Background

The universally accepted neonatal period is birth to the first 28 days of life and is the time in which the child is most vulnerable to death (United Nations Children’s Fund, 2019). The neonatal mortality (NM) rate is calculated using the number of deaths per 1000 live births in a given period (WHO, 2005). Globally, an estimated 5.4 million under-five deaths were reported in 2017 and of which around 2.5 million of them died in the first month of life; contributing to 47% of under-five deaths (United Nations Inter-agency Group for Child Mortality Estimation (UNIGME), 2017; World Health Organisation, 2019). Neonatal mortality is an urgent public health concern with about 6,500 neonatal deaths every day around the globe. Surprisingly, more than 80% of neonates are suffering from preventable causes of death (United Nations Inter-agency Group for Child Mortality Estimation (UNIGME), 2018; WHO, 2016a). Although the world has made significant improvements in reducing childhood mortality (United Nations Inter-agency Group for Child Mortality Estimation (UNIGME), 2018), remarkable disparities have been observed in reduction among high, and low-middle-income countries (LMICs) (United Nations Inter-agency Group for Child Mortality Estimation (UNIGME), 2017; World Health Organization, 2019). And, the trend for NM contribution to under-five mortality is persistently high since the inception of the millennium development goals; 31% in 1990, and 41% in 2018 (Lopez, 2014; Mejía-Guevara et al., 2019; Tekelab et al., 2019a, 2019b).

The highest number of NM occurred in Sub-Saharan Africa (SSA) and South Asia countries each accounting for 39% and 38%, respectively (United Nations Inter-agency Group for Child Mortality Estimation (UNIGME), 2019). The SSA countries have the highest rate (27 per 1000 live births) of NM worldwide and from the top 10 countries contributing to NM rates in the world, eight countries are located in this region (Jena et al., 2020; United Nations Inter-agency Group for Child Mortality Estimation (UNIGME), 2017). Despite significant progress in maternal and child mortality, neonatal health problems remained part of the unfinished agenda in many East African countries, including Ethiopia (Abate et al., 2020; Gebremedhin et al., 2016). In Ethiopia, there are high proportions of neonatal deaths; being one of the top ten countries prominently affected by NM, and is one of the top five countries contributing to half of NM in the globe (Jena et al., 2020; Wright, 2014).

In an attempt to reduce the high toll of NM (Berhan & Berhan, 2014; Jena et al., 2020), the government of Ethiopia developed a National Newborn and Child Survival Strategy which also help to accelerate the achievement of the sustainable development goal (SDG) target 3.2 for ending preventable neonatal deaths or stillbirths to as few as 12 per 1000 live or total births (UN-DESA, 2017). Addressing this goal would save the lives of 5 million newborns from 2018 to 2030 (Hug et al., 2019; United Nations Inter-agency Group for Child Mortality Estimation (UNIGME), 2018; WHO Press Release, 2017). However, current trends showed more than 60 countries, including Ethiopia will miss this target (United Nations Inter-agency Group for Child Mortality Estimation (UNIGME), 2018). Therefore, attaining ambitious survival goals needs ensuring universal access to safe, effective, high-quality, and affordable care for women and children (WHO, 2015a). More importantly, in Ethiopia, the decline of NM remained stagnant; according to the mini Ethiopian demographic health survey (EDHS) 2019 report, the NM rate was 30 per 1000 live births; NM is the highest in the world and the country continues to suffer from the steepest reduction of odds of neonatal survival in the world (Ethiopian Public Health Institute ICF, 2019).

Effective and timely maternal health care services before conception, during pregnancy, and childbirth could save nearly 3 million newborns in high-burden countries (Tekelab et al., 2019a, 2019b). Antenatal care is recognized as one of the fundamental strategies to reduce stillbirth and NM irrespective of the socio-demographic background (Arunda et al., 2017; Gregory et al., 2016; Lambon-Quayefio & Owoo, 2014; Mohamed et al., 2016; Singh et al., 2014; WHO, 2015b). It is an ideal entry point for maternal and neonatal health care to ensure access to several health care interventions (Ibrahim et al., 2012; Raatikainen et al., 2007; WHO, 2016c). An estimated 10–20% of NM is averted by the provision of ANC services (Darmstadt et al., 2005; WHO, 2009); although the focused ANC model which was developed in the 1990s is associated with more perinatal deaths than the 2016 world health organization (WHO) positive pregnancy experience ANC model (WHO, 2016b, 2016c).

