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Specialised antenatal clinics for women with a pregnancy at

high risk of preterm birth (excluding multiple pregnancy) to

improve maternal and infant outcomes (Review)

Whitworth M, Quenby S, Cockerill RO, Dowswell T

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2011, Issue 9

http://www.thecochranelibrary.com

Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

http://www.thecochranelibrary.com

T A B L E O F C O N T E N T S

1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

8DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

9ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

10REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

18DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis 1.1. Comparison 1 Specialised antenatal care versus routine care, Outcome 1 Perinatal death. . . . . . 19

Analysis 1.2. Comparison 1 Specialised antenatal care versus routine care, Outcome 2 Extremely preterm birth (< 28 weeks’

gestation). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Analysis 1.3. Comparison 1 Specialised antenatal care versus routine care, Outcome 3 Development of antenatal

complications - preterm labour. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Analysis 1.4. Comparison 1 Specialised antenatal care versus routine care, Outcome 4 Preterm birth - adjusted for cluster

design effect (ICC 0.002). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Analysis 1.5. Comparison 1 Specialised antenatal care versus routine care, Outcome 5 Sensitivity analysis. Preterm birth

(adjusted for cluster design effect using upper CI, ICC 0.0041). . . . . . . . . . . . . . . . . 22

Analysis 1.6. Comparison 1 Specialised antenatal care versus routine care, Outcome 6 Very preterm birth (birth before 34

weeks’ gestation). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Analysis 1.7. Comparison 1 Specialised antenatal care versus routine care, Outcome 7 Gestation at birth. . . . . 23

Analysis 1.9. Comparison 1 Specialised antenatal care versus routine care, Outcome 9 Caesarean section. . . . . 24

Analysis 1.13. Comparison 1 Specialised antenatal care versus routine care, Outcome 13 Neonatal intensive care unit

admission. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Analysis 1.19. Comparison 1 Specialised antenatal care versus routine care, Outcome 19 Costs associated with care. . 25

Analysis 1.20. Comparison 1 Specialised antenatal care versus routine care, Outcome 20 Costs associated with newborn

inpatient care (US $). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Analysis 1.21. Comparison 1 Specialised antenatal care versus routine care, Outcome 21 Number of antenatal visits. 26

Analysis 1.27. Comparison 1 Specialised antenatal care versus routine care, Outcome 27 Preterm birth - all studies,

unadjusted data. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

27HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

27CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

28DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

28SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

28DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .

28INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

iSpecialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

[Intervention Review]

Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Melissa Whitworth1, Siobhan Quenby2, Ruth O Cockerill3, Therese Dowswell4

1St Mary’s Hospital, Manchester, UK. 2Clinical Sciences Research Institute, University of Warwick, Coventry, UK. 3Department of

Obstetrics, St Mary’s Hospital, Manchester, UK. 4Cochrane Pregnancy and Childbirth Group, Department of Women’s and Children’s

Health, The University of Liverpool, Liverpool, UK

Contact address: Melissa Whitworth, St Mary’s Hospital, Central Manchester and Manchester Children’s University Hospitals NHS

Trust, Hathersage Road, Manchester, M13 0JH, UK. [email protected].

Editorial group: Cochrane Pregnancy and Childbirth Group.

Publication status and date: New, published in Issue 9, 2011.

Review content assessed as up-to-date: 24 July 2011.

Citation: Whitworth M, Quenby S, Cockerill RO, Dowswell T. Specialised antenatal clinics for women with a pregnancy at high risk

of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes. Cochrane Database of Systematic Reviews 2011, Issue 9. Art. No.: CD006760. DOI: 10.1002/14651858.CD006760.pub2.

A B S T R A C T

Background

Amongst the risk factors for preterm birth, previous preterm delivery is a strong predictor. Specialised clinics for women with a history

of spontaneous preterm delivery have been advocated as a way of improving outcomes for women and their infants.

Objectives

To assess using the best available evidence, the value of specialised antenatal clinics for women with a pregnancy at high risk of preterm

delivery when compared with ’standard’ antenatal clinics.

Search methods

We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 June 2011).

Selection criteria

All published, unpublished, and ongoing randomised controlled trials (including cluster-randomised trials) examining specialised

compared with standard antenatal clinic care for women with a singleton pregnancy considered at high risk of preterm labour.

Data collection and analysis

Two review authors independently assessed trial quality and extracted data.

Main results

We included three trials with 3400 women, all carried out in the USA. All focused on specialised clinics for women at high risk of

preterm birth. Gestational age at delivery, preterm delivery, or both were primary outcomes in all studies. The interventions in the

three trials differed.

Overall there was very little data on our prespecified outcomes. For most outcomes a single study provided data, hence there was not

the statistical power to detect any possible differences between groups. There was no clear evidence that specialised antenatal clinics

reduce the number of preterm births.

1Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

mailto:[email protected]

Authors’ conclusions

Specialised antenatal clinics are now an accepted part of care in many settings, and carrying out further randomised trials may not be

possible. Any future research in this area should include psychological outcomes and should focus on which aspects of service provision

are preferred by women. Such research could underpin further service development in this area.

P L A I N L A N G U A G E S U M M A R Y

Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to

improve outcomes for women and babies

Women who have had a previous preterm birth are at increased risk of having another premature birth. Babies who are born before

the 37th week of pregnancy, and particularly those born before the 34th week, are at greater risk of suffering problems at birth and

of disability in childhood. ’Specialised’ antenatal clinics have been suggested for women at high risk of a preterm birth as a way of

improving health outcomes for the women and their infants. This review of three randomised controlled trials involving 3400 women

in the USA found that there was no reduction in the number of preterm births in women attending specialised antenatal clinics. The

results were difficult to interpret, as the trials were conducted in slightly different ways and offered slightly different care. The trials were

all conducted in the 1980s, before the introduction of many of the screening tests currently offered in specialised antenatal clinics such

as ultrasound assessment of cervical length. There was no information available on the effect of specialised antenatal care on maternal

wellbeing or long-term outcome.

B A C K G R O U N D

Preterm birth occurs in up to 6% to 10% of all births and is as-

sociated with perinatal mortality and morbidity (Lumley 2003).

Nearly half of all preterm births are due to preterm labour. Preterm

birth is associated with emotional and economic costs to both the

family and society (Petrou 2001). Once congenital anomalies are

excluded, preterm birth is responsible for the majority of neonatal

deaths and is the major cause of disability in childhood (Hack

1999). The majority of mortality and morbidity occurs with ex-

tremely preterm birth (defined as birth before 28 weeks’ gestation).

However, whilst the incidence of death and long-term handicap

is relatively low in those born after 32 weeks, they make up over

80% of all preterm deliveries and therefore this group of infants

has a significant impact upon the burden that preterm birth makes

on public health (Kramer 2000). Despite research over the past

few decades, no decrease in the incidence of preterm birth has oc-

curred, although there have been improved survival and outcomes

for premature infants.

Amongst the risk factors for preterm birth, previous preterm de-

livery is a strong predictor and the earlier the birth the more likely

it is to be repeated at the same gestation (Hoffman 1984). Other

risk factors include cervical weakness, cervical trauma, and stress

(El-Bastawissi 1999; Iams 2004; Ruis 2003). Specialised clinics for

women with a history of spontaneous preterm delivery have been

advocated, with non-randomised cohort data suggesting improved

perinatal outcomes with the provision of intensive antenatal ed-

ucation, continuity of carer and individualised care (Bienstock

2001). Such specialised clinics may also see women with previous

preterm prelabour rupture of the membranes, previous late mis-

carriage (16 weeks 0 days to 23 weeks 6 days of gestation), or prior

cervical surgery. Prediction of risk may utilise ultrasound assess-

ment of cervical length and the presence of fetal fibronectin in cer-

vico-vaginal secretions. The package of care offered in such clinics

may include promising prophylactic interventions for labour pre-

vention including progesterone, clindamycin or cervical cerclage

(Althuisius 1998; Da Fonesca 2003; Ugwumadu 2003). However,

stress has been associated with enhanced risk of preterm delivery

and there is evidence that, whilst some pregnant women welcome

referral to a specialist clinic during pregnancy, others experience it

as unsettling (Jackson 2006).

