Process of the reviews

Research questions

For each clinical topic, research questions were developed by the EAC based on the relevant research questions used in the NICE guidelines. The groups contracted to undertake reviews of the evidence related to these questions used a systematic method of literature searching and selection.

Search strategies

Searches were conducted in Medline, EMBASE, PsycInfo, Informit, Australian Medical Index and the Cochrane Database of Systematic Reviews. Search terms were searched for as keywords, exploded where possible, and as free text within the title and/or abstract, in the EMBASE and Medline databases, with modifications to suit the keywords and descriptors of other search platforms. The reference lists of included papers were reviewed to identify any peer-reviewed evidence that may have been missed in the
literature search.

As the search strategies were very specific to each clinical area reviewed, studies on all groups were included rather than aiming to identify studies on particular groups. This process identified evidence on socioeconomic disparities where these exist (for example number of antenatal visits, adolescent mothers, asymptomatic bacteriuria, access to screening for chromosomal abnormalities and oral health)

Appraisal of the evidence

Abstracts of studies within the review period and in English were reviewed. Exclusion criteria included:

• already included in NICE guidelines;
• not specific to target population (eg specific to non-pregnant women or high-risk women only);
• not specific to first trimester;
• does not answer research question;
• does not meet criteria for grading (eg no outcomes reported or high risk of bias); and
• narrative review or opinion paper (editorial, letter, comment).

Evidence included in the reviews was graded as per NHMRC designations (see Table D1).

Table D1: Designations of levels of evidence according to type of research question

Level	Intervention	Diagnostic accuracy	Prognosis	Aetiology	Screening intervention
I	Systematic review of level II studies	A systematic review of level II studies	A systematic review of level II studies	A systematic review of level II studies	A systematic review of level II studies
II	A randomised controlled trial	A study of test accuracy with an independent, blinded comparison with a valid reference standard, among consecutive persons with a defined clinical presentation	A prospective cohort study	A prospective cohort study	A randomised controlled trial
III-1	Pseudorandomised trial	A study of test accuracy with independent, blinded comparison with a valid reference standard, among non-consecutive persons with a defined clinical presentation	All or none	All or none	Pseudorandomised controlled trial (ie alternate allocation or some other method)
III-2	A comparative study with concurrent controls: Non-randomised experimental trial Cohort study Case-control study Interrupted time series with control group	A comparison with reference standard that does not meet the criteria required for Level II and III-1 evidence	Analysis of prognostic factors amongst persons in a single arm of a randomised controlled trial	A retrospective cohort study	A comparative study with concurrent controls: Non-randomised, experimental trial Cohort study Case-control study
III-3	A comparative study without concurrent controls: Historical control study Two or more single arm study Interrupted time series without parallel control	Diagnostic case-control study	A retrospective cohort study	A case-control study	A comparative study without concurrent controls: Historical control study Two or more single arm study
IV	Case series with either post-test or pre-test/ post-test outcomes	Study of diagnostic yield (no reference standard)	Case series, or cohort study of persons at different stages of disease	A cross-sectional study or case series	Case series

Source: NHMRC Levels of Evidence and Grades of Recommendations for Developers of Guidelines (NHMRC 2009).
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Grading of the evidence

Grading of the body of evidence involved:

• review of the evidence base, including the number of studies, level of evidence and quality of studies (eg risk of bias), and consistency across studies;
• examination of the effect size, the relevance of the evidence base to the research question and whether the risks and benefits had been considered in terms of clinical impact; and
• judgement by members of the EAC of the generalisability of the body of evidence to the target population for the Guidelines and the applicability of the body of evidence to the Australian healthcare context, taking into account feasibility issues (workforce, geographical distance, cost) and existing health care systems.

The Evidence Statement Form/Matrix (adapted from NHMRC Levels of Evidence and Grades for Recommendations for Developers of Guidelines [2009]) was used for each research question addressed. The form was used as the basis of discussion regarding the key components, which were rated according to the matrix shown in Table D2. Conflicts of interest (eg where an EAC member was author of evidence under consideration) were declared at the commencement of discussion of each topic.

