Effectiveness and cost-effectiveness of home-based postpartum care on neonatal mortality and exclusive breastfeeding practice in low-and-middle-income countries: a systematic review and meta-analysis

Background Early postpartum facility discharge negatively impacts mothers’ proper and effective use postnatal care. Cognizant of these facts, home-based postnatal care practices have been promoted to complement facility-based care to reduce neonatal mortality. This systematic review evaluated the effectiveness and cost-effectiveness of home-based postnatal care on exclusive breastfeeding practice and neonatal mortality in low-and-middle-income countries. Methods Randomized trials and quasi-experimental studies were searched from electronic databases including PubMed, Popline, Cochrane Central Register of Controlled Trials and National Health Service Economic Evaluation databases. Random-effects meta-analysis model was used to pool the estimates of the outcomes accounting for the variability among studies. Results We identified 14 trials implementing intervention packages that included preventive and promotive newborn care services, home-based treatment for sick neonates, and community mobilization activities. The pooled analysis indicates that home-based postpartum care reduced neonatal mortally by 24% (risk ratio 0.76; 95% confidence interval 0.62–0.92; 9 trials; n = 93,083; heterogeneity p < .01) with no evidence of publication bias (Egger’s test: Coef. = − 1.263; p = .130). The subgroup analysis suggested that frequent home visits, home visits by community health workers, and community mobilization efforts with home visits, to had better neonatal survival. Likewise, the odds of mothers who exclusively breastfed from the home visit group were about three times higher than the mothers who were in the routine care group (odds ratio: 2.88; 95% confidence interval: 1.57–5.29; 6 trials; n = 20,624 mothers; heterogeneity p < .01), with low possibility of publication bias (Coef. = − 7.870; p = .164). According to the World Health Organization’s Choosing Interventions that are Cost-Effective project recommendations, home-based neonatal care strategy was found to be cost-effective. Conclusions Home visits and community mobilization activities to promote neonatal care practices by community health workers is associated with reduced neonatal mortality, increased practice of exclusive breastfeeding, and cost-effective in improving newborn health outcomes for low-and-middle-income countries. However, a well-designed evaluation study is required to formulate the optimal package and optimal timing of home visits to standardize home-based postnatal interventions.


Background
Globally, about three-quarters of neonatal deaths occur during the first week of life, of which about half occur in the home [1]. More than half of all neonatal deaths could be averted with care being provided during the postpartum period (i.e., 30% of all neonatal deaths can be averted with care of small and ill neonates, 12% with care of healthy neonates, and 10% with immediate newborn care) [2]. A wealth of evidence exists on a range of cost-effective life-saving maternal and newborn health (MNH) interventions essential to end preventable maternal and neonatal deaths [2,3]. But, in low-and-middleincome countries (LMICs), access to evidence-based high impact interventions improving maternal and neonatal mortality is often low [4][5][6].
Despite the critical importance of the postnatal period to promote optimal essential neonatal care practices as well as to save the lives of neonates [2], many women and their newborns do not have access to health care during the early postnatal period. This puts both the women and their newborns at an increased risk of morbidity and mortality [7]. Furthermore, due to cultural practices, mothers and newborns spend most of the postnatal period in the home regardless of place of birth [8]. Early postpartum discharge from facility is another factor that contributes to the lack of proper postnatal care (PNC) use [9,10].
Cognizant of these facts, providing home-based postpartum care is crucial to reach mothers and newborns [9]. As a result, home-based postnatal care practices have been promoted to complement facility-based care to improve early postpartum MNH care as well as to reduce neonatal mortality [11,12].
Evidence in developing countries shows that communitybased postpartum interventions are effective in improving MNH service use [3,[12][13][14][15][16][17]. However, there is limited evidence of the effectiveness as well as cost-effectiveness of home-based postpartum care strategy [18] and it is also an area where there is a critical knowledge gap, globally [19].
Thus, this systematic review evaluated the effectiveness and cost-effectiveness of home-based PNC on exclusive breastfeeding practice and neonatal mortality in LMICs.