The aim of this review is to assess, using the best available evi-

dence, the value of such specialised antenatal clinics for women

with a pregnancy at high risk of preterm birth when compared

with ’standard’ antenatal clinic attendance. The primary outcomes

relate to maternal and neonatal morbidity, and maternal and peri-

natal mortality. In women with multiple pregnancy, who have an

increased risk of premature delivery, specialised clinics have been

advocated in an attempt to improve perinatal outcomes. The value

of specialised antenatal care for women with a multiple pregnancy

2Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

when compared with ’standard’ antenatal care is the subject of a

different Cochrane review (Dodd 2007).

O B J E C T I V E S

To assess, using the best available evidence, the value of specialised

antenatal clinics for women with a pregnancy at high risk of

preterm delivery when compared with ’standard’ antenatal clinics.

M E T H O D S

Criteria for considering studies for this review

Types of studies

All published, unpublished, and ongoing randomised controlled

trials including cluster-randomised trials. We have included quasi-

randomised controlled trials.

Types of participants

Pregnant women with a singleton pregnancy considered by the

trial authors to be at high risk of preterm labour.

Types of interventions

’Specialised’ antenatal clinics (as defined by trial authors) com-

pared with ’standard’ antenatal clinic care (as defined by trial au-

thors).

Types of outcome measures

Primary outcomes

1. Perinatal death (defined as stillbirth after trial entry, or

death of a liveborn infant up to seven days of age).

2. Extremely preterm birth (defined as birth less than 28

weeks’ gestation).

Secondary outcomes

Secondary outcomes relate to pregnancy outcomes,

complications, satisfaction and costs

Pregnancy outcomes

1. Development of antenatal complications (including

preterm labour (actual or suspected), preterm prelabour ruptured

membranes, intrauterine growth restriction (estimated fetal

weight less than 10th centile for gestational age)).

2. Preterm birth (defined as birth before 37 weeks’ gestation).

3. Very preterm birth (defined as birth before 34 weeks’

gestation).

4. Gestation at birth.

5. Instrumental vaginal birth.

6. Infection requiring intravenous antibiotics.

7. Mode of birth.

8. Postnatal depression.

9. Breastfeeding.

Complications for infants

1. Neonatal intensive care unit admission.

2. Respiratory distress syndrome.

3. Parameters of birth asphyxia (neonatal irritability, neonatal

seizures, neonatal hypotonia, abnormal level of consciousness,

neonatal apnoea, tube feeding greater than 48 hours).

4. Complications of prematurity.

5. Disability at childhood follow-up (including deafness,

blindness, neurodisability or cerebral palsy).

Measures of satisfaction

1. Women’s satisfaction.

Costs

1. Costs associated with ’specialised’ antenatal care versus

’standard’ care.

2. Number of antenatal visits.

3. Number of antenatal admissions and length of admission.

4. Length of maternal postnatal stay.

5. Length of stay in neonatal intensive care unit.

6. Infant length of hospital stay.

We have included outcomes in the analysis if data were available ac-

cording to original allocation and reasonable measures were taken

to minimise observer bias. Only outcomes with available data ap-

pear in the analysis tables. In order to minimise the risk of bias,

we have based the conclusions solely on the pre-stated outcomes.

Search methods for identification of studies

We searched the Cochrane Pregnancy and Childbirth Group’s Tri-

als Register by contacting the Trials Search Co-ordinator (30 June

2011).

3Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

The Cochrane Pregnancy and Childbirth Group’s Trials Register

is maintained by the Trials Search Co-ordinator and contains trials

identified from:

1. quarterly searches of the Cochrane Central Register of

Controlled Trials (CENTRAL);

2. weekly searches of MEDLINE;

3. weekly searches of EMBASE;

4. handsearches of 30 journals and the proceedings of major

conferences;

5. weekly current awareness alerts for a further 44 journals

plus monthly BioMed Central email alerts.

Details of the search strategies for CENTRAL, MEDLINE, and

EMBASE, the list of handsearched journals and conference pro-

ceedings, and the list of journals reviewed via the current aware-

ness service can be found in the ‘Specialized Register’ section

within the editorial information about the Cochrane Pregnancy

and Childbirth Group.

Trials identified through the searching activities described above

are each assigned to a review topic (or topics). The Trials Search

Co-ordinator searches the register for each review using the topic

list rather than keywords.

We did not apply any language restrictions.

Data collection and analysis

Selection of studies

Two review authors independently assessed for inclusion all the

studies we identified as a result of the search strategy. We resolved

any disagreement through discussion.

Data extraction and management

We designed a form to extract data. For eligible studies, at least

two review authors extracted the data using the agreed form. We

resolved discrepancies through discussion. We entered data into

Review Manager software (RevMan 2011) and checked for accu-

racy.

When information regarding any of the above was unclear, we

attempted to contact authors of the original reports to provide

further details.

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 for Systematic Reviews of Interventions (Higgins 2011). We resolved any disagreement by discussion.

(1) Sequence generation (checking for possible selection

bias)

We have described for each included study the method used to

generate the allocation sequence and assessed whether it should

have produced 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); or

• unclear risk of bias.

(2) Allocation concealment (checking for possible selection

bias)

We have described for each included study the method used to

conceal the allocation sequence and determined whether interven-

tion 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) Blinding (checking for possible performance bias)

We have described for each included study the methods used, if

any, to blind study participants and personnel from knowledge

of which intervention a participant received. With an interven-

tion such as the provision of specialised clinics blinding women

and clinic staff to group allocation is not generally feasible, it may

however be possible, for some outcomes, to blind outcome asses-

sors. We considered studies to be at lower risk of bias if outcome

assessment was blinded or if we judged that the lack of blinding

would have been unlikely to have affected the results. We assessed

blinding separately for different outcomes or classes of outcomes.

We assessed the methods as:

• low, high, or unclear risk of bias for outcome assessors.

(4) Incomplete outcome data (checking for possible attrition

bias through withdrawals, dropouts, protocol deviations)

We have described for each included study, and for each outcome

or class of outcomes, the completeness of data including attrition

and exclusions from the analysis. We have stated whether attrition

and exclusions were reported, 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 likely to be

related to outcomes. We assessed methods as:

4Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

http://www.mrw.interscience.wiley.com/cochrane/clabout/articles/PREG/frame.html

• low risk of bias;

• high risk of bias;

• unclear risk of bias.

(We had intended to exclude data from the analysis where loss to

follow-up for a particular outcome was greater than 20%; however,

in two of the included trials information about exclusions and

attrition was not clear, so we have included all outcome data as

reported by study authors.)

(5) Selective reporting bias

We have described for each included study 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 was clear that all of the study’s pre-

specified outcomes and all expected outcomes of interest to the

review were reported);

• high risk of bias (where not all the study’s pre-specified

outcomes were reported; one or more reported primary

outcomes were not pre-specified; outcomes of interest were

reported incompletely and so could not be used; study failed to

include results of a key outcome that would have been expected

to have been reported);

• unclear risk of bias.

(6) Other sources of bias

We have described for each included study any important concerns

we had about other possible sources of bias.

We assessed whether each study was free of other problems that

could put it at risk of bias:

• low risk of other bias;

• high risk of other bias;

• unclear risk of other bias.

(7) Overall risk of bias

We have made 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 assessed

the likely magnitude and direction of the bias and whether we

considered it is likely to impact on the findings. We planned to

explore the impact of the level of bias through undertaking sensi-

tivity analyses - see Sensitivity analysis.

Measures of treatment effect

Dichotomous data

For dichotomous data, we have presented results as summary risk

ratio with 95% confidence intervals.

Continuous data

For continuous data, we have used the mean difference if out-

comes were measured in the same way between trials. We used the

standardised mean difference to combine trials that measured the

same outcome, but used different methods.