A systematic review and meta-analysis performed in SSA reported that ANC utilization contributed to the reduction of NM (Tekelab et al., 2019a, 2019b). However, the study does not include adequate primary studies from Ethiopia and its effect was not evaluated in the context of Ethiopia; indeed, there is variation in the practice of maternal health services. In Ethiopia, some studies found that the risk of NM is reduced in births of women with at least one ANC visit compared to no ANC visit (Alebel et al., 2020; Debelew et al., 2014; Kidus et al., 2019; Orsido et al., 2019; Worku et al., 2012) whereas others found no relationship between having an ANC visit and NM (Demisse et al., 2017; Elmi Farah et al., 2018; Wakgari & Wencheko, 2013; Worku et al., 2014). Hence the reported disparities in the effect of ANC on neonatal outcomes in these fragmented studies call for the importance of having robust evidence emanated from several primary studies, representing the various geographical area of the country. Therefore, in Ethiopia where there is a high proportion of NM, the availability of strong abridged evidence on the effect of ANC on NM would offer reliable evidence for policymakers to critically reinforce the ANC program and design optimal ANC service.

Methods

The present systematic review and meta-analysis methodology was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist (Moher et al., 2015).

Eligibility Criteria

The eligibility criteria for this systematic review and meta-analysis include observational (cross-sectional, case–control, and cohort) studies with the following criteria: (i) the studies that included women who gave birth without any specific risk factors; (ii) the studies were conducted in the perinatal period provided that if the studies differentiate early neonatal death as the death of neonate with in the first seven days and neonatal mortality was defined a death during the first 28 days of life; (iii) studies that reported the risk of perinatal or neonatal mortality; (iv) the ANC utilization was considered as possible factors/exposure for neonatal mortality; and (v) the article is published in the English language. However, articles that focus on the number of ANC visits to determine NM (i.e., without yes/no response for ANC visit) were excluded from the meta-analysis. Further, studies emanated from review, commentary, editorials, fact sheets, and policy briefs were not included in the analysis.

PICO

Population::

live birth neonates.

Intervention::

neonates born to women who utilized at least one ANC visit.

Comparison::

neonates born to women who did not utilize at least one ANC visit.

Outcome::

neonatal mortality.

Information Sources and Search Strategy

Searching of PubMed, EMBASE, CINAHL, and HINARI databases were carried out from January 1990 to June 2020. We reasonably selected the year of publication (1990) as focused antenatal care has been implemented since 1990. We also retrieved records through the Cochrane Central library and Google Scholar. Searching was performed using the following key/Medical Subject Heading (Mesh) terms: “Antenatal care”, “prenatal care”, “obstetrics”, “pregnancy care”, “maternity care” “maternal health services”, “perinatal mortality”, “neonatal mortality”, “neonatal death”, “newborn death”, “Ethiopia” (Table S1).

Study Selection

The selection of the studies involved three steps. First, duplicates were removed and eligible articles were screened based on their title and abstract by two authors (GT and KS) independently. Second, full-text studies were evaluated based on the predetermined inclusion criteria. Third, the methodological quality appraisal was performed for studies that met the inclusion criteria. Any disparity between the two reviewers was resolved through discussion and common consensus. Overall, preferred reporting items for systematic reviews and meta-analysis flow chart was used to record the selection process of the studies (Fig. 1).

Fig. 1
figure 1

Articles selection procedure flow chart for the systematic review and meta-analysis from 1990 to 2020

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Data Extraction

The data extraction template was prepared using an excel sheet. The authors read all included studies in detail to extract pertinent data for the review based on first author, year of publication, study setting, study design, sample size, number of dead neonates and survivors among ANC attendants, and number of dead neonates and survivors among non-ANC attendants (Table1).

