The purpose of this review was to evaluate the effectiveness of interventions focused on the delivery or organisation of antenatal care as a means of reducing infant mortality or its three major causes (PTB, congenital anomalies, SIDS/SUDI) in disadvantaged and vulnerable women.
We identified 36 primary reports of eligible studies evaluating interventions in a range of disadvantaged and vulnerable populations including socioeconomically disadvantaged/low-income women in general, socioeconomically disadvantaged/low-income women with additional clinical risk factors for adverse pregnancy outcome, and four other specific groups at risk of adverse pregnancy outcome: teenagers, substance users, indigenous women and HIV positive women.
Overall, the quality of evidence was poor and, for most of the interventions considered, there was insufficient evidence to evaluate consistency of findings across multiple studies. Less than half of the included evaluations were considered to have 'adequate' internal validity. Even for interventions shown to be effective in higher quality studies, such as group antenatal care, we considered that the evidence was too sparse to reliably conclude that the interventions were effective in reducing PTB or neonatal mortality in the disadvantaged and vulnerable populations considered, or that the findings could be generalised to other disadvantaged populations.
We concluded that the evidence relating to seven interventions, although inconclusive, indicated a possible beneficial effect on PTB or on infant mortality.
The following four models of comprehensive antenatal care were considered promising:
Findings of one well-conducted RCT  suggested that group antenatal care might reduce PTB in socioeconomically disadvantaged women. A cohort study evaluating the same model of group antenatal care  did not show a consistent beneficial effect on PTB, but the study was too small to detect an effect on this outcome. The group antenatal care model is well defined and described and would appear to be transferable to non-US healthcare systems.
Trials of two broad, multifaceted, clinic-based PTB prevention programmes targeting disadvantaged women with additional clinical risk factors for PTB suggested that such interventions might be effective in reducing PTB. The two interventions evaluated [43, 48] were not identical but appeared to share the common approach of targeting a broad range of risk factors in women identified as being at higher-risk. Such programmes would potentially be transferable to non-US healthcare systems, although only one of the two reports provided sufficient detail to enable replication of the main elements of the programme .
The intensive, multi-component TIPPS programme evaluated by Reece  was considered promising with regard to possible effects on PTB despite methodological limitations of the evaluation. The TIPPS intervention itself was designed specifically to address the problems and needs of a disadvantaged local population in North Philadelphia and it is unclear whether the intervention is transferable or the findings generaliseable to other setting. However, some elements of the intervention and the need-based approach to developing 'locally customised' services may merit further examination and evaluation.
The two overlapping evaluations of the New York Prenatal Care
Assistance Program (PCAP) [38, 55] suggested that the PCAP programme might be effective in reducing PTB in HIV positive women, some of whom were drug users. The programme aims to improve outcomes by improving the quality of care through a process of clinic accreditation with financial incentives to 'accredited' providers. The effect of PCAP on other outcomes has also been evaluated in a wider population of socioeconomically disadvantaged women . The use of enhanced payments to providers providing enhanced services is potentially transferable to other healthcare systems but it is unclear whether the specific services covered by PCAP accreditation would be relevant in other settings.
Three interventions provided as an adjunct to standard antenatal care were also considered promising:
Two nutritional programmes were tentatively considered promising. An evaluation of the Higgins Nutrition Intervention Program in pregnant teenagers indicated a possible beneficial effect on PTB in this population, despite the methodological limitations of the study ; and the evaluation of a home visiting programme focussing on nutritional education (the Florina Intervention Program) also suggested a possible beneficial effect on PTB in a low-income rural population in Greece [42, 57]. The Florina Intervention Program was evaluated in isolated agricultural population in Greece with a low-calorie, seasonal diet based on home produce and domestic livestock ; the relevance and generalisability of the nutritional elements of the intervention to more urbanised populations is unclear.
A single US-based study indicated that maternity care coordination might have a beneficial effect on infant mortality in socially disadvantaged women in the USA . However, it is unclear to what extent these findings can be generalised to other healthcare systems since some elements of the intervention may be specific to the healthcare and welfare systems in the USA.
Although we identified seven studies evaluating 'teen' clinics, no conclusions could be drawn regarding the effectiveness of such clinics because of problems of study design and selection bias in the included studies.
We found insufficient evidence of adequate quality to draw any conclusions regarding the effectiveness of the other interventions evaluated.
Strengths and limitations of this systematic review
In line with our aim to identify the best available evidence on antenatal care interventions targeting socially disadvantaged and vulnerable women we did not restrict ourselves to particular study designs and we designed our searches to reflect this breadth of interest. This lack of specificity may be seen as both strength and a weakness of this review.
The inclusion of less methodologically rigorous evaluations increased the volume of material identified and reviewed and also presented methodological challenges with regard to quality assessment. Furthermore, in practice, it did not add greatly to the evidence regarding effectiveness. Nevertheless, the inclusion and systematic quality appraisal of such evaluations may have served the useful function of highlighting the lack of robust evidence supporting the effectiveness of some widely studied interventions, e.g. 'teen' clinics.