Unit of analysis issues

Cluster-randomised trials

We have included one cluster-randomised trial in the analyses

along with individually-randomised trials. We adjusted the stan-

dard error for results from this study using the methods described

in the Handbook (Higgins 2011). No estimate of the intraclus- ter correlation co-efficient (ICC) was provided for this trial and

so we used a published ICC from another trial of antenatal care

(Piaggio 2001). As we used an ICC from another source, we have

conducted sensitivity analyses to investigate the effect of variation

in the ICC. Where we identified both cluster-randomised and

individually-randomised trials examining the same outcomes, we

synthesised the relevant information. We considered it reasonable

to combine the results from both, provided that there was little

heterogeneity between the study designs, and the interaction be-

tween the effect of intervention and the choice of randomisation

unit was considered to be unlikely.

Dealing with missing data

For included studies, we have noted levels of attrition. We planned

to explore the impact of including studies with high levels of miss-

ing data in the overall assessment of treatment effect by using sen-

sitivity analysis; but in this version of the review, with so few stud-

ies contributing data, we did not think further analysis would shed

any further light on findings. In updates of the review, if more data

are added, we will carry out sensitivity analysis excluding data from

studies (or for particular outcomes) where there are high levels of

missing data.

For all outcomes, we have carried out analyses, as far as possible,

on an intention-to-treat basis, i.e. we attempted to include all par-

ticipants randomised to each group in the analyses, and analysed

all participants in the group to which they were allocated, regard-

less 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 were known

to be missing.

5Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

Assessment of heterogeneity

We assessed statistical heterogeneity in each meta-analysis using

the T², I² and Chi² statistics. We have regarded heterogeneity as

substantial if I² is greater than 30% and either T² is greater than

zero, or there is a low P value (less than 0.10) in the Chi² test for

heterogeneity.

Assessment of reporting biases

If there were 10 or more studies in the meta-analysis we planned to

investigate reporting biases (such as publication bias) using funnel

plots. In this version of the review, insufficient studies contributed

data and we did not generate funnel plots. In updates, if more

data become available we will assess funnel plot asymmetry visu-

ally, and use formal statistical tests; 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 we

detect asymmetry in any of these tests or by a visual assessment,

we will perform exploratory analyses to investigate it.

Data synthesis

We have carried out statistical analysis using the Review Manager

software (RevMan 2011). We have 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 sufficiently similar. Where we suspected

clinical heterogeneity, or if we detected substantial statistical het-

erogeneity, we have used random-effects meta-analysis to produce

an overall summary if an average treatment effect across trials was

considered clinically meaningful.

Where we have used random-effects analyses, we have presented

results as the average treatment effect with 95% confidence inter-

val, and the estimates of T² and I².

Subgroup analysis and investigation of heterogeneity

We planned to carry out the following subgroup analyses:

1. parity (nulliparous versus multiparous women);

2. type of care received (that is, time that specialised care

commenced; number of antenatal visits; use of ultrasound);

3. use of cervical length measurements (transvaginal

ultrasound versus no transvaginal ultrasound).

We planned to restrict subgroup analyses to primary outcomes.

We planned to assess differences between subgroups by inspec-

tion of the subgroups’ confidence intervals; with non-overlapping

confidence intervals suggesting a statistically significant difference

in treatment effect between the subgroups. In view of the small

number of studies contributing data we did not think there would

be sufficient information for any particular subgroup to explore

possible subgroup differences and so in this version of the review

we did not perform these additional analyses. If further studies are

added in updates, we will consider carrying out further analyses.

Sensitivity analysis

We planned to carry out sensitivity analyses to evaluate the effect

of trial quality. In this version of the review, so few trials con-

tributed data that we did not think sensitivity analysis would help

in the interpretation of results. One outcome included data from

a cluster-randomised trial, and for this outcome we carried out

a sensitivity analysis where we varied the value of the ICC using

a more conservative value (upper 95% confidence interval for a

published ICC (Piaggio 2001)).

R E S U L T S

Description of studies

See: Characteristics of included studies; Characteristics of excluded

studies.

Results of the search

Using the search strategy, we identified 15 reports describing the

methods and findings from seven randomised trials (several of the

studies resulted in multiple publications). We have included three

of these trials in the review and have excluded four.

Included studies

All three included trials were carried out in the USA. All trials fo-

cused on specialised clinics for women at high risk of preterm birth,

and gestational age at delivery, preterm delivery, or both, were pri-

mary outcomes in all studies. The interventions in the three trials

differed slightly. In a study in Ohio (Iams 1989), women attended

clinics and had cervical examinations weekly between 20 and 36

weeks’ gestation and were advised on the signs and symptoms of

labour onset. In the Pennsylvania trial (Main 1989), women at-

tended weekly or twice-weekly clinics from 22 weeks’ gestation;

and again women were educated on the early signs of labour and

had cervical assessment. In the West Los Angeles 1994 trial, clinics

rather than women were randomised (five experimental clinics and

three control). Women attending experimental clinics had fort-

nightly visits and had three classes on preterm birth prevention.

In addition, in a nested study, women were randomised to one

of four secondary interventions (bed rest, psychosocial support,

oral progestin or a placebo). Participants in both experimental and

control clinics received psychosocial and nutritional screening and

were offered crisis intervention. We have set out further details on

these studies in the Characteristics of included studies tables.

6Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

Excluded studies

We excluded four studies: three because the samples included

women with multiple pregnancies and separate results were not

reported for singletons (Collaborative Group 1993; Goldenberg

1990; Pittsburgh 1989); finally, the study by Beazley 2001 was

reported in a brief abstract, we were not able to assess risk of bias,

and it was not clear how many women were randomised to in-

tervention and control groups. We have provided further infor-

mation on these studies in the Characteristics of excluded studies

tables.

Risk of bias in included studies

Allocation

In the study by Iams 1989 there was little information on study

methods; the way the randomisation sequence was generated and

methods used to conceal allocation were not clear. In the Main

1989 trial, allocation was by a quasi-randomised method. The

West Los Angeles 1994 study was a cluster-randomised trial; eight

clinics were randomised using a blocked technique.

Blinding

Blinding women and care providers to treatment group is difficult

to achieve with an intervention involving different models of care.

Women would be aware of their more frequent attendance and

so would clinic staff. In the cluster-randomised trial, randomisa-

tion at the clinic level would be likely to reduce bias associated

with contamination. This study also examined additional inter-

ventions, and within the nested study in experimental clinics, it

would be difficult to blind women and staff to these additional

interventions (e.g. bed rest) although one of the four groups re-

ceived a placebo. It is not clear whether lack of blinding represents

a serious source of bias in these studies.

Incomplete outcome data

Rates of attrition and exclusion in the control and experimental

groups were not clearly set out in two studies (Iams 1989; Main

1989). In the Main 1989 study, there appeared to be little loss to

follow-up for the primary outcome (preterm birth), although there

were relatively high levels of missing data for neonatal outcomes as

approximately 20% of infant case-notes were not reviewed. In the

West Los Angeles 1994 study, loss to follow up was less than 10%;

however, even small losses may be important in studies examining

a relatively infrequent outcome, especially if loss is not balanced

across groups, as those most vulnerable to poor outcomes may be

over-represented amongst those who are not followed up.

Selective reporting

Without access to study protocols, it is difficult assess selective

reporting bias. All three studies reported the number of preterm

births, although other key outcomes (for example, perinatal death

and extreme prematurity) were not reported. It is not clear whether

or not this information was collected.

Other potential sources of bias

We have noted in the Characteristics of included studies tables

other possible sources of bias, and any factors which we thought

affected our interpretation of results. One of the included studies

was a cluster randomised trial; in the trial report results had not

been adjusted for cluster design effect. In order to pool results from

this trial with those from trials where women were randomised,

where sufficient information was available to allow us to do so,

we used the generic inverse variance method and adjusted the

standard error of results from the cluster randomised-trial to take

account of design effect.

