Cochrane Database of Systematic Reviews

Hydration for treatment of preterm labour (Review)

Stan CM, Boulvain M, Pfister R, Hirsbrunner-Almagbaly P

Stan CM, Boulvain M, Pfister R, Hirsbrunner-Almagbaly P.

Hydration for treatment of preterm labour.
Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD003096.
DOI: 10.1002/14651858.CD003096.pub2.

www.cochranelibrary.com

Hydration for treatment of preterm labour (Review)

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Analysis 1.5. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 5 Delivery before 37
weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Analysis 1.6. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 6 Delivery before 34
weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Analysis 1.7. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 7 Delivery before 32
weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Analysis 1.8. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 8 Admission to neonatal
intensive care unit. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Analysis 1.13. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 13 Cost of treament
(first 24 hours, in US$). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Analysis 1.14. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 14 Use of tocolytic
drugs (not prespecified). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Analysis 1.15. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 15 Time to delivery
(days, not prespecified). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
Analysis 2.4. Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks), Outcome 4
Delivery before 34 weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Analysis 2.5. Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks), Outcome 5
Delivery before 37 weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Analysis 2.10. Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks), Outcome
10 Admission to neonatal intensive care unit. . . . . . . . . . . . . . . . . . . . . . . . 20
Analysis 2.13. Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks), Outcome
13 Cost of treament (first 24 hours, in US$). . . . . . . . . . . . . . . . . . . . . . . . 21
Analysis 2.14. Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks), Outcome
14 Use of tocolytic drugs (not prespecified). . . . . . . . . . . . . . . . . . . . . . . . 21
Analysis 2.15. Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks), Outcome
15 Time to delivery (days, not prespecified). . . . . . . . . . . . . . . . . . . . . . . . 22
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . . 24
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Hydration for treatment of preterm labour (Review) i

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]

Hydration for treatment of preterm labour

Catalin M Stan1 , Michel Boulvain2 , Riccardo Pfister3 , Pascale Hirsbrunner-Almagbaly4

1 Private
Practice, Lausanne, Switzerland. 2 Dpartement de Gyncologie et dObsttrique, Unit de Dveloppement en Obsttrique,
Maternit Hpitaux Universitaires de Genve, Genve 14, Switzerland. 3 Division de Neonatologie et Soins Intensifs, Departement
de Pdiatrie, Hpitaux Universitaires de Genve, Geneva 14, Switzerland. 4 Dpartement de Gyncologie et dObsttrique, Hpitaux
Universitaires de Genve, Geneva 14, Switzerland

Contact address: Catalin M Stan, Private Practice, Avenue Vinet 16, Lausanne, 1004, Switzerland. catalin.stan@hin.ch.

Editorial group: Cochrane Pregnancy and Childbirth Group.

Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 11, 2013.
Review content assessed as up-to-date: 3 October 2013.

Citation: Stan CM, Boulvain M, Pfister R, Hirsbrunner-Almagbaly P. Hydration for treatment of preterm labour. Cochrane Database
of Systematic Reviews 2013, Issue 11. Art. No.: CD003096. DOI: 10.1002/14651858.CD003096.pub2.

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT
Background
Hydration has been proposed as a treatment for women with preterm labour. Theoretically, hydration may reduce uterine contractility
by increasing uterine blood flow and by decreasing pituitary secretion of antidiuretic hormone and oxytocin.
Objectives
To evaluate the effectiveness of intravenous or oral hydration to avoid preterm birth and its consequences in women with preterm
labour.
Search methods
We searched the Cochrane Pregnancy and Childbirth Groups Trials Register (30 September 2013) and bibliographies of relevant
papers.
Selection criteria
Randomised controlled trials, including women with a viable pregnancy less than 37 completed weeks gestation and presenting with
preterm labour, comparing intravenous or oral hydration with no treatment. The intervention might or might not be associated with
bed rest. Studies comparing tocolytic drugs with intravenous fluids used in the control group as a placebo were not included in this
review.
Data collection and analysis
Two review authors independently assessed the reports, to determine if the study met the inclusion criteria and to evaluate the
methodological quality. Data were extracted independently by two of the review authors. The results were expressed as risk ratios (RR)
for dichotomous outcomes and mean difference (MD) for continuous outcomes.
Main results
Two studies, including a total of 228 women with preterm labour and intact membranes, compared intravenous hydration with bed
rest alone. Risk of preterm delivery, before 37 weeks (RR) 1.09; 95% confidence interval (CI) 0.71 to 1.68), before 34 weeks (RR
0.72; 95% CI 0.20 to 2.56) or before 32 weeks (RR 0.76; 95% CI 0.29 to 1.97), was similar between groups. Admission to neonatal
intensive care unit occurred with similar frequency in both groups (RR 0.99; 95% CI 0.46 to 2.16). Cost of treatment was slightly
Hydration for treatment of preterm labour (Review) 1
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
higher (US$39) in the hydration group. This difference was not statistically significant and only includes hospital costs during a visit
of less than 24 hours. No studies evaluated oral hydration.

Authors conclusions

The data are too few to support the use of hydration as a specific treatment for women presenting with preterm labour. The two
small studies available do not show any advantage of hydration compared with bed rest alone. Intravenous hydration does not seem
to be beneficial, even during the period of evaluation soon after admission, in women with preterm labour. Women with evidence of
dehydration may, however, benefit from the intervention.

PLAIN LANGUAGE SUMMARY

Hydration for treatment of preterm labour

Unless they are dehydrated, there seems to be no benefit from additional intravenous fluids for women in preterm labour.

Preterm birth (before 37 weeks) can cause health problems and be life-threatening for babies. As women in preterm labour often
have lower amounts of fluid in their circulation, using an intravenous drip to increase the womans blood volume is sometimes tried
(hydration). It has been hoped that the extra fluid might somehow slow down contractions. However, from the limited information
available (two studies involving 228 women), the review found that there is no evidence of a benefit in the use of hydration to help
prevent preterm labour, although it may be helpful for women who are dehydrated.

BACKGROUND
Preterm birth occurs in 9.6% to 12.2% of pregnancies (Beck 2010;
Martin 2011). Prematurity is the leading cause of infant deaths
and is responsible for 35% of the perinatal mortality (Callaghan
2006). An evaluation of a cohort of neonates admitted to an in-
tensive care unit after delivery at 20 to 26 weeks showed an over-
all survival of 57% (Costeloe 2012). Infants born preterm often
require prolonged and expensive care in specialised units (Russel
2007). Among infants with birthweight less than 750 g, 23% of
the survivors assessed at school age will suffer from neurodevelop-
mental impairment and 5% from cerebral palsy (Wilson-Costello
2007). Infants weighting between 1000 g and 1500 g at birth are
also at risk of severe mental disability (8%) and of cerebral palsy
(6%) (Hack 1994; Oskoui 2013).
women are often evaluated for a period of time after admission,
to differentiate between true and false labour.
Neonatal mortality and morbidity decrease as gestational age
or birthweight, or both, increases (Bird 2010; Callaghan 2006;
Costeloe 2012; Moutquin 2003). Thus, prolongation of preg-
nancy would be expected to decrease neonatal mortality and im-
prove subsequent child development by reducing the effects of pre-
maturity. However, prolonging the pregnancy is not a guarantee
that the outcome for the infant will be improved (Hackney 2013).
There are conditions, such as intra-amniotic infection, haemolytic
disease or impaired fetal growth, for which preterm delivery may
be beneficial. In these cases, prolonging the pregnancy may have
adverse consequences for the health and the development of the
infant.

