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Research Priorities for the Reduction of Perinatal and Neonatal
Morbidity and Mortality in Developing Country Communities
William Moss, MD, MPH
Gary L. Darmstadt, MD, MS
David R. Marsh, MD, MPH
Robert E. Black, MD, MPH
Mathuram Santosham, MD, MPH
Although post - neonatal and child mortality rates have declined
dramatically in many developing countries in recent decades, neonatal
mortality rates have remained relatively unchanged. Neonatal mortality now
accounts for approximately two - thirds of the 8 million deaths in children
less than 1 year of age, and nearly four - tenths of all deaths in children less
than 5 years of age. Worldwide, 98% of all neonatal deaths occur in
developing countries, mostly at home, and largely attributable to infections,
birth asphyxia and injuries, and consequences of prematurity, low birth
weight and congenital anomalies. We review principal determinants of
neonatal morbidity and mortality during the antenatal, intrapartum and
postpartum periods, and propose priority community - based research
activities to develop, test and adapt inexpensive, practical and sustainable
interventions during these periods to reduce perinatal and neonatal
morbidity and mortality in developing countries.
Journal of Perinatology (2002) 22, 484 – 495 doi:10.1038/sj.jp.7210743
MAGNITUDE AND CAUSES OF NEONATAL MORBIDITY
AND MORTALITY
Despite global declines in under-five and infant mortality rates in
recent decades, neonatal mortality rates have remained relatively
unchanged.1 Mortality during the first 28 days of life now accounts
for two-thirds of deaths in children less than 1 year of age, and
nearly four-tenths of all deaths in children less than 5 years of
age.2 – 4 A recent analysis found that the loss of healthy life from
Department of International Health ( W.M., G.L.D., R.E.B, M.S. ), Bloomberg School of Public
Health, The Johns Hopkins Medical Institutions, Baltimore, MD, USA; and Office of Health
( G.L.D., D.R.M. ), Save the Children Federation - US, Washington, DC, USA.
newborn deaths represented 8.2% and 13.6% of the burden of disease
in Sub-Saharan Africa and South Asia, respectively, or 27 and 53
million years of life lost in those two respective regions alone.5 The
analysis, however, highlighted the dearth of information available on
neonatal outcomes in developing countries, particularly at the
community level, and the potential for currently available figures to
underestimate the magnitude of the problem. Thus, epidemiological
research is needed to make available more accurate data on risk
factors and causes of neonatal morbidity and mortality, and
improved and validated neonatal verbal autopsy instruments are
needed in order to collect accurate data.
For every death during the neonatal period, it is estimated that
another stillbirth has occurred; when combined with the two-thirds
of neonatal deaths that occur during the first week of life, perinatal
deaths nearly equal the number of deaths during the entire first year
of life.6,7 Estimates from the World Bank suggest that perinatal
deaths account for approximately 7% of the global burden of disease,
exceeding that due to malaria and vaccine-preventable infections
combined.8
Worldwide, 98% of all neonatal deaths occur in developing
countries, most often at home, outside the formal health care system,
and largely due to infections (32%), birth asphyxia and injuries
(29%), and consequences of prematurity and congenital anomalies
(34%).9 Infections may account for approximately half of newborn
deaths at the community level.10 Low birth weight (LBW) is an
overriding factor in the majority of the deaths.1
Conditions that affect the neonate, including LBW, impact not
only neonatal mortality but also long-term morbidity through effects
on neurological and cognitive development and associations with
chronic diseases such as diabetes, cardiovascular disease and chronic
lung disease.11 Thus, interventions that prevent morbidity during the
neonatal period have the potential to be highly cost-effective and
impact health far beyond the neonatal period.
In this review, we present a conceptual framework for maternal
and neonatal health care, and in this context, propose priority
research activities to improve perinatal and neonatal health and
survival in developing country communities.
This work was supported by the Johns Hopkins Family Health and Child Survival Cooperative
Agreement with the United States Agency for International Development, and by Save the
Children Federation-US through a grant from the Bill and Melinda Gates Foundation.
CONCEPTUAL FRAMEWORK AND CONTEXT OF
NEONATAL HEALTH CARE AND RESEARCH
Address correspondence and reprint requests to Gary L. Darmstadt, MD, Saving Newborn Lives
Initiative, Office of Health, Save the Children Federation - US, 2000 M Street, NW, Washington,
DC 20036, USA.
Improving newborn health and survival depends in large measure on
more effectively implementing what we already know works.
Journal of Perinatology 2002; 22:484 – 495
# 2002 Nature Publishing Group All rights reserved. 0743-8346/02 $25
484
www.nature.com / jp
Improving Perinatal and Neonatal Outcomes
Although many advances in obstetric and neonatal care are costly
and require technology not available in resource-poor countries, a
substantial proportion of perinatal and neonatal morbidity and
mortality in developing countries could be prevented through
appropriate adaptations and applications of inexpensive, relatively
simple methods to improve antenatal, obstetric and neonatal care. In
many cases, however, further research is needed to devise, adapt and
evaluate sustainable solutions, particularly at the community level.
Currently, most newborn deaths in developing country
communities are due to failure to: (1) identify and address
socioeconomic, cultural and logistical barriers to proper maternal
Moss et al.
and newborn care and care seeking; (2) implement basic preventive
measures (e.g., administration of tetanus toxoid, early exclusive
breastfeeding); and, (3) promptly identify and manage sick
newborns. Save the Children Federation-US has developed a
conceptual framework for household and community newborn and
maternal care that focuses attention on: (1) use of routine maternal
and newborn care and services of good quality; (2) response to
maternal danger signs; (3) response to the non–breathing newborn;
(4) care for the LBW baby; and, (5) response to newborn danger
signs, particularly those of infection (Figure 1).12 This framework
emphasizes that, because the health of the mother and the newborn
Figure 1. Conceptual framework of maternal and neonatal care, emphasizing the need to focus on ( upper panel ) adaptation and expanded implementation
of essential maternal and newborn care measures, and, ( lower panel ) major determinants of perinatal and neonatal morbidity and mortality, particularly care
of the LBW infant; and recognition of and appropriate response to maternal and neonatal danger signs, particularly those signaling birth asphyxia and neonatal
infections.
Journal of Perinatology 2002; 22:484 – 495
485
Moss et al.
Improving Perinatal and Neonatal Outcomes
Table 1 Criteria for Research to Have an Optimal Impact in
Developing Countries
( 1 ) Potential for major impact on key neonatal health status indicator, for
example, principal determinants of perinatal and neonatal
morbidity and mortality
( 2 ) Biologically plausible and based on relevant local formative research
( 3 ) Addresses a critical information gap
( 4 ) Potential to influence policy
( 5 ) Research can be conducted in a reasonable period of time
( 6 ) Feasibility and affordability of the research project in the local setting
( 7 ) Projected feasibility and affordability of adaptation, replication and
scaling - up of the intervention being tested in a programmatic
context, for example, feasibility and affordability of sustained
integration of the intervention( s ) into the health care system
( 8 ) Population / culturally appropriate
( 9 ) Has support from policymakers, stakeholders and program managers
within the country and community in which the research will be
conducted
are inextricably linked, intervention strategies must encompass
antenatal and intrapartum health care of the mother and immediate
and routine postpartum care of the mother and neonate to optimally
impact perinatal and neonatal health outcomes. Strategies to reduce
neonatal morbidity and mortality also must be implemented within
and integrated into a sustainable health system infrastructure.
