012), 252 group ¼ 10) and ventilatory support (intervention group ¼ 2;
women with PTL were assessed for eligibility. Of these, 96 control group ¼ 5) was higher in the control group, but this
women received acute tocolysis with nifedipine during which difference was not significant (p ¼ .483, p ¼ .199, respectively).
time, labour progressed in 29/96; there was PROM in 15/96 The composite neonatal morbidity was also similar in the two
and APH in 2/96 who had to be excluded. The remaining 50 groups. This was compared with regards to the development
women with arrested PTL were randomised into the study of RDS, IVH, NEC and sepsis/meningitis in the neonate. There
(maintenance tocolysis) and the control group. Figure 1 was no significant difference between the two groups
shows the CONSORT flowchart. The demographic characteris- (p ¼ .470, NS). The perinatal mortality was 2/25 in the inter-
tics were comparable in the two groups (Table 1). Majority vention group and 3/25 in the controls (p ¼ .637, NS). The
(86%) were between 20 and 30 years and the age and parity two mortalities in the intervention group were due to RDS in
distribution of the women in the two groups were similar. neonates born at 28þ 5/7 weeks and 27þ 6/7 weeks weighing
The mean gestation at admission was 30þ4/7 in the interven- 1.143 kg and 895 g, respectively. These two women had a
tion group and 30þ6/7 in controls (p ¼ .582, NS). The median latency period of 4 and 5 days, respectively. At 27þ 6/7 weeks,
cervical dilatation and effacement was similar in the two a neonate weighing 895 g would be categorised as having
groups; 2.5 cm and 60%. In each group, 15/25 (60%) women mild growth restriction and not severe growth restriction as
had no risk factor for PTB and 10/25 (40%) had risk factors per our hospital growth charts (Table 4). Only women with
for PTB. Urogenital infection was present in 4/25 in the study severe growth restriction had been excluded. In the control
and 5/25 in the control group (vaginal candidiasis in two, group, there was one stillbirth in a woman who received
urinary infection with E.coli in five and Klebsiella in two). They acute tocolysis at 26þ 5/7 weeks gestation, had recurrence of
were treated with combination vaginal tablet or antibiotics PTL at 29þ 6/7 weeks and delivered a stillborn boy weighing
(nitrofurantoin, cephalexin) and repeat urine culture was 700g (severe foetal growth restriction). She did not have
sterile. severe foetal growth restriction at recruitment, there was no
Though more women in the intervention group delivered congenital malformation and she did not consent to an
at term and 34 weeks as compared to the control group, autopsy. The second death was of a baby boy delivered at
the difference was not significant (Table 2). In the interven- 27þ 1/7 weeks gestation weighing 988 g who died due to sep-
tion group, 7/25 (28%) women and in the control group 2/25 sis on day 5 of life. This woman had received acute tocolysis
(8%) women delivered at term (p ¼ .066). In the intervention at 26þ 6/7 weeks gestation. The third death was of a baby
group 15/25 (60%) and in the control group 11/25 (44%) delivered at 36þ 6/7 weeks weighing 1.75 kg who developed
delivered after 34 weeks (p ¼ .258). There was a single episode respiratory distress and died due to late onset neonatal sepsis
of recurrent PTL in 15/25 (60%) women in the intervention after being in the NICU on a ventilator for 12 days. This neo-
group and in 14/25 (56%) women in the control group nate had severe growth restriction which had set in during
(p ¼ .774). These episodes were prior to 34 weeks in all except the course of pregnancy, but at the time of recruitment at
in one woman in the intervention group which occurred at 31þ 6/7 weeks there was no foetal growth restriction. There
34þ6/7 weeks. The recurrent PTL episodes were managed with were no major maternal side effects noted during mainten-
acute tocolysis with nifedipine, however, all these women ance tocolysis. 12 women had side-effects during acute tocol-
delivered with 48 h of recurrent PTL. The woman with recur- ysis (headache and tachycardia) which were self-limiting. Of
rent PTL at 34þ6/7 weeks was managed with rest and these, six women received maintenance tocolysis and only
4 A. AGGARWAL ET AL.

