Planned early delivery versus expectant management of the term suspected compromised baby for improving outcomes
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To compare the fetal and maternal outcome in expectant management versus planned early delivery for women presenting with a suspected compromised fetus from 37 weeks' gestation or greater.
Background
Fetal compromise can occur secondary to problems related to maternal, fetal or placental factors which result in inadequate oxygen or nutrient supply to the fetus. The presentation of fetal compromise in the term pregnancy is variable and can be suspected based on a number of factors. Intrauterine growth restriction (IUGR) and decreased fetal movement (DFM) are both indicative of either long‐term or short‐term placental insufficiency. Investigations routinely performed to assess fetal well‐being, such as the cardiotocograph or ultrasound parameters such as amniotic fluid volume, fetal biometry and fetal/umbilical artery dopplers, can produce results leading to suspicion of a compromised fetus. Pathological results would necessitate the need for immediate delivery, but the management for 'suspicious' results remains unclear.
Determining the optimal timing of delivery in pregnancies with a suspected compromised fetus remains an issue even after 37 weeks' gestation. The balance between allowing the fetus to remain in utero for the development of full lung maturation must be weighed against removing the fetus from an environment suspected to be harmful. Expectant management may result in complications associated with postmaturity such as perinatal mortality, meconium aspiration syndrome (Gülmezoglu 2006), hypoxic ischaemic encephalopathy and neonatal sepsis (Cheng 2008). Conversely, planned early delivery may result in increased intervention and poor fetal outcomes. Previous studies have documented a correlation between induction of labour at term and adverse outcomes such as increased caesarean section rate (Seyb 1999). Other studies found that the incidence of respiratory morbidity was halved for each week of prolongation of pregnancy between 37 and 39+6 weeks (Morrison 1995; Stutchfield 2005). The complications of planned early delivery may not be justified, especially in cases of misdiagnosis. However, a recent randomized controlled trial that compared preventive labour induction with expectant management for women with pre‐specified risk factors actually showed a reduction in adverse outcomes such as caesarean section rate and neonatal intensive care unit admission and an increase in uncomplicated vaginal deliveries (Nicholson 2008).
The decision to deliver the fetus immediately or wait either until labour commences or further signs merit delivery varies significantly among populations, institutions and practitioners within single institutions. In view of the high number of adverse outcomes associated with a suspected compromised fetus at term, there is a need to assess the benefits and harms of planned early delivery versus expectant management of women with a term pregnancy.
Description of the condition
The suspected compromised fetus in a term pregnancy can be identified by one of the following.
1. Clinical suspicion
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Maternal perception of decreased fetal activity is a common complaint, and one of the most frequent causes of unplanned visits in pregnancy. Between 4% and 15% will contact care providers with such concerns in the third trimester (Froen 2004). DFM has a well‐established role as an adaptive response to the various stages of placental insufficiency and hypoxia (Froen 2008). Normal fetal movements (FM) are a highly specific indicator of fetal viability, and women presenting with DFM have higher risk of stillbirth, fetal growth restriction, fetal distress, preterm birth and other associated outcomes (Froen 2008). Randomized trials however have not shown that routine counting of fetal movements in low‐risk pregnancies improves outcomes, and there is a lack of guidelines for the management of DFM as acknowledged in a recent Cochrane review (Hofmeyr 2011). The two guidelines currently available, from the Royal College of Obstetrics and Gynaecology in the UK and the Australia New Zealand Stillbirth Alliance, are based on consensus rather than strong evidence (ANZSA 2010; RCOG 2011).
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Fundal height measurement is a simple, inexpensive and widely used clinical screening test in assessing fetal growth and development in low‐risk populations despite the low detection rate with this method alone (Kean 1996).
2. Sonographic biometry/growth measurements
The accurate measurement and documentation of biometric parameters provide an important basis for the evaluation of fetal growth in the suspicion of growth disturbances such as intrauterine growth restriction and macrosomia.