Relatively more emphasis, for example, must be placed on
integration of neonatal health care into safe motherhood and child
survival programs. Moreover, because the majority of births and
neonatal deaths occur in the home, there is an urgent need to
understand traditional maternal and newborn care practices and
illness recognition and care-seeking behavior for the newborn in the
community. Mothers must be aided in understanding their crucial
role in maintaining good health during pregnancy and the health of
their infant after birth, and must be empowered and equipped to seek
and obtain appropriate care for themselves and their newborn.
Similarly, health care providers at all levels must be better educated
on essential newborn care; and closer links between the home, health
center and regional hospital must be forged. It is also imperative that
researchers anticipate how their findings can be translated into
programs and communicate closely from the outset with those who
will be responsible (e.g., governmental officials, stakeholders,
program managers) for prioritizing scarce resources and integrating
and locally adapting interventions into existing programs. However,
when considering where to invest in research, funding agencies
should adhere to criteria that ensure these principles have been
considered in the study’s conception and design (Table 1).
Major areas of research needed to advance newborn health and
survival include: (1) epidemiological research to identify
contributing factors in newborn deaths; (2) formative research to
better understand current local beliefs and practices and the reasons
for them, so that effective behavior change strategies can be
developed and evaluated; (3) operations research to better
understand how to deliver affordable, proven, life-saving
preventative and curative care; (4) community-based effectiveness
trials of promising models of maternal and newborn care; and, (5)
trials aimed to advance the state of the art in selected aspects of
community-based essential newborn health monitoring and care.
In this report, we highlight current knowledge and gaps in
understanding, as a foundation for outlining priority future research
Table 2 Research to Improve Maternal and Newborn Health: Antenatal Interventions
Maternal education and status
Maternal nutrition
Maternal immunization
Maternal infection
486
o Improve understanding of the sociocultural factors that influence maternal health and capacity, including issues of gender
equality and workload
o Delineate causal pathways linking maternal education to reductions in perinatal and neonatal mortality
o Develop and test strategies to improve health - seeking behavior and to optimize birth spacing
o Evaluate the effectiveness of micronutrient and vitamin supplementation ( e.g., multivitamins / nutrients, zinc, vitamin A,
calcium, vitamin C ) during pregnancy and the neonatal period on neonatal immune function, morbidity and mortality
o Evaluate the feasibility, sustainability and cost - effectiveness of strategies to improve maternal dietary intake before and
during pregnancy, for example, supplemental feeding, dietary fortification, food distribution, nutritional counseling
o Evaluate the effectiveness of iron supplementation and treatment with antihelminths and antimalarials in reducing
maternal anemia, preterm and LBW delivery and perinatal and neonatal morbidity and mortality, particularly in women
with milder forms of anemia
o Identify health care system and sociocultural barriers to tetanus toxoid immunization, and develop strategies to improve
access of women of child - bearing age to tetanus toxoid vaccine
o Conduct trials to evaluate the efficacy of maternal immunization with pneumococcal and Hib conjugate vaccines in
preventing neonatal infections
o Evaluate the efficacy of empiric antibiotic therapy for treatment of urinary tract infections and sexually transmitted
infections, and after premature or prolonged rupture of membranes to reduce premature birth
o Conduct surveillance studies to establish the prevalence and etiology of bacterial vaginosis in developing countries, and
evaluate simple diagnostic methods and treatment algorithms
o Develop, implement, and evaluate strategies to prevent and treat malaria in pregnant women as part of routine antenatal
care in areas of high malaria endemicity, including the integration into routine antenatal care of intermittent treatment
for the prevention of malaria in pregnant women
o Develop optimal strategies to prevent perinatal and breast milk transmission of HIV ( see below )
Journal of Perinatology 2002; 22:484 – 495
Improving Perinatal and Neonatal Outcomes
Moss et al.
Table 3 Research to Improve Obstetric and Early Neonatal Care: Intrapartum Interventions
Obstetric care
Prevention and management of HIV infection
o Develop strategies to ensure universal skilled care at delivery
o Conduct community-based studies to determine traditional birth practices; knowledge, attitudes and beliefs
regarding routine obstetric practices; and sociocultural factors that impact health-seeking behavior for
obstetric care
o Evaluate birth attendant training curricula, continuing medical education and quality assurance
o Identify barriers to, and evaluate strategies to improve quality and access to emergency obstetric care
o Define the role of chlorhexidine cleansing of the birth canal and/or the newborn in prevention of
neonatal umbilical cord and skin infections, and septicemia
o Define cost-effective strategies to prevent mother-to-child HIV transmission, for example, single-dose
nevirapine; impact of short-course treatment on later transmission via breastfeeding; need for longer
courses of therapy plus early weaning; role of combination regimens; appropriate target population
(e.g., all pregnant women or those with documented infection) in settings with various levels of health
care infrastructure and resources (e.g., rapid testing and counseling available)
o Define optimal breastfeeding strategies in areas with high HIV prevalence
o Define HIV case definition and prognostic criteria, strategies for primary prophylaxis of opportunistic
infections and severe bacterial infections, vaccination schedules (e.g., possible need to withhold BCG,
immunological response to vaccines), role of micronutrient supplementation in high-risk infants
o Define the role of chlorhexidine cleansing of the birth canal and/or the newborn in prevention of
mother-to-child HIV transmission
(see Tables 1–6) in each of the major programmatic phases of
maternal and newborn care (Figure 1).
MATERNAL HEALTH AND ANTENATAL CARE
Research activities to enhance maternal health and antenatal care
(Table 2) can have a profound effect on reducing perinatal and
neonatal morbidity and mortality.13 Overall, pregnancy and delivery
complications are implicated in more than half of newborn
deaths.2,4
Maternal Education and the Status of Women
The relationship between maternal education and perinatal and
neonatal mortality is complex but several studies have demonstrated
reduced rates of infant and child mortality in association with
increased levels of maternal education.14,15 This association is partly
explained by the economic advantages and access to health care
afforded by education. Potential links between maternal education
and reduced perinatal and neonatal mortality also include
appropriate birth spacing and health-seeking behavior, particularly
for prenatal care. Infants born to mothers who do not receive prenatal
care have nearly a 25% increase in neonatal mortality, and the risk of
perinatal mortality is highest in women with very short and very long
intervals between pregnancies.16
Fundamental to enhancing maternal health and capacity is the
promotion of gender equality and improvement of women’s status in
the home and the community. Gender bias may also impact
adversely on the care provided to female newborns, although greater
understanding is needed of contributing factors, its cultural context
and ways to effect change.
Maternal Nutrition
Poor maternal nutrition before and during pregnancy impacts
adversely on pregnancy outcome and infant survival, and can
Table 4 Research to Improve Neonatal Care: Immediate Postpartum Interventions
Birth asphyxia, hypoglycemia, hypothermia
Breastfeeding
Journal of Perinatology 2002; 22:484 – 495
o Determine neonatal encephalopathy rates and outcomes (disabilities) in the community
o Develop and evaluate simple and inexpensive prenatal and obstetric interventions to reduce the risk of
birth asphyxia
o Evaluate the ability of traditional birth attendants and community health workers to identify and
successfully resuscitate asphyxiated neonates using simple methods such as tactile stimulation and clearing
of upper airway secretions using an oral mucus suction trap, and artificial breathing using a
mouth-to-mask, tube-and-mask, or bag-mask technique
o Develop strategies (e.g., behavioral change communication) to reduce the incidence of hypothermia and
hypoglycemia through such interventions as proper drying and swaddling, immediate and exclusive
breastfeeding, recognition and rewarming of hypothermic neonates, cultural adaptation of skin-to-skin contact
o Evaluate the acceptability, safety, and impact of Kangaroo Mother Care in the home, in nurseries with limited
resources, and in critically ill, preterm and very LBW neonates
o Determine underlying factors that influence decisions regarding breastfeeding
o Devise and evaluate culturally sensitive strategies for promoting early, exclusive breastfeeding, particularly
for LBW newborns
487
Moss et al.