Assessed for eligibility (n= 252)

Excluded (n= 156)


• Multiple gestation (n=24)
• PTL with ruptured membranes (n=36)
Enrolment • >34 weeks gestation (n=79)
• APH (n=9)
• Hypertension (n=8)

Excluded (n=46)
Started on acute tocolysis (n=96)
*Had spontaneous ruptured
membranes (n=15)
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*Delivered before completion of


acute tocolysis (n=29)
*antepartum haemorrhage (n=2)

Arrested PTL (n=50)


Randomisation

Allocated to Intervention group (n= 25) Allocated to Control group (n=25)

Allocation

Lost to follow-up (n=0) Lost to follow-up (n=0)


Follow-Up
Discontinued intervention (n= 0) Discontinued intervention (n=0)

Analysed (n= 25) Analysed (n=25)


Excluded from analysis (n= 0) Excluded from analysis (n=0)
Analysis

Figure 1. The CONSORT flowchart.

one had tachycardia with headache which resolved after slow-release calcium-channel blocker, which prevents calcium
decreasing the dose of nifedipine retard tablet to 10 mg bd uptake in the myometrial cell, hence preventing it from con-
from 20 mg 8 hourly. She had experienced similar symptoms tracting. Some of the earlier trials did not show any benefit
during acute tocolysis also. She received maintenance tocoly- of maintenance tocolysis with nifedipine in pregnancy pro-
sis from 27þ 4/7 weeks to 34 weeks and delivered at 39 weeks longation or improving the perinatal outcome (Carr et al.
after spontaneous onset of labour. 1999; Lyell et al. 2008; Roos et al. 2013; Uma et al. 2012;
Parry et al. 2014). On the other hand, Sayin et al. reported a
significant pregnancy prolongation and increased gestational
Discussion age at delivery with maintenance tocolysis but there was no
improvement in perinatal outcomes (Sayin et al. 2004). Table
The current accepted management of PTL includes acute 4 shows the details of the available studies on maintenance
tocolysis for 48 h which is then discontinued. The role of tocolysis. The Creasy and Herron criteria was used to diag-
maintenance tocolysis is controversial. The most common nose PTL in the present study (Holbrook et al. 1987). The
drug studied for maintenance tocolysis is oral nifedipine, a study and control group women had a median cervical
JOURNAL OF OBSTETRICS AND GYNAECOLOGY 5

Table 1. Demographic and baseline characteristics of the study and control groups.
Intervention group (n ¼ 25)
Characteristic (maintenance tocolysis) Control group (n ¼ 25) p Value
Age in years (mean ± SD) 25.40 ± 4.29 24.16 ± 2.93 .239
Range (years) 20–35 20–31
BMI (kg/m2) (mean ± SD) 22.13 ± 3.1 21.23 ± 2.65 .277
Nulliparous (%) 12 (48%) 9 (36%) .390
Para 1 6 (24%) 12 (48%)
Para 2 4 (16%) 2 (8%)
Para 3 3 (12%) 2 (8%)
Number of women with risk factors for PTB 10 (40%) 10 (40%) 1.000
Previous PTB 5 (20%) 7a (28%)
Urogenital infection 5 (20%) 4 (16%)
Gestation at admission in weeks (mean ± SD) 30þ4/7 ± 2 30þ6/7 ± 2þ2/7 .582
Range (weeks) 27–33þ6/7 26 þ3/7
–33þ6/7
Cervical dilatation at admission in cm Median (IQR) 2.5 (2.5–3.5) 2.5 (2.5–3.5) .716
Range (cm) 1–4 1–4
Effacement at admission (%) median (IQR) 60 (45–70) 60 (50–65) .434
Range (%) 20–100 20–100
a
One woman had previous PTB plus urogenital infection.
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Figure 2. Kaplan–Meier analysis showing trend for pregnancy prolongation.