Methods
Researchers determined the review methods in advance and we registered the protocol on the International Prospective Register of Systematic Reviews (PROSPERO) (registration number: CRD42018106006).

Inclusion and exclusion criteria
Randomized trials and quasi-experimental studies that report effectiveness or cost-effectiveness of postpartum home-based interventions on practice of exclusive breastfeeding and neonatal mortality or economic evaluation studies that compared home-based interventions with routine care were included. Articles written in the English language, with no publication date restriction to get adequate studies and interventions implemented in LMIC were considered for this study.
Citations without abstracts and/or full text, commentaries, letters, duplicate studies and editorials, studies written by different languages other than English were excluded from the review. Additionally, studies were excluded if it, 1) did not report on postpartum home visit, newborn mortality, exclusive breastfeeding, or cost, 2) did not have comparator, and 3) were not done in LMIC setting.

Search strategy
The research team searched peer-reviewed journal articles from electronic databases including PubMed, Popline, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials and National Health Service (NHS) Economic Evaluation databases. For more articles, reference lists of the initial search were also checked.
First, we identified concepts including 1) effectiveness or cost-effectiveness, 2) postpartum care or neonatal care, and 3) LMICs using the PICO review acronym-Population, Intervention, Comparison, and Outcome. Then for each concept, search terms (including synonyms and MeSH terms) were identified and used in a variety of combinations for these concepts. For database search, combination of the following keywords were used "(postnatal care OR postpartum OR puerper* OR post partum OR post natal OR neonatal OR newborn) AND (home visit OR home care OR facilit* OR hospital care OR health center care OR facility based care OR home care service*) AND (infant mortality OR neonatal mortality) OR (breastfeeding OR exclusive breastfeeding) OR (cost benefit analysis OR cost analysis OR efficien* OR health care cost OR economic evaluation OR cost effectiveness OR impact OR effect*))". A search strategy for PubMed, Popline, Cochrane Central Register of Controlled Trials and NHS Economic Evaluation databases are included in the additional file (Additional file 1). ClinicalTrials.gov was searched for recently completed trials.

Definition of terms
Intervention Interventions-including counseling; examination and management; and provision of services-provided to women and newborns in the first six weeks after birth at home by health providers or community health workers.
Any home visit innovations, initiatives, approaches, or activities carried out during the postnatal period, with the aim of either providing maternal and newborn health service or influencing maternal and newborn careseeking behavior and practices, including home-based treatment for illness, community mobilization efforts, and any home-based/community-based neonatal interventions, were considered as home-based postnatal care.

Comparison
Routine postnatal care provided to mothers who delivered in a health facility on discharge or care provided after discharge within six weeks when the women visited the facility. Usually, in LMICs, PNC is provided on discharge after facility delivery within 6 h and when the women visited the facility for family planning or immunization services after discharge within six weeks.

Settings
Low-and-Middle-Income Countries are countries with a gross domestic product (GDP) per capita of less than US $4655 as categorized by the World Bank in 2017. The list of countries is included in the additional file (Additional file 1).

Outcomes
The definitions for the outcome variables-neonatal mortality, exclusive breastfeeding, and cost-effectiveness-are given below.
Neonatal mortality: neonates who died within the first 28 days of life.
Exclusive breastfeeding: women who exclusively breastfed their child as per the age of the neonate determined by each study at the time of the survey.
Cost-effectiveness: Cost per effect as measured by the cost per home visit, per life-saved (or death averted), per life-year saved (or years of life lost averted), or per disability-adjusted life-year (DALY) averted.
The cost results reported in non-US dollars (USD) were converted to USD and inflated to 2016 prices [20,21]. The GDP per capita was used as a benchmark to consider against the cost-effectiveness of the intervention. For this purpose, the 2016 country's USD prices were used [21]. World Health Organization (WHO) considers strategies and interventions to be cost-effective if the cost per DALY averted is less than three times the GDP per capita and highly costeffective if less than the GDP per capita [22].

