Regimens of fetal surveillance for impaired fetal growth
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the effects of antenatal fetal surveillance regimens (combination of methods of surveillance at a specified frequency) on (i) perinatal mortality and neonatal morbidity; (ii) timing of birth and birthweight; (iii) maternal outcomes (induction of labour and caesarean section); and (iv) length of antenatal hospital admission.
Background
Description of the condition
Impaired fetal growth is a disturbance of normal fetal growth that results in a fetus that fails to grow at a predicted rate. A neonate with low birthweight for gestation is classified as very small‐for‐gestational age (SGA) (less than 3rd percentile) or SGA (less than 10th percentile). SGA as a biometric definition includes those fetuses that have failed to reach their growth potential (fetal growth restriction or intrauterine growth restriction) and also those fetuses that are constitutionally small. A fetus or neonate may be of normal birthweight but still significantly lighter than its growth potential (Baschat 2006). In practice, it may be difficult to accurately differentiate the constitutionally small fetus from one with decreased growth when compared to its potential. Impaired fetal growth may be due to maternal, fetal or uteroplacental causes. Excluding fetal chromosomal or structural abnormalities, abnormal placental vascular development accounts for the majority of true impairment of fetal growth in singleton pregnancies (Baschat 2006).
Fetal growth restriction is associated with increased perinatal mortality and morbidity (Baschat 2001; Gardosi 1998), adverse neurological outcomes such as cerebral palsy and poor long‐term neurodevelopmental outcomes (Yanney 2004). There may also be an association with adverse health events in adult life. Optimal management of the growth restricted fetus has three main aspects: firstly, identification of the fetus at risk in the general population (risk factors may be of assistance); secondly, confirmation of the diagnosis of impaired fetal growth and distinction from the healthy small fetus; and thirdly, ongoing care of the growth restricted fetus, culminating in decisions about mode and timing of birth (Baschat 2005; Breeze 2007).
Antenatal surveillance of some form is essential in providing information about the health of the fetus and also in aiming to reduce the morbidity and mortality that is associated with impaired fetal growth. Over recent years, there has been increasing knowledge of the arterial and venous Doppler findings in placental insufficiency and their physiological significance (such as declining metabolic status) and it is thought that a deterioration in the fetal condition can be detected by noting these changes (Baschat 2001; Baschat 2005). With increasing test availability and knowledge about the pathophysiological processes that occur in the fetus with impaired fetal growth, it has become common place for obstetricians to rely on an increasing number of tests in combination, such as fetal movement assessment, cardiotocography, biophysical profile and arterial and venous Doppler velocimetry (Baschat 2001; Baschat 2005). This is known in the literature as integrated fetal assessment or testing.
Description of the intervention
In practice, after the diagnosis of fetal growth restriction or impaired fetal growth the obstetrician will rarely use a single surveillance method and will commonly implement an antenatal fetal surveillance regimen that consists of a combination of the available methods each at a specified frequency. Choice of monitoring interval depends on anticipated speed of clinical deterioration and the risk for impending acidaemia and stillbirth (Baschat 2005). Consequently, frequency of monitoring may be increased if suspicion is high for impending deterioration.
How the intervention might work
Based on the knowledge of progressive changes that occur in the fetus with impaired fetal growth when these pregnancies are followed prospectively, it is advocated that by using a number of different surveillance methods (often adding extended Doppler tests to more traditional tests) deterioration in the fetal condition may be detected in utero and allow optimal timing of birth of a fetus in the best condition possible.
Why it is important to do this review
There are currently numerous varying local and personal policies and a lack of evidence‐based guidelines with regard to antenatal surveillance regimens for the fetus suspected to have impaired fetal growth. It is the goal of this systematic review to assess the benefits and risks associated with the use of various regimens of fetal surveillance.
Objectives
To assess the effects of antenatal fetal surveillance regimens (combination of methods of surveillance at a specified frequency) on (i) perinatal mortality and neonatal morbidity; (ii) timing of birth and birthweight; (iii) maternal outcomes (induction of labour and caesarean section); and (iv) length of antenatal hospital admission.
Methods
Criteria for considering studies for this review
Types of studies
Published and unpublished randomised and quasi‐randomised trials evaluating the effects of one or more described antenatal fetal surveillance regimens. Studies which compare a particular regimen with 'standard care' will only be included if standard care involves what has been defined as a regimen. We will not include studies that compare to no specific surveillance.
Types of participants
Women with pregnancies deemed by the investigators to be affected by impaired fetal growth or fetal growth restriction. (The minimum requirement for this review; estimated fetal weight less than 10th percentile or abdominal circumference less than 10th percentile, using local intrauterine growth charts.)
Types of interventions
Described antenatal fetal surveillance regimens. A regimen for the purpose of the review should be two or more surveillance methods. Each surveillance method should be performed at a specified interval. Possible surveillance methods to be included: fetal movement monitoring, cardiotocography, biophysical profile, Doppler ultrasound of the umbilical artery and fetal venous and arterial circulation (eg ductus venosus or middle cerebral artery). For the purpose of the review, we would expect a study to randomise women to different regimens of surveillance (ie different combinations of surveillance methods or at applying methods at different intervals).