dilatation of 2.5 cm and effacement of 60%, showing that present study (2 and 2.5 cm in the study and control group,
they had established PTL. Some of the reported studies had respectively), the women in their study may have been at a
recruited women with similar cervical dilatation as the pre- lower risk of PTB due to less contraction frequency (Lyell
sent study (Sayin et al. 2004; Lyell et al. 2008), whereas others et al. 2008). The PTB rate in the control group of any study is
had recruited women with lesser cervical dilatation (Carr an indicator of the risk of PTB among the women recruited
et al. 1999; Roos et al. 2013; Parry et al. 2014). The number of to that study. The women in the present study were at a
days of pregnancy prolongation in either group were the higher risk of PTB as compared to the other reported studies
highest (46.8 and 50.8) in the NIFTY study where the cervical as the women in the control group had a high rate of PTB
dilatation was 0 cm and positive foetal fibronectin was used (92%) and only 8% achieved term gestation, whereas the
to diagnose PTL. These women were possibly at a lower risk women in the control group of the other studies had a lower
of PTB and hence, the benefit of maintenance tocolysis may PTB rate as compared to the present study (33–62% achieved
not be clearly evident in them (Parry et al. 2014). Lyell et al. term gestation). Therefore, the non-significant trends
included women with 6 contractions per hour, while the observed with maintenance tocolysis in the present study in
present study included women with 8 contractions per the form of more women achieving term gestation, more
hour. Though their mean cervical dilatation was similar to the days of pregnancy prolongation and reduced neonatal
6 A. AGGARWAL ET AL.

Table 2. Gestational age at delivery and pregnancy.


Intervention group (n ¼ 25)
Characteristic (maintenance tocolysis) Control group (n ¼ 25) p Value
Median number of days the maintenance tocolysis was received 14
IQR 3–25.5
Range 2–47
Median number of days the pregnancy was prolonged 20 14 .269
IQR 2.5–51 1–27.5
Gestation at delivery in days (Mean ± SD) 242.04 ± 23.17 234.52 ± 21.33 .239
Range 195–274 189–271
Gestation at delivery in weeks (Mean ± SD) 34þ4/7 ± 3þ2/7 33þ3/7 ± 3þ0/7
þ6/7
Range 27 –39þ1/7 27–38þ5/7
Number of women who delivered 37 weeks 7 (28%) 2 (8%) .066
Number of women who delivered preterm (<37 weeks) 18 (72%) 23 (92%)
Number of women who delivered 34 weeks 15 (60%) 11 (44%) .258
Number of women who delivered <34 weeks 10 (40%) 14 (56%)
Number of women with an episode of recurrent PTL 15 (60%) 14 (56%) .774

Table 3. Neonatal outcome in the two groups.


Intervention group (n ¼ 25)
Characteristic (maintenance tocolysis) Control group (n ¼ 25) p Value
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Birth weight in g (Mean ± SD) 2266.76 ± 726.90 1880.16 ± 590.00 .044


Median APGAR score (IQR)
1 minute 8 (8–8) 8 (7–8) .437
5 minutes 9 (9–9) 9 (9–9) .395
10 minutes 10 (10–10) 10 (10–10) .146
Median hospital stay in days (IQR) 4 (2–10) 5.5 (2.25–12) .608
Number of neonates needing neonatal ICU care 8 (32%) 10 (40%) .483
Number of neonates needing ventilatory support 2 (8%) 5 (25%) .199
Number of neonates with composite morbidity 6 (24%) 8 (33.3%) .470
RDS 3 2 .672
IVH 0 1 .302
Sepsis/meningitis 5 7 .456
Apnoea of prematurity 3 2 .672
NEC 0 0
Perinatal mortality 2 (8%) 3 (12%) .637

Table 4. Birth weight charts of the PGIMER, Chandigarh, India.