Selection and management of results
The search returned 1081 records after removing duplicates. Endnote reference manager was used to upload search results and create library of all search results for the purpose. Two review authors (GT and CB) independently screened the titles and abstracts yielded by the search against the inclusion criteria. We obtained full reports for all titles that appear to meet the inclusion criteria. Discrepancies between reviewers regarding the decision of inclusion were resolved through discussions.
During the title and abstract review stage, publications were excluded based on the exclusion criteria. Additionally, at the full-text review stage, publications were excluded if it did not report on our outcome measures and presented secondary rather than primary analysis (in which case the references were checked for more articles for inclusion).
Accordingly, 42 full articles were identified from screening titles and abstracts. The final synthesis was based on 14 journal articles. The results of the search and the process of screening and selecting studies for inclusion are illustrated using the study flow diagram seen below (Fig. 1).

Quality assessment
The risk of bias of each included study was assessed using the Cochrane Collaboration criteria: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete data, selective reporting and other biases [23]. Through discussion, researchers evaluated the possible risk of bias of each of the six domains from the extracted information and rated as high risk, low risk or unclear, if there was insufficient detail reported in the study, based on the criteria for judging the risk of bias. Graphic representations of risk of bias within and across studies were computed using Review Manager Software v5.3 (RevMan) software [23,24].
In cluster-randomized trials, allocation concealment was treated as low risk if trials randomized all clusters at once though it lacked concealment of an allocation sequence [23]. In addition, recruitment bias, contamination bias, baseline imbalance, loss of clusters, and lost to follow-up were considered in the analysis of the risk of bias in cluster-randomized trials.
The quality of the evidence pertaining to the outcomes was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach based on study limitations, consistency of effect, imprecision of effect estimates, indirectness of evidence and potential publication bias [23]. Researchers jointly evaluated the quality of the evidence for each outcome through discussion and a Summary Findings table was produced using GRADEPro software [25].
Standard reporting checklists-Preferred Reporting Items for Systematic and Meta-Analysis (PRISMA) for systematic review and meta-analysis and International Society for Pharmacoeconomics and Outcomes Research (ISPOR) for the trial-based cost-effectiveness analysiswere followed to establish minimum information that should be included when reporting.
The quality of the trial-based cost-effectiveness studies was assessed based on the core items recommended for conducting economic analyses alongside clinical trials [26]. Each study was given a 1-point score for each item fully met, 0.5 for partially met, and 0 for none. Then, trials that scored 75% or more were categorized as high quality, trials scored between 50 and 74% were ranked as medium, and studies scored less than 50% scores were rated as poor.

Data extraction
The first reviewer (GT) completed the data extraction form for all studies using RevMan software [23,24], and the second reviewer (CB) assessed the accuracy of the extracted data. Differences were resolved through discussions. For those cluster-randomized trials where the analysis did not properly account for cluster design or did not have sufficient information regarding proper accounting of cluster design, we extracted the data after correcting the analysis to reduce the size of each trial to its effective sample size as described in the Cochrane Handbook [23]. The effective sample size of a single intervention group in a cluster-randomized trial is its original sample size divided by the design effect. The design effect is given by.
where M is the average cluster size and ICC is the intra-cluster correlation coefficient.
We identified a trial [33] which included more than two arms. As such, we combined the groups using the methods described in the Cochrane Handbook [23] to analyze them.

Data synthesis
Descriptive information about the eligible studies was summarized using text and Tables. A narrative synthesis was used to analyze and interpret the findings.
Random-effects meta-analysis model [23,34] was used to pool the estimates of the outcomes, accounting for the variability among studies using Stata v15 [35]. Both single and multiple level meta-regression analysis was done to identify the independent predictor variables for the outcome of interest.
The results were presented as risk ratio (RR) & odds ratio (OR) with 95% confidence intervals and the estimates of Tau 2 and I 2 statistic for heterogeneity. We also investigated the presence of publication and other bias in the extracted data using funnel plot and Stata's "metabias" command [34,35].
However, meta-analysis was not appropriate for the cost-effectiveness outcomes as the analytic approaches were different among trials which makes it difficult to combine the outcomes together.

