The Effectiveness of Regionalization of Perinatal Care and Specific Facility-Based Interventions: A Systematic Review

According to the World Health Organization (WHO), the postnatal period is the time from the delivery to the first 6 weeks of birth and is significant for the health of the newborn and the mother. According to WHO estimates, almost 800 women lost their lives every day during and after pregnancy due to preventable complications in 2020 and 1 million neonates die within the first 24 h of life while 2.3 million babies died within the first 28 days of life in 2022 [1, 2]. The United Nations Sustainable Development Goal (SDG) 3 aims to reduce neonatal mortality to less than 12 per 1,000 live births and maternal mortality ratio to less than 70 per 100,000 live births and ensure universal access to all aspects of reproductive healthcare services by 2030 [3].

Integrated maternal and newborn postnatal care (PNC) can improve survival and take a step closer to meeting SDG 3 [4]. The concept of regionalization was first put forth by Canada in 1968, its development was initiated in the USA in 1971 [5], and perinatal regionalization was defined by WHO’s Regional Office for Europe as a method that rationalizes existing healthcare services to ensure that each pregnant woman and newborn infant are cared for in an appropriate facility [6]. Regionalization aims to provide comprehensive healthcare services to pregnant women and newborns to ensure equitable care based on their needs within a given geographical area. This approach involves categorizing healthcare facilities into different levels of care (primary, secondary, and tertiary), ranging from basic to advanced, to provide the right level of resources and expertise for each patient especially important for premature and low birthweight newborns.

A significant disparity exists in perinatal health outcomes between different countries and regions [4] which can be improved by optimizing the allocation of resources and access to specialized services. Although the statistics have improved over the decades, the inequities in perinatal healthcare are still prevalent, particularly in low- and middle-income countries (LMICs) [7]. Targeted measures can address potential complications, offer support for mothers, monitor, manage postpartum issues, and provide essential education on newborn care [8]. Effective interventions contribute significantly to a smoother postnatal recovery, fostering a positive start to the mother-child relationship, promoting optimal health outcomes. Therefore, postnatal services that include accessible healthcare facilities, skilled birth attendance, parental education, and immunization should be made available to all women and newborns and incorporated into the existing programs [9, 10].

To support the establishment of policies and infrastructure for PNC, it is important to understand the effectiveness of interventions during the postnatal period. If PNC services are implemented and extensively evaluated, they have the potential to bring about enduring enhancements in health systems [8, 10] and help make a significant stride toward achieving the SDGs. This systematic review is one of a set of reviews that updates the “Lancet Every Newborn” 2014 series and aims to evaluate whether existing intervention studies can provide proof of the effectiveness of regionalization for improving perinatal outcomes and facility-based interventions to improve PNC coverage and outcomes for mothers and newborns.

Interventions targeting maternal and neonatal health were identified by the “Lancet Every Newborn” series published in 2014 [11]. The evidence from the series was updated, the most current interventions relevant to the topic of interest were identified, and where applicable, a subgroup analysis of LMICs was conducted. This paper is part of a supplement that provides a thorough synthesis of perinatal and PNC strategies by examining various interventions. A range of methodological approaches was used to synthesize the overall and LMIC-specific evidence, and the detailed methodology is published elsewhere; below is the brief methodology for this paper [12]. We updated evidence from an existing review [13] on the effectiveness of regionalization on perinatal outcomes and did a primary systematic review of all interventions for facility-based PNC interventions to improve overall coverage and uptake according to the PRISMA guidelines (online suppl. Appendix B; for all online suppl. material, see https://doi.org/10.1159/000541384).

The included studies utilized an experimental or quasi-experimental design including randomized controlled trials (RCTs), controlled before-after studies, before-after studies without controls, controlled after-only studies, and interrupted time series. To update the review on the effectiveness of regionalization on perinatal outcomes [13], three databases – Ovid Medline, PubMed, and Embase – were searched to identify studies published between March 2011 and April 2023 to be included. Medical subject heading terms and keywords were used to curate a search strategy for each database (added to the online suppl. Appendix). Studies included an intervention involving the implementation of a regionalized perinatal program including levels of care and/or a referral network in that area and reported perinatal outcomes like maternal mortality and morbidity, neonatal mortality and morbidity, birth weight, stillbirth, and place of delivery.

