Research results from a registry supporting efforts to improve maternal and child health in low and middle income countries

In high-income countries during the last century, there have been massive reductions
in maternal, fetal and neonatal mortality. However, in many low-income and some middle
income countries (LMIC), improvements in these outcomes have been slow to materialize
1], 2]. In these areas, maternal mortality is often a hundred-fold and fetal and neonatal
mortality 20-fold greater than in high income countries. Reasons for these differences
are often not clear, but certainly include a large number of non-facility births,
untrained and unskilled birth attendants and lack of basic medical equipment and medications.
World-wide, an estimated 60 million women give birth each year outside of health facilities,
mainly at home. Fifty-two million of these births are assisted by a traditional birth
attendant or family member and not a skilled birth attendant 3].

In order to improve outcomes, policy makers in LMIC countries as well as members of
the global health community need to know the prevalence of adverse outcomes as well
as the factors associated with these outcomes. Unfortunately, in most of the areas
with the worst outcomes, there are few data available upon which to base decisions
on how to improve these outcomes. Two general approaches are used. The first is conducting
randomized trials of specific interventions to determine if those interventions improve
outcomes. The second is to monitor these outcomes and the factors that may be associated
with changes in these outcomes over time. In virtually all high income countries,
this later approach, often in the form of vital statistics registries, is used to
provide this surveillance. However, in LMIC, this type of data is often not available,
and there is little information upon which to base policy decisions. For this reason,
in addition to accomplishing randomized trials of specific interventions, the Global
Network for Women’s and Children’s Health Research (Global Network) initiated the
registry described below.

The Maternal Newborn Health Registry (MNHR) of the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Global Network was created
in 2008. Prior to that time, a prototype of the MNHR was used to measure outcomes
in the Global Network’s First Breath Trial 4]. On completion of the trial, the investigators maintained and improved the prototype
because they appreciated the scientific value of collecting prospective data describing
population-based demographics, processes of care and pregnancy outcomes in low-resource
communities. The MNHR is now used to monitor trends in these characteristics over
time. It also serves as a method to obtain outcomes for a number of cluster randomized
trials including those on antenatal corticosteroids, emergency obstetric and neonatal
care, and routine obstetric ultrasound.

One of the outstanding characteristics of the MNHR is its sheer volume. Monitoring
nearly 70,000 pregnant women per year has allowed the MNHR to collect data on more
than 500,000 births over its history, which provides a sufficient sample size to assess
stillbirth and neonatal mortality, as well as maternal mortality, a relatively rare
event. We believe this is one of the largest LMIC registries of prospectively collected
pregnancy data in existence. Another attribute of the MNHR is the diversity and stability
of the Global Network sites. The Global Network includes sites from sub-Saharan Africa
(Democratic Republic of Congo [DRC], Kenya, and Zambia), South Asia (Belgaum and Nagpur,
India, Pakistan) and Latin America (Guatemala, Argentina). Since its inception, only
one site has been added and only one site has been dropped from the MNHR. The GN sites
also show a great diversity with respect to the characteristics of the women and the
resources available for their care. Some sites have almost universal hospital delivery
while others show a proportion of home deliveries as high as 58 %. In some sites,
70 % of deliveries are assisted by physicians whereas in other sites, 55 % of deliveries
are assisted by traditional birth attendants 5]. Within each country site, between 6 and 20 geographic areas (clusters), with about
500 deliveries per year, are closely monitored to provide data for the MNHR.

In this supplement, we have assembled manuscripts that not only highlight the productivity
and value of the MNHR, but also address issues crucial to improving pregnancy outcomes
in these sites. When developing the guidelines for the manuscripts, we decided to
restrict the data reported to that collected from 2010 to 2013, which included data
from all sites which were active during that time. The pregnancy outcomes for 2014
births were not complete when the analysis data sets were created, and although data
from 2008 to 2009 were available for some sites, we generally elected not to present
that data because the data forms changed substantially early in its history, and the
quality of data improved in later years.

This supplement can be seen conceptually as divided into several components. The first
component deals with registry management and quality control. Four papers are included
in this category which includes the overall description of the MNHR by Bose, et al.5]. Goudar et al. summarize the extensive work the registry investigators have put into ensuring that
the MNHR has complete and quality data, focusing on defined metrics to evaluate the
quality of the data and the ongoing monitoring methodologies employed by the registry
6]. Kodkany et al. describe how the Belgaum, India staff utilize Ministry of Health family planning
and other pregnancy registers to ensure nearly complete registration of pregnancies
7]. Also, to facilitate first trimester enrollment in the MNHR, their staff conduct
frequent house-to-house canvassing to identify pregnant women. This process allows
tracking of all outcomes of pregnancy, including first trimester losses. Finally,
Marete et al. document the very low rate of women lost to follow up across all sites and also the
characteristics associated with those lost compared to those for whom follow up data
were available 8]. For population-based registries, complete ascertainment is crucial and these papers
document the extent to which the sites have endeavored to ensure both the completeness
and accuracy of the data.