Assessment of heterogeneity
The P-value of the Chi-squared test of heterogeneity and the I 2 and Tau 2 statistics were examined for heterogeneity between the trials to judge whether there were any apparent differences in the direction or size of the treatment effect between studies. The thresholds for the presence of heterogeneity among the trials were determined if the value of I 2 was greater than 30%, and the value of Tau 2 was greater than zero or the P-value of the Chi 2 test for heterogeneity was greater than 0.1.

Subgroup analysis
We undertook subgroup analysis to examine the effect of home visit on neonatal mortality varied by 1) number or frequency of PNC visits (< 3 vs. > 3 visits), 2) coverage of PNC visits made to the mother and/or newborn that is proportion of neonates and/mothers receiving a postnatal visit in the intervention areas/clusters) (< 70% vs. > 70%), 3) type of care (preventive interventions vs preventive and curative interventions, 4) type of health worker (health professionals vs. community health workers (CHWs)), 5) intervention components (community mobilization efforts and home visits vs. home visits alone), 6) time of home visits (antepartum and postpartum vs. postpartum only), and 7) publication year (< 2008 vs. > 2008). Likewise, subgroup analysis was done for exclusive breastfeeding outcome which varied by, 1) number or frequency of PNC visits (< 3 vs. > 3 visits), 2) coverage of PNC visits (< 70% vs. > 70%), 3) duration of intervention or follow-up (< 4 vs. > 4 weeks), 4) age at exclusive breastfeeding (neonatal period vs. more than neonatal period), 5) type of health worker (health professionals vs. CHWs), and 6) publication year (< 2008 vs. > 2008).
In subgroup analysis, we presented both randomeffects and fixed-effects model estimates to visualize the presence of small-study effects; however, due to substantial heterogeneity, we preferred to discuss the results acquired from random-effects model.

Sensitivity analysis
We conducted a sensitivity analysis excluding trials that evaluated the effect of home-based follow-up of neonates born at and recruited from hospitals, to determine the pooled estimate of trials with home-based neonatal care which had poor access to health facilities.

Description of studies
The characteristics of included studies are given in Table 1 below. Fourteen articles (2 randomized controlled trials (RCT), 11 cluster-randomized trials, and 1 quasi-experimental studies) were included. All included trials were published from 1999 to 2017.
Most of the trials were conducted in predominantly rural districts that had poor infrastructure (poor roads, communications, education, and health services). However, three studies were conducted in urban [33] or peri-urban [36,37] settings which were within a short distance to the countries' capital cities (Table 1).
Twelve trials recruited CHWs and three studies employed health professionals including midwives and nurses. Health workers were trained for about a week to make home visits to offer preventive and promotive newborn care services. Table 2 presents the intervention packages implemented in each trial. All trials conducted     postpartum home visits to promote newborn care practices; 11 trials did both antepartum and postpartum home visits. Moreover, nine trials conducted community activities [28,29,[38][39][40][41][42][43] in addition to home visits to promote newborn care practices. Five of the studies trained providers/CHWs to identify sick newborns, refer them to facilities, and if referral was not possible to treat sick newborns in addition to preventive and promotive newborn care services [38,40,42,44,45] (Table 2). Regarding the implementation strength of the studies, defined here as frequency of home visits and coverage of visits, each trial had an average of 4 postpartum home visits and an average of 1 antepartum visit (usually at third trimester). Likewise, coverage of home visits, proportion of mothers and/or their newborns received postpartum home visit, ranged from 30 to 100% (median 79%).
Studies' follow-up period ranged from 1 to 24 weeks postpartum and more than half of the studies (53%, n = 8) followed-up mothers and their newborns for one week after delivery. The exclusive breastfeeding outcome definition varied across studies; three trials [29,37,44] determined exclusive breastfeeding at neonatal age while others determined at 3 months [36], 4 months [33], or 6 months [46]. Three studies observed exclusive breastfeeding in the previous 24 h recall at 12 weeks of age [37], 24 weeks of age [36], and age between days 26 to 32 after birth [29] ( Table 2).