For the de novo reviews on specific facility-based interventions to increase PNC coverage, we conducted a comprehensive search including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL databases. We also searched clinical trial registries including the WHO International Clinical Trials Registry Platform (ICTRP) and the US National Library of Medicine (ClinicalTrials.gov), and the reference lists of any articles selected for inclusion in this review to identify additional relevant studies. Studies were included if interventions in the antenatal and postnatal period focused on preparation for motherhood, or providing support during and after childbirth, the interventions in the postnatal period focused on newborn care, or if the interventions directly impacted postnatal outcomes and were carried out in a facility-based setting. Studies that focused on breastfeeding interventions were not included in this review, as they are covered in a separate review in the series.

Implementation of a regionalized perinatal program included levels of care such as primary, secondary, and tertiary levels, and a referral network in that region.

Interventions aimed at enhancing transport services, ranging from the provision of transport vouchers to initiatives focused on improving overall transport accessibility to access timely facility care.

Interventions that utilize mHealth (mobile health) refer to the use of mobile devices to provide healthcare services or information to patients. This can include mobile applications, text messages, or other technology-based aids to disseminate information. Interventions that utilize telecommunication such as video conferencing, phone calls, and online messaging provide healthcare services that enable healthcare providers to evaluate and treat patients virtually and allow for monitoring of patients through remote consultations.

Interventions encompassed educational initiatives targeted toward mothers during both antenatal and postnatal visits at the facility level. These educational programs aimed to equip mothers with essential information and skills related to prenatal and PNC.

Interventions focused on capacity building within the healthcare system, encompassing training, supervision, and mentoring initiatives for healthcare workers. Additionally, interventions targeted facility strengthening through upgrades, equipment supplies, and operational enhancements.

Interventions established and supported maternity waiting homes and maternity units. Maternity waiting homes provide a residential space for expectant mothers to stay near healthcare facilities as they approach their delivery date, ensuring timely access to skilled care.

Interventions incorporated comprehensive postnatal packages, comprising a range of services for both mothers and infants, alongside additional incentives like health financing schemes, subsidized insurance packages, etc.

Search results were imported into Covidence for the removal of duplicates and screening. Title, abstract, and full-text screening were carried out independently by two authors. Disagreements were resolved through discussion and by consulting a third author if needed. Data extraction was also carried out in duplicate by two authors. Only studies published in English were included with no restrictions on geographical location.

Meta-analysis was conducted on RevMan 5.4.1, and estimates of outcomes were reported as risk ratio (RR) for studies with a separate comparison arm or odds ratio (OR) for before-after studies with 95% confidence interval (CI) for dichotomous data and mean difference with 95% CI for continuous data. For the regionalization review update, data from the original review were pooled with the latest findings to create forest plots, and separate analysis was conducted for before-after studies and studies with a comparison arm. Exact numbers were calculated where rates and total births and live births were reported. Random-effects model was used in analyses involving more than one study due to diversity in interventions. Subgroup analysis was conducted where relevant for all outcomes of interest reported in studies from LMICs, classified according to the World Bank criteria for the respective years in which the studies were conducted [14].

Risk of bias (ROB) was assessed using Cochrane ROB tool for all RCTs and ROB in non-randomized studies-intervention tool for all other study designs [15, 16]. Certainty of evidence of analyses which included intervention-control studies only was assessed using grading of recommendation assessment, development and evaluation (GRADE) approach [17]. We were unable to conduct a sensitivity analysis because of the inadequate number of studies that were included in our pooled analysis.

Based on the search, we updated one review on the effectiveness of regionalization on perinatal outcomes and conducted a de novo review on the effectiveness of facility-based interventions to improve PNC for mothers and newborns. Most RCTs had a high ROB due to lack of blinding, and non-randomized intervention studies had high ROB due to potential for confounding as well as lack of blinding leading to bias in measurement of outcomes (domain-wise ROB assessment for all studies given in online suppl. Appendix C3). Findings are summarized in the following section, and further details are given in online supplementary Files 1.

Electronic searches identified 8,578 studies. After the title and abstract screening, 86 full texts were reviewed. Finally, eight full-text papers were included in the updated review from five primary studies along with ten full-text papers from eight primary studies in the original review (Fig. 1).

The new studies included in the update were conducted in Tanzania, Uganda, Zambia, the Democratic Republic of Congo, and Ukraine, while those in the original review were conducted in USA, Canada, and France. Before-after and controlled intervention designs were utilized in the studies. Descriptions of interventions in studies published before 2011 are given in the original review [13].