Preterm birth usually follows either preterm labour, preterm
prelabour rupture of membranes or a medical decision to termi-
nate the pregnancy because of maternal or fetal disease. About
one-third to one-half of preterm births are the consequence of
preterm labour without preterm prelabour rupture of the mem-
branes (Henderson 2012). Identification of women who will give
birth preterm among those presenting with symptoms of preterm
labour is difficult. As yet, risk factors, biological markers and ul-
trasonography are limited predictors of preterm delivery (Chang
2013; Faron 1998; Goldenberg 2008; Owen 2010). Therefore,
Hydration for treatment of preterm labour (Review)
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Despite the development of various therapeutic interventions in
recent decades, little progress has been made in reducing the inci-
dence of preterm birth (Haas 2012; Martin 2011). Pharmacolog-
ical agents currently used to inhibit uterine contractions include
betamimetics, magnesium sulphate, prostaglandin inhibitors, cal-
cium channel blockers and oxytocin receptor antagonists (Haas
2012; Mackeen 2011). Some authors, based on uncontrolled ob-
servations, have suggested that intravenous hydration might de-
crease contractions or delay the delivery in women presenting
with preterm contractions (Bieniarz 1971; Goodlin 1981). Stud-
2
ies on plasma volume reported that women with preterm labour
had lower plasma volumes than control women with a normal
pregnancy (Goodlin 1981). An uncontrolled case series showed
that 48% of women admitted with preterm labour did not de-
liver within 10 days, and one-third delivered after 37 weeks, when
treated with bed rest and plasma volume expansion (Valenzuela
1983). The above studies suffer from the limitations of not pro-
viding a comparison with controls, and, as diagnosis of preterm
labour that will end in preterm birth is difficult, these results may
have been achieved without any intervention.
How might plasma volume expansion reduce the risk of preterm
birth? A possible mechanism is that volume expansion inhibits
contractions by increasing uterine blood flow, thus stabilising de-
cidual lysosomes and decreasing prostaglandin production (Guinn
1997). Volume expansion, through left atrial distension, decreases
the secretion of antidiuretic hormone from the posterior pituitary
through the Henry-Gauer reflex (Bieniarz 1971; Guinn 1997).
The hypothesis is that oxytocin secretion will decrease simulta-
neously (Bieniarz 1971); however, this mechanism has only been
described in animal models (Gauer 1976).
Preterm birth is related to significant neonatal mortality and infant
morbidity. Despite important research, prediction and treatment
of preterm labour has little impact in decreasing the incidence of
preterm births. Hydration of women in preterm labour may de-
crease uterine contractions by decreasing prostaglandin produc-
tion or oxytocin secretion. This procedure may have a place in the
management of preterm labour.
OBJECTIVES
To evaluate the effectiveness of intravenous or oral hydration to
avoid preterm birth and its consequences in women with preterm
labour.
METHODS
Criteria for considering studies for this review
Types of studies
Randomised controlled trials, with or without blinding, with loss
to follow-up of less than 20% of women originally randomised.
Types of participants
Women with a viable pregnancy less than 37 completed weeks
gestation presenting with preterm labour, as defined by the au-
thors. A separate analysis was performed for women included be-
fore 34 completed weeks gestation. A subgroup comparison of
Hydration for treatment of preterm labour (Review)
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
women with a multiple pregnancy was planned, but insufficient
data were available.
Types of interventions
Intravenous or oral hydration compared with no treatment. The
intervention might or might not be associated with bed rest. We
have not considered in this review studies comparing tocolytic
drugs with intravenous fluids used in the control group as a
placebo.
Types of outcome measures
Primary outcomes
Perinatal death or severe neonatal morbidity (defined as
respiratory distress syndrome, intracranial haemorrhage,
necrotising enterocolitis, neonatal sepsis or seizures).
Secondary outcomes
Prolongation of pregnancy more than 48 hours and seven
days.
Gestational age at delivery: more than 28 weeks, 32 weeks,
34 weeks and 37 weeks.
Perinatal outcomes: low birthweight (less than 2500 g),
very low birthweight (less than 1500 g), Apgar score less than
seven at five minutes, perinatal death, neonatal morbidity as
separate outcomes (respiratory distress syndrome, intracranial
haemorrhage, necrotising enterocolitis, neonatal sepsis or
seizures, patent ductus arteriosus, hypoglycaemia), admission to
neonatal unit and need for mechanical ventilation.
Long-term sequelae: neurologic impairment and chronic
lung disease.
Serious maternal outcomes: death, cardiac arrest,
respiratory arrest, pulmonary oedema, cardiac arrhythmias.
Other maternal outcomes: hypotension, chest pain,
dyspnoea, nausea, vomiting, headaches, endometritis,
chorioamnionitis, hyperglycaemia, hypokalaemia, womens
assessment of their treatment.
Percentage of caesarean section, instrumental delivery or other out-
comes that the authors of the original trials have reported would
have been included in the analysis, if available. Economic evalua-
tions of this therapy were included as an outcome. Mean interval
between randomisation and delivery and the use of tocolytic drugs
are reported as additional outcome measures (not prespecified).
3
Search methods for identification of studies
Electronic searches
We searched the Cochrane Pregnancy and Childbirth Groups
Trials Register by contacting the Trials Search Co-ordinator (30
September 2013).
The Cochrane Pregnancy and Childbirth Groups Trials Register
is maintained by the Trials Search Co-ordinator and contains trials
identified from:
1. monthly searches of the Cochrane Central Register of
Controlled Trials (CENTRAL);
2. weekly searches of MEDLINE;
3. weekly searches of Embase;
4. handsearches of 30 journals and the proceedings of major
conferences;
5. weekly current awareness alerts for a further 44 journals
plus monthly BioMed Central email alerts.
Details of the search strategies for CENTRAL, MEDLINE and
Embase, the list of handsearched journals and conference pro-
ceedings, and the list of journals reviewed via the current aware-
ness service can be found in the Specialized Register section
within the editorial information about the Cochrane Pregnancy
and Childbirth Group.
Trials identified through the searching activities described above
are each assigned to a review topic (or topics). The Trials Search
Co-ordinator searches the register for each review using the topic
list rather than keywords.
Searching other resources
We examined bibliographies of identified studies for references to
other trials.
We did not apply any language restrictions.
Data collection and analysis
Methods used in previous versions of the review are set out in
Appendix 1. For this update, although no new trials were added,
we re-examined the trials already included in the review and carried
out assessments of risk of bias and data analysis using up-to-date
methods as set out in the Cochrane Handbook for Systematic Reviews
of Interventions (Higgins 2011).
Selection of studies
Two review authors independently assessed eligibility for inclusion
of studies identified as a result of the search strategy. We resolved
any disagreement through discussion or, if required, we consulted
a third person.
Hydration for treatment of preterm labour (Review)
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Data extraction and management
We designed a form to extract data. For eligible studies, two review
authors extracted the data. We resolved discrepancies through dis-
cussion or, if needed, we consulted a third person. We entered data
into Review Manager software (RevMan 2012), and checked for
accuracy.
If information regarding any of the above was unclear, we planned
