Hydration for treatment of preterm labour

  • Review
  • Intervention

Authors


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 Group's 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 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.

Résumé scientifique

Hydratation dans le traitement du travail prématuré

Contexte

L'hydratation a été proposée comme traitement destiné aux femmes en travail prématuré. En théorie, l'hydratation peut réduire la contractilité utérine en augmentant le flux sanguin utérin et en diminuant la sécrétion hypophysaire de l'hormone antidiurétique et de l'ocytocine.

Objectifs

Évaluer l'efficacité de l'hydratation intraveineuse ou orale afin d'éviter un accouchement prématuré, ainsi que ses conséquences chez les femmes dont l'accouchement est prématuré.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre d'essais du groupe Cochrane sur la grossesse et la naissance (30 septembre 2013) et les bibliographies des articles pertinents.

Critères de sélection

Des essais contrôlés randomisés, incluant des femmes dont la grossesse est viable et inférieure à 37 semaines révolues et présentant un travail prématuré, qui comparent l'hydratation intraveineuse ou orale à l'absence de traitement. L'intervention peut, ou pas, être associée à l'alitement. Les études comparant des médicaments tocolytiques à des perfusions intraveineuses de liquides pratiquées dans le groupe témoin en guise de placebo n'étaient pas incluses dans la présente revue.

Recueil et analyse des données

Deux auteurs de la revue ont indépendamment évalué les rapports afin de déterminer si l'étude répondait aux critères d'inclusion et d'évaluer sa qualité méthodologique. Deux des auteurs de la revue ont indépendamment extrait des données. Les résultats étaient exprimés sous la forme de risques relatifs (RR) pour les résultats dichotomiques et d'une différence moyenne pour les résultats continus.

Résultats principaux

Deux études, incluant un total de 228 femmes présentant un travail prématuré et des membranes intactes, comparaient l'hydratation intraveineuse à l'alitement seul. Les risques d'accouchement prématuré, avant 37 semaines (RR 1,09 ; intervalle de confiance (IC) à 95 % 0,71 à 1,68), avant 34 semaines (RR 0,72 ; IC à 95 % 0,20 à 2,56) ou avant 32 semaines (RR 0,76 ; IC à 95 % 0,29 à 1,97), étaient similaires entre les groupes. L'admission en unité de soins intensifs néonataux survenait à une fréquence similaire dans les deux groupes (RR 0,99 ; IC à 95 % 0,46 à 2,16). Le coût du traitement était légèrement plus élevé (39 US$) dans le groupe d'hydratation. Cette différence n'était pas statistiquement significative et inclut uniquement les frais d'hospitalisation pour une visite inférieure à 24 heures. Aucune étude n'a examiné l'hydratation orale.

Conclusions des auteurs

Les données n'étaient pas suffisamment nombreuses pour recommander le recours à l'hydratation comme traitement spécifique des femmes présentant un travail prématuré. Les deux études disponibles et de petite taille ne montrent aucun effet bénéfique de l'hydratation par rapport à l'alitement seul. L'hydratation intraveineuse ne semble pas avoir d'effets bénéfiques, même lors de la période d'évaluation peu après l'admission, chez les femmes présentant un travail prématuré. Toutefois, les femmes présentant des signes de déshydratation peuvent bénéficier de cette 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 woman's 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.

Résumé simplifié

Hydratation dans le traitement du travail prématuré

Sauf cas de déshydratation, il semblerait que les perfusions intraveineuses de suppléments de liquides ne présentent aucun effet bénéfique chez les femmes en travail prématuré.

Un accouchement prématuré (avant 37 semaines) peut provoquer des problèmes de santé et se révéler potentiellement mortel pour les bébés. Étant donné que les femmes en travail prématuré présentent généralement une baisse de la quantité de liquide dans leur organisme, une mise sous perfusion est parfois pratiquée (hydratation) afin d'essayer d'augmenter le volume sanguin de la femme. Ceci, dans l'espoir que ce supplément de liquide permette en quelque sorte de ralentir les contractions. Toutefois, d'après les informations limitées disponibles (deux études impliquant 228 femmes), la revue a trouvé qu'il n'existe aucune preuve d'un effet bénéfique de l'hydratation dans la prévention du travail prématuré, bien qu'elle puisse être bénéfique pour les femmes déshydratées.

Notes de traduction

Traduit par: French Cochrane Centre 19th December, 2013
Traduction financée par: Ministère du Travail, de l'Emploi et de la Santé Français

Laički sažetak

Davanje dodatne tekućine za liječenje preuranjenih trudova

Prema trenutnim dokazima iz istraživanja nema koristi od davanja dodatne intravenske tekućine ženama kod prijevremenog poroda osim ako su žene dehidrirane.