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IUGR is defined as failure of a baby to reach its growth potential. This can be due to maternal, fetal or placental factors and implies a pathological process distinct from defining a baby as small‐for‐gestational age. IUGR identified in the antepartum period refers to a fetus with sonographically measured fetal dimensions, particularly abdominal circumference or estimated weight, below an age‐specific threshold, typically the 10th percentile (Maulik 2004). IUGR is considered one of the major complications of pregnancy. It increases the risk of perinatal mortality and morbidity, as well as long‐term adverse consequences such as adult onset cardiovascular disease (Maulik 2006). Perinatal complications include prematurity, oligohydramnios, non‐reassuring fetal heart rate patterns with a higher incidence of cesarean delivery, birth asphyxia, low Apgar score, neonatal hypoglycaemia, hypocalcaemia, polycythaemia, hyperbilirubinaemia, hypothermia, apnoea, seizure disorders, and infection (Maulik 2004).
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Macrosomia describes a large fetus, with an estimated fetal weight greater than the 90th percentile after correcting for sex and ethnicity, or greater than 4500 g. This condition is associated with increased fetal and neonatal morbidity and mortality. Most complications are related to delivery, including shoulder dystocia and birth trauma. Macrosomia associated with maternal diabetes carries a higher risk of intrauterine death. Monitoring of fetal weight can be used to determine the optimal time for delivery (Nyberg 2004). Outcomes looking at the effects of labour induction for suspected fetal macrosomia is the focus of another Cochrane review (Irion 1998) and will not be included in this review.
3. Doppler ultrasound
Doppler ultrasound provides a non‐invasive method for the study of fetal haemodynamics and uses these findings for assessing the condition of the fetus. Doppler studies are valuable in high‐risk women and generally, when performed earlier than 34 weeks' gestation (Alfirevic 2010). The ability of this test to identify a compromised baby at term is less clear. When inadequate vascularization of the placenta occurs (placental insufficiency), the following haemodynamic changes in the feto‐placental circulation develop, often in a progressive fashion.
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Umbilical artery Doppler can detect increased resistance or absent or reversed end‐diastolic flow. This reflects increasing placental vascular resistance.
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Fetal arterial Doppler (e.g. middle cerebral artery or aortic isthmus) can detect decreased resistance, indicative of protection of blood flow to the fetal brain in impaired placental function.
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Fetal venous Doppler (e.g. ductus venosus or inferior vena cava) can detect abnormalities which reflect preterminal impairment of cardiac function and fetal acidosis.
4. Cardiotocography
Cardiotocography (CTG) is widely used as a screening test to indicate a normal condition of the fetus, with fetal heart rate response to movement being categorized as either reactive (normal) or nonreactive (abnormal) (Evertson 1979). Early studies indicated that a nonreactive antenatal CTG was associated with fetal acidosis and fetal demise (Brown 1981). However, a Cochrane review looking at antenatal CTG for fetal assessment showed no clear evidence that antenatal CTG improves perinatal outcomes (Grivell 2010) with the majority of studies being of low quality.
During the intrapartum period, a CTG may be described as normal, suspicious or pathological. Although clinical guidelines clearly recommend expediting delivery for a pathological CTG (NICE/RCOG 2007), management for the suspicious CTG is less prescriptive.
5. Biophysical profile
Biophysical profile consists of CTG in combination with ultrasound to detect changes in fetal behavior such as fetal movement, tone and breathing, and amniotic fluid volume (oligohydramnios, polyhydramnios), while monitoring the fetal heart rate. The combination of CTG and amniotic fluid volume assessment alone is called the modified biophysical profile.
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Oligohydramnios is defined in the term pregnancy as having an amniotic fluid index (AFI) of less than 5 cm or a single deepest vertical pocket measurement of less than 2 cm. It occurs in about 1% to 5% of pregnancies at term (Moore 1997). A number of studies over the past 15 years have shown an association between oligohydramnios and poor fetal outcomes. These were predominantly retrospective studies, which failed to control for the presence of factors known to be associated with oligohydramnios such as IUGR and urogenital malformations.
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Polyhydramnios refers to excessive accumulation of amniotic fluid typically diagnosed when the AFI is greater than 20 cm or the single deepest vertical measures more than 8 cm. The incidence of polyhydramnios in a general obstetric population ranges from 0.2% to 1.6%. The relation between clinically obvious polyhydramnios and poor perinatal outcome has been well documented. However, much less is known about mild, unexplained polyhydramnios, which usually is initially suggested by sonographic examination late in gestation. One study concluded that mild idiopathic polyhydramnios (defined as having an amniotic fluid index of 24.1 to 39.9) in late gestation is relatively common and except for a higher incidence of large for gestational age fetuses, is not associated with an increased risk of adverse perinatal outcomes (Smith 1992).