Types of outcome measures
Primary outcomes
Infant
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Perinatal mortality or serious neonatal morbidity, as defined by the trial authors
Maternal
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Emergency caesarean section for fetal distress
Secondary outcomes
Infant
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Stillbirth
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Neonatal death
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Hypoxic ischaemic encephalopathy
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Admission to neonatal special care and or intensive care unit
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Gestational age at birth
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Low birthweight for gestation at birth (as defined by individual trial)
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Birthweight
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Preterm birth
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Low Apgar scores at five minutes (as defined by trial)
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Cord blood acidosis
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Metabolic acidosis or lactic acidosis
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Respiratory distress syndrome
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Use of ventilatory support
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Use of inotropic support
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Necrotising enterocolitis
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Grade III or IV intraventricular haemorrhage
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Duration of neonatal hospital stay
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Longer‐term neurodevelopmental outcomes
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Cerebral palsy
Maternal
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Antenatal hospital admission
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Induction of labour
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Caesarean section
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Operative vaginal delivery
Use of healthcare services
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For infant: length of stay in neonatal special care and or intensive care unit
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For mother: length of antenatal hospital admission
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Costs of monitoring
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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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 given a code (or codes) depending on the topic. The codes are linked to review topics. The Trials Search Co‐ordinator searches the register for each review using these codes rather than keywords.
We will not apply any language restrictions.
Data collection and analysis
Selection of studies
We will assess for inclusion all potential studies we identify as a result of the search strategy. We will resolve any disagreement through discussion or, if required, consult an outside person.
Data extraction and management
We will design a form to extract data. At least two review authors will extract the data using the agreed form. We will resolve discrepancies through discussion. We will use the Review Manager software (RevMan 2007) to double enter all the data or a subsample.
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 methodological quality of included studies
We will assess the validity of each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2006). Methods used for generation of the randomisation sequence will be described for each trial.
(1) Selection bias (randomisation and allocation concealment)
We will assign a quality score for each trial, using the following criteria:
(A) adequate concealment of allocation: such as telephone randomisation, consecutively numbered, sealed opaque envelopes;
(B) unclear whether adequate concealment of allocation: such as list or table used, sealed envelopes, or study does not report any concealment approach;
(C) inadequate concealment of allocation: such as open list of random‐number tables, use of case record numbers, dates of birth or days of the week.
(2) Attrition bias (loss of participants, for example, withdrawals, dropouts, protocol deviations)
We will assess completeness to follow up using the following criteria:
(A) less than 5% loss of participants;
(B) 5% to 9.9% loss of participants;
(C) 10% to 19.9% loss of participants;
(D) more than 20% loss of participants.
(3) Performance bias (blinding of participants, researchers and outcome assessment)
We will assess blinding using the following criteria:
(1) blinding of participants (yes/no/unclear);
(2) blinding of caregiver (yes/no/unclear);
(3) blinding of outcome assessment (yes/no/unclear).
Measures of treatment effect
We will carry out statistical analysis using RevMan 2007. We will use fixed‐effect meta‐analysis for combining data in the absence of significant heterogeneity if trials are sufficiently similar. If heterogeneity is found, we will explore this by sensitivity analysis followed by random‐effects if required.
Dichotomous data
For dichotomous data, we will present results as summary relative risk with 95% confidence intervals.
Continuous data
For continuous data, we will use the weighted mean difference if outcomes are measured in the same way between trials. We will use the standardised mean difference to combine trials that measure the same outcome, but use different methods. If there is evidence of skewness, this will be reported.
Dealing with missing data
We will analyse data on all participants with available data in the group to which they are allocated, regardless of whether or not they received the allocated intervention. If in the original reports participants are not analysed in the group to which they were randomised, and there is sufficient information in the trial report, we will attempt to restore them to the correct group.
Assessment of heterogeneity
We will apply tests of heterogeneity between trials, if appropriate, using the I‐squared statistic. If we identify high levels of heterogeneity among the trials (exceeding 50%), we will explore it by prespecified subgroup analysis and perform sensitivity analysis. A random‐effects meta‐analysis will be used as an overall summary if this is considered appropriate. It may be an appropriate option not to combine trials in the presence of heterogeneity.
Subgroup analyses
We will conduct planned subgroup analyses classifying whole trials by interaction tests as described by (Deeks 2001).
We plan to carry out the following subgroup analyses: diagnosis of impaired fetal growth before or after 32 weeks, normal or abnormal umbilical artery doppler at time of diagnosis.
Sensitivity analyses
We will carry out sensitivity analysis to explore the effect of trial quality. This will involve analysis based on an A, B, C, or D rating of selection bias and attrition bias. We will exclude studies of poor quality in the analysis (those rating B, C, or D) in order to assess for any substantive difference to the overall result.