Improving Perinatal and Neonatal Outcomes
Table 5 Research Activities to Improve Neonatal Care: Routine Postpartum Interventions
Community-based neonatal care
Skin care
Umbilical cord care
o Determine traditional newborn care practices in the home, and identify sociocultural factors that impact
the care given, including health-care seeking behavior, and attitudes toward and of health care providers
o Develop and evaluate packages of practices for the routine post-partum care of neonates born in the community
(e.g., hygiene, thermal control, promotion of early and exclusive breast feeding, application of prophylactic antibiotics
to the eyes, optimal skin and hygienic cord care, recognition of and care seeking for danger signs)
o Identify and evaluate culturally acceptable, inexpensive neonatal skin care protocols, including the role of bathing in
neonates born to an HIV-infected mother
o Determine whether the presence of vernix is associated with improved thermoregulation and reduced infections
o Evaluate the role of oil massage in improving skin condition and skin barrier function, thermal control and
prevention of infections, and as a source of nutrients such as essential fatty acids
o Devise and evaluate simple, inexpensive, culturally acceptable umbilical cord care protocols at the community level
o Evaluate the impact of antiseptic treatments (e.g., chlorhexidine) to the umbilical cord stump on rates of cord infection
and neonatal sepsis
result in spontaneous abortion, stillbirth, congenital malformation, intrauterine growth retardation (IUGR), preterm delivery
and perinatal and neonatal death.17 Malnutrition also increases
the risk of maternal infection, which further impacts on
perinatal and neonatal morbidity and mortality. Because much
of brain growth occurs during late pregnancy and early infancy,
maternal malnutrition also can impair early childhood
development.18
Improving the nutritional status of pregnant women through
supplemental feeding, dietary fortification, food distribution, and
nutrition counseling has received renewed attention following results
obtained recently in The Gambia. A package of interventions
including locally produced nutritional supplements (i.e., biscuits)
was targeted toward pregnant women, and reduced LBW from 17% to
11% and rates of perinatal and early neonatal mortality by 49% and
40%, respectively.19 Although encouraging, these findings require
confirmation with culturally appropriate interventions in different
settings, and research needs to focus on developing feasible and
sustainable approaches to improving maternal dietary intake during
pregnancy.
Several approaches to reducing maternal anemia, including iron
supplementation and treatment with antihelminths or antimalarials,
also are effective in reducing LBW and perinatal and neonatal
mortality.20 – 22 Severe anemia contributes significantly to maternal
mortality,23 and interventions to reduce it will likely decrease both
maternal and neonatal deaths. Additional data are particularly
needed on whether these interventions will reduce perinatal and
neonatal mortality in less severely anemic pregnant women.
Research in recent years has demonstrated that reductions in
perinatal and neonatal morbidity and mortality may also be
achieved through interventions to reduce maternal micronutrient
deficiencies.24 Maternal supplementation with iodine and folate is
well known to reduce hypothyroidism and neural tube defects,
respectively. Maternal zinc supplementation may also have
beneficial effects on maternal and infant health.25 In Peru, zinc
supplementation during pregnancy enhanced fetal neurological
Table 6 Research to Reduce Morbidity and Mortality From Neonatal Infections
Causes of infections
Recognition and management of serious illness
Antimicrobial regimens for community-based
treatment of neonatal infections
488
o Conduct community-based surveillance in conjunction with laboratory
diagnostic techniques to identify the principal bacterial and viral causes
of neonatal infections, and the risk factors for acquiring these infections
o Develop, evaluate and validate the use of simple clinical algorithms
by caregivers and community health workers to identify neonatal infections
o Evaluate feasible and effective epidemiological and microbiological methods
for determining antibiotic susceptibility patterns of bacteria isolated from
neonates in the community
o Devise and evaluate simple, inexpensive, standard empiric antibiotic regimens
based on regional antimicrobial resistance patterns and WHO
recommendations, and evaluate their impact on pathogen antibiotic
susceptibility patterns
o Evaluate the feasibility and effectiveness of alternative strategies for
treatment of serious neonatal infections, including treatment in the home
and use of oral antibiotics, alone or in combination with parenteral agents
o Evaluate the ability of community-health workers to use treatment
algorithms in the management of acute infectious illness in neonates
o Evaluate the impact of infection control programs, including antibiotic
use policies on rate of antimicrobial resistance in health care facilities
caring for neonates
Journal of Perinatology 2002; 22:484 – 495
Improving Perinatal and Neonatal Outcomes
development and immunity, and reduced the risk of diarrhea and
respiratory tract infections during the first year of life.26 Another
study in Bangladesh found decreased incidence of diarrhea and skin
infections in LBW infants of mothers provided supplemental zinc
during pregnancy.27 Maternal vitamin A supplementation significantly reduced maternal mortality in Nepal by 40%,28 although
there was no impact on infant mortality through age 6 months.29
Vitamin A supplementation early in the newborn period, however, is
under evaluation as a potentially promising approach.30 Several
trials suggest calcium supplementation can lower rates of preterm
delivery and might be effective in preventing pre-eclampsia.18,24
The Cochrane group has concluded that calcium supplements may
prove beneficial in areas with marginal calcium intakes.31 Zinc
and vitamin C are critical for maintaining the integrity of the
amnion,32 and premature rupture of membranes is an important
cause of LBW and perinatal and neonatal mortality. Studies are
needed to assess whether supplementation with these nutrients
prevents premature rupture of membranes in developing countries.
Recently, maternal supplementation with mixtures of multiple
nutrients has received attention as a potentially cost-effective
strategy for improving both maternal and neonatal health and
survival, but little data are yet available on impact. Multivitamin
and mineral supplementation to low-income urban women in the
United States during pregnancy reduced the risk of LBW by 44%, of
preterm delivery before 34 weeks’ gestation by 39%, and IUGR by
43%.33 Further studies in different settings are necessary to confirm
these findings.
Maternal Immunity and Immunization
Immunization of pregnant women to enhance maternal immunity
and the transplacental transfer of antibodies to the fetus is an
effective strategy for the prevention of neonatal tetanus. Despite
recommendations on the use of tetanus toxoid in pregnant women
and women of childbearing age, average worldwide coverage
(measured by the indicator for two doses of tetanus toxoid, ‘‘TT2’’) is
only 65%, and between 300,000 and 400,000 cases of neonatal
tetanus occur each year, resulting in approximately 248,000 deaths
in 1997.34 Increased understanding of sociocultural barriers, leading
to improved access to prenatal care and TT are simple and
inexpensive measures to reduce the substantial number of deaths due
to tetanus.
The high incidence of infectious diseases in young infants in
developing countries suggests that in many cases, maternally derived
antibodies fail to provide adequate protection. For example, infection
with Streptococcus pneumoniae accounts for 10% of deaths
(220,000 deaths per annum) globally in infants less than 90 days of
age.35 The high incidence of invasive pneumococcal disease in early
infancy may reflect maternal-to-fetal transfer of insufficient levels
of, or poorly functioning, anti–capsular pneumococcal antibodies.
Knowledge of the pathophysiology of maternal–fetal transfer of
anti–capsular antibody is critical to developing maternal and
neonatal immunization strategies, as variable amounts of transJournal of Perinatology 2002; 22:484 – 495
Moss et al.
placentally acquired antibody may render neonates susceptible to
disease or interfere with the response to early immunization.