to contact authors of the original reports to request further infor-
mation.
Assessment of risk of bias in included studies
Two review authors independently assessed risk of bias for each
study using the criteria outlined in the Cochrane Handbook
(Higgins 2011). We resolved any disagreement by discussion or
by involving a third assessor.
(1) Random sequence generation (checking for possible
selection bias)
For each included study, we have described the method used to
generate the allocation sequence in sufficient detail to allow an
assessment of whether it should produce comparable groups.
We assessed the method as:
low risk of bias (any truly random process, e.g. random
number table; computer random number generator);
high risk of bias (any non-random process, e.g. odd or even
date of birth; hospital or clinic record number);
unclear risk of bias.
(2) Allocation concealment (checking for possible selection
bias)
For each included study, we have described the method used to
conceal allocation to interventions prior to assignment, and assess
whether intervention allocation could have been foreseen in ad-
vance of, or during recruitment, or changed after assignment.
We assessed the methods as:
low risk of bias (e.g. telephone or central randomisation;
consecutively numbered sealed opaque envelopes);
high risk of bias (open random allocation; unsealed or non-
opaque envelopes, alternation; date of birth);
unclear risk of bias.
(3.1) Blinding of participants and personnel (checking for
possible performance bias)
For each included study, we have described the methods used, if
any, to blind study participants and staff from knowledge of which
intervention a participant received. We considered studies to be at
low risk of bias if they were blinded, or if we judged that the lack
of blinding would be unlikely to affect results.
4
We assessed the methods as:
low, high or unclear risk of bias for participants;
low, high or unclear risk of bias for personnel.
(3.2) Blinding of outcome assessment (checking for possible
detection bias)
For each included study, we have described the methods used, if
any, to blind outcome assessors from knowledge of which inter-
vention a participant received.
We assessed methods as low, high or unclear risk of bias.
(4) Incomplete outcome data (checking for possible attrition
bias due to the amount, nature and handling of incomplete
outcome data)
For each included study and each outcome or class of outcomes,
we have described the completeness of data including attrition
and exclusions from the analysis. We have stated whether attri-
tion and exclusions were reported, and the numbers included in
the analysis at each stage (compared with the total randomised
participants), reasons for attrition or exclusion where reported,
and whether missing data were balanced across groups or were
related to outcomes. Where sufficient information was reported,
we planned to re-include missing data in the analyses.
We assessed methods as:
low risk of bias (e.g. no missing outcome data; missing
outcome data balanced across groups);
high risk of bias (e.g. numbers or reasons for missing data
imbalanced across groups; as treated analysis done with
substantial departure of intervention received from that assigned
at randomisation);
unclear risk of bias.
(5) Selective reporting (checking for reporting bias)
For each included study, we have described how we investigated
the possibility of selective outcome reporting bias and what we
found.
We assessed the methods as:
low risk of bias (where it is clear that all of the studys pre-
specified outcomes and all expected outcomes of interest to the
review have been reported);
high risk of bias (where not all the studys pre-specified
outcomes have been reported; one or more reported primary
outcomes were not pre-specified; outcomes of interest are
reported incompletely and so cannot be used; or study failed to
include results of a key outcome that would have been expected
to have been reported);
unclear risk of bias.
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Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(6) Other bias (checking for bias due to problems not
covered by (1) to (5) above)
For each included study, we have described any important con-
cerns we have about other possible sources of bias, such as baseline
imbalance between groups.
We assessed whether each study was free of other problems that
could put it at risk of bias and assessed each as:
low risk of other bias;
high risk of other bias;
unclear whether there is risk of other bias.
(7) Overall risk of bias
We made explicit judgements about whether studies are at high risk
of bias, according to the criteria given in the Cochrane Handbook
(Higgins 2011). With reference to (1) to (6) above, we assessed
the likely magnitude and direction of the bias and whether we
considered it was likely to impact on the findings. We planned
to explore the impact of the level of bias through undertaking
sensitivity analyses - see Sensitivity analysis.
Measures of treatment effect
Dichotomous data
For dichotomous data, we present results as summary risk ratio
with 95% confidence intervals.
Continuous data
For continuous data, we present the mean difference with 95%
confidence intervals. In updates we will use the standardised mean
difference to combine trials that report the same outcome, but are
measured in different ways.
Unit of analysis issues
Cluster-randomised trials
We did not identify any cluster-randomised trials in this version
of the review. In future updates if such trials are identified we will
include them in the analyses along with individually-randomised
trials. We will adjust their sample sizes using the methods described
in the Cochrane Handbook (Higgins 2011), using an estimate of
the intracluster correlation co-efficient (ICC) derived from the
trial (if possible), from a similar trial or from a study of a similar
population. If we use ICCs from other sources, we will report this
and conduct sensitivity analyses to investigate the effect of varia-
tion in the ICC. If we identify both cluster-randomised trials and
individually-randomised trials, we plan to synthesise the relevant
5
information. We will consider it reasonable to combine the re-
sults from both if there is little heterogeneity between the study
designs and the interaction between the effect of intervention and
the choice of randomisation unit is considered to be unlikely.
We will also acknowledge heterogeneity in the randomisation unit
and perform a sensitivity analysis to investigate the effects of the
randomisation unit.
Cross-over trials
Cross-over studies were not included; this is not a suitable design
for this type of intervention.
Other unit of analysis issues
If we had identified any trials with more than two arms (multi-
arm trials), we planned to include all arms relevant to the scope
of the review. If such trials are identified when we update the
review, where appropriate, we will combine arms (using methods
described in the Cochrane Handbook (Higgins 2011)) to create a
single pair-wise comparison. If it is not appropriate to combine
them, we will present results separately for each arm, sharing results
for the control arm between each to avoid double counting (for
dichotomous outcomes we will divide the number of events and
total sample by two, for continuous outcomes we will assume the
same mean and standard deviation but halve the control sample
size for each comparison).
Dealing with missing data
For included studies, we noted levels of attrition. We planned to
explore the impact of including studies with high levels of missing
data in the overall assessment of treatment effect by using sensi-
tivity analysis; in this version of the review only two trials were
included so we did not carry out this planned additional analysis.
For all outcomes, we carried out analyses, as far as possible, on
an intention-to-treat basis, i.e. we attempted to include all partic-
ipants randomised to each group in the analyses, and all partici-
pants are analysed in the group to which they were allocated, re-