The significantly higher mean birth weight in the intervention
Birth weight in grams
group (2266 vs 1880 g in controls, p ¼ .044) could be attrib-
Weeks of gestation 2SD 1SD Appropriate for gestation þ1SD þ2SD uted to the achievement of more deliveries at term gestation
27 185 473 861 1149 1407 in the intervention group (28 vs 8% in controls, p ¼ .06).
28 666 914 1162 1410 1608
29 861 1088 1315 1542 1769 Sayin et al. also observed a trend toward higher birth weight
30 837 1139 1441 1743 2045 in the intervention group (2744 vs 2677 g in controls,
31 549 1058 1567 2076 2585 p ¼ .0688; NS) as more women achieved term gestation with
32 844 1295 1746 2197 2648
33 1210 1517 1824 2131 2438 maintenance tocolysis (Sayin et al. 2004). In the present
34 1229 1670 2111 2552 2993 study, 92% of the babies in the control group were preterm
35 1438 1879 2320 2761 3200 and their mean birth weight (1880 g) was lower than the
36 1674 2117 2560 3003 3446
37 1918 2339 2760 3181 3602 mean birth weight of babies of the control group of the
38 2020 2440 2864 3286 3708 other studies. This further strengthens our observation of
39 2095 2517 2939 3361 3783 having a population of women at a higher risk of PTB than
40 2178 2593 3008 3424 3838
41 2205 2678 3151 3624 4097 the other mentioned studies. In the present study, two
42 2130 2555 2980 3405 3830 women clinically diagnosed to have vaginal candidiasis on
43 2079 2505 2931 3357 3783 speculum examination were treated. Vaginal swabs were not
collected to screen for bacterial vaginosis because though
bacterial vaginosis increases the risk of preterm labour, rou-
hospital stay may achieve significance in a larger study. Sayin tine screening and treatment of asymptomatic women is
et al. reported significant pregnancy prolongation with main- unclear. A Cochrane meta-analysis of 7847 symptomatic or
tenance tocolysis (26.65 ± 18.89 vs 16.14 ± 12.91 days in con- asymptomatic women with bacterial vaginosis showed that
trols; p ¼ .007) (Sayin et al. 2004). The present study found its treatment did not significantly reduce preterm birth-
20 days gained by maintenance tocolysis and 14 days in the <37 weeks (OR 0.88, 95%CI 0.71–1.09), even in the subgroup
control group, which is lower than the number of days of of 421 women with prior preterm birth (OR 0.78, 95%CI
pregnancy prolongation in the control group of the other 0.42–1.48). (Brocklehurst et al. 2013). The Centre for Disease
reported studies (Table 5). This further supports that the Control (CDC), USA, does not recommend routine screening
women in the present study were at a higher risk of PTB. in asymptomatic pregnant women (Workowski et al. 2015).
JOURNAL OF OBSTETRICS AND GYNAECOLOGY 7

To conclude, maintenance tocolysis did not result in statis-

28% vs 23%; NS

32% vs 40%; NS
33.3% vs 23.5%;
requirement
(study vs
tically significant prolongation of pregnancy or reduction in

controls)

30% in each

40% in each
NICU


group

group
neonatal hospital stay. There were no major maternal side

NS
effects with its use except for headache in a few women was

NA
self-limiting. The strength of the present study is that the
women were in established PTL and at a higher risk of a PTB
2497 vs 2496;

2929 vs 2830;

2047 vs 2035;
2744 vs 2677

2282 vs 2450

2266 vs 1880
Mean birth
weight. (g)

as compared to some of the previous studies due to observa-


(study vs
controls)

(p ¼ .06)

(p ¼ .04)
(p ¼ .3)
tion of a higher rate of PTB in the control group (92%) as
NS

NS

NS
compared to the other studies (38 to 67%, Table 5). The limi-

NA
tations are a small sample size, and being an open label
study where a placebo was not used in the control group. It
(weeks) (study

36.92 vs 35.59
35 vs 35.2; NS
Gestation at

vs controls)
35.4 vs 35.3;

34.1 vs 34.2;
(p ¼ .003)

36.1 vs 36.8

may be difficult to recruit sufficient number of women with


delivery

(p ¼ .02)

(p ¼ .23)
37 vs 35.1
Mean

34þ4/7 vs
33þ3/7
(NS)
cervical dilatation and effacement suggesting established PTL,
NS

NS which gets inhibited with acute tocolysis without the women


rupturing the membranes or having vaginal bleeding.
Table 5. Characteristics of subjects, mean gestation at delivery and neonatal outcome after maintenance tocolysis with nifedipine in literature and the present study.

Multicentric trials or an individual patient data analysis of


Percent delivering
at term (study vs

39% vs 37%, NS
33% vs 33% NS

60% vs 40% NS
62% vs 38% at

smaller studies may be useful and help to assess the effect-


controls)

51% vs 62%

32% vs 34%
36 weeks
(p ¼ .07)

(p ¼ .06)
28% vs 8%

iveness of maintenance tocolysis.


Downloaded by [University of Florida] at 13:49 08 August 2017

Disclosure statement
No potential conflict of interest was reported by the authors.
26.65 vs 16.14
Mean days of

of pregnancy
prolongation

37 vs 32; NS

34 vs 32; NS

30 vs 32; NS
(p ¼ .007)

(p ¼ .269)
46.8 vs 50.8
(study vs
controls)

(p ¼ .48)

20 vs 14

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