Three papers [18‒20] were published to report the impact of Saving Mothers, Giving Life (SMGL) initiative carried out in pilot districts of Uganda and Zambia. The multi-partner initiative was implemented between 2012 and 2017 and evaluated health facilities, pregnancy outcomes, and maternal deaths. Existing emergency obstetric and neonatal care (EmONC) facilities were upgraded, and new ones were established to include more operation theatres, maternity wards, neonatal special care units, laboratories, pharmacies with adequate medicine supplies, etc. Mobile and community outreach clinics were also introduced as part of preventive services, and subsidized transport vouchers were distributed to improve access to antenatal and PNC services at facilities.

Multiple initiatives have been launched in different regions of Tanzania to improve healthcare delivery and perinatal outcomes. Prasad et al. [21] outlined a 13-year Program to Reduce Maternal Deaths in Tanzania which was implemented in the Kigoma region of Tanzania between 2006 and 2019 over 3 phases. It involved strengthening existing health facilities by renovating or building operation theatres, providing an emergency call system, linking health centers with pharmacies, and organizing local transport systems to respond to obstetric emergencies, as well as sustaining the changes by planning and managing the EmONC service delivery budget within the district councils. Dominico et al. [22] reported the impact of this program on the utilization of facilities, maternal and neonatal outcomes, and management of obstetric emergencies.

Comprehensive Community-Based Rehabilitation, a nongovernmental organization in Tanzania, partnered with the regional government in Dar es Salam to improve perinatal care in the region by focusing on 22 public health facilities that accounted for 60% of the city’s births. Sequeira Dmello et al. [23] assessed the interventions which included infrastructure upgrades, capacity building, and a referral network for technical and administrative support. Facility-based maternal mortality ratio, stillbirths, and neonatal deaths were compared before and after the implementation of changes.

Ten health centers in the Kigoma, Morogoro, and Pwani regions of Tanzania were upgraded to improve accessibility to comprehensive EmONC services (3 of the selected health centers were 150 km away from the nearest hospital with comprehensive EmONC services). Nyamtema et al. [24] reported mean monthly deliveries in the health facilities before and after upgrades at the health centers.

Two studies, both from LMICs, reported facility maternal mortality rates. Before-after comparison reported significantly lower facility MMRs (estimate OR: 0.43 [95% CI: 0.34–0.55], 2 studies). Five studies utilizing before-after comparisons reported a lower risk of stillbirth (OR: 0.70 [95% CI: 0.54–0.89], 5 studies); LMIC-specific estimates showed a nonsignificant reduction (Table 1).

Three before-after studies reported neonatal mortality and suggested no statistically significant difference (OR: 0.74 [95% CI: 0.51–1.09], 3 studies); LMIC-specific estimates were also similar (OR: 0.89 [95% CI: 0.69–1.16], 2 studies). Two before-after studies reported significantly lower perinatal mortality after regionalization (OR: 0.54 [95% CI: 0.50–0.58], 2 studies), and LMIC-specific estimate was similar (OR: 0.54 [95% CI: 0.50–0.58], 1 study) (Table 1).

Our search identified over four hundred full-text studies, of which 76 were included in the final analysis (Fig. 2). There was overlapping evidence in multiple categories; hence, some studies have been repeated in the following comparisons. Out of the 76 studies, 27 had capacity building-related interventions for the provider, 19 studies had mHealth interventions, 14 evaluated the impact of facility-based maternal education, 6 had incentive programs, 4 were related to transport, and 2 were related to the set-up of maternity units.

Four studies utilizing before-after design or with a comparison arm assessed the impact of providing transport to pregnant women from LMICs [25‒28] (Table 2). Three studies focused on improving interfacility transport, and one study from Uganda implemented the use of transport vouchers and baby kits (Table 3). The use of baby kits and transport vouchers significantly increased the rates of postnatal coverage (OR 6.89 [95% CI: 5.15–9.21], 1 study). A significant reduction in maternal mortality was observed (OR: 0.55 [95% CI: 0.40–0.74], 1 study). The effect of transport interventions on neonatal mortality (RR: 0.76 [95% CI: 0.66–0.88], 1 study) and perinatal mortality (RR: 0.86 [95% CI: 0.77–0.95], 1 study) was also significant. GRADE assessment of neonatal and perinatal mortality of intervention-control studies indicated very low certainty of evidence (online suppl. Table E1).

Two studies utilized a before-after design set-up maternity homes and units in addition to standard hospital care [29, 30]. Both were conducted in LMICs and included designated areas for triage, labor, birth, postoperative patients, and nursing staff. New public sinks, shared bathrooms, and video screens were included to enhance community education. A significant reduction (Table 4) in stillbirth was noted (OR: 0.75 [95% CI: 0.61–0.93], 1 study), whereas no significant effect was found on maternal mortality (OR: 1.67 [95% CI: 0.63–4.47], 1 study).