Prijevremeni porod (prije 37. tjedna) može uzrokovati zdravstvene i po život opasne probleme kod djece. Kako žene kod prijevremenog poroda često imaju niže količine tekućine u cirkulaciji, ponekad se pokušava povećati volumen krvi žene (hidratacija) pomoću intravenske infuzije. To se radi jer se očekuje da bi dodatna tekućina nekako mogla usporiti trudove. Međutim, temeljem ograničenih dostupnih informacijama (dvije studije koje uključuju 228 žena), ovaj Cochrane sustavni pregled je utvrdio da trenutno nema dokaza da hidratacij može imati koristan učinak na sprječavanje prijevremenog poroda, iako to može biti korisno za žene koje su dehidrirane.

Bilješke prijevoda

Cochrane Hrvatska
Prevela: Božena Armanda
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr

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 intensive care unit after delivery at 20 to 26 weeks showed an overall 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 neurodevelopmental 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).

Preterm birth usually follows either preterm labour, preterm prelabour rupture of membranes or a medical decision to terminate 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 membranes (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 ultrasonography are limited predictors of preterm delivery (Chang 2013; Faron 1998; Goldenberg 2008; Owen 2010). Therefore, 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 pregnancy would be expected to decrease neonatal mortality and improve subsequent child development by reducing the effects of prematurity. 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.

Despite the development of various therapeutic interventions in recent decades, little progress has been made in reducing the incidence of preterm birth (Haas 2012; Martin 2011). Pharmacological agents currently used to inhibit uterine contractions include betamimetics, magnesium sulphate, prostaglandin inhibitors, calcium channel blockers and oxytocin receptor antagonists (Haas 2012; Mackeen 2011). Some authors, based on uncontrolled observations, have suggested that intravenous hydration might decrease contractions or delay the delivery in women presenting with preterm contractions (Bieniarz 1971; Goodlin 1981). Studies 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 deliver 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 providing 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 decidual 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 simultaneously (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 decrease uterine contractions by decreasing prostaglandin production 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 authors. A separate analysis was performed for women included before 34 completed weeks' gestation. A subgroup comparison of 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, women's assessment of their treatment.

Percentage of caesarean section, instrumental delivery or other outcomes that the authors of the original trials have reported would have been included in the analysis, if available. Economic evaluations 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).

Search methods for identification of studies

Electronic searches

We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register by contacting the Trials Search Co-ordinator (30 September 2013).

The Cochrane Pregnancy and Childbirth Group’s 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 proceedings, and the list of journals reviewed via the current awareness 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.

Data extraction and management

We designed a form to extract data. For eligible studies, two review authors extracted the data. We resolved discrepancies through discussion 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 information.

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 advance 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.

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 intervention 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 attrition 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 study’s pre-specified outcomes and all expected outcomes of interest to the review have been reported);

  • high risk of bias (where not all the study’s 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.

(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 concerns 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 variation in the ICC. If we identify both cluster-randomised trials and individually-randomised trials, we plan to synthesise the relevant information. We will consider it reasonable to combine the results 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 sensitivity 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 participants randomised to each group in the analyses, and all participants are analysed in the group to which they were allocated, regardless 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 Tau², I² and Chi² statistics. We would have regarded heterogeneity as substantial if an I² was greater than 30% and either the Tau² greater than zero, or there was a low P value (less than 0.10) in the Chi² test for heterogeneity.

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 clinical heterogeneity sufficient to expect that the underlying treatment effects differed between trials, or if substantial statistical heterogeneity 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 Chi² statistic and P value, and the interaction test I² value.

Sensitivity analysis

If we had included cluster-randomised trials in the review, we planned to carry out sensitivity analysis. We also planned sensitivity 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.

Results

Description of studies

Two studies were included (Guinn 1997; Helfgott 1994). Both trials included women with preterm contractions and cervical modifications (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, hydration and hydration+morphine were compared with bed rest. The first two groups were combined, as there is no evidence of a tocolytic 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 decisions 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 ruptured 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 follow-up in the study of Guinn 1997.

Selective reporting

Selective reporting bias was not obvious although assessments were made from published study reports.

Other potential sources of bias

In both studies randomised groups appeared comparable at baseline, 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 significant 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 hydration. Allowing a period of evaluation before beginning therapeutic 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 dehydration. 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 women's 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 membranes, 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 in women admitted with preterm labour. Women with evidence of dehydration may, 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 Dowswell's and Sonja Henderson's 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.

Data and analyses

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Comparison 1. Hydration versus no treatment/bed rest alone (all women)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Perinatal death00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
2 Severe neonatal morbidity00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
3 Prolongation of pregnancy more than 48 hours00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
4 Prolongation of pregnancy more than seven days00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
5 Delivery before 37 weeks2228Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.71, 1.68]
6 Delivery before 34 weeks1118Risk Ratio (M-H, Fixed, 95% CI)0.72 [0.20, 2.56]
7 Delivery before 32 weeks1110Risk Ratio (M-H, Fixed, 95% CI)0.76 [0.29, 1.97]
8 Admission to neonatal intensive care unit1118Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.46, 2.16]
9 Low birthweight (less than 2500 g)00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
10 Very low birthweight (less than 1500 g)00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
11 Maternal death00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
12 Women's assessment of their treatment00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
13 Cost of treament (first 24 hours, in US$)1103Mean Difference (IV, Fixed, 95% CI)39.0 [-26.11, 104.11]
14 Use of tocolytic drugs (not prespecified)2234Risk Ratio (M-H, Fixed, 95% CI)0.83 [0.57, 1.20]
15 Time to delivery (days, not prespecified)2228Mean Difference (IV, Fixed, 95% CI)-0.99 [-7.85, 5.87]
Analysis 1.5.