One of the important features of the MNHR is its ability to evaluate important pregnancy
outcomes including maternal, fetal and neonatal mortality. Bauserman et al. report the prevalence of maternal mortality and the characteristics associated with
mortality 9]. With more than 500,000 births, this is one of the only low-resource country data
sets that have a sufficient number of maternal deaths to evaluate this outcome. Of
note, the maternal mortality ratio decreased from 166 in 2010 to 126 in 2013 among
all sites, with the exception of Pakistan where maternal mortality increased over
that period. Similarly, the paper by Dhaded et al. addressed the risk factors associated with neonatal mortality and reported a 7-day
neonatal mortality rate (NMR) of 20.6 per 1000 live births and a 28-day NMR of 25.7
per 1000 live births 10]. The very wide range in 28 day NMR across the sites, ranging from 10 in Argentina
to 50 in Pakistan, was emphasized. McClure et al. describe the risk factors associated with over 2,500 stillbirths 11]. Importantly, they report that the majority of stillbirths in these low-resource
areas were not macerated and many were greater than 2500 g at birth. These results
strongly suggest that many stillbirths occurred in labor and were of sufficient size
and maturity to survive had they been delivered alive. Thus, with appropriate obstetrical
care most of these deaths were preventable. Across all three studies, worse pregnancy
outcomes were generally observed among women with lower education levels, less access
to antenatal care and those who were delivered outside the formal health setting.

Four papers in this series explore specific topics that are of special interest to
the public health community. Althabe et al. report wide ranges in the percent of adolescent pregnancies across the sites 12]. For example, the proportion of births to adolescents in the sub-Saharan African
and Latin American sites ranged from 16.1 % (Guatemala) to 26.0 % (Argentina). In
the South Asian sites this proportion ranged from 2.0 % (Nagpur, India) to 9.6 % (Belgaum,
India). In this study, the risks for adverse maternal outcomes among adolescents were
not markedly different than those of women in their twenties. However, risks of preterm
birth and LBW were significantly higher among both early and older adolescents, with
the highest risks observed in the youngest (15 years) group. Harrison et al. examined risk factors related to prolonged and obstructed labor 13]. Virtually every pregnancy outcome was worse in women with prolonged/obstructed labor,
and these outcomes were particularly bad among women in the African sites compared
to women in other Global Network sites. Patel et al. identified characteristics associated with lack of breastfeeding in low-resource
settings and associated outcomes 14]. Pasha et al. report that, despite relatively high contraceptive usage in a few of the sites, overall
there was a large unmet need for family planning services across the sites 15]. If contraceptive usage was increased, teenage pregnancies reduced, better obstetric
care provided for women having prolonged labors, and better support of breast feeding,
we believe many of the adverse pregnancy outcomes in these sites could be reduced.

Finally there are three papers focusing on issues related to pregnancy outcomes in
a single country. Goudar et al. examined the relationship between increasing use of facilities for delivery and pregnancy
outcomes in sites in India, where substantial government effort has promoted facility
rather than home births 16]. They report a modest decline in the stillbirth rate that was temporally associated
with an increase in the prevalence of facility births, but not a corresponding improvement
in neonatal mortality. Garces et al. report reductions in maternal mortality, fetal mortality and neonatal mortality in
the Western Highlands of Guatemala between 2010 and 2013 17]. Those reductions were temporally correlated with increasing hospital delivery, births
attended by skilled rather than unskilled birth attendants, and increasing use of
caesarean section. The reduction in infant mortality was most pronounced in infants
born between 1500 g and 2500 g. Pasha et al. report disappointing trends in obstetric and neonatal care and pregnancy outcomes
in the Thatta area of Pakistan 18]. Maternal, fetal and neonatal mortality were two to three-fold higher in Pakistan
than in any other site in the Global Network. These differences were associated with
lower levels of maternal education and lower quality of antenatal and obstetric care
in Pakistan compared with the other sites. Taken together, these papers demonstrate
that improvements in outcomes can occur with better access to and utilization of facility
care for delivery. On the other hand, the data from Pakistan illustrate the very poor
pregnancy outcomes that occur when a poor, uneducated population is provided low quality
care.

In summary, the breadth of topics covered by the papers in this supplement using data
from a prospective pregnancy outcome registry presents a powerful picture of pregnancy
and its outcomes in the developing world and shows the value of a population-based
registry focused on pregnancy. With additional years, trends over time will become
even more apparent, and the scientific value of the registry should become even greater.
In addition to the manuscripts in this supplement, previously published papers using
data from the MNHR have described the relationship between maternal mortality and
stillbirth and neonatal mortality. Papers describing the methodology for determining
maternal, fetal and neonatal causes of death and the effects of indoor air pollution
on pregnancy outcomes in the Global Network sites are in press. Registry data has
also been incorporated into larger data bases to evaluate neonatal infections and
the role of birth weight on neonatal mortality. We believe that the MNHR has made
a substantive contribution by providing information to inform public health and medical
strategies to improve care and to reduce pregnancy-related mortality.