In this study, women’s use of antenatal services increased considerably over the course of the 3-year MNCH intervention, with the number of women receiving 3 or more ANC visits increasing from 40% to 81%. In both areas (icddr,b and government SAs), women receiving more ANC visits were more likely to seek facility-based delivery care. However, increased ANC visits were only associated with reduced perinatal mortality in the icddr,b area. In addition, increased ANC visits appear to mediate a large portion of the observed 36% reduction in the odds of perinatal mortality during the MNCH intervention in icddr,b SA [
20]. This was likely a direct result of the ANC provided rather than a subsidiary increase in use of skilled facility care, as increased facility delivery did not mediate the reduction in perinatal mortality. The study findings confirm earlier observations that ANC is associated with positive health care behavior and improved perinatal survival [
6,
26,
27]. It also suggests that standardized antenatal care provided through the program may have played a substantial role in reducing perinatal mortality (particularly early neonatal mortality) - an important indicator in achieving Millennium Development Goal (MDG) for child survival (MDG-4) in low-income settings.
The present study has several strengths. Prospectively collected information on ANC visits and outcome data in two areas, one of which implemented an MNCH intervention aimed at improving ANC coverage and quality, permits us to examine the effect of a changing pattern of ANC use on perinatal survival. Important social and demographic factors including gestational age were also available for adjustment of potential confounding effects. However, we were unable to determine to what extent the individual intervention contributed to the perinatal mortality reduction. Also, we did not collect information on how ANC facilitated the referral of complicated women and neonates from community to facility level in the government SA. This information (referral and subsequent treatment) was collected in icddr,b SA but is not currently available and will be reported separately.
There are several study limitations which need to be acknowledged. Due to the long-standing acceptability and proven effectiveness of several interventions included in the ANC program, randomization is not a feasible option for the package; as a result, observational studies are a necessary design [
1]. Due to differences of ANC packages between icddr,b and government SAs, it is difficult to compare the effect of ANC across the two sites. However, prior to the strengthening of ANC services by the MNCH program when the components of ANC services were more comparable between two areas, the effect of ANC was only observed in the icddr,b SA. The observed lack of association between ANC and perinatal mortality in the government SA suggests the existing ANC service in the government SA is not providing the expected benefits due to lack of quality of care and linkage between community and facility-based services. In the second analysis we used a before-after design to examine further how the use of ANC services after initiation of the MNCH program played a role in the observed reduction of perinatal mortality. We describe in detail the limitations, especially the difficulty of comparing across service areas and the challenge of inferring the intervention effect with observational data [
20]. In the present study, we adjusted for important socio-demographic variables including the calendar of year of birth to address potential confounding. Three findings, (i) the observed high effect estimates (odds ratio about 2), (ii) the dose–response relationship between exposure to ANC and outcome (perinatal mortality), and (iii) the apparent mediation of the intervention effect by high ANC coverage, provides additional support for the effectiveness of the ANC services in the present study. Nonetheless, the associations observed may be due to factors related to the selection of study groups or to other forms of unmeasured confounding.
ANC visits were strongly associated, in a dose-dependent way, with perinatal mortality in the icddr,b SA, but we did not observe such effects in the government SA. ANC visits may improve perinatal outcome for several reasons. First, ANC introduces women and their families to the formal health system which makes them more likely to use health facilities for delivery [
27-
29]. The fact that increased facility use for delivery did not mediate the post-intervention reduction in perinatal mortality makes this hypothesis less plausible. Second, antenatal education (counseling) can increase the understanding of mothers and/or family members about early recognition of danger signs during pregnancy and delivery and basic newborn care, and therefore facilitates the use of the existing health system or improved home care (such as warmth, exclusive/immediate breast feeding) at appropriate times [
27,
30,
31]. Third, incorporating and maintaining quality evidence-based interventions in the ANC package may also increase the coverage of services conducive to improving perinatal health. The availability of evidence-based interventions and the presence of an effective linkage between community and facility-based services might explain the observed difference of associations between ANC visits and perinatal mortality in two areas.