Six studies utilizing both a before-after study design and a comparison arm evaluated incentive packages provided to pregnant women; all studies were conducted in LMICs [31‒36]. Incentive packages included health financing schemes like obstetric insurance, 24-h facility stays, and continuum of care training for healthcare providers. A significant effect was found on PNC coverage in the study utilizing a comparison arm (RR: 1.13 [95% CI: 1.03–1.25], 1 study). Three before-after studies showed no significant effect on PNC visits (OR: 2.73 [95% CI: 0.35–21.17], 3 studies) all of which were from LMICs.

There was no significant reduction in maternal mortality, neonatal mortality, and perinatal mortality (exact estimates given in Table 5), while one study conducted in a LMIC suggested a decrease in infant mortality (RR: 0.79 [95% CI: 0.65–0.96], 1 study), stillbirths (RR: 0.60 [95% CI: 0.44–0.81], 1 study). Use of family planning methods increased significantly after the incentives (OR: 3.16 [95% CI: 1.64–6.09], 1 before-after study, and RR: 1.21 [95% CI: 1.06–1.38], 1 intervention-control study). A significant improvement was noted on completion of vaccination (RR: 1.51 [95% CI: 1.45–1.57], 1 study), neonatal health problems (RR: 0.76 [95% CI: 0.59–0.99], 1 study), cord care practices (OR: 2.68 [95% CI: 2.02–3.56], 1 study), and under-5 mortality (RR: 0.79 [95% CI: 0.66–0.94], 1 study), while the effect was not significant on maternal health problems and exclusive breastfeeding (estimates in Table 4). GRADE assessment of neonatal, maternal, perinatal, and infant mortality of intervention-control studies indicated low and very low certainty of evidence (online suppl. Table E2).

Nineteen studies assessed mHealth to assist mothers during the postnatal period. Seven of these interventions were conducted in HICs and 12 studies in LMICs [37‒55].

There was no significant difference in PNC coverage in randomized trials (RR: 1.59 [95% CI: 0.83–3.06], 5 studies) overall, but LMIC-specific estimates showed a significantly higher postnatal coverage after telemedicine intervention (RR: 2.54 [95% CI: 1.22–5.28], 3 studies). Overall, the effect of mHealth interventions was not statistically significant on maternal health problems (RR: 0.78 [95% CI: 0.58–1.06], 2 studies), but LMIC-specific estimate showed a significant decrease (RR: 0.69 [95% CI: 0.51–0.94], 1 study). The effect of telemedicine on neonatal health problems was not significant overall (RR: 0.95 [95% CI: 0.60–1.51], 4 studies) or in LMICs (RR: 1.08 [95% CI: 0.54–2.17], 2 studies). The impact of mHealth on exclusive breastfeeding was also not significant in intervention and control groups following interventions (RR: 1.62 [95% CI: 0.55–4.78], 2 studies). Evidence regarding the rates of immunization following mHealth was not statistically significant (RR: 1.10 [95% CI: 0.98–1.25], 1 study). There was a significant decrease in maternal mortality (OR: 0.46 [95% CI: 0.21–0.98], 1 study) and infant mortality (OR: 0.65 [95% CI: 0.45–0.95], 1 study) in LMICs. GRADE assessment of maternal and infant mortality indicated very low certainty of evidence (online suppl. Table E3).

For maternal education which was provided by health workers or disseminated through web programs or mobile health, 14 studies were systematically assessed, out of which five were conducted in HICs including China, South Africa, Iran, Taiwan, and Singapore; LMIC-specific studies were from India, Lebanon, Nepal, and Nigeria [27, 36, 56‒67]. After providing mothers with guidance on newborn care, the coverage of PNC was examined through two methodologies: randomized trials and before-after designs. Our findings suggested a statistically significant difference in PNC utilization overall in studies with a comparison arm (RR: 1.34 [95% CI: 1.23–1.45], 3 studies). There was a significant decrease in neonatal mortality (OR: 0.75 [95% CI: 0.66–0.84], 2 studies), perinatal mortality (RR: 0.86 [95% CI: 0.77–0.95], 1 study), infant mortality (RR: 0.79 [95% CI: 0.65–0.96], 1 study), stillbirth (RR: 0.61 [95% CI: 0.45–0.82], 1 study), maternal health problems (RR: 0.85 [95% CI: 0.77–0.93], 1 study), and neonatal health problems (RR: 0.73 [95% CI: 0.74–0.88], 1 study) in LMICs. Exclusive breastfeeding increased overall (RR: 1.23 [95% CI: 1.04–1.44], 6 studies) but was not significant in LMICs (RR: 1.05 [95% CI: 0.94–1.16], 4 studies). Thermal protection and skin-to-skin practices for newborns and preterm births were not significantly changed after the intervention (exact estimates in Table 6). GRADE assessment of neonatal, perinatal, and infant mortality and stillbirth indicated very low certainty of evidence (online suppl. Table E4).