gardless of whether or not they received the allocated intervention.
The denominator for each outcome in each trial is the number
randomised minus any participants whose outcomes are known
to be missing.
Assessment of heterogeneity
We assessed statistical heterogeneity using the Tau, I and Chi
statistics. We would have regarded heterogeneity as substantial if
an I was greater than 30% and either the Tau greater than zero,
or there was a low P value (less than 0.10) in the Chi test for
heterogeneity.
Hydration for treatment of preterm labour (Review)
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Assessment of reporting biases
If in future updates there are 10 or more studies in the meta-
analysis, we will investigate reporting biases (such as publication
bias) using funnel plots. We will assess funnel plot asymmetry
visually. If asymmetry is suggested by a visual assessment, we will
perform exploratory analyses to investigate it.
Data synthesis
We carried out statistical analysis using Review Manager software
(RevMan 2012). We used fixed-effect meta-analysis for combining
data where it was reasonable to assume that studies were estimating
the same underlying treatment effect: i.e. where trials examined
the same intervention, and the trials populations and methods
were judged to be sufficiently similar. If we had suspected clin-
ical heterogeneity sufficient to expect that the underlying treat-
ment effects differed between trials, or if substantial statistical het-
erogeneity had been detected, we planned to use random-effects
meta-analysis to produce an overall summary, provided an average
treatment effect across trials was considered clinically meaningful.
In this version of the review, only two studies were included; we
carried out meta-analysis for very few outcomes and no important
statistical heterogeneity was identified.
Subgroup analysis and investigation of heterogeneity
The following comparisons were performed: any type of hydration
versus bed rest alone.
Subgroup analysis would have included:
oral versus intravenous hydration, and
prelabour preterm rupture of membranes versus intact
membranes
However, separate data were not available. We have set out data
separately for a study that included women at less than 34 weeks
of gestation but did not perform any formal subgroup analysis.
If data for subgroups become available for future updates, we will
assess subgroup differences by interaction tests available within
RevMan (RevMan 2012). We will report the results of subgroup
analyses quoting the Chi statistic and P value, and the interaction
test I value.
Sensitivity analysis
If we had included cluster-randomised trials in the review, we
planned to carry out sensitivity analysis. We also planned sensitiv-
ity analysis according to trial quality; temporarily excluding trials
at high risk of bias due to inadequate allocation concealment to
explore whether this has any impact on the direction or size of the
effect estimate. In this version of the review we did not carry out
any sensitivity analysis as insufficient data were available. If more
data are included in updates, we will carry out planned sensitivity
analysis using our primary outcomes only.
6
RESULTS
Description of studies
Two studies were included (Guinn 1997; Helfgott 1994). Both tri-
als included women with preterm contractions and cervical modi-
fications (see Characteristics of included studies). Gestational age
at entry ranged from 24 to 37 weeks (Helfgott 1994) and from 20
to 34 weeks (Guinn 1997). Non-reassuring fetal status, suspicion
of infection, maternal disease, contraindication for tocolysis, and
obvious labour were exclusion criteria. In Helfgott 1994, hydra-
tion and hydration+morphine were compared with bed rest. The
first two groups were combined, as there is no evidence of a to-
colytic effect of morphine.
Risk of bias in included studies
The two studies included are of generally good methodological
quality.
Allocation
Both studies used computer-generated randomisation sequences
and allocations were concealed in opaque sealed envelopes opened
sequentially.
Blinding
Blinding of women and clinical staff was not attempted in either
study. The lack of blinding of staff may have affected clinical de-
cisions that may have had an impact on outcomes introducing a
serious risk of bias.
Blinding of outcome assessment was not mentioned, except that
in the Helfgott 1994 trial monitor tracings of uterine contractions
were reported to have been examined by blinded assessors.
Incomplete outcome data
Eight women were excluded from the analysis (five for
pyelonephritis, one refused the allocated treatment, one had rup-
tured membranes and one withdrew her consent) and six women
were lost to follow-up in Helfgott 1994. This may have caused a
selection bias if loss to follow-up was associated with unfavourable
outcomes. There were apparently no exclusions nor losses to fol-
low-up in the study of Guinn 1997.
Selective reporting
Selective reporting bias was not obvious although assessments were
made from published study reports.
Hydration for treatment of preterm labour (Review)
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Other potential sources of bias
In both studies randomised groups appeared comparable at base-
line, and no obvious other bias was identified.
Effects of interventions
A total of 228 women with preterm labour and intact membranes
were included in the identified studies.
Primary Outcomes
Neither study reported on our primary outcomes (perinatal death
or serious neonatal morbidity).
Secondary outcomes
Neither study reported on pregnancy prolongation of more than
48 hours or 7 days.
Preterm delivery before 37 weeks was similar (risk ratio (RR) 1.09;
95% confidence interval (CI) 0.71 to 1.68) in the hydration and
control groups (Analysis 1.5). Delivery before 34 weeks (RR 0.72;
95% CI 0.20 to 2.56) or before 32 weeks (RR 0.76; 95% CI 0.29
to 1.97) were also similar between groups (Analysis 1.6; Analysis
1.7). Admission to neonatal intensive care unit occurred with the
same frequency in both groups (RR 0.99; 95% CI 0.46 to 2.16)
(Analysis 1.8).
No other prespecified perinatal or maternal morbidity outcomes
were reported.
Cost of treatment was slightly higher (US$39) in the hydration
group (Guinn 1997). This difference was not statistically signif-
icant and only included hospital costs during a visit of less than
24 hours. The interval between randomisation and delivery (not
prespecified) was similar in the two groups. Slightly less use of
tocolytic drugs (not prespecified) was reported in the hydration
group, but this difference was not statistically significant (RR 0.83;
95% CI 0.57 to 1.20) (Analysis 1.14).
Limited data are available for the subgroup of women included
before 34 weeks. Results are similar to those reported in all women
(Comparison 2). No trials evaluated oral hydration therapy.
DISCUSSION
The two included studies were of good methodological quality.
Both used intravenous hydration. They reported no significant
benefit of hydration, as compared with bed rest in women with
preterm labour. The diagnosis of preterm labour is difficult, as
shown by the fact that less than 30% of the participants delivered
preterm. Also, only about 30% of women received tocolytic drugs
after a period of evaluation with either bed rest alone or hydra-
tion. Allowing a period of evaluation before beginning therapeutic
7
interventions with tocolytic drugs is probably justified. This may
avoid unnecessary treatment and any associated risk of side effects.
It does not seem beneficial to use intravenous hydration during this
period of evaluation, except in women with evidence of dehydra-
tion. For this subgroup of women hydration should not be more
efficient as treatment of preterm labour, but could avoid maternal
or fetal complications related to hypovolaemia. Although the trials
are of good methodological quality, the number of participants is
too small to assess the impact on substantive outcomes such as
perinatal morbidity and mortality. The economic evaluation only
takes into account short-term direct hospital costs associated with