Risk of bias in included studies
The risk of bias of included trials is presented in Fig. 2.

Incomplete outcome data and selective reporting
One trial had high risk of reporting bias [33]. Most studies had low risk of attrition; however, one trial [37] had unclear risk of reporting bias.

Other potential sources of Bias
Other potential sources of bias including baseline imbalances were identified in two studies [33,44]. Moreover, possible cluster-level time-varying unmeasured confounders including regional pregnancy leave and employment policy might bias the exclusive breastfeeding outcome. However, there is no compelling reason to believe that these systematically influenced the intervention areas but not in the comparison areas unless otherwise, it happened after allocation of the treatment.

Effects of interventions
The Summary of Findings table gives estimates of the effects of home-based PNC on neonatal health outcomes as well as grading the level of evidence (Table 3).

Sensitivity analysis
Sensitivity analysis was conducted excluding trials that evaluated the effect of home-based follow-up of neonates born in and recruited from hospitals [33]. Following removal of this trial, the overall pooled estimate increased by only 1% (RR 0.75, 95% CI 0.62-0.91) with a slight increase in heterogeneity between studies (I 2 = 70.9%; p = .001) indicating no or little difference in the outcome and results were not driven by a trial that recruited newborns from hospitals.

Subgroup analysis and meta-regression
The subgroup analysis revealed that more than three PNC home visits contributed to reduction in neonatal mortality Trials with coverage of home visits of 70% and above, showed non-statistically significant greater reduction in neonatal mortality (RR: 0.70; 95% CI: 0.50-0.99) than trials with less than 70% coverage of home visits (RR: 0.87; 95% CI: 0.76-1.00). Likewise, statistically non-significant trend towards a greater effect on mortality was observed with curative (inject-able antibiotics) and preventive interventions (RR: 0.82; 95% CI: 0.63-1.05), as compared to only preventive intervention (RR: 0.70; 95% CI: 0.48-1.03; heterogeneity P = .016) ( Table 4).  In single-level meta-regression, only year of publication was significantly associated with neonatal mortality (p = <.01). However, in multiple level meta-regression, no independent predictor variables were found (result not shown).

Test of publication bias
The funnel plot (Fig. 4) appeared symmetrical, which suggests no evidence of small-study effects. The Egger's test also indicated low possibility of publication bias (Coef. = − 1.263; p = .130).

Test of publication bias
The funnel plot appeared symmetrical (result not shown). The Egger's test also indicated low possibility of publication bias (Coef. = −7.870; p = .164).

Cost-effectiveness
The cost-effectiveness results are presented in Table 6 below. Three trials reported the incremental cost for neonatal mortality outcomes. Different cost-effectiveness     and cost-utility measures were used. All three trials reported cost per neonatal death averted [40,38,43] or newborn life-year saved [40,43]. One trial used costutility measures (i.e., cost per DALYs gained) [40]. According to World Health Organization's Choosing Interventions that are Cost-Effective project (WHO-CHOICE) recommendations [49], considering cost per neonatal death averted, newborn life-year saved, and DALY averted measures, home-based neonatal care strategies were found to be cost-effective.