Table 1 List of the included studies in the meta-analysis to determine the effect of ANC visits on neonatal mortality in Ethiopia, 2020
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Measurement

An outcome variable (NM) was defined as the death of the neonate within the first four weeks (28 days) of life (Lander, 2006). The presence or absence of an ANC visit was used as an exposure variable. Antenatal care visit refers to a woman's pregnancy checkup once or more from a health facility that is given by a skilled attendant during pregnancy (WHO, 2006).

Individual Study’s Quality Assessment

The review authors rigorously assessed the quality of included studies using the Risk of Bias Assessment Tool for Non-Randomized Studies (RoBANS) (Kim et al., 2013). Accordingly, six parameters (selection bias, confounding bias, performance bias, attrition bias, and reporting bias) were used to evaluate the quality of the studies. Each article was allocated to one of three possible groups; ‘low risk’, ‘high risk’, and ‘unclear’ based on these parameters (Table S2).

Data Synthesis and Analysis

A Microsoft excel spreadsheet was used to extract data from potentially eligible articles; then exported to Comprehensive Meta-analysis (CMA) version 2. software for analysis. The overall impact of maternal ANC utilization on NM was carried out by using a DerSimonian and Laird random-effects model (DerSimonian & Laird, 1986) and the risk ratio with a 95% confidence interval (CI) was determined. The existence of heterogeneity among included studies was checked using the I2 test statistic, which defines the percentage of total variation among studies due to heterogeneity rather than chance (Hardy & Thompson, 1998). Hence, subgroup analysis was conducted to explore the presence of possible sources of heterogeneity among studies. The pooled effect size was reported in the form of a risk ratio with 95% CI. A p-value of less than 0.05 was considered statistically significant. Furthermore, the presence of publication bias was investigated by using a visual inspection of funnel plot and Egger’s regression intercept (Egger et al., 1997).

Results

Study Characteristics

We identified 6117 studies during initial searching, of which, 44 full-text articles were assessed against eligibility criteria. Thus, 16 studies were excluded due to lack of exposure variable (6 articles) (Desalew et al., 2020; Gizaw et al., 2014; Mediratta et al., 2020; Mekonnen et al., 2013; Mengesha et al., 2016; Seid et al., 2019), absence of outcome variable (5 articles) (Andargie et al., 2013; Goba et al., 2018; Roro et al., 2018; Tadesse & Fantahun, 2017; Wolde et al., 2019), an outcome variable was compared with the number of ANC visits (3 articles) (Mersha et al., 2019; Tewabe et al., 2018; Haile et al., 2020) and insufficient data (2 articles) (Hadgu et al., 2020; Tura et al., 2020). Finally, 28 original studies were retained for this systematic review and meta-analysis (Fig. 1).