the initial visit and the first 24 hours. There is no evidence of an
economic benefit of hydration. No trials assessed womens view/
satisfaction with treatment.
AUTHORS CONCLUSIONS
Implications for practice
The data are too few to support the use of hydration as a specific
treatment for women presenting with preterm labour. The two
small studies available, conducted in women with intact mem-
branes, do not show any advantage of hydration compared with
bed rest alone. Intravenous hydration does not seem to be ben-
eficial, even during the period of evaluation in women admitted
with preterm labour. Women with evidence of dehydration may,
REFERENCES
References to studies included in this review
Guinn 1997 {published data only}
Guinn DA, Goepfert AR, Owen J, Brumfield C, Hauth
JC. Management options in women with preterm uterine
contractions: a randomized clinical trial. American Journal
of Obstetrics and Gynecology 1997;177:8148.
Guinn DA, Goepfert AR, Owen J, Brumfield CG, Hauth
JC. Management options in women with preterm uterine
contractions: a randomized clinical trial. American Journal
of Obstetrics and Gynecology 1997;176(1 Pt 2):S44.
Helfgott 1994 {published data only}
Helfgott AW, Willis DC, Abuhmaad A, Raimer K, Blanco
JD. Effect of hydration and/or sedation in threatened
preterm labor (abstract). American Journal of Obstetrics and
Gynecology 1991;164:310.
Helfgott AW, Willis DC, Blanco JD. Is hydration and
sedation beneficial in the treatment of threatened preterm
labor? A preliminary report. Journal of Maternal and Fetal
Medicine 1994;3:3742.
References to studies excluded from this review
Hydration for treatment of preterm labour (Review)
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
however, benefit from the intervention.
Implications for research
Hydration does not seem to be a promising intervention in the
treatment of women with suspected preterm labour. However, as
the data available are scarce, the use of this intervention should
limited to randomised trials with substantive outcomes.
ACKNOWLEDGEMENTS
Therese Dowswell for her help in preparing the 2013 update
and Sonja Henderson for her administrative support. Therese
Dowswells and Sonja Hendersons work was financially supported
by the UNDP/UNFPA/UNICEF/WHO/World Bank Special
Programme of Research, Development and Research Training
in Human Reproduction (HRP), Department of Reproductive
Health and Research (RHR), World Health Organization. The
named authors alone are responsible for the views expressed in this
publication.
The National Institute for Health Research (NIHR) is the largest
single funder of the Cochrane Pregnancy and Childbirth Group.
The views and opinions expressed therein are those of the authors
and do not necessarily reflect those of the NIHR, NHS or the
Department of Health.
Pircon 1989 {published data only}
Pircon RA, Strasser HT, Kirz DS, Towers CV. Controlled
trial of hydration and bedrest vs bedrest alone in the
evaluation of preterm uterine contractions. Proceedings
of 9th Annual Meeting of the Society of Perinatal
Obstetricians; 1989 Feb 1-4; New Orleans, Louisiana, USA.
1989:396.
Pircon RA, Strassner HT, Kirz DS, Towers CV. Controlled
trial of hydration and bed rest versus bed rest alone in
the evaluation of preterm uterine contractions. American
Journal of Obstetrics and Gynecology 1989;161:7759.
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Bieniarz 1971
Bieniarz J, Burd L, Motew M, Scommegna A. Inhibition of
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Bird TM, Bronstein JM, Hall RW, Lowery CL, Nugent R,
Mays GP. Late preterm infants: birth outcome and health
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Callaghan WM, MacDorman MF, Rasmussen SA, Qin C,
Lackritz EM. The contribution of preterm birth to infant
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Chang 2013
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Costeloe 2012
Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow
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Faron 1998
Faron G, Boulvain M, Irion O, Bernard PM, Fraser WD.
Prediction of preterm delivery by fetal fibronectin: a meta-
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Gauer 1976
Gauer OH, Henry JP. Neurohormonal control of plasma
volume. International Review of Physiology 1976;9:14590.
Goldenberg 2008
Goldenberg RL, Culhane JF, Iams JD, Romero R.
Epidemiology and causes of preterm birth. Lancet 2008;
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Goodlin 1981
Goodlin RC, Quaife MA, Dirksen JW. The significance,
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Haas 2012
Haas DM, Caldwell DM, Kirkpatrick P, McIntosh JJ,
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Hack 1994
Hack M, Taylor HG, Klein N, Eiben R, Schatschneider C,
Mercuri-Minich N. School-age outcomes in children with
birth weights under 750 g. New England Journal of Medicine
1994;331:7539.
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Hackney 2013
Hackney DN, Olson-Chen C, Thornburg LL. What do
we know about the natural outcomes of preterm labour?
A systematic review and meta-analysis of women without
tocolysis in preterm labour. Paediatric and Perinatal
Epidemiology 2013;27:45260.
Henderson 2012
Henderson JJ, McWilliam OA, Newnham JP, Pennell
CE. Preterm birth aetiology 2004-2008. Maternal factors
associated with three phenotypes: spontaneous preterm
labour, preterm pre-labour rupture of membranes and
medically indicated preterm birth. Journal of Maternal-Fetal
and Neonatal Medicine 2012;25:6427.
Higgins 2011
Higgins JPT, Green S, editors. Cochrane Handbook for
Systematic Reviews of Interventions Version 5.1.0 [updated
March 2011]. The Cochrane Collaboration, Available from
www.cochrane-handbook.org., 2011.
Mackeen 2011
Mackeen AD, Seibel-Seamon J, Grimes-Dennis J, Baxter
JK, Berghella V. Tocolytics for preterm premature rupture of
membranes. Cochrane Database of Systematic Reviews 2011,
Issue 10. [DOI: 10.1002/14651858.CD007062.pub2]
Martin 2011
Martin JA, Hamilton BE, Ventura SJ, Osterman MJ,
Kirmeyer S, Mathews TJ, et al. Births: final data for 2009.
National Vital Statistics Reports 2011;60:170.
Moutquin 2003
Moutquin JM. Classification and heterogeneity of preterm
birth. British Journal of Obstetrics and Gynaecology 2003;
110:303.
Oskoui 2013
Oskoui M, Coutinho F, Dykeman J, Jett N, Pringsheim T.
An update of the prevalence of cerebral palsy: a systematic
review and meta-analysis. Developmental Medicine and
Child Neurology 2013;55:50919.
Owen 2010
Owen J, Szychowski JM, Hankins G, Iams JD, SheffieldJS,
Perez-Delboy A, et al. Vaginal Ultrasound Trial Consortium.
Does midtrimester cervical length 25mm predict preterm
birth in high-risk women?. American Journal of Obstetrics
and Gynecology 2010;203:e15.
RevMan 2000 [Computer program]
The Cochrane Collaboration. Review Manager (RevMan).
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Collaboration. Review Manager (RevMan) [Computer
program]. Version 5.2.. Copenhagen: The Nordic
Cochrane Centre. The Cochrane Collaboration, 2012.
Russel 2007
Russel RB, Green NS, Steiner CA, Meikle S, Howse JL,
Poschman K, et al. Cost of hospitalisation for preterm and
9
 low birth weight infants in the United States. Pediatrics
2007;120:e19.
Valenzuela 1983
Valenzuela G, Cline S, Hayashi RH. Follow-up of hydration
and sedation in the pretherapy of premature labor. American
Journal of Obstetrics and Gynecology 1983;147:3968.
Wilson-Costello 2007
Wilson-Costello D, Friedman H, Minich N, Siner B, Taylor
G, Schluchter M, et al. Improved neurodevelopmental
Hydration for treatment of preterm labour (Review)
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
outcomes for extremely low birth weight infants in 2000-
2002. Pediatrics 2007;119:3745.
References to other published versions of this review
Stan 2002
Stan CM, Boulvain M, Pfister R, Hirsbrunner-Almagbaly
P. Hydration for treatment of preterm labour. Cochrane
Database of Systematic Reviews 2002, Issue 2. [DOI:
10.1002/14651858.CD003096]
Indicates the major publication for the study
10
CHARACTERISTICS OF STUDIES