Immunization of pregnant women with either a pneumococcal or
Haemophilus influenzae type b polysaccharide vaccine has been
shown to transfer sufficient antibody to protect the infant from
disease during the neonatal period,36 although efficacy trials of
immunization before or during pregnancy with these vaccines have
not yet been reported.
Maternal Infection
LBW is a principal contributor to neonatal morbidity and mortality.
Up to 70% or more of neonatal deaths in some countries, such as
India and Bangladesh, occur in infants with LBW.37 Approximately
two-thirds of infants in most developing countries with LBW suffer
from IUGR, whereas in developed countries, the majority of infants
with LBW are born prematurely.38 Risk factors for IUGR include low
pre-pregnancy maternal weight and height, low caloric intake
during pregnancy, pre-eclampsia, and maternal infection, especially
malaria.39 Preterm births may be responsible for one-quarter of all
perinatal deaths and one-quarter of all deaths among LBW infants
in the developing world, due to similar causes as for term,
appropriate-for-gestational-age infants.7
Several strategies have the potential to reduce premature and LBW
births in developing countries. Administration of antibiotics to
pregnant women with prolonged rupture of membranes may prolong
the time until labor and lessen the risk of preterm birth.40 Urinary
tract infections and sexually transmitted diseases, including HIV,
syphilis, gonorrhea and chlamydia have been associated with
increased risk of premature birth.41 Several trials have confirmed that
treating asymptomatic bacteriuria and symptomatic urinary tract
infections may reduce the incidence of premature birth.18 Moreover,
the condition of bacterial vaginosis, which involves replacement of
the normal Lactobacillus-predominant flora with other organisms,
occurs in up to 16% of women in the United States, and is associated
with a 40% increased risk of preterm delivery.42 Antibiotic treatment
of bacterial vaginosis in pregnant women in the United States who
previously had a preterm delivery significantly reduced the risk of a
subsequent preterm birth.43 Some studies have found high rates of
bacterial vaginosis in developing countries,44 but data are lacking on
the attributable risk for LBW and the impact of simple treatment
regimens for bacterial vaginosis in developing countries.
Malaria infection causes severe complications during pregnancy
and is a major public health problem in many developing
countries.45 In settings of moderate to high endemicity, malaria
may cause up to 30% of preventable LBW in newborns and account
for 3% to 5% of neonatal mortality.46 In settings of low endemicity,
malaria is associated with an increased risk of spontaneous
abortion and stillbirth. Presumptive treatment of pregnant women
in Kenya with sulfadoxine-pyrimethamine resulted in a protective
efficacy of 85% for maternal parasitemia, 39% for severe anemia,
22% for perinatal deaths and 38% for neonatal mortality.22 In
Malawi, two doses of sulfadoxine-pyrimethamine administered
489
Moss et al.
during the second and third trimesters resulted in reductions in
rates of LBW and preterm infants from 27% to 17% and 31% to
21%, respectively.47 Despite World Health Organization (WHO)
recommendations that antimalarial drugs be given for prevention
of malaria in pregnant women in endemic areas,48 many pregnant
women at risk do not receive appropriate prevention or treatment as
part of prenatal care. Although chloroquine is safe for the treatment
of susceptible Plasmodium falciparum in pregnant women, a
variety of alternate regimens might be considered for the treatment
of pregnant women infected with chloroquine-resistant P.
falciparum. However, the efficacy and effectiveness of these
regimens are not fully understood, and are likely to change under
local drug pressure. Alternative interventions are currently available
(e.g., insecticide-impregnated bed nets in areas of low malaria
transmission)49,50 and others are under development (e.g.,
vaccines, new drugs); their role in malaria prevention in
pregnancy requires evaluation. Potential interactions with other
factors, such as concurrent HIV infection51 or other causes of
maternal anemia, also may affect the efficacy of intervention
strategies and require further evaluation.
Although the devastating impact of HIV infection on health care
and educational systems, particularly in areas of Sub-Saharan
Africa, cannot be underestimated, the impact of maternal HIV
infection on perinatal and neonatal outcomes is not yet well defined.
Maternal HIV infection, however, appears to be associated with
increased risk of spontaneous abortion, stillbirth, preterm birth, and
IUGR.52 Administration of a single dose of nevirapine to mothers at
onset of labor and to their newborns within 72 hours of delivery
reduced mother-to-infant transmission of HIV during the first 14 to
16 weeks of life by almost 50% compared to short-course zidovudine
therapy.53 However, the impact of this regimen on later transmission
associated with breastfeeding remains to be addressed. Because the
cumulative risk of transmission through breastfeeding increases with
time,54 there may be a need for longer courses of antiviral therapy,
perhaps in combination with early weaning. In South Africa,
exclusive breastfeeding was associated with a significantly lower risk
of HIV transmission than mixed feeding, although this relationship
needs to be further evaluated prospectively.55
INTRAPARTUM CARE
Nearly two-thirds of all births in developing countries occur at home,
and in approximately half of deliveries, skilled care is not available.4
Skilled care at delivery has been associated historically with lower
neonatal mortality rates,56 but provision for skilled attendance at
delivery and management of obstetric emergencies is a first-order
operational challenge. Reduction in perinatal and neonatal mortality
as a consequence of improved detection and management of
complicated labor requires a functioning referral system and the
availability of a hierarchy of trained and supervised health care
providers, including home or dispensary care provided by skilled
community-based delivery attendants; trained midwives and/or
490
Improving Perinatal and Neonatal Outcomes
nurses at first-line health facilities; and physicians trained in
emergency obstetric care at district or regional hospitals. Meanwhile,
priority research activities to improve labor and delivery care
(Table 3) include education of pregnant women and their families
in essential elements of clean and safe delivery, and recognition of
maternal and newborn danger signs. Interventions to train, monitor,
and supervise community health care workers in the recognition of
complications of labor and delivery, and in appropriate referral of
women with these problems also are priorities.
IMMEDIATE NEWBORN CARE
Approximately two-thirds of all neonatal mortality occurs in the first
week of life, emphasizing the importance of care, and research to
improve care, given in the early postpartum period (i.e., the first
week of life) (Table 4). In general, however, postpartum visitation
for the newborn is largely unknown in many developing countries.
Moreover, cultural practices often prescribe a period of seclusion for
the mother and newborn, placing further constraints on receiving
and seeking care. Thus, developing a better understanding of home
care practices, leading to effective behavior change communication
strategies to promote healthy behaviors while discouraging harmful
practices, is a priority.
Birth Asphyxia, Hypoglycemia, and Hypothermia
Intrapartum asphyxia is a major cause of perinatal and neonatal
morbidity and mortality. An estimated 4 to 9 million cases of birth
asphyxia occur each year, accounting for 24% to 61% of all perinatal
mortality.57 Proper resuscitation, however, is provided to only an
estimated 1 to 2 million neonates, and an estimated 1.2 million
newborns die annually of birth asphyxia.58 In Zimbabwe, preventable
causes were identified in three-quarters of newborns with birth
asphyxia.59 At delivery, most neonates can be successfully resuscitated
by simple techniques such as tactile stimulation and, in some cases,
clearing of upper airway secretions using a gauze-covered finger or
oral mucus trap.60 The need for mouth-to-mask, tube-and-mask
or bag-mask ventilation is exceptional, and can be accomplished
using room air.61 Extensive efforts to train physicians in neonatal
resuscitation, for example using WHO and American Academy of
Pediatrics-American Heart Association Neonatal Resuscitation
Program materials, are underway in many developing countries, and
are showing encouraging results in influencing behavior.62,63 Few
studies, however, especially community-based studies, have assessed
the risk factors, causes and sequelae of birth asphyxia in developing
countries, and few have evaluated appropriate methods to train
health workers and family members at the community level to
recognize birth asphyxia and provide simple interventions and
support.