Study Description

The majority of the included studies were published in the last five years. We included thirteen cohort (Alebel et al., 2020; Asmare, 2018; Debelew et al., 2014; Dessu et al., 2020; Elmi Farah et al., 2018; Mekasha et al., 2020; Mengistu, 2020; Orsido et al., 2019; Roro et al., 2019; Sahle-Mariam & Berhane, 1997; Tessema & Tesema, 2020; Worku et al., 2014; Worku et al., 2012), seven case–control (Alemu et al., 2020; Araya et al., 2015; Kolobo et al., 2019; Kolola et al., 2016; Mohamed et al. 2016; Tesfaye et al., 2019) and eight cross-sectional (Aragaw, 2016; Basha et al., 2020; Demisse et al., 2017; Kebede et al., 2012; Wakgari & Wencheko, 2013; Wesenu et al., 2017; Woday et al., 2019; Yehuala & Teka, 2015) design studies. The sample size of participants in the original studies ranged from 228 to 11,023 neonates. Eight studies were from Amhara regional state (Alebel et al., 2020; Alemu et al., 2020; Demisse et al., 2017; Kebede et al., 2012; Kolola et al., 2016; Mengistu et al., 2020; Worku et al., 2014; Yehuala & Teka, 2015), five studies were from Oromia regional state (Aragaw, 2016; Debelew et al., 2014; Kolobo et al., 2019; Roro et al., 2019; Wesenu et al., 2017), three studies were from South Nation Nationalities People (SNNP) (Dessu et al., 2020; Orsido et al., 2019; Tesfaye et al., 2019) and Addis Ababa city administration (Asmare, 2018; Sahle-Mariam & Berhane, 1997; Worku et al., 2012). There were also two studies from the Somali regional state (Elmi Farah et al., 2018; Mohamed et al., 2016); one national study (Mekasha et al., 2020), one study from Benishangul Gumz region (Kidus et al., 2019), Afar region (Woday et al., 2019), and Tigray region (Araya et al., 2015). Further, we also included studies from the 2011 and 2016 Ethiopian Demographic Health Survey reports (Basha et al., 2020; Tessema & Tesema, 2020; Wakgari & Wencheko, 2013). Table 1 reveals a total of 59,104 neonates were involved in the review to determine the pooled effect of at least one ANC visit on NM in Ethiopia.

Individual Study’s Risk of Bias

The risk of bias in the selection of participants in the study was low for all studies. The bias due to incomplete outcome data reporting or missing data as a result of attrition was low in most of the included studies. Measurement bias due to the inadequate measurement of risk factors was low among twenty-two studies. However, the risk of confounding bias was high in twelve studies, but low in eighteen studies that adjusted for major confounding variables during the final analysis (Table 2).

Table 2 Risk of bias among the included original studies on the effect of antenatal care on neonatal mortality in Ethiopia, 2020
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A Pooled Effect Size of Antenatal Care on Neonatal Mortality

From the 28 studies included in this review, 20 studies showed ANC services utilization was significantly associated with NM. The random pooled effect of ANC on NM was 0.59 (95% CI: 0.45, 0.77) for infants born to women who had at least one ANC visit compared to infants born to women who had no ANC visit (Fig. 2).

Fig. 2
figure 2

Overall pooled estim ate of ANC effect on neonatal mortality in Ethiopia, 2020

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Studies’ Heterogeneity and Publication Bias

Overall, there was considerable heterogeneity across the included studies, with I2 statistics = 95.3% and p-value < 0.001. Therefore, to explore the possible sources of heterogeneity, a subgroup analysis was carried out using study design, setting, and sample size. The heterogeneity that was present in the overall meta-analysis disappeared when the included studies were stratified by study region. For instance, in a subgroup analysis of Ethiopian Somalia region (RR = 0.64 [95% CI 0.46, 0.90]; p = 0.75 for the heterogeneity test, I2 = 0.0%) were not statistically heterogeneous. However, heterogeneity remained high within subgroups for sample size, study design, and setting. Stratification of the included studies by region also indicated a strong association between ANC and neonatal mortality; its association was found among studies conducted in the SNNP region compared to other regions and the overall pooled estimate. Accordingly, the risk ratio of neonatal mortality among infants born to women who had at least one ANC visit was 73% lower compared to infants born to women who had no ANC visit in a study conducted in the SNNP region (OR 0.27, 95% CI 0.17–0.42) (Table 3).

Table 3 Subgroup analysis of the studies included in the meta-analysis to determine the effect of ANC on neonatal mortality in Ethiopia, 2020
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The visual inspection of the funnel plot illustrated that studies assessing the effect of ANC on neonatal mortality were symmetrically distributed (Fig. 3). The Egger regression test also indicated no evidence of publication bias (p-value = 0.90). Hence, our meta-analysis is unlikely to suffer from publication bias.