The decision to review a broad category of interventions-antenatal care programmes involving the delivery or organisation of antenatal care-rather than identifying specific interventions a priori, has enabled us to provide an overview of a wide range of interventions. A more focussed approach examining a smaller range of specific interventions would have been more consistent with standard systematic reviewing methods, although developing and applying precise interventions definitions-required to ensure reproducible selection of studies-would potentially have been challenging. Furthermore, such an approach would have lacked the flexibility to review a broad, rather diffuse and poorly defined evidence base which was possible with our more comprehensive approach. However, a disadvantage is that a more comprehensive approach necessitates a degree of post hoc decision making . For example, following our initial searches we had to decide how best to classify and group the interventions. It is possible that different ways of classifying and grouping the interventions might have changed the 'weight of evidence' in favour of an intervention within scope of the review, but, given the limitations of the evidence, we think it unlikely that this would have resulted in major changes to our conclusions.
An unanticipated consequence of our 'generic' inclusion/exclusion criteria was the exclusion of some seemingly relevant interventions provided as an 'add on' to normal antenatal care. For example, studies relating to some welfare-based US programmes (such as the Special Supplemental Food Program for Women, Infants and Children (WIC)) were excluded not because the intervention was ineligible but because studies evaluating the intervention typically compared 'intervention recipients' with 'non-recipients', with the latter group including women who received no antenatal care. The studies were therefore excluded because they lacked a comparator group receiving standard antenatal care.
It is possible that we may have missed some relevant 'add on' interventions as a result of using non-specific antenatal care search terms (e.g. 'prenatal care') instead of more intervention specific terms. Similarly, socioeconomically disadvantaged study populations are not consistently indexed or mentioned in searchable elements of the bibliographic record. We took some additional steps to increase ascertainment of relevant material, including using an adapted version of an 'equity filter' (developed by the EPPI-Centre to identify material relating to health inequalities) in our searches, and 'snowballing' .
Although the titles of articles lacking an abstract were screened and the full-text retrieved where appropriate, there is the possibility that relevant studies lacking an abstract may have been missed; non-English language articles lacking an English abstract were not included.
Findings in relation to other published evidence
One previous review conducted in the early 1990 s sought to evaluate the "best" evidence relating to the effect of antenatal healthcare programmes on pregnancy outcomes, including infant mortality and gestational age at birth . The authors concluded that maternal care coordination, home visits by nurses and specially targeted smoking and nutritional programmes were associated with "optimized pregnancy outcomes for certain groups of women, including the poor and very young." Nevertheless, as in the present review, and for similar reasons, they urged caution in applying these findings.
Other published reviews have addressed the effectiveness of a range of specific antenatal care interventions but most without a focus on effectiveness in disadvantaged or vulnerable groups of pregnant women:
PTB prevention educational programmes for high risk women A systematic review and meta-analysis of RCTs of PTB prevention educational programmes  concluded that they appeared to have little benefit in reducing PTB and might result in an increased rate of diagnosis of preterm labour.
Home visiting programmes A review of the effect of home visits on a range of pregnancy outcomes including PTB (<37 weeks)  found that home visiting programmes in general, and more specific programmes (those providing social support and those providing medical care to women with complications) did not improve the preterm delivery rate or other pregnancy outcomes. A second review of interventions involving support during pregnancy for women at increased risk of LBW babies , found no effect on PTB (Risk ratio 0.92, 95% CI 0.83 - 1.01). A further 'review of reviews'  similarly concluded that there was insufficient evidence to suggest that home-visiting programmes had a beneficial impact on low birth weight or other pregnancy outcomes.
Telephone support A recent review of telephone support interventions concluded that they were ineffective at reducing PTB .
Nutritional interventions A review of the effectiveness of interventions to optimize gestational weight gain and diet in pregnant adolescents  concluded that such interventions had achieved "promising results" with regard to a range of pregnancy outcomes but found little evidence relating to effects on PTB. The review did not systematically assess the quality of the included material but noted that much of the evidence was methodologically flawed. A further review assessed the effects of a range of nutritional interventions during pregnancy, including advice to increase or reduce energy or protein intake . The authors concluded that although dietary advice appeared to be effective in increasing pregnant women's energy and protein intakes it was unlikely to confer major benefits on infant or maternal health. These findings do not support our tentative conclusions regarding the potentially 'promising' effect of the two programmes with a nutritional focus included in the present review (the Higgins nutritional intervention in teenagers , and the Florina home visiting programme which has a nutritional counselling focus ) and, on balance, may suggest that a more cautious interpretation of the evidence in favour of these two interventions would be warranted.
Midwife-led antenatal care A Cochrane review  did not find a significant beneficial effect of midwife-led antenatal care on PTB compared with other models of care (risk ratio 0.87, 95% CI 0.73-1.04). A second overlapping review of continuity of midwifery care vs. standard care  additionally found no significant effect on neonatal mortality (odds ratio 1.27, 95% CI 0.49 - 3.34). A third review examined the evidence relating to various aspects of antenatal care for low-risk women including the effectiveness of midwife/general practitioner-managed care vs. obstetrician/gynaecologist-led shared care  also found no significant effect on PTB (relative risk 0.80, 95% CI 0.59 - 1.10).
Antenatal care targeting specific vulnerable groups Rumbold and Cunningham reviewed the impact of antenatal care interventions on Australian indigenous women . They did not assess the quality of the included studies so the interpretation of their findings is uncertain.
With the exception of the findings relating to the possible ineffectiveness of nutritional interventions noted above, the findings of other published reviews appear consistent with our assessment of the effectiveness of antenatal care programmes in disadvantaged and vulnerable populations.