Discussions
The objective of this study was to systematically review the existing body of knowledge that explores the effectiveness and cost-effectiveness of home-based postpartum care on neonatal mortality and exclusive breastfeeding practice in LMICs.
The pooled analysis showed that home-based postpartum care is effective in reducing neonatal mortality and promoting exclusive breastfeeding practice in LMICs which have poor access to health care. Though on metaregression, no variable emerged as a significant predictor of an effect on neonatal mortality; the subgroup analysis suggested that more frequent postpartum home visits, combined community mobilization efforts with home visits, and interventions implemented prior to 2008 publication year, to had a greater reduction in neonatal mortality than their counterparts. Likewise, higher home visits may have encouraged more women to exclusively breastfeed.
The trials included in this review implemented a package of interventions that varied in intensity, components of interventions, duration of follow-up, and intervention provider. Some trials implemented both antepartum and postpartum home visits and other trials implemented postpartum home visits alone. Others included community mobilization efforts in addition to home-based promotion of newborn care practices. There were trials that included curative and preventive interventions, while others implemented preventive newborn care practices alone. Moreover, for breastfeeding outcome, there were variations in settings-some trials were conducted in predominantly in rural and others in peri-urban settings-as well as variations in how outcomes were measured and when-some trials determined exclusive breastfeeding at neonatal age while others determined at 3, 4, or 6 months. As such, due to the complex nature of the interventions, it was difficult to differentiate the independent effects of different components of interventions on neonatal mortality.
Our findings augment the WHO recommendations of home-based postpartum care strategy [19]. The findings are also in line with previous systematic reviews that report home-visit strategy as effective in reducing neonatal mortality [11]; cost-effective [15]; and promote the practice of exclusive breastfeeding [50].
Most of the trials were of acceptable quality with low or unknown risk of bias, except for the two trials where the possibility of bias was high-one trial [33] which used block randomization based on estimated number of hospital deliveries per day and had significant baseline imbalances and the other trial [41] which was quasiexperimental. We graded the quality of the evidence using the GRADE approach; the evidence was graded as moderate for neonatal mortality outcome (Table 3, above), with downgrading decisions due to risks of bias and imprecision of effects, and high for exclusive breastfeeding.
This review provides several lessons for implementers of MNH programs in LMICs like Ethiopia. First, lower- and middle-income countries have shortage of trained health care providers [51][52][53] as well as inequitable distribution of providers [54,55] which makes it difficult to intensify MNH care practices at facility level. This review illustrates that home-based MNH care can be practiced by community members through short term training on the packages needed to implement. Second, providing home-based MNH care might enable the implementers to access hard-to-reach areas, because people in LMICs have lower health-seeking behavior and they are far from health facilities.
In this review, we incorporated relevant subgroup and meta-regression analyses, explored any unit of analysis errors in the cluster randomized trials and appropriately combined all cluster-and individual-randomized trials together and no evidence of publication bias was found.
However, the review has limitations. First, there are high levels of unexplained heterogeneity. Second, in many countries, postpartum care is not clearly defined in national guidelines and standards [9]. This might create variability in the control group defining facility-level routine postpartum care. Third, the estimates of cost and resource used which are sensitive to variability across settings which might limit the generalizability and transferability of cost-effectiveness results beyond the study settings. Fourth, included studies used different cost-effectiveness and cost-utility measures as well as different analytic viewpoints which makes estimating the pooled estimate difficult. Finally, comparing costeffectiveness outcomes against GDP per capita as a threshold does not necessarily ensure that the strategy is affordable.
Well-designed evaluation of such interventions is required to establish the effectiveness of different intervention packages as well as to formulate the optimal packages and optimal timing of home visits and specific responsibilities of community health workers. Analytic viewpoint is one dimension that can affect study results. Large multi-center economic evaluation studies examining the impact of different analytic perspectives, implementation strength and willingness-to-pay parameters both in the intervention and comparison groups are required to understand well the degree to which strategies can be replicated elsewhere.

Conclusions
Home visits and community mobilization activities to promote optimal neonatal care practices by community health workers is associated with reduced neonatal mortality, increased practice of exclusive breastfeeding, and cost-effectiveness in improving newborn health outcomes for low-and-middle-income countries which have poor access to facility-based care. The subgroup analysis suggested that more than three PNC home visits, home visits by community health workers, community mobilization efforts with home visits, and interventions implemented prior to 2008 publication year to had better neonatal survival. Likewise, groups of mothers who received more home visit coverage and more weeks of follow-up were more exclusively breastfed their babies. The pooled estimates of outcome variables have high levels of unexplained heterogeneity so that results should be interpreted with caution. Furthermore, a well-designed evaluation study is warranted to formulate the optimal package of interventions for specific health cadres and optimal timing of home visits.
Additional file 1. Search Strategy.docx. This is a survey strategy used to search for articles from databases.