Fig. 3
figure 3

Funnel plot of studies on the pooled effect of ANC visit on NM in Ethiopia, 2020

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Discussion

Despite there is promising progress in reducing infant mortality and under-five mortality in Ethiopia, the decline for NM remained stagnant in recent years, which contributes to the highest rate of neonatal death in the SSA region. To reduce the high burden of neonatal mortality, the Ethiopian ministry of health designed and implanted maternal health services, most notably ANC services as one of the essential strategies. The current systematic review and meta-analysis, therefore, aimed to determine the effect of ANC on NM in Ethiopia, after including a large number of primary studies that characterize the wider geographical areas of the country.

This review showed that women who had at least one ANC visit were less likely to lose their neonates compared to neonates born to women who had no ANC visit. Accordingly, there is a 41% reduction in the risk of NM among infants born to women who had at least one ANC visit compared to infants born to women who had no ANC visit. This is in line with a review reported from SSA which indicated a 39% reduction in the risk of NM among infants born to women who initiated at least one ANC visit (Tekelab et al., 2019a, 2019b). Similarly, the finding of this systematic review and meta-analysis is in line with the study conducted in Zimbabwe, where utilization of ANC substantially reduces the likelihood of NM (Makate & Makate, 2017). A demographic and health survey done in SSA also reported a 48% reduction in the risk of NM among infants born to women who received at least one ANC visit compared to their counterparts (Doku & Neupane, 2017).

This notable effect of ANC against NM is because, ANC is one of the essential approaches to tackle NM (Canavan et al., 2017) through ensuring WHO recommendations for pregnant women such as disease prevention, early identification, and treatment of pregnancy complications which in turn help to reduce the risk of neonatal infection and death. The provision of folic acid supplementation, the distribution of insecticide-treated bed-net (ITN) for malaria prevention, and early detection and treatment of syphilis, including urinary tract infections during ANC visits (WHO, 2016c) are also widely important to avert the leading contributors of NM such as preterm birth and low birth weight (Cogswell et al., 2003; Siega-Riz et al., 2006; Zeng et al., 2008).

Antenatal care is an entry point for women to adhere to the continuum of care (institutional delivery, postnatal care, and infant immunization) (Ejigu et al., 2018; Fekadu et al., 2019; Haile et al., 2020). Hence, the use of these services would reduce neonatal mortality through the provision of quality essential newborn care (Alamneh et al., 2020), neonatal resuscitation (Lee et al., 2011; Patel et al., 2017), newborn immunization (Babirye et al., 2012; Boulton et al., 2019; Kassahun et al., 2015), promotion of breastfeeding, and advice on maternal nutrition (Alebel et al., 2018; Arage & Gedamu, 2016). The finding of this study implies that reinforcing ANC service utilization by skilled health care providers is a cost-effective intervention approach for the survival of newborns and the well-being of neonates, especially in Ethiopia, where the country is disproportionately affected by NM. This highlights ANC visit plays a crucial role to reduce NM; policy designers and program implementers should strengthen the ANC services utilization.

Strength and Limitations of the Study

The inclusion of several studies in the pooled analysis through the use of a comprehensive search strategy that fairly represents the wider geographical area of the country could closely determine the effect of ANC on the neonatal outcome, hence, this would offer strong implications to reinforce the existing maternal health policy. In this review, almost all the original studies that fitted to the review topic were published in the last five years which indicates, that the study raised NM reduction through ANC service provision is a relatively current issue. However, the interpretation of this study should bear in mind the following limitations. First, the inclusion of participants from the NICU population in some of the primary studies possibly affects the result. Second, the use of retrospective data and community-based study settings in some of the primary studies could be subjected to recall bias. Last, we do not investigate the quality of ANC visits based on service contents as the focus was mainly on the association between ANC visits and NM.

Conclusion

According to this finding NM markedly declined among infants born to women who had as few as one ANC visit compared to infants born to women who had no ANC visit. Therefore, to accelerate the progress in the reduction of newborn death in Ethiopia, promoting the utilization of ANC services by skilled providers is mandatory. Further, to reduce the unacceptably high NM, the review implies health care providers should strive to retain pregnant women within the continuum of care which in turn prevents the death of the neonates from sepsis and complications of preterm birth.