Another important finding of the present study is that achieving high ANC coverage in the icddr,b SA explained much of the 36% reduction of perinatal mortality observed due to initiation of MNCH program. Among potential mediators of this reduction, including facility use, gestational age, and increased number of antenatal visits, the number of ANC visits was the only factor that substantially attenuated the observed post-intervention reduction in perinatal mortality (Table ). This finding suggests that ANC services played a key role in observed perinatal mortality reduction in the icddr,b area. In addition to a considerable increase in ANC coverage (women with ≥3 visits increased from 40% to 81%), the MNCH ANC package included several new components which were strengthened through training, refresher training, and regular quality control check-up of available services (Table ). Counseling and training during each ANC session focusing on evidence-based practices, identifying risk factors, and involving support persons may have played an important role. Prenatal interventions such as birth preparedness, micronutrient and/or iron-folate and anthelmintic supplementation, risk tracking and appropriate management such as antibiotic use for preterm premature rupture of membrane, corticosteroid treatment for women with risk or in preterm labor, and induction of labor for post-term pregnancy are also recognized to improve perinatal health [
6,
32,
33]. Although this study cannot discriminate the independent effects of these specific components, facilitating access to this suite of evidence-based interventions in the icddr,b area appears to have played an important part in improving perinatal survival. However, selection of an individual intervention should be based on the cost-effectiveness of the available evidence-based interventions.
Universal coverage of delivery care by skilled attendant is one target of MDG-5 [
34]. The latest maternal health survey in Bangladesh shows that the national facility delivery rate increased significantly in the last 5 years to 23%, which is similar to the government SA in the present study [
35]. In the present study we observed that ANC was associated with increased facility delivery practice in icddr,b and government SAs. Several studies in Bangladesh also report associations between ANC and increased uptake of facility delivery [
4,
36]. Our findings are also consistent with studies conducted in low- and middle-income countries that ANC uptake is associated with 3–4 times increase in facility delivery rate [
28,
37].
Very few studies have evaluated the association between ANC care and perinatal mortality in low- and middle-income countries. One study conducted in Kenya found that women who received two antenatal care visits had better perinatal outcomes than those who received less than two antenatal visits [
11]. Another study in Jamaica found that mothers who started ANC in the first trimester decreased the risk of perinatal death [
38]. It is difficult to compare the effect estimate observed in the present study with these earlier studies due to differences in services included in the studies. However, the observed 1.5 to 2 times increased risk of perinatal mortality among women with no ANC visits in earlier studies is similar to the findings we observed [
11,
39].
The feasibility of scaling up ANC services like those implemented in the icddr,b SA into the existing health system and program in Bangladesh or other low-income countries is an important and outstanding question. There is strong similarity between icddr,b SA and government SAs on the basic infrastructure and human resources. In Bangladesh, existing ANC care in government areas is provided by paramedics at union level sub-centers which are equivalent to the icddr,b sub-centers. In the sub-district level hospital, which is equivalent to icddr,b Matlab Hospital, ANC services are provided by nurse-midwives or doctors as is the case in the icddr,b hospital. The Government of Bangladesh has recently established about 16,000 community clinics, each covering a population of about 6,000, where basic ANC will be provided through community health workers. However, the success of ANC in the icddr,b area likely relied on several additional elements not currently available in the government SA: (1) guidelines for specific elements of the ANC package, (2), foundational and refresher training of health care providers including development of a users’ guide, (3) standardized counseling on evidence-based interventions and risk factor, and involving support person in this process, (4) linkages between outreach, community, and facility levels to improve the management of complications, and (5) a process of monitoring, evaluation and supervision of the offered services at regular intervals. In addition, a system needs to be put in place in the government SA to ensure appropriate supplies to meet local needs. These initiatives could be linked with other ongoing activities in many Upazilas (sub-districts) through the government services such as Demand Side Financing [
40], which provides incentives for uptake of at least 3 ANC services for the poorest group of women in the community.