Effects of interventions

Specialised antenatal clinics versus routine care:

three studies with 3400 women

Primary outcomes

Perinatal death (defined as stillbirth after trial entry, or death

of a liveborn infant up to seven days of age)

Perinatal death was reported in one of the included studies with

outcome data for 302 infants (Main 1989). There was no evidence

of a significant difference between groups; overall, there were 13

deaths, seven in the treatment group and six in the control group

(risk ratio (RR) 1.25, 95% confidence interval (CI) 0.43 to 3.62).

Extremely preterm birth (defined as birth less than 28 weeks’

gestation)

This outcome was reported in one study with data for 376 women

(Main 1989). There was no clear evidence of a difference between

women attending specialist clinics compared with those receiving

routine care (RR 0.77, 95% CI 0.26 to 2.25).

7Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

Secondary outcomes

Antenatal complications

The number of women being admitted with antenatal compli-

cations (including preterm labour (actual or suspected), preterm

prelabour ruptured membranes, intrauterine growth restriction

(estimated fetal weight less than 10th centile for gestational age))

was reported in one study (370 women) (Iams 1989). There was

no statistically significant difference between groups (RR 1.29,

95% CI 0.90 to 1.86).

Preterm birth (birth before 37 weeks’ gestation)

All three included studies provided data for this outcome (3400

women). One of the studies used a cluster-randomisation tech-

nique and so the standard error has been adjusted (West Los

Angeles 1994). When data from the three studies were pooled,

it appeared that there were fewer preterm births in the treatment

group compared with controls, but the difference between groups

was not statistically significant (RR 0.87, 95% CI 0.69 to 1.08

(adjusted data, inverse variance method Analysis 1.4)). For this

outcome, we carried out a sensitivity analysis whereby, for the

cluster-randomised trial, we used the upper 95% CI for the ICC

(most conservative value); in this analysis, while the weight of the

cluster-randomised trial was reduced, this adjustment made very

little difference to results (RR 0.87, 95% CI 0.69 to 1.11 (ad-

justed data, inverse variance method Analysis 1.5 )). (In Analysis

1.27 we have set out the original data for the three studies; again

results were similar and although the 95% CI was narrower the

difference between groups still did not reach statistical significance

(unadjusted RR 0.85, 95% CI 0.70 to 1.03).)

Very preterm birth (before 34 weeks)

One study contributed data to this outcome and there was no

evidence of differences between groups (RR 1.05, 95% CI 0.50

to 2.21) (Main 1989).

Other secondary outcomes

There was no significant evidence of differences between women

attending specialised clinics and women receiving routine care

for any of the following secondary outcomes: gestational age at

birth (Analysis 1.7); caesarean section (Analysis 1.9); or neonatal

intensive care unit admission (Analysis 1.13).

There were no data reported for our remaining secondary out-

comes.

Costs of care and process variables

Two studies examined the costs associated with care (Main 1989;

West Los Angeles 1994). However, in one of these studies (West

Los Angeles 1994), a sub-sample of approximately 10% of the

total sample only was included in the cost-analysis (280/2705

women). Further, in this study there was no adjustment for cluster

design effect and in the data and analyses tables we have therefore

presented unadjusted data for cost outcomes.

When data from the Main 1989 and West Los Angeles 1994 stud-

ies were pooled there was no significant evidence that specialised

clinics and routine management differed in terms of the total cost

of care for women (Analysis 1.19).

The cost of newborn infant care was examined in the West Los

Angeles 1994 trial and appeared to be reduced in infants of women

attending the experimental clinics compared with controls. How-

ever, results were not simple to interpret. The authors suggest that

the cost difference was due to a combination of fewer preterm

births in the experimental group, a lower relative rate of delivery

at less than 32 weeks’ gestation, and lower mean costs for infants

of comparable gestations (Analysis 1.20). They did not comment

on what interventions were required by babies in the different

groups or whether the two groups had different rates of steroid

administration which may have impacted on neonatal condition

at delivery.

In the West Los Angeles 1994 study women in the control group

had fewer antenatal clinic visits with a mean of 4.9 clinic atten-

dances compared with a mean of 6.6 for women in the experimen-

tal group (mean difference 1.7, 95% CI 0.72 to 2.68) (Analysis

1.21).

D I S C U S S I O N

Summary of main results

Overall there was very little data on our pre-specified outcomes.

For most outcomes a single study provided data, hence there may

have been insufficient statistical power to detect any possible differ-

ences between groups. There was no clear evidence that specialised

antenatal clinics reduce the number of preterm births. Perinatal

death was reported in only one of the included studies and there

was no evidence of a significant difference between groups. .

Overall completeness and applicability of evidence

Interpreting the findings of this review is not straightforward.

Preterm birth is a multi-factorial disorder and hence a complex

intervention such as a package of antenatal care is a logical solution

to preventing its recurrence. The antenatal care needs to be aimed

8Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

at managing diverse contributing factors such nutritional deficien-

cies, smoking cessation, dental hygiene, infection, cervical weak-

ness, pro-thrombotic tendency, psycho-social stress and excessive

uterine contractility. The review includes only three trials, which

tackled potential contributing factors to varying degrees, and the

same outcomes were not reported for all trials. Furthermore, the

three trials varied in the nature of the services provided as part of

the specialised antenatal clinic. Two studies included repeat digi-

tal cervical assessment (RDCA) in the treatment arm (Iams 1989;

Main 1989I). Whilst there is no evidence that RCDA is effective

as a routine intervention in the antenatal clinic as a screening test

for the risk of preterm birth in average risk pregnancies, it has not

been thoroughly evaluated as a component of a complex interven-

tion such as a specialist antenatal clinic, targeting preterm birth

(Alexander 2010). This makes interpretation of our results more

difficult. In addition, the trials were all conducted in the 1980s

prior to the introduction of many of the screening tests currently

offered in specialised antenatal clinics e.g. fetal fibronectin testing

and ultrasound assessment of cervical length. There is clear evi-

dence that antenatal steroids improve neonatal survival and reduce

neonatal morbidity (Roberts 2006), hence the ability to accurately

predict preterm labour in a specialised clinic would ensure that

women received the steroids prior to delivery. The problem is that

at present the current predictive tests (cervical length monitoring

and fetal fibronectin) are not sufficiently specific to make them

cost effective (Honest 2009).

Quality of the evidence

The quality of the evidence in these three trials was mixed, and

the methods used to conceal allocation were at high or unclear

risk of bias in the two trials where women were randomised (Iams

1989; Main 1989). In the cluster-randomised trial findings were

not adjusted for cluster design effect; and while we attempted to

take account of possible design effects for some outcomes we did

not have sufficient information to adjust the cost data reported in

the West Los Angeles 1994 trial. Missing data were a concern in

two of the included trials; even small losses may be important in

studies examining relatively infrequent outcomes, as those most

vulnerable to poor outcomes may be over-represented amongst

those who are not followed up.

Potential biases in the review process

We are aware of potential biases in the reviewing process; and

we took steps to minimise bias (e.g. two authors independently

assessed study eligibility, carried out data extraction and assessed

risk of bias).

A U T H O R S ’ C O N C L U S I O N S

Implications for practice

Since the publication of the trials included in this review (1989 to

1994) there have been further meta-analyses of trials of individual

treatments that were effective at preventing preterm birth: proges-

terone (Barros 2010; Honest 2009; Rode 2009); smoking cessa-

tion (Barros 2010); eradication of asymptomatic bacteriuria (Iams

2010); appropriate use of cerclage (Iams 2010I); and calcium sup-

plementation (Hofmeyr 2010). Implementation of evidence from

clinical trials is notoriously slow and incomplete (Bodribb 2010).

Hence, it may be that a future trial of specialised antenatal clinic

would show evidence of benefit because of improved implemen-

tation of these interventions that have been more recently shown

to be effective.

Importantly, it is not known whether preventing preterm birth

reduces neonatal morbidity and mortality as it may be that re-

taining a fetus in an unfavourable intrauterine environment has

a detrimental effect on in utero development. Hence, any future

trials need to report both short and long-term neonatal outcomes

(Kenyon 2008).