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

Analysis 1.6.

Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 6 Delivery before 34 weeks.

Analysis 1.7.

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

Analysis 1.8.

Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 8 Admission to neonatal intensive care unit.

Analysis 1.13.

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

Analysis 1.14.

Comparison 1 Hydration versus no treatment/bed rest alone (all women), Outcome 14 Use of tocolytic drugs (not prespecified).

Analysis 1.15.

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

Comparison 2. Hydration versus no treatment/bed rest alone (women included before 34 weeks)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Prolongation of pregnancy more than 48 hours00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
2 Prolongation of pregnancy more than seven days00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
3 Delivery before 32 weeks00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
4 Delivery before 34 weeks1118Risk Ratio (M-H, Fixed, 95% CI)0.72 [0.20, 2.56]
5 Delivery before 37 weeks1118Risk Ratio (M-H, Fixed, 95% CI)1.32 [0.72, 2.42]
6 Low birthweight (less than 2500 g)00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
7 Very low birthweight (less than 1500 g)00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
8 Perinatal death00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
9 Severe neonatal morbidity00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
10 Admission to neonatal intensive care unit1118Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.46, 2.16]
11 Maternal death00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
12 Women's assessment of their treatment00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
13 Cost of treament (first 24 hours, in US$)1103Mean Difference (IV, Fixed, 95% CI)39.0 [-26.11, 104.11]
14 Use of tocolytic drugs (not prespecified)1118Risk Ratio (M-H, Fixed, 95% CI)0.72 [0.31, 1.70]
15 Time to delivery (days, not prespecified)1118Mean Difference (IV, Fixed, 95% CI)-4.30 [-13.61, 5.01]
Analysis 2.4.

Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks), Outcome 4 Delivery before 34 weeks.

Analysis 2.5.

Comparison 2 Hydration versus no treatment/bed rest alone (women included before 34 weeks), Outcome 5 Delivery before 37 weeks.

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.

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$).

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).

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).

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.

What's new

Last assessed as up-to-date: 3 October 2013.

DateEventDescription
17 December 2013AmendedThe 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

DateEventDescription
3 October 2013New citation required but conclusions have not changedReview updated.
30 September 2013New search has been performedSearch updated. No new trials identified.
31 May 2009New search has been performedSearch updated. No new trials identified.
24 April 2008AmendedConverted to new review format.
27 June 2007New search has been performedSearch 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.

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.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Guinn 1997

MethodsRandomised controlled trial with 3 arms and individual randomisation.
ParticipantsWomen 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.
InterventionsControl group: bed rest alone (56 women).
Experimental group: IV hydration with 500 mL cristalloids over 20 minutes followed by 200 mL/hour (62 women).
OutcomesInterval from randomisation to delivery and to discharge, gestational age at delivery, delivery before 34 and 37 weeks, costs.
NotesA third group treated with terbutaline is not included in this review.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk“computer-generated randomization 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 (performance bias)
All outcomes
High riskThe treatment regimens were different, and clinical decisions (which may have had an impact on outcomes) were made by staff who knew which treatment women were receiving.
Blinding of outcome assessment (detection bias)
All outcomes
High riskBlinding of outcome assessors was not mentioned and treatment was likely to have been recorded in patient records “outcome data were abstracted from the medical record and the computerized perinatal database”.
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll participants seem to be accounted for.
Selective reporting (reporting bias)Unclear riskAssessment from published study report.
Other biasLow riskGroups appeared similar at baseline, other bias not apparent.

Helfgott 1994

  1. a

    IM: intramuscular
    IV: intravenous

MethodsRandomised controlled trial. 3 arms with individual randomisation.
ParticipantsWomen 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.
InterventionsControl 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).
OutcomesInterval from randomisation to delivery, delivery before 32 and 37 weeks, need for additional treatment.
NotesHydration only and hydration + morphine groups were combined for the purpose of this review.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk“the assignments were computer generated".
Allocation concealment (selection bias)Low riskAllocations were “placed in sealed opaque envelopes, and opened at the time of entry”.
Blinding of participants and personnel (performance bias)
All outcomes
High riskWomen and clinicians were not blinded, which may have affected clinical decisions about their care.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskIt was stated that some outcome assessment was blinded, but for other outcomes it was no clear that assessors were blind to treatment group. “The monitor tracings were analysed by a blinded observer so as not to bias the information regarding uterine contractions upon entry and completion of the study”.
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk5 out of 124 women were enrolled into the study but then excluded. Another 3 subsequently left the study. Delivery information was available for 110 women, (11.3% attrition).
Selective reporting (reporting bias)Unclear riskAssessment from published study report.
Other biasLow riskGroups appeared comparable at baseline. Other bias not apparent.

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Pircon 1989Inadequate 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.

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