Lack of success in achieving considerable reductions in neonatal mortality is a contributory factor in failing to achieve Millennium Development Goal 4.2.6 million neonates still die each year, with preterm birth and infections the two leading causes. Maternal infections and environmental and infant factors influence acquisition of viral and bacterial infections in the perinatal and neonatal period. Scaling up evidence-based interventions addressing maternal risk factors and underlying causes could reduce neonatal infections by 84%. The emergence of new infections and increasing antimicrobial resistance present public health challenges that must be addressed to achieve substantial reductions in neonatal mortality.
Key points
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Globally, 2.6 million neonates die each year, with preterm birth, infections, and intrapartum-related conditions being the leading causes.
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Maternal, environmental, and infant factors are closely linked to neonatal health and influence acquisition of infection in the perinatal and neonatal period.
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Evidence-based preventive and therapeutic interventions have been identified that address risk factors and underlying causes of neonatal infections.
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The emergence of new infections, such as Zika, and increasing antimicrobial resistance present challenges that must be addressed to achieve substantial reductions in neonatal mortality.
Burden and epidemiology
Significant progress has been made toward reducing child mortality in low- and middle-income countries (LMIC). Younger-than-5 deaths have decreased from 12.7 million in 1990 to 5.8 million in 2015, of which 2.6 million were neonates. In spite of a notable reduction in younger-than-5 mortality, the decrease in neonatal mortality has been unsatisfactory. Forty-five percent of younger-than-5 mortality now occurs in the first month of life. In addition to 2.6 million newborn deaths, there are an estimated additional 2.6 million still births, of which an estimated 12% are attributable to fetal infections.
In 2015, the world transitioned from Millennium Development Goals to Sustainable Development Goals (SDGs). Along with intrapartum causes and preterm birth complications, infections are a major direct cause of neonatal deaths. Preventing and managing neonatal infections are crucial to achieve subgoal 3.2 of SDGs, which aims to end preventable deaths of newborns and children younger than 5 years by 2030.
This article addresses neonatal infections that are primarily acquired in the perinatal period (late pregnancy, intrapartum, and postnatal period) ( Table 1 ) and manifest clinically in the perinatal and neonatal period. Maternal infections acquired by the neonate early in pregnancy, such as rubella, syphilis, and toxoplasmosis, are not considered.
| Early Pregnancy | Midpregnancy | Late Pregnancy | Intrapartum | Postnatal | |
|---|---|---|---|---|---|
| Rubella | + | — | — | — | — |
| Toxoplasmosis | + | + | — | — | — |
| Syphilis | — | + | + | — | — |
| Cytomegalovirus | + | + | + | + | + |
| Zika virus | ++ | + | + | — | — |
| Chickenpox | — | — | + | + | + |
| Herpes simplex virus | — | — | — | + | — |
| HIV | — | — | + | ++ | + |
| Hepatitis B | — | — | — | + | — |
| Group B streptococcus | — | — | — | + | — |
Conventionally, the perinatal period begins at 22 completed weeks of gestation and ends 7 days after birth. The neonatal period represents the first 28 days of life. The relative lack of structural barriers and an immature immune system put neonates at greater risk of infection and mortality. Preterm birth (36%), infections (23%), and intrapartum-related conditions, such as birth asphyxia (23%), are responsible for the greatest number of neonatal deaths ( Fig. 1 ). However, in the late neonatal period (>7 days), 48% of deaths are attributable to infections, the leading cause of death in this period (see Fig. 1 ).
Burden and epidemiology
Significant progress has been made toward reducing child mortality in low- and middle-income countries (LMIC). Younger-than-5 deaths have decreased from 12.7 million in 1990 to 5.8 million in 2015, of which 2.6 million were neonates. In spite of a notable reduction in younger-than-5 mortality, the decrease in neonatal mortality has been unsatisfactory. Forty-five percent of younger-than-5 mortality now occurs in the first month of life. In addition to 2.6 million newborn deaths, there are an estimated additional 2.6 million still births, of which an estimated 12% are attributable to fetal infections.
In 2015, the world transitioned from Millennium Development Goals to Sustainable Development Goals (SDGs). Along with intrapartum causes and preterm birth complications, infections are a major direct cause of neonatal deaths. Preventing and managing neonatal infections are crucial to achieve subgoal 3.2 of SDGs, which aims to end preventable deaths of newborns and children younger than 5 years by 2030.
This article addresses neonatal infections that are primarily acquired in the perinatal period (late pregnancy, intrapartum, and postnatal period) ( Table 1 ) and manifest clinically in the perinatal and neonatal period. Maternal infections acquired by the neonate early in pregnancy, such as rubella, syphilis, and toxoplasmosis, are not considered.
| Early Pregnancy | Midpregnancy | Late Pregnancy | Intrapartum | Postnatal | |
|---|---|---|---|---|---|
| Rubella | + | — | — | — | — |
| Toxoplasmosis | + | + | — | — | — |
| Syphilis | — | + | + | — | — |
| Cytomegalovirus | + | + | + | + | + |
| Zika virus | ++ | + | + | — | — |
| Chickenpox | — | — | + | + | + |
| Herpes simplex virus | — | — | — | + | — |
| HIV | — | — | + | ++ | + |
| Hepatitis B | — | — | — | + | — |
| Group B streptococcus | — | — | — | + | — |
Conventionally, the perinatal period begins at 22 completed weeks of gestation and ends 7 days after birth. The neonatal period represents the first 28 days of life. The relative lack of structural barriers and an immature immune system put neonates at greater risk of infection and mortality. Preterm birth (36%), infections (23%), and intrapartum-related conditions, such as birth asphyxia (23%), are responsible for the greatest number of neonatal deaths ( Fig. 1 ). However, in the late neonatal period (>7 days), 48% of deaths are attributable to infections, the leading cause of death in this period (see Fig. 1 ).