Maternal factors such as late‐onset gestational diabetes and mild hypertension/pre‐eclampsia and the contribution to fetal compromise have been the focus of other Cochrane reviews and therefore will not be included in this one (Boulvain 2001; Novikova 2011).
Description of the intervention
We will compare planned early birth with expectant management.
Planned early birth is planned delivery soon after presentation of a suspected compromised fetus. Delivery should be within 24 hours of randomization. The mode of delivery may either be via induction of labour by any means and a vaginal delivery, or by caesarean section.
Expectant management involves waiting more than 24 hours for spontaneous onset of labour in the absence of any other pregnancy complications or induction of labour for post‐maturity greater than 41 weeks.
How the intervention might work
If a baby is suspected to be compromised, earlier delivery may result in improved outcomes compared with expectant management where further compromise and/or emergency delivery may occur.
Why it is important to do this review
Fetal compromise in pregnancy is difficult to assess. Many cases have no obvious cause and management has to be aimed at determining the optimum time of delivery.
Objectives
To compare the fetal and maternal outcome in expectant management versus planned early delivery for women presenting with a suspected compromised fetus from 37 weeks' gestation or greater.
Methods
Criteria for considering studies for this review
Types of studies
Randomized or quasi‐randomized controlled trials comparing expectant management versus planned early delivery for women with a suspected compromised fetus from 37 weeks' gestation or more.
In studies in which gestational ages overlap the more than 37 weeks' gestation inclusion criteria, we will attempt to extract gestational age specific data from the studies. If necessary, we will contact researchers to provide further information.
Studies looking at immediate versus deferred delivery in pregnancies less than 36 weeks' gestation in whom there is clinical suspicion of fetal compromise are the focus of another Cochrane Review (Stock 2011).
We will consider studies published only as an abstract for inclusion and add these to 'Studies awaiting classification' pending further information.
Types of participants
Pregnant women who are at 37 weeks' gestation or more presenting with clinical suspicion of fetal compromise as defined by trialists. We will include women presenting with decreased fetal movement, abnormal ultrasound and BPP results, abnormal growth measurements, and non‐reassuring CTG tracings. Women with any other known medical disorders will not be included.
Types of interventions
We will compare planned early birth with expectant management.
Planned early birth is planned delivery soon after presentation of a suspected compromised fetus. Delivery should be within 24 hours of randomization. The mode of delivery may either be via induction of labour by any means, or by caesarean section.
Expectant management involves waiting more than 24 hours for spontaneous onset of labour or if immediate delivery becomes necessary in the absence of any other pregnancy complications OR induction of labour for post‐maturity greater than 41 weeks.
Types of outcome measures
Primary outcomes
Fetal, neonatal and infant
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Mortality (stillbirth ‐ death of fetus prior to birth; neonatal death ‐ death within the first 28 days of birth; or infant death ‐ death after the first 28 days).
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Major neonatal morbidity (i.e. one or more of the following: hypoxic ischaemic encephalopathy (HIE) ‐ grade 2 or 3, necrotizing enterocolitis (NEC), need for ongoing ventilation, meconium aspiration syndrome, seizures, need for therapeutic hypothermia).
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Neurodevelopmental disability/impairment.
Maternal and birth
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Maternal mortality.
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Significant maternal morbidity (one or more of the following: significant post partum haemorrhage requiring blood transfusion; maternal admission to intensive care unit; uterine rupture; hysterectomy).
Secondary outcomes
Fetal, neonatal and infant
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Gestational age at birth.
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Respiratory distress syndrome.
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Apgar score less than seven at five minutes.
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Rescuscitation required.
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Use of mechanical ventilation.
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Days of mechanical ventilation.
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Birthweight less than the 10th centile.
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Meconium aspiration.
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Seizures.
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Admission to neonatal intensive care unit.
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Length of stay in neonatal intensive care unit.
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Interval between randomization and delivery.
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Sepsis as defined by administration of antibiotics for more than three days.
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Moderate or severe hypoxic ischaemic encephalopathy (grade II or III).