Implications for research

As specialised antenatal clinics for women with a pregnancy at

high risk of preterm delivery are now an accepted part of antenatal

services in many areas, it will be difficult to carry out further

randomised studies. However, the trials included in the review

included no information on psychological outcomes for women.

Some studies have suggested that whilst some pregnant women

welcome referral to a specialist clinic during pregnancy, others

experience it as unsettling (Jackson 2006). Any future research in

this area should examine which aspects of service provision are

preferred by women. Such research could underpin further service

development in this area.

A C K N O W L E D G E M E N T S

As part of the pre-publication editorial process, this review has been

commented on by two peers (an editor and referee who is external

to the editorial team), a member of the Pregnancy and Childbirth

Group’s international panel of consumers and the Group’s Statis-

tical Adviser.

9Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

R E F E R E N C E S

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the Society of Perinatal Obstetricians; 1989 Feb 1-4; New

Orleans, Louisiana, USA. 1989:387.

Main 1989 {published data only} ∗ Main DM, Gabbe SG, Richardson D, Strong S. Can

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Main DM, Richardson DK, Hadley CB, Gabbe SG.

Controlled trial of a preterm labor detection program:

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West Los Angeles 1994 {published data only}

Hobel CJ, Bemis RL. West Area Los Angeles prematurity

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Hobel CJ, Bragonier R, Ross M, Bear M, Bemis R, Mori

B. West Los Angeles premature prevention program:

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112. ∗ Hobel CJ, Ross MG, Bemis RL, Bragonier JR, Bear M,

Mori B. West Los Angeles preterm birth prevention project

(LAPPP): program impact. American Journal of Obstetrics

and Gynecology 1992;166:363.

Hobel CJ, Ross MG, Bemis RL, Bragonier JR, Nessim

S, Sandhu M, et al.The West Los Angeles preterm birth

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American Journal of Obstetrics and Gynecology 1994;170:

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Ross MG, Sandhu M, Bemis R, Nessim S, Bragonier JR,

Hobel C. The West Los Angeles preterm birth prevention

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Ross MG, Sandhu M, Bemis R, Nessim S, Bragonier JR,

Mori B, et al.West Los Angeles preterm birth prevention

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1992;166:367.

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Beazley 2001 {published data only}

Beazley D, Mercer B, Meyer N, Carr T. The Memphis

preterm birth project: prediction and prevention of preterm

birth in extremely high risk women [abstract]. American

Journal of Obstetrics and Gynecology 2001;185(6 Suppl):S86.

Collaborative Group 1993 {published data only}

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a preterm birth prevention program. American Journal of

Obstetrics and Gynecology 1993;169:352–66.

Creasy RK. United States multicenter preterm birth

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187–204.

Goldenberg 1990 {published data only}

Goldenberg RL, Davis RO, Copper RL, Corliss DK,

Andrews JB, Carpenter AH. The Alabama Preterm Birth

Prevention Project. Obstetrics & Gynecology 1990;75:933–9.

Pittsburgh 1989 {published data only}

Mueller-Heubach E. Results of a three-year prospective

controlled randomized trial of preterm birth prevention at

the University of Pittsburgh. Advances in the Prevention of

Low Birthweight: an International Symposium; 1988 May

8-11; Cape Cod, Massachusetts, USA. 1988:61–6.

Mueller-Heubach E, Reddick D, Barnett B, Bente R.

Preterm birth prevention: evaluation of a prospective

controlled randomized trial. American Journal of Obstetrics

and Gynecology 1989;160:1172–8.

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D, Van Giejn HP. Cervical incompetence prevention

randomisation cerclage trial (CIPRACT); effect of

therapeutic cerclage with bed rest v bed rest only on cervical

length. Ultrasound in Obstetrics & Gynecology 1998;12:

312–7.

Barros 2010

Barros FC, Bhutta ZA, Batra M, Hansen TN, Victora

CG, Rubens CE, GAPPS Review Group. Global report

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Bienstock 2001

Bienstock JL, Ural SH, Blakemore K, Pressman EK.

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55:692–5.

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birth in women at increased risk: a randomised placebo-

controlled double blind study. American Journal of Obstetrics

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Dodd 2007

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Hack 1999

Hack M. Consideration of the use of health status,

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Higgins 2011

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Hoffman HJ, Bakketeig lS. Risk factors associated with

the occurrence of preterm birth. Clinical Obstetrics and

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Hofmeyr 2010

Hofmeyr GJ, Lawrie TA, Atallah AN, Duley L. Calcium

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Jackson CJ, Bosio P, Habiba M, Waugh J, Kamal P, Dixon-

Woods M. Referral and attendance at a specialist antenatal

clinic: qualitative study of women’s views. BJOG: An

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Kenyon S, Pike K, Jones DR, Brocklehurst P, Marlow N,

Salt A, et al.Childhood outcomes after prescription of

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Kramer M, Demissie K, Yang H, Platt RW, Sauve R, Liston

R. The contribution of mild and moderate preterm birth to

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Lumley J. Defining the problem: epidemiology of preterm

birth. BJOG: an international journal of obstetrics and

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Petrou S, Sach T, Davidson L. The long-term costs of

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Hammerum MS, Mohapeloa H, et al.Systematic review

of progesterone for the prevention of preterm birth in

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Scandinavica 2009;88(11):1180–9.

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Ruis RJ, Fullerton J, Dudley DJ. The interrelationships

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Ugwumadu A, Manyonda I, Reid F, Hay P. Effect of early

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12Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

C H A R A C T E R I S T I C S O F S T U D I E S

Characteristics of included studies [ordered by study ID]

Iams 1989

Methods Randomised controlled trial of routine antepartum care versus routine antepartum care

plus a preterm birth prevention clinic in which symptoms and signs of labour were taught

and the cervix examined at weekly visits between 20 and 36 weeks’ gestation

Participants 370 pregnant women considered high risk for preterm birth based on use of the Creasey

Scoring system (Creasy 1980). Women were selected from 2829 women attending pre-

natal clinic at the Department of Obstetrics and Gynecology, Ohio State University,

Ohio

Interventions Preterm birth prevention clinic in which symptoms and signs of labour were taught and

the cervix examined at weekly visits between 20 and 36 weeks’ gestation

Outcomes Preterm labour diagnosed before 37 weeks’ gestation when cervical changes accompanied

persistent uterine contractions despite bedrest and intravenous hydration, or, if the cervix

was already 2 cm dilated and/or 50% effaced, when 8 contractions/hour persisted despite

bedrest and parenteral hydration

Notes

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence generation (selection

bias)

Unclear risk Insufficient information about the se-

quence generation process to permit judge-

ment of risk of bias

Allocation concealment (selection bias) Unclear risk Insufficient information about the se-

quence generation process to permit judge-

ment of risk of bias

Blinding (performance bias and detection

bias)

All outcomes

Unclear risk Insufficient information about the se-

quence generation process to permit judge-

ment of risk of bias

Incomplete outcome data (attrition bias)

All outcomes

Unclear risk No reporting of attrition or exclusions.

Selective reporting (reporting bias) Unclear risk Insufficient information about the se-

quence generation process to permit judge-

ment of risk of bias.

Other bias Unclear risk Does not explicitly state that only single-

ton pregnancies were included in the study.

13Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

Iams 1989 (Continued)

No comment is made on what cut-off was

used for the Creasy scoring system to de-

fine women as of high risk of preterm birth

(Creasy 1980).