Risk factors for neonatal and perinatal infections
Maternal Health and Infections
Poor maternal health and inadequate access to health care are determinants for neonatal outcomes.
Maternal infections
Infections during pregnancy are associated with spontaneous abortion, stillbirth, preterm delivery, and low birth weight (LBW). Moreover, some infections are transmitted to the fetus, resulting in neonatal morbidity or fetal loss. Transmission can occur hematogenously from mother to baby or as an ascending infection via the uterine cervix. Early onset sepsis (EOS) and most infections in the perinatal period are associated with maternal factors. A neonate’s immature immune system depends on maternal antibodies that cross transplacentally. However, maternal infections occurring close to term may not generate sufficient immune protection to pass to the fetus.
Cytomegalovirus (CMV), rubella virus, varicella-zoster virus, hepatitis B and C, and Zika virus can transmit to the fetus through the blood. Important organisms acquired by the ascending route are group B streptococcus (GBS), herpes simplex virus (HSV), and Escherichia coli . Chances of acquiring certain infections intrapartum increase with vaginal deliveries, and clinicians may opt for cesarean deliveries in such cases.
Premature rupture of membranes
Premature rupture of membranes (PROM) is when the amniotic sac ruptures more than 1 hour before the onset of labor. Ruptured membranes increase the risk of maternal infection, preterm birth, and EOS. Some estimates show that nearly 10% of neonates develop infection following PROM, whereas others report lower (4%) or higher (33%) rates. Risk is directly proportional to the time membranes rupture before delivery: the earlier the membranes rupture, the higher the risk of infection.
Organisms most commonly associated with EOS secondary to PROM include GBS. Studies in low-income settings report predominantly gram-negative organisms. Gram-positive species, such as GBS and Staphylococcus aureus , though detected, were not as common as in developed settings.
Intra-amniotic infection
Aside from other causes, a mother can develop fever during labor due to chorioamnionitis or intra-amniotic infection (IAI). IAI is associated with adverse pregnancy and neonatal outcomes, including stillbirth, preterm birth, and infections. Risk of neonatal septicemia in these cases is estimated at 5% to 15%. Neonatal outcomes are influenced by not only causative organisms but also birth weight and timing of antibiotic therapy.
Other risk factors for acquiring infection
Environmental Factors
Late-onset neonatal infections are commonly associated with nosocomial or community-related environment factors.
Hospital-acquired infections
Hospitals, especially nurseries and intensive care units, are high-risk environments for acquiring infections. Infants are in frequent contact with health care workers, leading to spread of pathogenic organisms, especially multidrug-resistant types. With increasing facility-based deliveries in LMIC, the risk of hospital-acquired infections has also increased. Some studies from high-income countries (HIC) report that more than 20% of critically ill newborns who survive greater than 2 days acquire a nosocomial infection. Major pathways for nosocomial spread of organisms in neonate are summarized in Box 1 .
Excessive vaginal examinations of mother
Lack of aseptic delivery
Inadequate hand hygiene and glove use
Failures in sterilization/disinfection or handling/storage of multiuser equipment, instruments, and supplies leading to contamination
Inadequate environmental cleaning and disinfection
Overuse of invasive devices
Reuse of disposable supplies without safe disinfection/sterilization procedures
Failures in isolation procedures/inadequate isolation facilities for babies infected with antibiotic-resistant or highly transmissible pathogens
Unhygienic bathing and skin care
Absence of mother-baby cohorting
Inappropriate and prolonged use of antibiotics
Lack of knowledge, training, and competency regarding infection control practice
Overcrowded and understaffed labor and delivery rooms
Community-acquired infections
Because of social and economic factors, many births, especially in rural areas of LMIC, take place at home. Risk of community-acquired infections in such home-delivered infants is higher. Other factors, such as lack of skilled birth attendants, unhygienic delivery practices, and unsterile cord cutting, further increase the risk of infections. In other settings, newborns discharged from the hospital can also acquire infections from household or community contact.
Infant Factors
Compared with other infants, those who have bacterial sepsis frequently possess distinctive risk factors, such as preterm birth, LBW, PROM, maternal IAI, and birth asphyxia.
The 20 million LBW babies born globally each year are either preterm or small for gestational age (or both). Vulnerability to hypothermia, immature immune systems, and an underdeveloped skin barrier predispose them to infections. Preterm birth is considered the chief risk factor for acquiring neonatal infections immediately before, during, or after delivery. Preterm birth complications are now the number one killer of children younger than 5 years.
Evidence indicates a low Apgar score at birth is associated with increased risk of infection-attributable neonatal mortality. Fetal hypoxia and hypothermia can impair immune mechanisms as well as predispose to birth asphyxia, a risk factor for infections.
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