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Need for therapeutic hypothermia.
Maternal and birth
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Caesarean section ‐ elective.
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Caesarean section ‐ emergency.
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Placental abruption.
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Pre‐eclampsia.
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Induction of labour.
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Mode of induction of labour.
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Vaginal birth.
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Assisted vaginal birth.
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Days of antenatal hospitalization.
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Days of postnatal hospitalization.
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Maternal satisfaction.
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Views of care.
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Postnatal depression.
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Postnatal infection.
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Breastfeeding.
Search methods for identification of studies
Electronic searches
We will contact the Trials Search Co‐ordinator to search the Cochrane Pregnancy and Childbirth Group’s Trials Register.
The Cochrane Pregnancy and Childbirth Group’s Trials Register is maintained by the Trials Search Co‐ordinator and contains trials identified from:
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quarterly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);
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weekly searches of MEDLINE;
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weekly searches of EMBASE;
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handsearches of 30 journals and the proceedings of major conferences;
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weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.
Details of the search strategies for CENTRAL and MEDLINE, 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 will cross reference published guidelines and other review articles. We plan to contact researchers to provide further information should this be required.
We will not apply any language restrictions.
Data collection and analysis
Selection of studies
Two review authors will independently assess for inclusion all the potential studies we identify as a result of the search strategy. We will resolve any disagreement through discussion or, if required, we will consult a third person.
Data extraction and management
We will design a form to extract data. For eligible studies, two review authors will extract the data using the agreed form. We will resolve discrepancies through discussion or, if required, we will consult a third person. We will enter data into Review Manager software (RevMan 2011) and check for accuracy.
When information regarding any of the above is unclear, we will attempt to contact authors of the original reports to provide further details
Assessment of risk of bias in included studies
Two review authors will independently assess risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will resolve any disagreement by discussion or by involving a third assessor.
(1) Random sequence generation (checking for possible selection bias)
We will describe for each included study the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.
We will assess the method as:
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low risk of bias (any truly random process, e.g. random number table; computer random number generator);
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high risk of bias (any non‐random process, e.g. odd or even date of birth; hospital or clinic record number); or
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unclear risk of bias.
(2) Allocation concealment (checking for possible selection bias)
We will describe for each included study the method used to conceal allocation to interventions prior to assignment and will assess whether intervention allocation could have been foreseen in advance of, or during recruitment, or changed after assignment.
We will assess the methods as:
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low risk of bias (e.g. telephone or central randomization; consecutively numbered sealed opaque envelopes);
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high risk of bias (open random allocation; unsealed or non‐opaque envelopes, alternation; date of birth);
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unclear risk of bias.
(3.1) Blinding of participants and personnel (checking for possible performance bias)
We will describe for each included study the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We will consider that studies are at low risk of bias if they were blinded, or if we judge that the lack of blinding would be unlikely to affect results. We will assess blinding separately for different outcomes or classes of outcomes.
We will assess the methods as:
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low, high or unclear risk of bias for participants;
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low, high or unclear risk of bias for personnel;
(3.2) Blinding of outcome assessment (checking for possible detection bias)
We will describe for each included study the methods used, if any, to blind outcome assessors from knowledge of which intervention a participant received. We will assess blinding separately for different outcomes or classes of outcomes.
We will assess methods used to blind outcome assessment as:
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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)
We will describe for each included study, and for each outcome or class of outcomes, the completeness of data including attrition and exclusions from the analysis. We will state whether attrition and exclusions were reported and the numbers included in the analysis at each stage (compared with the total randomized participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. Where sufficient information is reported, or can be supplied by the trial authors, we will re‐include missing data in the analyses which we undertake.
We will assess methods as:
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low risk of bias (e.g. no missing outcome data; missing outcome data balanced across groups);
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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 randomization);
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unclear risk of bias.
(5) Selective reporting (checking for reporting bias)
We will describe for each included study how we investigated the possibility of selective outcome reporting bias and what we found.
We will assess the methods as:
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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);
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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; study fails to include results of a key outcome that would have been expected to have been reported);
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unclear risk of bias.
(6) Other bias (checking for bias due to problems not covered by (1 )to (5 )above)
We will describe for each included study any important concerns we have about other possible sources of bias.