Hypothermia and hypoglycemia may be prevented through simple
and inexpensive interventions. Risk factors for hypoglycemia include
birth asphyxia, prematurity and hypothermia.64 Hypothermia is
common in developing countries, affecting more than half of all
Journal of Perinatology 2002; 22:484 – 495
Improving Perinatal and Neonatal Outcomes
newborns in many communities, and is associated with an increased
risk of mortality.65 – 67 Hypothermia also is associated with increased
rates of morbidity, including increased risk of neonatal infections,
coagulation defects, acidosis, delayed fetal-to-newborn circulatory
adjustment, hyaline membrane disease, and brain hemorrhage.68,69
Hypothermia can be prevented by simple measures such as ensuring
a warm environment during delivery; early breastfeeding and skinto-skin contact with the mother; proper bathing, drying and
swaddling; and prompt identification and rewarming of hypothermic
neonates. Basic knowledge and practice of thermal control, however,
generally are inadequate among health care providers and families
in developing countries.70
Kangaroo Mother Care, in essence skin-to-skin contact between
neonate and the mother, is a low-technology, inexpensive measure
that affords significant potential benefit, particularly among
hospitalized LBW neonates, including promotion of breastfeeding
and mother–infant bonding, improved thermal control, faster
growth, lower frequency of illness including some infections, shorter
duration of hospital stay, and stabilization of physiologic and
behavioral functioning.71 Randomized controlled trials have not
been conducted, however, on the impact of Kangaroo Mother Care in
the home on neonatal or infant mortality.
Breastfeeding
A wide variety of benefits of breastfeeding have been well documented,
including reduced risk of hypothermia, hypoglycemia, necrotizing
enterocolitis, omphalitis, acute respiratory infections, diarrhea,
septicemia, and mortality, particularly in the late neonatal period.72
Moreover, replacement of colostrum with pre-lacteal feeds increased
the risk of neonatal mortality in The Gambia,73 and mixed
supplemental feeding was associated with increased rates of
diarrhea,74,75 respiratory illness,76,77 and mother-to-child
transmission of HIV.78 Although breastfeeding is common,
immediate and exclusive breastfeeding, despite its benefits, is not
normal practice in many developing countries, particularly for LBW
newborns.79 Recent community-based behavior change research
shows promise in increasing immediate initiation of breastfeeding
and exclusive breastfeeding to 3 to 6 months of age.80 – 82 Further
emphasis must be placed on programmatic implementation of early,
exclusive breastfeeding through enhanced understanding of barriers,
leading to effective implementation of culturally sensitive behavioral
change communication strategies.83 Further research also is needed
to more precisely define the role of breastfeeding in areas of high HIV
prevalence.84 Formative research from Zambia suggests many women
are reluctant to stop breastfeeding for fear of being stigmatized as HIV
infected.85 A recent pooled analysis of data from six developing
countries showed a six-fold increase in mortality due to infectious
diseases in the first 2 months of life among those not breastfed, and
declining levels of protection with increasing maternal schooling
suggested that it may be difficult, if not impossible to provide
safe breast milk substitutes to children from underprivileged
populations.86
Journal of Perinatology 2002; 22:484 – 495
Moss et al.
POSTPARTUM NEWBORN CARE
Several simple neonatal care practices in the home promoted and/
or instituted by skilled caregivers, traditional birth attendants and/
or community health workers can markedly reduce neonatal
morbidity and mortality.6,87,88 These practices include thermal
control to prevent and treat hypothermia; exclusive breastfeeding;
antibiotic prophylaxis of ophthalmia neonatorum; hygienic skin
and umbilical cord care; surveillance for, special care for and
identification of illness in LBW infants; and recognition and
management of infections. Further operational research is needed
to locally adapt and to understand barriers to implementation of
these interventions, and to make them more widely available
(Table 5).
Skin Care
Epithelial barriers provide first-line defense against invasion of
pathogenic organisms, but are developmentally immature, easily
injured, and often functionally compromised in neonates,
particularly premature infants who account for approximately
one-fourth of all mortality in LBW infants.89 Little is known,
however, about the impact of routine skin care practices on neonatal
health, including bathing, vernix removal, oil massage, the impact of
interventions to enhance skin barrier function, or the role of topical
antiseptic agents on rates of infection.89 – 91
Umbilical Cord Care
Proper umbilical cord care reduces bacterial colonization and
infection of the cord as well as neonatal tetanus and sepsis.92
Several antibacterial agents, including chlorhexidine, triple dye
and povidone-iodine have been shown to reduce umbilical
colonization in hospitalized newborns.89 Little is known, however,
about traditional umbilical cord practices in the community, and
the feasibility, acceptability and efficacy of application of topical
antiseptics by caregivers, birth attendants or community health
workers to prevent and treat umbilical cord infections. In rural
Pakistan, application of ghee (clarified butter) heated with cow
dung to the umbilical stump was associated with neonatal
tetanus, but in cases in which topical antimicrobial agents were
applied to promote wound healing, ghee was not used,
suggesting that promotion of antimicrobial applications as a
substitute for ghee might be an effective strategy in this setting.93
No randomized controlled, community-based data are available
on the impact of antimicrobial applications to the umbilical
cord, compared to either routine care in the community or clean
cord care on rates of umbilical cord infections and neonatal
sepsis.
Neonatal Infections
Community-based studies to identify the agents of neonatal
infections. Infections account for 30% to 50% of all neonatal
deaths in developing countries, with pneumonia, tetanus, sepsis
491
Moss et al.
and diarrhea the most common causes.3,10 Knowledge of the
etiology of infectious diseases in neonates in developing countries
is based almost entirely on studies of hospitalized infants or on
retrospective, verbal autopsy-based surveys in the community,
neither of which may accurately reflect the true burden of disease
in the community. To devise the most effective strategies for
preventing and treating neonatal infections in developing countries
(Table 6), identification of the etiologic agents of neonatal
infections and their antimicrobial susceptibility patterns in the
community must be determined on a regional basis.88 The
principal prospective study identifying the etiologic agents of
community-acquired neonatal infections, based on laboratory
diagnostic testing in conjunction with medical history and clinical
examination, was conducted by the WHO in Ethiopia, The
Gambia, Papua New Guinea, and The Philippines from 1990 to
1993.94 This study, however, relied on evaluation of sick patients
self-referred to health care facilities, did not include neonates who
died at home, and may not have provided a representative sample
of agents of infectious diseases in the community in many
developing countries.
Recognition and management of neonates with potentially
serious illness. To devise simple, inexpensive management
strategies for reducing the morbidity and mortality of neonatal
infections, risk factors, historical information, and clinical signs and
symptoms predictive of serious neonatal infections (pneumonia,
sepsis and meningitis) must be identified for use in first-line health
care facilities and at home by trained caregivers and health care
workers.95
Antimicrobial regimens for treatment of neonatal infections
in the community. Knowledge of the antimicrobial resistance
patterns of common neonatal bacterial pathogens is essential for
planning empiric antimicrobial therapy for the treatment of
neonatal infections. Currently, WHO recommends that acutely
infected neonates less than 2 months of age be treated in a
health care facility capable of administering parenteral antibiotics
(e.g., benzylpenicillin or ampicillin plus an aminoglycoside, such
as gentamicin).96,97 Every attempt should be made to deliver this
standard of care. Hospitalization and parenteral treatment of
neonates is not feasible in many communities, however. Thus,
alternative treatment strategies are needed, including the
feasibility and efficacy of therapy in the home and treatment with
oral antibiotics.