For this intervention, 27 studies were included out of which 21 studies were from LMICs [25, 27, 36, 68‒91]. Six studies used before-after analysis of which two were from HICs and four from LMICs. Two studies were RCTs of which one was from HIC and one from LMIC. Overall, the intervention had a significant effect on PNC coverage in before-after analysis (OR: 1.28 [95% CI: 1.07–1.53], 1 study), but in studies with a comparison arm, the effect was not significant overall (RR: 0.81 [95% CI: 0.46–1.45], 4 studies) or in LMICs (RR: 0.65 [95% CI: 0.33–1.26], 3 studies).

Maternal mortality was evaluated in ten studies using before-after analysis, out of which eight were from LMICs and two were conducted in HICs. A study in China implemented a government-led initiative to improve emergency obstetric care and increase delivery rates in rural areas – a comprehensive public health project covering maternal health through regular examinations and education across all trimesters. Postpartum visits within 28 days addressed puerperal health, breastfeeding, neonatal care, and overall health education. Nurse-assisted antenatal care in an international collaboration showed positive outcomes. In Uganda, a private facility provided onsite training to improve care standards. Tanzania, Nigeria, and Cameroon adopted targeted approaches to enhance emergency obstetric care, including financial incentives for midwives and quality improvement initiatives. Overall, a significant impact was seen on rates of maternal mortality (OR: 0.37 [95% CI: 0.29–0.46], 5 studies).

Neonatal mortality was evaluated in three intervention-control studies conducted in LMICs where interventions such as group antenatal care focused on enhancing neonatal care. A significant impact was noted (RR: 0.61 [95% CI: 0.48–0.79], 3 studies). Before-after analyses from two studies from China and Cameroon focused on early essential newborn care. Another study from China reported the effects of a government-led initiative on neonatal mortality. In Rwanda, the effect of WHO newborn training and its association with early neonatal mortality was observed. Maternal, neonatal, and child health was a prime focus in intervention packages provided in Pakistan and Bangladesh. Overall, a significant effect was seen (OR: 0.72 [95% CI: 0.53–0.98], 4 studies) on neonatal mortality, and LMIC-specific estimate was also similar (OR: 0.63 [95% CI: 0.54–0.74], 3 studies). Perinatal mortality reported by before-after and intervention-control studies suggested a significant decrease in LMICs (OR: 0.53 [95% CI: 0.45–0.62], 2 studies, and RR: 0.86 [95% CI: 0.77–0.95], 1 study). Infant mortality decreased significantly in before-after and intervention-control comparisons (OR: 0.50 [95% CI: 0.43–0.59], 1 study, and RR: 0.79 [95% CI: 0.65–0.96], 1 study). A significant effect was noted on under-5 mortality in LMICs (RR: 0.79 [95% CI: 0.66–0.94], 1 study) and preterm births overall in before-after comparison (OR: 0.39 [95% CI: 0.19–0.81], 1 study), but intervention-control comparison showed no significant effect (RR: 1.04 [95% CI: 0.84–1.29], 1 study).

Completion of scheduled vaccinations, family planning use, cord care, and skin-to-skin practices for newborns improved significantly after the interventions in LMICs, while exclusive breastfeeding increased overall and in LMICs (exact estimates in Table 7). GRADE assessment of neonatal, perinatal, infant, and under-5 mortality and stillbirth indicated very low evidence of certainty (online suppl. Table E5).

This review suggests variable impacts of interventions on maternal and neonatal health outcomes. Capacity building, regionalization, and transport interventions had a positive effect on maternal mortality. Regionalization, maternal education, and capacity building reduced neonatal mortality. Postnatal healthcare coverage was increased through maternal education and transport interventions. Most of these effects were seen in before-after study designs.