Characteristics of included studies [ordered by study ID]

Guinn 1997

Methods Randomised controlled trial with 3 arms and individual randomisation

Participants Women at 20 to 34 weeks of gestation, with a singleton pregnancy, intact membranes at

risk for preterm delivery. Risk of preterm delivery was defined as: 3 or more contractions
per 30 minutes, cervical dilatation of 1 cm or less, cervical effacement less than 80%.
Exclusion criteria were non-reassuring fetal status, suspicion of infection and maternal
disease

Interventions Control group: bed rest alone (56 women).

Experimental group: IV hydration with 500 mL cristalloids over 20 minutes followed
by 200 mL/hour (62 women)

Outcomes Interval from randomisation to delivery and to discharge, gestational age at delivery,
delivery before 34 and 37 weeks, costs

Notes A third group treated with terbutaline is not included in this review

Risk of bias

Bias Authors judgement Support for judgement

Random sequence generation (selection Low risk computer-generated randomization

bias) schedule

Allocation concealment (selection bias) Low risk Consenting women were assigned to one
of three treatment groups by opening the
next sealed, opaque envelope

Blinding of participants and personnel High risk The treatment regimens were different, and
(performance bias) clinical decisions (which may have had an
All outcomes impact on outcomes) were made by staff
who knew which treatment women were
receiving

Blinding of outcome assessment (detection High risk Blinding of outcome assessors was not
bias) mentioned and treatment was likely to
All outcomes have been recorded in patient records out-
come data were abstracted from the medi-
cal record and the computerized perinatal
database

Incomplete outcome data (attrition bias) Low risk All participants seem to be accounted for.
All outcomes

Hydration for treatment of preterm labour (Review) 11

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Guinn 1997 (Continued)

Selective reporting (reporting bias) Unclear risk Assessment from published study report.

Other bias Low risk Groups appeared similar at baseline, other

bias not apparent

Helfgott 1994

Methods Randomised controlled trial. 3 arms with individual randomisation

Participants Women at 24 to 37 weeks of gestation, with a singleton pregnancy, intact membranes

at risk for preterm delivery. Risk of preterm delivery was defined as: regular painful
contractions, cervical dilatation of 4 cm or less, cervical effacement less than 100%.
Exclusion criteria were contraindication to tocolytics, obvious labour

Interventions Control group: bed rest alone (40 women).

Experimental groups:
IV hydration only: 500 mL lactate Ringer over 30 minutes (34 women).
IV hydration and morphine: hydration as above and 8-12 mg of morphine sulphate IM
(42 women)

Outcomes Interval from randomisation to delivery, delivery before 32 and 37 weeks, need for
additional treatment

Notes Hydration only and hydration + morphine groups were combined for the purpose of
this review

Risk of bias

Bias Authors judgement Support for judgement

Random sequence generation (selection Low risk the assignments were computer gener-
bias) ated.

Allocation concealment (selection bias) Low risk Allocations were placed in sealed opaque
envelopes, and opened at the time of entry

Blinding of participants and personnel High risk Women and clinicians were not blinded,
(performance bias) which may have affected clinical decisions
All outcomes about their care

Blinding of outcome assessment (detection Unclear risk It was stated that some outcome assessment
bias) was blinded, but for other outcomes it was
All outcomes no clear that assessors were blind to treat-
ment group. The monitor tracings were
analysed by a blinded observer so as not to
bias the information regarding uterine con-
tractions upon entry and completion of the
study

Hydration for treatment of preterm labour (Review) 12

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Helfgott 1994 (Continued)

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk 5 out of 124 women were enrolled into the
study but then excluded. Another 3 sub-
sequently left the study. Delivery informa-
tion was available for 110 women, (11.3%
attrition)

Selective reporting (reporting bias) Unclear risk Assessment from published study report.

Other bias Low risk Groups appeared comparable at baseline.

Other bias not apparent

IM: intramuscular
IV: intravenous

Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Pircon 1989 Inadequate method of concealment of the allocation (alternate date). Women in the control group were treated with
hydration after 2 hours if contractions persisted. 3 women were readmitted after the initial treatment and included
again in the study, with a cross-over of the intervention. Report of the results is unclear

Hydration for treatment of preterm labour (Review) 13

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DATA AND ANALYSES

Comparison 1. Hydration versus no treatment/bed rest alone (all women)

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Perinatal death 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
2 Severe neonatal morbidity 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
3 Prolongation of pregnancy more 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
than 48 hours
4 Prolongation of pregnancy more 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
than seven days
5 Delivery before 37 weeks 2 228 Risk Ratio (M-H, Fixed, 95% CI) 1.09 [0.71, 1.68]
6 Delivery before 34 weeks 1 118 Risk Ratio (M-H, Fixed, 95% CI) 0.72 [0.20, 2.56]
7 Delivery before 32 weeks 1 110 Risk Ratio (M-H, Fixed, 95% CI) 0.76 [0.29, 1.97]
8 Admission to neonatal intensive 1 118 Risk Ratio (M-H, Fixed, 95% CI) 0.99 [0.46, 2.16]
care unit
9 Low birthweight (less than 2500 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
g)
10 Very low birthweight (less than 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
1500 g)
11 Maternal death 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
12 Womens assessment of their 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
treatment
13 Cost of treament (first 24 1 103 Mean Difference (IV, Fixed, 95% CI) 39.0 [-26.11, 104.
hours, in US$) 11]
14 Use of tocolytic drugs (not 2 234 Risk Ratio (M-H, Fixed, 95% CI) 0.83 [0.57, 1.20]
prespecified)
15 Time to delivery (days, not 2 228 Mean Difference (IV, Fixed, 95% CI) -0.99 [-7.85, 5.87]
prespecified)