We will assess whether each study was free of other problems that could put it at risk of bias:
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low risk of other bias;
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high risk of other bias;
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unclear whether there is risk of other bias.
(7) Overall risk of bias
We will make explicit judgements about whether studies are at high risk of bias, according to the criteria given in the Handbook (Higgins 2011). With reference to (1) to (6) above, we will assess the likely magnitude and direction of the bias and whether we consider it is likely to impact on the findings. We will 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 will present results as summary risk ratio with 95% confidence intervals.
Continuous data
For continuous data, we will use the mean difference if outcomes are measured in the same way between trials. We will use the standardized mean difference to combine trials that measure the same outcome, but use different methods.
Unit of analysis issues
We will not include cluster‐randomized trials in the analyses.
Dealing with missing data
For included studies, we will note levels of attrition. We will explore the impact of including studies with high levels of missing data in the overall assessment of treatment effect by using sensitivity analysis.
For all outcomes, we will carry out analyses, as far as possible, on an intention‐to‐treat basis, i.e. we will attempt to include all participants randomized to each group in the analyses, and analyze all participants 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 will be the number randomized minus any participants whose outcomes are known to be missing.
Assessment of heterogeneity
We will assess statistical heterogeneity in each meta‐analysis using the T², I² and Chi² statistics. We will regard heterogeneity as substantial if T² is greater than zero and either I² is greater than 30% or there is a low P value (less than 0.10) in the Chi² test for heterogeneity.
Assessment of reporting biases
If 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, and use formal tests for funnel plot asymmetry. For continuous outcomes we will use the test proposed by Egger 1997, and for dichotomous outcomes we will use the test proposed by Harbord 2006. If asymmetry is detected in any of these tests or is suggested by a visual assessment, we will perform exploratory analyses to investigate it.
Data synthesis
We will carry out statistical analysis using the Review Manager software (RevMan 2011). We will use fixed‐effect meta‐analysis for combining data where it is reasonable to assume that studies are estimating the same underlying treatment effect: i.e. where trials are examining the same intervention, and the trials’ populations and methods are judged sufficiently similar. If there is clinical heterogeneity sufficient to expect that the underlying treatment effects differ between trials, or if we detect substantial statistical heterogeneity, we will use random‐effects meta‐analysis to produce an overall summary if an average treatment effect across trials is considered clinically meaningful. We will treat the random‐effects summary as the average range of possible treatment effects and we will discuss the clinical implications of treatment effects differing between trials. If the average treatment effect is not clinically meaningful we will not combine trials.
If we use random‐effects analyses, we will present the results as the average treatment effect with its 95% confidence interval, and the estimates of T² and I².
Subgroup analysis and investigation of heterogeneity
If we identify substantial heterogeneity, we will investigate it using subgroup analyses and sensitivity analyses. We will consider whether an overall summary is meaningful, and if it is, use random‐effects analysis to produce it.
We plan to carry out the following subgroup analyses.
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Singleton and multiple pregnancies.
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Term (37 to 40+6 weeks) and post‐term (>/= 41 weeks) pregnancies.
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Reason for suspected compromise, e.g. decreased fetal movement or suspected IUGR.
We will use the following outcomes in subgroup analysis.
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Perinatal mortality.
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Major neonatal morbidity.
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Neonatal neurodevelopmental disability/impairment.
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Maternal mortality.
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Significant maternal morbidity
For fixed‐effect inverse variance meta‐analyses we assess differences between subgroups by interaction tests. For random‐effects and fixed‐effect meta‐analyses using methods other than inverse variance, we will assess differences between subgroups by inspection of the subgroups’ confidence intervals; non‐overlapping confidence intervals indicate a statistically significant difference in treatment effect between the subgroups.
Sensitivity analysis
We will perform sensitivity analysis to explore the effect of trial quality on results, where there is risk of bias associated with the quality of some of the included trials. We will also use sensitivity analysis to explore the effects of fixed‐effect or random‐effects analysis for outcomes with statistical heterogeneity and the effects of any assumptions made.
We will use the following outcomes in sensitivity analysis.
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Perinatal mortality.
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Major neonatal morbidity.
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Neonatal neurodevelopmental disability/impairment.
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Maternal mortality.
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Significant maternal morbidity.