A study in Nigeria noted that only 29% of newborns received PNC [92]. Ensuring the availability and accessibility of PNC can have a cascading impact on maternal healthcare. A smooth transition from delivery at a healthcare facility to PNC utilization is crucial for maternal and neonatal well-being as the interconnected approach promotes a continuum of care, ultimately contributing to improved maternal and newborn health outcomes.

Women from higher socioeconomic backgrounds are more likely to have knowledge of and carry out beneficial newborn care practices than women from lower socioeconomic backgrounds. This is likely due to their easy access to health interventions at well-distributed facilities, skilled delivery, and the ability to make multiple antenatal care visits. Conversely, those of middle socioeconomic status may exhibit mixed findings, possibly influenced by work pressures, unfavorable financial conditions, and sociocultural factors impacting their likelihood to adopt recommended newborn care practices, such as exclusive breastfeeding [93, 94].

A systematic review from sub-Saharan Africa explored interventions to improve adherence to antenatal care and PNC. A study from Ethiopia found that only 36.8% of women received PNC service within 6 weeks after delivery and discussed the factors associated with utilization of postnatal services [95]. Several obstacles hinder the successful utilization of interventions aimed at improving PNC, and these include resource constraints, including financial limitations [96] and inadequate healthcare infrastructure that can also impede the implementation of new postnatal programs, more so in conflict settings [97]. Additionally, challenges in training and mobilizing healthcare professionals to execute these interventions, especially in regions with healthcare workforce shortages, pose significant barriers, and while perinatal regionalization is important and effective, implementation of multifaceted programs in all levels of healthcare is complex.

Our analysis of telemedicine or mHealth interventions showed comparable effects on postnatal coverage, immunization, maternal and neonatal health problems, while other reviews which included observational studies as well reported a positive impact of mHealth on skilled birth attendance, antenatal and postnatal healthcare visits, and immunization coverage especially in low resource settings like sub-Saharan Africa and Southern Asia [98, 99]. Telemedicine can also bring together community stakeholders, healthcare providers, and patients to enhance perinatal regionalization, effectively reducing infant mortality and aiding in informed transport decisions, ensuring only necessary transfers to larger centers, while also supporting smaller nurseries through improved consultation services [100]. Similarly, transport interventions in a perinatal network or collaboration within the same geographic area can improve appropriate healthcare provision [101]. Our analysis also showed a positive impact of maternal educational interventions on newborn outcomes, and a Cochrane review outlines similar results with the integration of education components within perinatal intervention packages for mothers as well as other family members, especially in LMIC settings [102].

A key limitation of this review was that only a small number of studies reported relevant outcomes for each intervention, limiting the amount of pooled data for generating overall estimates. Since several studies implemented multiple types of interventions such as capacity building, transport, mHealth, etc., there was some overlap of data within the review and the exact effect estimates of independent interventions might be impacted.

Future research should prioritize tailored interventions and sustainable strategies to ensure comprehensive improvements in maternal and neonatal health globally. The findings highlight a significant research gap in addressing adherence to antenatal care and PNC. Urgent attention is required to develop interventions from existing literature to capitalize on the promising outcomes observed in the reviewed behavioral interventions to fill these gaps [103]. More robust additional studies are needed to evaluate the impact of perinatal regionalization and other perinatal interventions on both neonatal and maternal health outcomes which should incorporate randomized field experiments for optimal research validity. Cost-effectiveness studies for all perinatal interventions should also be conducted to make strong recommendations for policymaking, and support should be provided to implement and evaluate relevant programs in LMICs.

Findings from our review indicate that perinatal regionalization, transport, and capacity-building interventions as well as maternal education and telemedicine have a positive impact on maternal and neonatal outcomes. Efforts should be diverted to scale these in high burden settings; however, the evidence also highlights the need for stronger evidence from more robust trials especially in resource-limited settings to inform focused policymaking and infrastructure investments and optimize healthcare strategies to enhance maternal and newborn health.

We thank the Aga Khan University for providing internal resources.

A statement of ethics is not applicable because the study is based exclusively on published literature.

The authors have no conflicts of interest to declare.

This study is supported by the Bill and Melinda Gates Foundation Grant (#INV-042789). The funders played no role in the design, data collection, data analysis, and reporting of this study.

A.A.A., H.A.N., and S.H. carried out the literature review. A.A.A., H.A.N., and Z.A. extracted data from the reviews/studies and drafted the paper. A.A.A. and H.A.N. entered data into RevMan, carried out the analysis, and interpreted the results. R.Y. and M.A. reviewed and edited the manuscript. J.K.D. and Z.A.B. provided supervision for each step and contributed to the critical revision of the manuscript.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.