Two studies conducted in India suggest that treatment of
neonatal infection in the home by trained community health
workers can substantially reduce neonatal morbidity and mortality.
In a treatment trial of neonatal pneumonia, village health workers
and traditional birth attendants were trained in safe and hygienic
delivery practices, neonatal care, and to identify neonates with
pneumonia based on a simple set of clinical criteria.98 Neonates in
the intervention area with suspected pneumonia were empirically
492
Improving Perinatal and Neonatal Outcomes
given co-trimoxazole orally for 7 days. The mortality rate among
neonates with pneumonia in the intervention area was decreased by
40% compared to the neonates in the control area. In a second
trial, village health workers were trained to provide health
education to pregnant women, diagnose and manage birth
asphyxia, identify premature and LBW (i.e., high risk) infants,
provide thermal control, encourage breast feeding, administer
vitamin K, treat skin infections, and identify and treat sick
newborns.10 For neonates with suspected sepsis, oral co-trimoxazole
and intramuscular gentamicin were administered in the home. This
package of intervention resulted in an approximately 60% reduction
in neonatal mortality at an estimated cost of US$5.30 per neonate.
Although promising, adaptation of this home-based care model
and confirmation of the impact, feasibility and sustainability in
other settings are needed.
CONCLUSIONS
The number of lives lost in the perinatal and neonatal period
exceeds that of any other period in life of a similar duration.
Moreover, as successes with child survival programs reduce infant
and child mortality rates, the proportion of infant and under-five
deaths that occur in the neonatal period is rising. Thus, in order
to sustain gains in child survival made in recent decades,
attention must be focused on reduction of morbidity and mortality
in the newborn period.
A common misconception persists that neonatal care necessarily
requires highly technical and costly interventions delivered by
specialists. We believe that immediate gains in reducing neonatal
health will come in large measure through implementation of
simple, proven interventions during the antenatal, intrapartum and
postpartum periods on a broader scale; improved understanding of
traditional, home-based practices, and development of effective
behavior change communication strategies to promote healthy
behaviors; improved care of the LBW infant; improved prevention,
recognition and management of neonatal illness, particularly birth
asphyxia and infections at the community level; and integration of
neonatal interventions within safe motherhood and child survival
programs. Much is already known about how to effectively care for
newborn infants, and operational research on how to translate this
knowledge into effective programs; effectiveness trials of promising
interventions; and monitoring of progress are areas of immediate
need. In this review, we have also outlined a number of priority
research activities to advance the state-of-the-art in newborn care.
Effective implementation of newborn care, and innovative research
planned in coordination with policy makers, stakeholders and
program managers which addresses principal causes of morbidity
and mortality and will lead to cost-effective, acceptable and
sustainable interventions, particularly at the community level
(Tables 1–6), may now hold the greatest potential and promise
for improving the survival and health of future generations of
children.
Journal of Perinatology 2002; 22:484 – 495
Improving Perinatal and Neonatal Outcomes
References
1. Black RE, Kelley L, editors. Child Health Research Project. Special Report,
Reducing perinatal and neonatal mortality. Oct 1999. p. 1 – 48.
2. World Health Organization. Mother – baby package: implementing safe
motherhood in countries. Maternal Health and Safe Motherhood Programme.
Geneva: WHO; 1994. ( FHE / MSM / 94.11 ).
3. Stoll BJ. The global impact of neonatal infection. Clin Perinatol 1997;24:
1 – 21.
4. Saving Newborn Lives. State of the World’s Newborns. Washington, DC: Save
the Children Federation - US; 2001. p. 1 – 49.
5. Hyder AA, Morrow RH, Wali S, McGuckin J. Burden of Disease for Neonatal
Mortality in South Asia and Sub - Saharan AfricaWashington, DC: Save the
Children Federation - US; 2001. p. 1 – 93.
6. World Health Organization. Essential newborn care. Report of a technical
working group. Geneva: WHO; 1996. ( WHO / FRH / MSM / 96.13 ).
7. Goldenberg RL, Rouse DJ. Prevention of premature birth. N Engl J Med
1998;339:313 – 20.
8. World Bank. World Development Report: Investing in health. Oxford,
England: Oxford University Press; 1993.
9. World Health Organization 2001 estimates.
10. Bang AT, Bang RA, Baitule SB, Reddy MH, Deshmukh MD. Effect of home based neonatal care and management of sepsis on neonatal mortality: field
trial in rural India. Lancet 1999;354:1955 – 61.
11. Moore SE. Nutrition, immunity and the fetal and infant origins of disease
hypothesis in developing countries. Proc Nutr Soc 1998;57:241 – 7.
12. Marsh DR, Darmstadt GL, Moore J, Daly P, Oot D, Tinker A. Advancing
Newborn Health and Survival: A Conceptual Framework. Washington, DC:
Save the Children Federation - US; 2001. p. 1 – 20.
13. Walsh JA, Measham AR, Feifer CN, Gertler PJ. The impact of maternal health
improvement on perinatal survival: cost - effective alternatives. Int J Health
Plan Manage 1994;9:131 – 49.
14. Victora CG, Huttly SR, Barros FC, Lombardi C, Vaughan JP. Maternal
education in relation to early and late child health outcomes: findings from
a Brazilian cohort study. Soc Sci Med 1992;34:899 – 905.
15. van Ginneken JK, Lob - Levyt J, Gove S. Potential interventions for preventing
pneumonia among young children in developing countries: promoting
maternal education. Trop Med Int Health 1996;1:283 – 94.
16. Harrison KA. The importance of the educated healthy woman in Africa.
Lancet 1997;349:644 – 7.
17. Villar J, Gulmezoglu AM, de Onis M. Nutritional and antimicrobial
interventions to prevent preterm birth: an overview of randomized controlled
trials. Obstet Gynecol Surv 1998;53:575 – 85.
18. Crawford MA, Doyle W, Leaf A, Leighfield M, Ghebremeskel K, Phylactos A.
Nutrition and neurodevelopmental disorders. Nutr Health 1993;9:81 – 97.
19. Ceesay SM, Prentice AM, Cole TJ, et al. Effects on birth weight and perinatal
mortality of maternal dietary supplements in rural Gambia: 5 year
randomised controlled trial. BMJ 1997;315:786 – 90.
20. Preziosi P, Prual A, Galan P, Daouda H, Boureima H, Hercberg S. Effect of
iron supplementation on the iron status of pregnant women: consequences
for newborns. Am J Clin Nutr 1997;66:1178 – 82.
21. de Silva NR, Sirisena JL, Gunasekera DP, Ismail MM, de Silva HJ. Effect of
mebendazole therapy during pregnancy on birth outcomes. Lancet
1999;353:145 – 9.
22. Shulman CE, Dorman EK, Cutts F, et al. Intermittent sulphadoxine –
pyrimethimine to prevent severe anaemia secondary to malaria in pregnancy:
a randomised, placebo controlled trial. Lancet 1999;353:632 – 6.
Journal of Perinatology 2002; 22:484 – 495
Moss et al.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
Rush D. Nutrition and maternal mortality in the developing world. Am J Clin
Nutr 2000;72( 1 Suppl ):212S – 40S.
Ladipo OA. Nutrition in pregnancy: mineral and vitamin supplements. Am J
Clin Nutr 2000;72( Suppl ):280S – 90S.
Caulfield LE, Zavaleta N, Shankar AH, Merialdi M. Potential contribution of
maternal zinc supplementation during pregnancy to maternal and child
survival. Am J Clin Nutr 1998;68( 2 Suppl ):499S – 508S.