Comparison 2. Hydration versus no treatment/bed rest alone (women included before 34 weeks)

No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size

1 Prolongation of pregnancy more 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
than 48 hours
2 Prolongation of pregnancy more 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
than seven days
3 Delivery before 32 weeks 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
4 Delivery before 34 weeks 1 118 Risk Ratio (M-H, Fixed, 95% CI) 0.72 [0.20, 2.56]
5 Delivery before 37 weeks 1 118 Risk Ratio (M-H, Fixed, 95% CI) 1.32 [0.72, 2.42]
6 Low birthweight (less than 2500 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
g)
Hydration for treatment of preterm labour (Review) 14
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
7 Very low birthweight (less than 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
1500 g)
8 Perinatal death 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
9 Severe neonatal morbidity 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
10 Admission to neonatal intensive 1 118 Risk Ratio (M-H, Fixed, 95% CI) 0.99 [0.46, 2.16]
care unit
11 Maternal death 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
12 Womens assessment of their 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
treatment
13 Cost of treament (first 24 1 103 Mean Difference (IV, Fixed, 95% CI) 39.0 [-26.11, 104.
hours, in US$) 11]
14 Use of tocolytic drugs (not 1 118 Risk Ratio (M-H, Fixed, 95% CI) 0.72 [0.31, 1.70]
prespecified)
15 Time to delivery (days, not 1 118 Mean Difference (IV, Fixed, 95% CI) -4.30 [-13.61, 5.01]
prespecified)

Analysis 1.5. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 5
Delivery before 37 weeks.

Review: Hydration for treatment of preterm labour

Comparison: 1 Hydration versus no treatment/bed rest alone (all women)

Outcome: 5 Delivery before 37 weeks

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Guinn 1997 19/62 13/56 48.3 % 1.32 [ 0.72, 2.42 ]

Helfgott 1994 19/73 11/37 51.7 % 0.88 [ 0.47, 1.64 ]

Total (95% CI) 135 93 100.0 % 1.09 [ 0.71, 1.68 ]

Total events: 38 (Treatment), 24 (Control)
Heterogeneity: Chi2 = 0.85, df = 1 (P = 0.36); I2 =0.0%
Test for overall effect: Z = 0.39 (P = 0.70)
Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Hydration for treatment of preterm labour (Review) 15

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 1.6. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 6
Delivery before 34 weeks.

Review: Hydration for treatment of preterm labour

Comparison: 1 Hydration versus no treatment/bed rest alone (all women)

Outcome: 6 Delivery before 34 weeks

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Guinn 1997 4/62 5/56 100.0 % 0.72 [ 0.20, 2.56 ]

Total (95% CI) 62 56 100.0 % 0.72 [ 0.20, 2.56 ]

Total events: 4 (Treatment), 5 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.50 (P = 0.61)
Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Analysis 1.7. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 7
Delivery before 32 weeks.

Review: Hydration for treatment of preterm labour

Comparison: 1 Hydration versus no treatment/bed rest alone (all women)

Outcome: 7 Delivery before 32 weeks

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Helfgott 1994 9/73 6/37 100.0 % 0.76 [ 0.29, 1.97 ]

Total (95% CI) 73 37 100.0 % 0.76 [ 0.29, 1.97 ]

Total events: 9 (Treatment), 6 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.56 (P = 0.57)
Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Hydration for treatment of preterm labour (Review) 16

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 1.8. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 8
Admission to neonatal intensive care unit.
Review: Hydration for treatment of preterm labour

Comparison: 1 Hydration versus no treatment/bed rest alone (all women)

Outcome: 8 Admission to neonatal intensive care unit

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Guinn 1997 11/62 10/56 100.0 % 0.99 [ 0.46, 2.16 ]

Total (95% CI) 62 56 100.0 % 0.99 [ 0.46, 2.16 ]

Total events: 11 (Treatment), 10 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.02 (P = 0.99)
Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Analysis 1.13. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 13 Cost
of treament (first 24 hours, in US$).

Review: Hydration for treatment of preterm labour

Comparison: 1 Hydration versus no treatment/bed rest alone (all women)

Outcome: 13 Cost of treament (first 24 hours, in US$)

Mean Mean
Study or subgroup Treatment Control Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Guinn 1997 54 246 (172) 49 207 (165) 100.0 % 39.00 [ -26.11, 104.11 ]

Total (95% CI) 54 49 100.0 % 39.00 [ -26.11, 104.11 ]

Heterogeneity: not applicable
Test for overall effect: Z = 1.17 (P = 0.24)
Test for subgroup differences: Not applicable

-100 -50 0 50 100

Favours treatment Favours control

Hydration for treatment of preterm labour (Review) 17

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 1.14. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 14 Use
of tocolytic drugs (not prespecified).

Review: Hydration for treatment of preterm labour

Comparison: 1 Hydration versus no treatment/bed rest alone (all women)

Outcome: 14 Use of tocolytic drugs (not prespecified)

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Guinn 1997 8/62 10/56 28.6 % 0.72 [ 0.31, 1.70 ]

Helfgott 1994 33/76 20/40 71.4 % 0.87 [ 0.58, 1.30 ]

Total (95% CI) 138 96 100.0 % 0.83 [ 0.57, 1.20 ]

Total events: 41 (Treatment), 30 (Control)
Heterogeneity: Chi2 = 0.15, df = 1 (P = 0.70); I2 =0.0%
Test for overall effect: Z = 1.00 (P = 0.32)
Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Analysis 1.15. Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 15 Time
to delivery (days, not prespecified).

Review: Hydration for treatment of preterm labour

Comparison: 1 Hydration versus no treatment/bed rest alone (all women)

Outcome: 15 Time to delivery (days, not prespecified)

Mean Mean
Study or subgroup Treatment Control Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Guinn 1997 62 55.7 (26.9) 56 60 (24.7) 54.3 % -4.30 [ -13.61, 5.01 ]

Helfgott 1994 73 49.91 (25.63) 37 46.96 (25.68) 45.7 % 2.95 [ -7.20, 13.10 ]

Total (95% CI) 135 93 100.0 % -0.99 [ -7.85, 5.87 ]

Heterogeneity: Chi2 = 1.06, df = 1 (P = 0.30); I2 =6%
Test for overall effect: Z = 0.28 (P = 0.78)
Test for subgroup differences: Not applicable

-10 -5 0 5 10
Favours control Favours treatment

Hydration for treatment of preterm labour (Review) 18

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 2.4. Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34
weeks), Outcome 4 Delivery before 34 weeks.