Table D2: Components of body of evidence considered when grading each recommendation

Please note the contents of table is described as below so that this table is easily accessible.
Evidence base
A - One or more level I studies with a low risk of bias or several level II studies with low risk of bias
B - One or two level II studies with a low risk of bias or systematic review/several level III studies with a low risk of bias
C - One or two level III studies with a low risk of bias or level I or II studies with a moderate risk of bias
D - Level IV studies or level I to III studies/systematic review with a high risk of bias

Consistency
A - All studies consistent
B - Most studies consistent and inconsistency can be explained
C - Some inconsistency, reflecting genuine uncertainty around question
D - Evidence in inconsistent
NA - Not Applicable – one study only

Clinical Impact
A - Very large
B - Moderate
C - Slight
D - Restricted
UD - Unable to be determined

Generalisability
A - Evidence directly generalisable to target population
B - Evidence directly generalisable to target population with some caveats
C - Evidence not directly generalisable to target population but could be sensibly applied
D - Evidence not directly generalisable to target population and hard to judge whether it is sensible to apply

Applicability
A - Evidence directly applicable to Australian healthcare context
B - Evidence applicable to Australian healthcare context with few caveats
C - Evidence probably applicable to Australian healthcare context with some caveats
D - Evidence not applicable to Australian healthcare context

Source: NHMRC Levels of Evidence and Grades of Recommendations for Developers of Guidelines (NHMRC 2009).
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Formulating and grading of recommendations

The systematic reviewers provided grades for the evidence base and consistency of the evidence. EAC members then applied grades for the clinical impact, generalisability and applicability of the evidence. The overall grade of the evidence was then determined, based on a summation of the rating for each individual component of the body of evidence. Where NICE recommendations were used, these were adapted to the Australian context and language used in the Guidelines. If there was no
NICE recommendation or recent evidence required a change to the recommendation, these were formulated by EAC members. Initial wording of recommendations was agreed by a quorum of the EAC and recommendations were then circulated to all members and further discussed at a teleconference. All recommendations were then discussed with the Working Group for Aboriginal and Torres Strait Islander Women’s Antenatal Care.

Any notes relevant to developing the recommendation, including barriers to implementing the recommendations and support required for successful uptake of the Guidelines, were recorded.

Consensus-based recommendations

Consensus-based recommendations were formulated when a systematic review of the evidence was conducted but no good quality evidence identified. Initial wording of consensus-based recommendations was agreed by a quorum of the EAC and recommendations were then circulated to all members and further discussed at a teleconference. All recommendations were then discussed with the Working Group for Aboriginal and Torres Strait Islander Women’s Antenatal Care.

Practice points

Practice points (PPs) were developed to cover areas that were beyond the scope of the systematic reviews but where it was determined by the EAC that practical advice is needed. The formulation of PPs involved a process of:

• identifying areas where advice was required or PPs were needed as adjuncts/corollaries of recommendations and/or other PPs; and
• discussion of a PP by members of the EAC and the Working Group for Aboriginal and Torres Strait Islander Women’s Antenatal Care until consensus on the wording was reached.

Limitations of the review methodology

This review used a structured approach to reviewing the literature. However, all types of study are subject to bias, with systematic reviews being subject to the same biases seen in the original studies they include, as well as to biases specifically related to the systematic review process. Reporting biases are a particular problem related to systematic reviews and include publication bias, time-lag bias, multiple publication bias, language bias and outcome reporting bias (see Glossary).

Some of these biases are potentially present in these reviews. Only data published in peer-reviewed journals were included. Unpublished material was not included as such material typically has insufficient information upon which to base quality assessment, and it has not been subject to the peer-review process. In addition, the search was limited to English-language publications only, so language bias is also a potential problem. Outcome reporting bias and inclusion criteria bias are unlikely as the methodology used in the review and the scope of the review was defined in advance.

The studies were initially selected by examining the abstracts of these articles. Therefore, it is possible that some studies were inappropriately excluded prior to examination of the full text article. However, where detail was lacking, ambiguous papers were retrieved as full text to minimise this possibility.