Merialdi M, Caulfield LE, Zavaleta N, Figueroa A, DiPietro J. Adding zinc to
prenatal iron and folate supplements improves fetal neurobehavioral
development. Am J Obstet Gynecol 1999;180:483 – 90.
Osendarp SJM, van Raaij JMA, Darmstadt GL, Baqui AH, Hautvast JJGA, Fuchs
GJ. Zinc supplementation during pregnancy reduced morbidity from
diarrheal diseases and impetigo in low - birth - weight infants during the
first six months of life: a randomized, placebo - controlled trial. Lancet
2001;357:1080 – 5.
West KP Jr, Katz J, Khatry SK, et al. Double - blind, cluster randomized trial of
low - dose supplementation with vitamin A or B - carotene on mortality related
to pregnancy in Nepal. BMJ 1999;318:570 – 5.
Katz J, West KP Jr, Khatry SK, et al. Low - dose vitamin A or beta - carotene
supplementation does not reduce early infant mortality: a double - masked,
randomized, controlled community trial in Nepal. Am J Clin Nutr
2000;71:1570 – 6.
Humphrey JH, Agoestina T, Wue L, et al. Impact of neonatal vitamin A
supplementation on infant morbidity and mortality. J Pediatr 1999;128:
489 – 96.
Atallah AN, Hofmeyr GJ, Duley L. Calcium supplementation during
pregnancy for preventing hypertensive disorders and related problems.
Cochrane Database Syst Rev; 2000. CD001059.
Parry S, Strauss JF. Premature rupture of the fetal membranes. N Engl J Med
1998;338:663 – 70.
Scholl TO, Hediger ML, Bendich A, Schall JI, Smith WK, Krueger PM. Use of
multivitamin / mineral prenatal supplements: influence on the outcome of
pregnancy. Am J Epidemiol 1999;146:134 – 41.
World Health Organization. Progress towards the global elimination of
neonatal tetanus, 1990 – 1998. Wkly Epidemiol Rec 1999;74:73 – 80.
World Health Organization. Meeting on Maternal and Neonatal Pneumococcal Immunization: 26 – 27 January 1998. Geneva: WHO; 1998. ( WHO /
VRD / GEN / 98.01 ).
Shahid NS, Steinhoff MC, Hoque SS, Begum T, Thompson C, Siber GR.
Serum, breast milk, and infant antibody after maternal immunisation with
pneumococcal vaccine. Lancet 1995;346:1252 – 7.
Bhave SA. Trends in perinatal and neonatal mortality and morbidity in
India. Indian Pediatr 1989;26:1094 – 9.
de Onis M, Blossner M, Villar J. Levels and patterns of intrauterine growth
retardation in developing countries. Eur J Clin Nutr 1998;52( Suppl 1 ):
S5 – 15.
Kramer MS. Determinants of low birth weight: methodological assessment
and meta - analysis. Bull WHO 1987;65:663 – 737.
Maymon E, Chaim W, Sheiner E, Mazor M. A review of randomized clinical
trials of antibiotic therapy in preterm premature rupture of the membranes.
Arch Gynecol Obstet 1998;261:173 – 81.
Lamont RF. Antibiotics for the prevention of premature birth. N Engl J Med
2000;342:581 – 3.
Hillier SL, Nugent RP, Eschenbach DA, et al. Association between bacterial
vaginosis and preterm delivery of a low - birth - weight infant. The Vaginal
Infections and Prematurity Study Group. N Engl J Med 1995;333:1737 – 42.
493
Moss et al.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
494
Joesoef MR, Schmid GP, Hillier SL. Bacterial vaginosis: review of treatment
options and potential clinical indications for therapy. Clin Infect Dis
1999;28( Suppl 1 ):S57 – 65.
Wawer MJ, Sewankambo NK, Serwadda D, et al. Control of sexually
transmitted diseases for AIDS prevention in Uganda: a randomised
community trial. Lancet 1999;353:525 – 35.
Nahlen BL. Rolling back malaria in pregnancy. N Engl J Med
2000;343:651 – 2.
Steketee RW, Wirima JJ, Slutsker L, Heymann DL, Breman JG. The problem of
malaria and malaria control in pregnancy in sub - Saharan Africa. Am J Trop
Med Hyg 1996;55( 1 Suppl ):2 – 7.
Schultz LJ, Steketee RW, Macheso A, Kazembe P, Chitsulo L, Wirima JJ. The
efficacy of antimalarial regimens containing sulfadoxine - pyrimethamine
and / or chloroquine in preventing peripheral and placental Plasmodium
falciparum infection among pregnant women in Malawi. Am J Trop Med
Hyg 1994;51:515 – 22.
World Health Organization Expert Committee on Malaria. WHO Tech Rep Ser
2000;892( i – v ):1 – 74.
Dolan G, ter - Kuile FO, Jacoutot V, et al. Bed nets for the prevention of malaria
and anaemia in pregnancy. Trans R Soc Trop Med Hyg 1993;87:620 – 6.
D’Alessandro U, Langerock P, Bennett S, Francis N, Cham K, Greenwood BM.
The impact of a national impregnated bed net programme on the outcome
of pregnancy in primigravidae in The Gambia. Trans R Soc Trop Med Hyg
1996;90:487 – 92.
Parise ME, Ayisi JG, Nahlen BL, et al. Efficacy of sulfadoxine - pyrimethamine
for prevention of placental malaria in an area of Kenya with a high
prevalence of malaria and human immunodeficiency virus infection. Am J
Trop Med Hyg 1998;59:813 – 22.
Brocklehurst P, French R. The association between maternal HIV infection
and perinatal outcome: a systematic review of the literature and meta analysis. Br J Obstet Gynaecol 1998;105:836 – 48.
Guay LA, Musoke P, Fleming T, et al. Intrapartum and neonatal single - dose
nevirapine compared with zidovudine for prevention of mother - to - child
transmission of HIV - 1 in Kampala, Uganda: HIVNET 012 randomised trail.
Lancet. 2000;354:795 – 802.
Nduati R, John G, Mborgi - Ngacha D, et al. Effect of breastfeeding and
formula feeding on transmission of HIV - 1: a randomized clinical trial. JAMA
2000;283:1167 – 74.
Coutsoudis A, Pillay K, Spooner E, Kuhn L, Coovadia HM, for the South Africa
Vitamin A Study Group. Influence of infant - feeding patterns on early
mother - to - child transmission of HIV - 1 in Durban, South Africa: a
prospective cohort study. Lancet 1999;354:471 – 6.
World Health Organization. Making Pregnancy Safer. Geneva: WHO; 2000.
( RHR00.6 ).
Ellis M. Birth asphyxia in developing countries: epidemiology, sequellae and
prevention. In: Costello A, Manandhar D, editors. Improving Newborn Health
in Developing Countries. London: Imperial College Press; 2000. p. 233 – 72.
World Health Organization. World Health Report, 1998: Life in the 21st
century — a vision for all. Geneva, Switzerland: WHO; 1998.
Aiken CG. The causes of perinatal mortality in Bulawayo, Zimbabwe. Cent Afr
J Med 1992;38:263 – 81.
Palme - Kilander C. Methods of resuscitation in low - Apgar - score newborn
infants — a national survey. Acta Paediatr 1992;81:739 – 44.
Saugstad OD, Rootwelt T, Aalen O. Resuscitation of asphyxiated newborn
infants with room air or oxygen: an international controlled trial: the Resair
2 study. Pediatrics 1998;102:e1.
Improving Perinatal and Neonatal Outcomes
62.
63.
64.
65.
66.
67.
68.
69.
70.
71.
72.
73.
74.
75.
76.
77.
78.
79.
80.
81.
82.