Main 1989

Methods Randomised controlled trial of routine antepartum care versus a preterm labour detection

clinic in which women were seen on a weekly or biweekly basis, the cervix examined at

each visit and education provided regarding subtle signs of labour

Participants All women were from the obstetric clinic of the University of Pennsylvania Hospital,

USA. 376 black women considered at high risk for preterm birth based on a Papiernik-

Creasey Scoring system value of 10 or more (Creasy 1980). 178 control patients and

198 women assigned to preterm labour detection clinic

Interventions Attendance at a preterm labour detection clinic on a weekly or biweekly basis from

22 weeks’ gestation. Cervical assessment by 1 of 3 physicians at each visit. Education

provided by a nurse specialist regarding subtle signs of labour

Outcomes Gestational age at delivery, birthweight, preterm PROM, inpatient costs, outpatient costs

Notes Higher rate of accrual into the intervention group due to: (1) high-risk women who par-

ticipated in the Preterm Labour Detection Clinic in earlier pregnancies being uniformly

assigned to it in subsequent pregnancy; (2) higher elective abortion and transfer of care

rates in control group

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence generation (selection

bias)

High risk Consecutive numbers of a random num-

bers table were used to allocate the first

479 participants whilst the second sam-

ple of 464 women was divided into groups

by birthday (even versus odd day of the

month)

Allocation concealment (selection bias) High risk Date of birth used for allocation of half of

participants.

Blinding (performance bias and detection

bias)

All outcomes

Low risk Neither the physicians or the control pa-

tients were made aware they were at high

risk of preterm birth. Not possible to blind

participants attending the preterm labour

detection clinic due to the frequency of at-

tendance

14Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

Main 1989 (Continued)

Incomplete outcome data (attrition bias)

All outcomes

High risk Insufficient reporting of attrition/exclu-

sions: there were missing data (approxi-

mately 20%) for neonatal outcomes as not

all infant case notes were examined

Selective reporting (reporting bias) Unclear risk Insufficient information about the se-

quence generation process to permit judge-

ment of risk of bias

Other bias Unclear risk Women included in study during more

than one pregnancy.

West Los Angeles 1994

Methods Eight West Los Angeles County prenatal clinics randomised to be either experimental or

control clinics. Women in experimental clinics offered a programme of more frequent

visits, preterm birth prevention education, psychosocial and nutritional screening and

crisis intervention. Women in control clinics offered routine county care plus psychoso-

cial and nutritional screening and crisis intervention

Participants 1774 high-risk patients in experimental clinics and 880 control clinic patients. Majority

of patients were Hispanic

Interventions Women in control clinics offered visits at 4-week intervals up to 30 weeks’ gestation, 2-

week intervals from 30-35 weeks’ gestation, and then weekly until delivery. Psychosocial

and nutritional screening and crisis intervention also offered. Women in experimental

clinics offered visits at 2-week intervals, 3 classes regarding preterm birth prevention,

psychosocial and nutritional screening and crisis intervention. Participants were ran-

domised to 1 of 4 secondary interventions (bed rest, social work, Provera or Provera-

matched control) or to no additional intervention

Outcomes Preterm birth rate, costs of antenatal care, inpatient preterm labour, delivery and postpar-

tum care, and newborn care. For continuous outcomes (costs and number of antenatal

visits) means and standard errors were reported. We calculated standard deviations in

order to include these data in the data and analyses tables

Notes

Risk of bias

Bias Authors’ judgement Support for judgement

Random sequence generation (selection

bias)

Unclear risk Cluster randomised therefore not applica-

ble; “these clinics were randomized with a

restricted block (grouped by size and per-

cent black) randomized scheme to identify

the clinic as either experimental (five clin-

ics) or control (three clinics)”

15Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

West Los Angeles 1994 (Continued)

Allocation concealment (selection bias) Unclear risk Cluster randomised therefore not applica-

ble.

Blinding (performance bias and detection

bias)

All outcomes

High risk Women randomised based on which clinic

they attended.

Incomplete outcome data (attrition bias)

All outcomes

Unclear risk All high-risk women accounted for in a flow

chart. 5%-7% of women assessed as high

risk lost to follow-up

Other bias Low risk

PROM: preterm rupture of membranes

Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion

Beazley 2001 Study design: randomised prospective trial.

Intervention: weekly contact with a nurse versus routine care.

Participants: 218 women at high risk of preterm birth

Outcomes: preterm birth before 37 weeks’ gestation and spontaneous preterm birth before 37 weeks’

gestation

Published in abstract form only. Not clear how many patients were in control and intervention groups

therefore analysis not possible. No decrease in the incidence of preterm birth or spontaneous preterm

birth in the intervention group (43% vs 41%, 35% vs 30% respectively)

Collaborative Group 1993 Study design: multi-centre randomised controlled trial.

Intervention: preterm labour prevention programme with additional visits, education about the signs

of preterm labour and cervical assessment at routine visits vs routine care.

Participants: 2395 women considered at high risk of preterm delivery.

Outcomes: spontaneous preterm birth by 36 and 37 completed weeks with and without PPROM, very

low birthweight (< 1500 g at birth), low birthweight (< 2500 g at birth).

Women with multiple pregnancies included in all the analyses. Creasy publication of data from a cohort

of the women included in the Collaborative Group on Preterm Birth Prevention publication

Goldenberg 1990 Study design: multi-centre randomised controlled trial.

Intervention: preterm labour prevention programme with weekly visits, education about the signs of

preterm labour and cervical assessment at routine visits vs routine care. Control women seen in different

clinics from intervention patients.

Participants: 678 women considered at high risk of preterm delivery.

Outcomes: spontaneous preterm birth at less than 37 completed weeks, very low birthweight (< 1500

16Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

(Continued)

g at birth), low birthweight (1500-2499 g at birth), spontaneous preterm PROM rate.

Women with multiple pregnancies included in all the analyses

Pittsburgh 1989 Study design: randomised controlled trial.

Intervention: preterm labour prevention programme with weekly visits, education about the signs of

preterm labour and cervical assessment at each visit vs routine care

Participants: 831 women considered at high risk of preterm delivery out of 5457 women screened.

Outcomes: spontaneous preterm birth at less than 37 completed weeks.

Women with multiple pregnancies included in all the analyses

vs: versus

17Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

D A T A A N D A N A L Y S E S

Comparison 1. Specialised antenatal care versus routine care

Outcome or subgroup title No. of

studies

No. of

participants Statistical method Effect size

1 Perinatal death 1 302 Risk Ratio (M-H, Fixed, 95% CI) 1.25 [0.43, 3.62]

2 Extremely preterm birth (< 28

weeks’ gestation)

1 376 Risk Ratio (M-H, Fixed, 95% CI) 0.77 [0.26, 2.25]

3 Development of antenatal

complications - preterm labour

1 370 Risk Ratio (M-H, Fixed, 95% CI) 1.29 [0.90, 1.86]

4 Preterm birth - adjusted for

cluster design effect (ICC

0.002)

3 Risk Ratio (Fixed, 95% CI) 0.87 [0.69, 1.08]

4.1 Individually randomised

trials

2 Risk Ratio (Fixed, 95% CI) 0.91 [0.68, 1.22]

4.2 Cluster randomisation 1 Risk Ratio (Fixed, 95% CI) 0.81 [0.58, 1.14]

5 Sensitivity analysis. Preterm

birth (adjusted for cluster

design effect using upper CI,

ICC 0.0041)

3 Risk Ratio (Fixed, 95% CI) 0.87 [0.69, 1.11]

5.1 Individually randomised

trials

2 Risk Ratio (Fixed, 95% CI) 0.91 [0.68, 1.22]

5.2 Cluster randomisation 1 Risk Ratio (Fixed, 95% CI) 0.81 [0.54, 1.22]

6 Very preterm birth (birth before

34 weeks’ gestation)

1 376 Risk Ratio (M-H, Fixed, 95% CI) 1.05 [0.50, 2.21]

7 Gestation at birth 1 2654 Mean Difference (IV, Fixed, 95% CI) -0.10 [-0.30, 0.10]

8 Infection requiring intravenous

antibiotics

0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

9 Caesarean section 1 376 Risk Ratio (M-H, Fixed, 95% CI) 1.11 [0.76, 1.62]

10 Postnatal depression 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

11 Breastfeeding 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

12 Instrumental vaginal birth 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

13 Neonatal intensive care unit

admission

1 302 Risk Ratio (M-H, Fixed, 95% CI) 0.62 [0.34, 1.12]