Review: Hydration for treatment of preterm labour

Comparison: 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks)

Outcome: 4 Delivery before 34 weeks

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Guinn 1997 4/62 5/56 100.0 % 0.72 [ 0.20, 2.56 ]

Total (95% CI) 62 56 100.0 % 0.72 [ 0.20, 2.56 ]

Total events: 4 (Treatment), 5 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.50 (P = 0.61)
Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Hydration for treatment of preterm labour (Review) 19

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 2.5. Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34
weeks), Outcome 5 Delivery before 37 weeks.

Review: Hydration for treatment of preterm labour

Comparison: 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks)

Outcome: 5 Delivery before 37 weeks

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Guinn 1997 19/62 13/56 100.0 % 1.32 [ 0.72, 2.42 ]

Total (95% CI) 62 56 100.0 % 1.32 [ 0.72, 2.42 ]

Total events: 19 (Treatment), 13 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.90 (P = 0.37)
Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Analysis 2.10. Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34
weeks), Outcome 10 Admission to neonatal intensive care unit.

Review: Hydration for treatment of preterm labour

Comparison: 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks)

Outcome: 10 Admission to neonatal intensive care unit

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Guinn 1997 11/62 10/56 100.0 % 0.99 [ 0.46, 2.16 ]

Total (95% CI) 62 56 100.0 % 0.99 [ 0.46, 2.16 ]

Total events: 11 (Treatment), 10 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.02 (P = 0.99)
Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Hydration for treatment of preterm labour (Review) 20

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 2.13. Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34
weeks), Outcome 13 Cost of treament (first 24 hours, in US$).

Review: Hydration for treatment of preterm labour

Comparison: 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks)

Outcome: 13 Cost of treament (first 24 hours, in US$)

Mean Mean
Study or subgroup Treatment Control Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Guinn 1997 54 246 (172) 49 207 (165) 100.0 % 39.00 [ -26.11, 104.11 ]

Total (95% CI) 54 49 100.0 % 39.00 [ -26.11, 104.11 ]

Heterogeneity: not applicable
Test for overall effect: Z = 1.17 (P = 0.24)
Test for subgroup differences: Not applicable

-100 -50 0 50 100

Favours treatment Favours control

Analysis 2.14. Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34
weeks), Outcome 14 Use of tocolytic drugs (not prespecified).

Review: Hydration for treatment of preterm labour

Comparison: 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks)

Outcome: 14 Use of tocolytic drugs (not prespecified)

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Guinn 1997 8/62 10/56 100.0 % 0.72 [ 0.31, 1.70 ]

Total (95% CI) 62 56 100.0 % 0.72 [ 0.31, 1.70 ]

Total events: 8 (Treatment), 10 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.74 (P = 0.46)
Test for subgroup differences: Not applicable

0.1 0.2 0.5 1 2 5 10

Favours treatment Favours control

Hydration for treatment of preterm labour (Review) 21

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Analysis 2.15. Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34
weeks), Outcome 15 Time to delivery (days, not prespecified).

Review: Hydration for treatment of preterm labour

Comparison: 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks)

Outcome: 15 Time to delivery (days, not prespecified)

Mean Mean
Study or subgroup Treatment Control Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Guinn 1997 62 55.7 (26.9) 56 60 (24.7) 100.0 % -4.30 [ -13.61, 5.01 ]

Total (95% CI) 62 56 100.0 % -4.30 [ -13.61, 5.01 ]

Heterogeneity: not applicable
Test for overall effect: Z = 0.91 (P = 0.37)
Test for subgroup differences: Not applicable

-10 -5 0 5 10
Favours treatment Favours control

APPENDICES

Appendix 1. Methods used in previous versions of the review

The identified reports were read independently by two review authors to determine if the study met the inclusion criteria and to evaluate
the methodological quality. Any disagreement was resolved by consensus.
Methodological quality of included trials was assessed using the methods described in the Cochrane Handbook (Clarke 2000): Grade A:
adequate concealment, Grade B: uncertain, Grade C: inadequate concealment. Other quality factors taken into consideration included
blinding and losses to follow-up. Data were extracted independently by two of the review authors. The results were expressed as risk
ratios for dichotomous outcomes and mean difference for continuous outcomes. Their 95% confidence intervals were computed, using
the Cochrane Review Manager software (RevMan 2000). In the case of significant heterogeneity between studies, a sensitivity analysis
would have been performed to assess the impact on the results of study quality and characteristics. The following comparisons were
performed: any type of hydration versus bed rest alone. Subgroup analysis would have included oral versus intravenous hydration and
prelabour preterm rupture of membranes versus intact membranes, but separate data were not available. A subgroup analysis of women
included at less than 34 weeks of gestation was performed.

Hydration for treatment of preterm labour (Review) 22

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
WHATS NEW
Last assessed as up-to-date: 3 October 2013.

Date Event Description

17 December 2013 Amended The graph labels for outcome 1.15 (time to delivery in days) were the wrong way around. We have
therefore corrected them. There are no implications for the text of the review

HISTORY
Protocol first published: Issue 2, 2001
Review first published: Issue 2, 2002

Date Event Description

3 October 2013 New citation required but conclusions have not Review updated.
changed

30 September 2013 New search has been performed Search updated. No new trials identified.

31 May 2009 New search has been performed Search updated. No new trials identified.

24 April 2008 Amended Converted to new review format.

27 June 2007 New search has been performed Search updated. One addtional trial report added to
Guinn 1997 and one additional trial report added to
Pircon 1989.

CONTRIBUTIONS OF AUTHORS
The 2013 update was prepared by Catalin Stan with contributions from the other authors.
Catalin Stan and Michel Boulvain wrote the protocol, extracted the data and drafted the text of the first version of this review (Stan
2002). Pascale Hirsbrunner-Almagbaly and Riccardo Pfister contributed to the protocol and to the final text of the review. Pascale
Hirsbrunner-Almagbaly did the initial search of the studies.

Hydration for treatment of preterm labour (Review) 23

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DECLARATIONS OF INTEREST
None known.

SOURCES OF SUPPORT

Internal sources
University of Geneva, Switzerland.

External sources
UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human
Reproduction (HRP), Department of Reproductive Health and Research (RHR), World Health Organization, Switzerland.

DIFFERENCES BETWEEN PROTOCOL AND REVIEW

We updated the Background and the Data collection and analysis text of the 2013 updated review.

INDEX TERMS

Medical Subject Headings (MeSH)

Bed Rest; Fluid Therapy [ methods]; Infusions, Intravenous; Obstetric Labor, Premature [ therapy]; Randomized Controlled Trials as
Topic

MeSH check words

Female; Humans; Pregnancy

Hydration for treatment of preterm labour (Review) 24

Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.