World Health Organization. Basic Newborn Resuscitation: A Practical Guide.
Geneva: WHO; 1997. ( WHO / RHT / MSM / 98.1 ).
Deorari AK, Paul VK, Singh M, Vidyasagar D, Medical Colleges Network.
Impact of education and training on neonatal resuscitation practices in 14
teaching hospitals in India. Ann Trop Paediatr 2001;21:29 – 33.
Costello AM, Manandhar DS. Perinatal asphyxia in less developed countries.
Arch Dis Child Fetal Neonatal Ed 1994;71:F1 – F3.
Johanson RB, Spencer SA, Rolfe P, Jones P, Malla DS. Effect of post – delivery
care on neonatal body temperature. Acta Paediatr 1992;81:859 – 63.
Tafari N. Hypothermia in the tropics: epidemiologic aspects. In: Sterky G,
Tafari N, Tunell R, editors. Breathing and Warmth at Birth: Judging the
Appropriateness of Technology. Stockholm: Swedish Agency for Research
Cooperation; 1985. p. 53 – 8.
Christensson K, Ransjo - Arvidson AB, Kakoma C, et al. Midwifery care
routines and prevention of heat loss in the newborn: a study in Zambia. J
Trop Pediatr 1988;34:208 – 12.
World Health Organization. Thermal Protection of the Newborn: A Practical
Guide. Geneva: WHO; 1997. ( WHO / RHT / MSM / 97.2 ).
Tunell R. Hypothermia: epidemiology and prevention. In: Costello A,
Manandhar D, editors. Improving Newborn Health in Developing Countries.
London: Imperial College Press; 2000. p. 207 – 20.
Dragovich D, Tamburlini G, Alisjahbana A, et al. Thermal control of the
newborn: knowledge and practice of health professional in seven countries.
Acta Paediatr 1997;86:645 – 50.
Cattaneo A, Davanzo R, Worku B, et al. Kangaroo mother care for low
birthweight infants: a randomized controlled trial in different settings. Acta
Paediatr 1988;87:976 – 85.
Huffman SL, Zehner ER, Victora C. Breastfeeding and Neonatal Mortality.
LINKAGES. Washington, DC: Academy for Educational Development; 1999.
Leach A, McArdle TF, Banya WAS, et al. Neonatal mortality in a rural area of
the Gambia. Ann Trop Paediatr 1999;19:33 – 43.
Raisler J, Alexander C, O’Compo P. Breastfeeding and infant illness: a dose –
response relationship? Am J Public Health 1999;89:25 – 30.
Perera BJC, Ganesan S, Jayarasa J, Ranaweera S. The impact of breastfeeding
practices on respiratory and diarrhoeal disease in infancy: a study from Sri
Lanka. J Trop Pediatr 1999;45:115 – 8.
Cesar JA, Victora CG, Barros FC, Santos IS, Flores JA. Impact of breastfeeding
on admission for pneumonia during postnatal period in Brazil: nested case –
control study. BMJ 1999;318:1316 – 20.
Wilson AC, Forsyth JS, Greene SA, Irvine C, Hau C, Howie PW. Relation of
infant diet to childhood health: seven year follow up of cohort of children in
Dundee infant feeding study. BMJ 1998;316:21 – 5.
Coutsoudis A, Pillay P, Spooner E, Kuhn L, Coovadia HM. Influence of infant
feeding patterns on early mother - to - child transmission of HIV - 1 in Durban,
South Africa: a prospective cohort study. Lancet 1999;354:471 – 6.
Adair LS, Popkin BM. Low birth weight reduces the likelihood of breastfeeding
among Filipino infants. J Nutr 1996;126:103 – 12.
Jakobsen MS, Sodemann M, Molbak K, Alvarenga I, Aaby P. Promoting
breastfeeding through health education at the time of immunizations: a
randomized trial from Guinea Bissau. Acta Paediatr 1999;88:741 – 7.
Morrow AL, Guerrero ML, Shults J, et al. Efficacy of home - based peer
counselling to promote exclusive breastfeeding: a randomised controlled trial.
Lancet 1999;353:1226 – 31.
Haider R, Ashworth A, Kabir I, Huttly SRA. Effect of community - based peer
counselors on exclusive breastfeeding practices in Dhaka, Bangladesh: a
randomized controlled trial. Lancet 2000;356:1643 – 7.
Journal of Perinatology 2002; 22:484 – 495
Improving Perinatal and Neonatal Outcomes
83.
84.
85.
86.
87.
88.
89.
Haider R, Kabir I, Ashworth A. Are breastfeeding promotion messages
influencing mothers in Bangladesh? Results from an urban survey in Dhaka,
Bangladesh. J Trop Pediatr 1999;45:315 – 8.
Coutsoudis A. Promotion of exclusive breastfeeding in the face of the HIV
pandemic. Lancet 2000;356:1620 – 1.
Piwoz EG, Chintu M, Ntombela N, et al. Infant feeding options for HIV +
women: findings and recommendations from formative research in Ndola,
Zambia. Second Conference on Global Strategies for the Prevention of HIV
Transmission from Mothers to Babies, September 1 – 6, 1999. Felicissimo and
Associates, Montreal, Canada.
WHO Collaborative Study Team on the Role of Breastfeeding in the
Prevention of Infant Mortality. Effect of breastfeeding on infant and child
mortality due to infectious diseases in less developed countries: a pooled
analysis. Lancet 2000;355:451 – 5.
Costello A, Manandhar D. Current state of the health of newborn infants in
developing countries. In: Costello A, Manandhar D, editors. Improving
Newborn Health in Developing Countries. London: Imperial College Press;
2000. p. 3 – 14.
Darmstadt GL, Black RE, Santosham M. Research priorities and
postpartum care strategies for the prevention and optimal management
of neonatal infections in less developed countries. Pediatr Infect Dis J
2000;19:739 – 50.
Darmstadt GL, Dinulos JG. Neonatal skin care. Pediatr Clin North Am
2000;47:757 – 82.
Journal of Perinatology 2002; 22:484 – 495
Moss et al.
90.
91.
92.
93.
94.
95.
96.
97.
98.
Hoath SB. The stickiness of newborn skin: bioadhesion and the epidermal
barrier. J Pediatr 1997;131:338 – 40.
Joglekar VM. Barrier properties of vernix caseosa. Arch Dis Child
1980;55:817 – 9.
Garner P, Lai D, Baea M, Edwards K, Heywood P. Avoiding neonatal death:
an intervention study of umbilical cord care. J Trop Pediatr 1994;40:24 – 8.
Bennett J, Macia J, Traverso H, et al. Neonatal tetanus associated with
topical umbilical ghee: covert role of cow dung. Int J Epidemiol
1999;28:1172 – 5.
WHO Young Infants Study Group. Conclusions from the WHO multicenter
study of serious infections in young infants. Pediatr Infect Dis J
1999;18:S32 – 4.
World Health Organization. Clinical signs and etiological agents of
pneumonia, sepsis, and meningitis in young infants: report of a meeting
November 21 to 24. Geneva: WHO; 1989.
World Health Organization. United Children’s Fund. Joint WHO / UNICEF
Statement on Early Immunization for HIV - Infected Children. Global
Programme on AIDS and Expanded Programme on Immunization; 1989.
World Health Organization. Acute Respiratory Infections in Children: Case
Management in Hospitals in Developing Countries. Geneva: WHO; 1990.
( WHO / ARI / 90.5 ).
Bang AT, Bang RA, Morankar VP, Sontakke PG, Solanki JM. Pneumonia in
neonates: can it be managed in the community? Arch Dis Child 1993;68:
550 – 6.
495