14 Respiratory distress syndrome 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

15 Parameters of birth asphyxia 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

16 Complications of prematurity 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

17 Disability at childhood follow-

0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

18 Women’s satisfaction 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]

19 Costs associated with care 2 604 Mean Difference (IV, Fixed, 95% CI) -16.67 [-367.00,

335.67]

20 Costs associated with newborn

inpatient care (US $)

1 290 Mean Difference (IV, Fixed, 95% CI) -2196.0 [-4322.06, -

69.94]

21 Number of antenatal visits 1 290 Mean Difference (IV, Fixed, 95% CI) 1.70 [0.72, 2.68]

22 Number of antenatal

admissions

0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]

18Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

23 Length of antenatal admissions 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]

24 Length of maternal postnatal

stay

0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]

25 Length of stay in neonatal

intensive care unit

0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]

26 Infant length of stay in hospital 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]

27 Preterm birth - all studies,

unadjusted data

3 3400 Risk Ratio (M-H, Fixed, 95% CI) 0.85 [0.70, 1.03]

27.1 Individual randomisation 2 746 Risk Ratio (M-H, Fixed, 95% CI) 0.90 [0.67, 1.21]

27.2 Cluster randomisation 1 2654 Risk Ratio (M-H, Fixed, 95% CI) 0.81 [0.62, 1.06]

Analysis 1.1. Comparison 1 Specialised antenatal care versus routine care, Outcome 1 Perinatal death.

Review: Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Comparison: 1 Specialised antenatal care versus routine care

Outcome: 1 Perinatal death

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

Main 1989 7/146 6/156 100.0 % 1.25 [ 0.43, 3.62 ]

Total (95% CI) 146 156 100.0 % 1.25 [ 0.43, 3.62 ]

Total events: 7 (Treatment), 6 (Control)

Heterogeneity: not applicable

Test for overall effect: Z = 0.40 (P = 0.69)

Test for subgroup differences: Not applicable

0.01 0.1 1 10 100

Favours treatment Favours control

19Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

Analysis 1.2. Comparison 1 Specialised antenatal care versus routine care, Outcome 2 Extremely preterm

birth (< 28 weeks’ gestation).

Review: Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Comparison: 1 Specialised antenatal care versus routine care

Outcome: 2 Extremely preterm birth (< 28 weeks’ gestation)

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

Main 1989 6/198 7/178 100.0 % 0.77 [ 0.26, 2.25 ]

Total (95% CI) 198 178 100.0 % 0.77 [ 0.26, 2.25 ]

Total events: 6 (Treatment), 7 (Control)

Heterogeneity: not applicable

Test for overall effect: Z = 0.48 (P = 0.63)

Test for subgroup differences: Not applicable

0.01 0.1 1 10 100

Favours treatment Favours control

Analysis 1.3. Comparison 1 Specialised antenatal care versus routine care, Outcome 3 Development of

antenatal complications - preterm labour.

Review: Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Comparison: 1 Specialised antenatal care versus routine care

Outcome: 3 Development of antenatal complications - preterm labour

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

Iams 1989 50/182 40/188 100.0 % 1.29 [ 0.90, 1.86 ]

Total (95% CI) 182 188 100.0 % 1.29 [ 0.90, 1.86 ]

Total events: 50 (Treatment), 40 (Control)

Heterogeneity: not applicable

Test for overall effect: Z = 1.38 (P = 0.17)

Test for subgroup differences: Not applicable

0.01 0.1 1 10 100

Favours treatment Favours control

20Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

Analysis 1.4. Comparison 1 Specialised antenatal care versus routine care, Outcome 4 Preterm birth -

adjusted for cluster design effect (ICC 0.002).

Review: Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Comparison: 1 Specialised antenatal care versus routine care

Outcome: 4 Preterm birth - adjusted for cluster design effect (ICC 0.002)

Study or subgroup log [Risk Ratio] Risk Ratio Weight Risk Ratio

(SE) IV,Fixed,95% CI IV,Fixed,95% CI

1 Individually randomised trials

Iams 1989 -0.34486 (0.24377) 21.9 % 0.71 [ 0.44, 1.14 ]

Main 1989 0.058596 (0.1916) 35.5 % 1.06 [ 0.73, 1.54 ]

Subtotal (95% CI) 57.4 % 0.91 [ 0.68, 1.22 ]

Heterogeneity: Chi2 = 1.69, df = 1 (P = 0.19); I2 =41%

Test for overall effect: Z = 0.63 (P = 0.53)

2 Cluster randomisation

West Los Angeles 1994 -0.2079 (0.175007) 42.6 % 0.81 [ 0.58, 1.14 ]

Subtotal (95% CI) 42.6 % 0.81 [ 0.58, 1.14 ]

Heterogeneity: not applicable

Test for overall effect: Z = 1.19 (P = 0.23)

Total (95% CI) 100.0 % 0.87 [ 0.69, 1.08 ]

Heterogeneity: Chi2 = 1.93, df = 2 (P = 0.38); I2 =0.0%

Test for overall effect: Z = 1.26 (P = 0.21)

Test for subgroup differences: Chi2 = 0.24, df = 1 (P = 0.63), I2 =0.0%

0.01 0.1 1 10 100

Favours experimental Favours control

21Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

Analysis 1.5. Comparison 1 Specialised antenatal care versus routine care, Outcome 5 Sensitivity analysis.

Preterm birth (adjusted for cluster design effect using upper CI, ICC 0.0041).

Review: Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Comparison: 1 Specialised antenatal care versus routine care

Outcome: 5 Sensitivity analysis. Preterm birth (adjusted for cluster design effect using upper CI, ICC 0.0041)

Study or subgroup log [Risk Ratio] Risk Ratio Weight Risk Ratio

(SE) IV,Fixed,95% CI IV,Fixed,95% CI

1 Individually randomised trials

Iams 1989 -0.34486 (0.24377) 25.1 % 0.71 [ 0.44, 1.14 ]

Main 1989 0.058596 (0.1916) 40.6 % 1.06 [ 0.73, 1.54 ]

Subtotal (95% CI) 65.7 % 0.91 [ 0.68, 1.22 ]

Heterogeneity: Chi2 = 1.69, df = 1 (P = 0.19); I2 =41%

Test for overall effect: Z = 0.63 (P = 0.53)

2 Cluster randomisation

West Los Angeles 1994 -0.2079 (0.208401) 34.3 % 0.81 [ 0.54, 1.22 ]

Subtotal (95% CI) 34.3 % 0.81 [ 0.54, 1.22 ]

Heterogeneity: not applicable

Test for overall effect: Z = 1.00 (P = 0.32)

Total (95% CI) 100.0 % 0.87 [ 0.69, 1.11 ]

Heterogeneity: Chi2 = 1.88, df = 2 (P = 0.39); I2 =0.0%

Test for overall effect: Z = 1.10 (P = 0.27)

Test for subgroup differences: Chi2 = 0.19, df = 1 (P = 0.66), I2 =0.0%

0.01 0.1 1 10 100

Favours experimental Favours control

22Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

Analysis 1.6. Comparison 1 Specialised antenatal care versus routine care, Outcome 6 Very preterm birth

(birth before 34 weeks’ gestation).

Review: Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Comparison: 1 Specialised antenatal care versus routine care

Outcome: 6 Very preterm birth (birth before 34 weeks’ gestation)

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

Main 1989 14/198 12/178 100.0 % 1.05 [ 0.50, 2.21 ]

Total (95% CI) 198 178 100.0 % 1.05 [ 0.50, 2.21 ]

Total events: 14 (Treatment), 12 (Control)

Heterogeneity: not applicable

Test for overall effect: Z = 0.13 (P = 0.90)

Test for subgroup differences: Not applicable

0.01 0.1 1 10 100

Favours treatment Favours control

Analysis 1.7. Comparison 1 Specialised antenatal care versus routine care, Outcome 7 Gestation at birth.

Review: Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Comparison: 1 Specialised antenatal care versus routine care

Outcome: 7 Gestation at birth

Study or subgroup Treatment Control Mean

Difference Weight Mean

Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

West Los Angeles 1994 1774 39.8 (2.3) 880 39.9 (2.5) 100.0 % -0.10 [ -0.30, 0.10 ]

Total (95% CI) 1774 880 100.0 % -0.10 [ -0.30, 0.10 ]

Heterogeneity: not applicable

Test for overall effect: Z = 1.00 (P = 0.32)

Test for subgroup differences: Not applicable

-100 -50 0 50 100

Favours treatment Favours control

23Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

Analysis 1.9. Comparison 1 Specialised antenatal care versus routine care, Outcome 9 Caesarean section.

Review: Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Comparison: 1 Specialised antenatal care versus routine care

Outcome: 9 Caesarean section

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

Main 1989 47/198 38/178 100.0 % 1.11 [ 0.76, 1.62 ]

Total (95% CI) 198 178 100.0 % 1.11 [ 0.76, 1.62 ]

Total events: 47 (Treatment), 38 (Control)

Heterogeneity: not applicable

Test for overall effect: Z = 0.55 (P = 0.58)

Test for subgroup differences: Not applicable

0.01 0.1 1 10 100

Favours treatment Favours control

Analysis 1.13. Comparison 1 Specialised antenatal care versus routine care, Outcome 13 Neonatal

intensive care unit admission.

Review: Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Comparison: 1 Specialised antenatal care versus routine care

Outcome: 13 Neonatal intensive care unit admission

Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

Main 1989 15/146 26/156 100.0 % 0.62 [ 0.34, 1.12 ]

Total (95% CI) 146 156 100.0 % 0.62 [ 0.34, 1.12 ]

Total events: 15 (Treatment), 26 (Control)

Heterogeneity: not applicable

Test for overall effect: Z = 1.60 (P = 0.11)

Test for subgroup differences: Not applicable

0.01 0.1 1 10 100

Favours treatment Favours control

24Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

Analysis 1.19. Comparison 1 Specialised antenatal care versus routine care, Outcome 19 Costs associated

with care.

Review: Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Comparison: 1 Specialised antenatal care versus routine care

Outcome: 19 Costs associated with care

Study or subgroup Treatment Control Mean

Difference Weight Mean

Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

Main 1989 (1) 162 5687 (4222) 152 5846 (4872) 12.1 % -159.00 [ -1170.22, 852.22 ]

West Los Angeles 1994 (2) 165 4174 (1811.2) 125 4171 (1453.4) 87.9 % 3.00 [ -372.89, 378.89 ]

Total (95% CI) 327 277 100.0 % -16.67 [ -369.00, 335.67 ]

Heterogeneity: Chi2 = 0.09, df = 1 (P = 0.77); I2 =0.0%

Test for overall effect: Z = 0.09 (P = 0.93)

Test for subgroup differences: Not applicable

-1000 -500 0 500 1000

Favours treatment Favours control

(1) Maternal charges

(2) Hospital costs for delivery and postpartum care (maternal)

Analysis 1.20. Comparison 1 Specialised antenatal care versus routine care, Outcome 20 Costs associated

with newborn inpatient care (US $).

Review: Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Comparison: 1 Specialised antenatal care versus routine care

Outcome: 20 Costs associated with newborn inpatient care (US $)

Study or subgroup Experimental Control Mean

Difference Weight Mean

Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

West Los Angeles 1994 165 3146 (5150) 125 5342 (11269) 100.0 % -2196.00 [ -4322.06, -69.94 ]

Total (95% CI) 165 125 100.0 % -2196.00 [ -4322.06, -69.94 ]

Heterogeneity: not applicable

Test for overall effect: Z = 2.02 (P = 0.043)

Test for subgroup differences: Not applicable

-1000 -500 0 500 1000

Favours experimental Favours control

25Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

Analysis 1.21. Comparison 1 Specialised antenatal care versus routine care, Outcome 21 Number of

antenatal visits.

Review: Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Comparison: 1 Specialised antenatal care versus routine care

Outcome: 21 Number of antenatal visits

Study or subgroup Treatment Control Mean

Difference Weight Mean

Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI

West Los Angeles 1994 165 6.6 (5.14) 125 4.9 (3.35) 100.0 % 1.70 [ 0.72, 2.68 ]

Total (95% CI) 165 125 100.0 % 1.70 [ 0.72, 2.68 ]

Heterogeneity: not applicable

Test for overall effect: Z = 3.40 (P = 0.00067)

Test for subgroup differences: Not applicable

-10 -5 0 5 10

Favours treatment Favours control

26Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

Analysis 1.27. Comparison 1 Specialised antenatal care versus routine care, Outcome 27 Preterm birth - all

studies, unadjusted data.

Review: Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes

Comparison: 1 Specialised antenatal care versus routine care

Outcome: 27 Preterm birth - all studies, unadjusted data

Study or subgroup Experimental Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI

1 Individual randomisation

Iams 1989 24/182 35/188 18.9 % 0.71 [ 0.44, 1.14 ]

Main 1989 46/198 39/178 22.5 % 1.06 [ 0.73, 1.54 ]

Subtotal (95% CI) 380 366 41.4 % 0.90 [ 0.67, 1.21 ]

Total events: 70 (Experimental), 74 (Control)

Heterogeneity: Chi2 = 1.70, df = 1 (P = 0.19); I2 =41%

Test for overall effect: Z = 0.70 (P = 0.48)

2 Cluster randomisation

West Los Angeles 1994 131/1774 80/880 58.6 % 0.81 [ 0.62, 1.06 ]

Subtotal (95% CI) 1774 880 58.6 % 0.81 [ 0.62, 1.06 ]

Total events: 131 (Experimental), 80 (Control)

Heterogeneity: not applicable

Test for overall effect: Z = 1.53 (P = 0.13)

Total (95% CI) 2154 1246 100.0 % 0.85 [ 0.70, 1.03 ]

Total events: 201 (Experimental), 154 (Control)

Heterogeneity: Chi2 = 2.01, df = 2 (P = 0.37); I2 =0%

Test for overall effect: Z = 1.63 (P = 0.10)

Test for subgroup differences: Chi2 = 0.26, df = 1 (P = 0.61), I2 =0.0%

0.1 0.2 0.5 1 2 5 10

Favours experimental Favours control

H I S T O R Y

Protocol first published: Issue 4, 2007

Review first published: Issue 9, 2011

Date Event Description

21 February 2008 Amended Converted to new review format.

20 July 2007 New citation required and major changes Substantive amendment

27Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)

C O N T R I B U T I O N S O F A U T H O R S

Melissa Whitworth wrote the protocol, carried out data extraction, assessed risk of bias, entered and checked data and contributed to

drafting the text of the review. Siobhan Quenby carried out data extraction and commented on the draft of the review. Ruth Cockerill

carried out data extraction, entered and checked data and contributed to drafting the text of the review. Therese Dowswell assisted with

data analysis and writing up the results.

D E C L A R A T I O N S O F I N T E R E S T

None known.

S O U R C E S O F S U P P O R T

Internal sources

• The University of Liverpool, UK.

External sources

• National Institute for Health Research (NIHR), UK.

TD is supported by the NIHR NHS Cochrane Collaboration Programme grant scheme award for NHS-prioritised centrally-

managed, pregnancy and childbirth systematic reviews: CPGS 10/4001/02

D I F F E R E N C E S B E T W E E N P R O T O C O L A N D R E V I E W

The methods section has been updated to reflect the Pregnancy and Childbirth Group’s updated methods text and the latest Handbook (Higgins 2011).

I N D E X T E R M S

Medical Subject Headings (MeSH)

∗Pregnancy Outcome; ∗Pregnancy, High-Risk; Patient Education as Topic; Premature Birth [diagnosis; ∗prevention & control]; Prenatal

Care [organization & administration; ∗standards]; Randomized Controlled Trials as Topic; Secondary Prevention

MeSH check words

Female; Humans; Pregnancy

28Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve

maternal and infant outcomes (Review)