NICHD Infant Mortality Research Information

NICHD’s research efforts related to infant mortality are aimed at understanding the causes of and contributors to infant mortality, preventing or reducing the most common causes of infant mortality, and treating life-threatening conditions in pregnant mothers and infants.

Major areas of NICHD research support relevant to infant mortality include preterm birth and birth outcomes, congenital anomalies, Sudden Infant Death Syndrome (SIDS), pregnancy complications, fetal development, birth processes, infections, genetic and metabolic disorders, and newborn screening, to name a few.

NICHD research goals on infant mortality include:

• Understanding the factors affecting the processes of labor and birth, especially as related to preterm birth and its prevention
• Building a comprehensive understanding of typical and atypical in utero development, including genetic, epigenetic, physiologic, metabolic, endocrinologic, nutritional, and pharmacologic regulation of fetal and placental growth
• Cataloging and identifying nutritional, environmental, and genetic factors that mediate infant health
• Understanding the etiology, pathophysiology, therapy, and follow-up of conditions that occur during the perinatal and neonatal period, including congenital anomalies, birth asphyxia, sequelae of prematurity and low birth weight, adaptation to extrauterine life, injury, and hyperbilirubinemia
• Understanding the physiologic, environmental, and medical factors that influence the course and outcome of pregnancy
• Understanding the mechanisms of SIDS, identifying infants at risk, and developing preventative measures
• Gaining a better understanding of the processes of infection in infants, the consequences of treatment in infants, and the most effective preventative measures
• Determining the demographic and epidemiologic factors that are related to infant mortality and contributors to infant mortality
• Developing and evaluating technologies and methods related to newborn screening

Through its intramural and extramural organizational units, NICHD conducts and supports a broad range of research projects on the causes of and contributors to infant mortality. Short descriptions of this research are included below.

• Institute Activities and Advances
• Other Activities and Advances

Institute Activities and Advances

For more than 50 years, NICHD's research has explored infant mortality. As research helps reduce or eliminate one cause, NICHD scientists turn their attention to another cause in the hopes that one day, it, too, can be reduced or eliminated as a cause of infant mortality. Some NICHD efforts include the following.

• Congenital Anomalies and Genetic Conditions
• Preterm Birth
• Sudden Infant Death Syndrome (SIDS)
• Infections
• Other Causes of and Contributors to Infant Mortality

Research on Congenital Anomalies and Genetic Conditions

Congenital anomalies are the leading cause of infant mortality in the United States and have been a primary focus of NICHD research since the Institute was founded. Today, Institute organizational units not only focus on fatal congenital anomalies, but also study congenital anomalies and genetic conditions associated with a range of disabilities in an effort to improve the quality of life for those living with these conditions and their families.

For example, the Developmental Biology and Congenital Anomalies Branch (DBCAB) supports basic and clinical research on typical and atypical development that relates to the causes and prevention of structural congenital anomalies, including congenital diaphragmatic hernia and neural tube defects. DBCAB also supports research on the congenital anomalies associated with many syndromic conditions that can reduce the likelihood that an infant will reach 1 year of age.

The Intellectual and Developmental Disabilities Branch (IDDB) supports the Urea Cycle Disorders Consortium and projects on other metabolic conditions to understand these disorders of metabolism, which can be fatal if not detected and treated.

The Division of Population Health Research (DiPHR) also conducts research on congenital anomalies from a population standpoint through its Epidemiology Branch. The Branch studies risk factors for neural tube defects and other congenital anomalies, as well as the effects of assisted reproductive technology on birth outcomes and other topics. Its research targets both nutritional factors that might reduce the risk of congenital anomalies and genetic variants. By studying these variants, researchers aim to identify mechanisms that contribute to congenital anomalies and explore strategies for preventing them.

Within the Division of Intramural Research, several programs and labs study conditions associated with infant mortality or shortened lifespan. For instance, the Bone and Extracellular Matrix Branch studies osteogenesis imperfecta, sometimes called brittle bone disease, which includes variants that are fatal during infancy. The Section on Developmental Genetics studies a group of diseases called neuronal ceroid lipofuscinoses, which also include variants that are fatal shortly after birth.

Key to reducing infant mortality from congenital anomalies and genetic disorders is early detection and treatment. In some cases, detection and treatment can prevent a condition from becoming fatal, while in other cases, they can improve outcomes and overall health. The IDDB supports a large portfolio of research on prenatal diagnosis and newborn screening. In addition, the intramural Program in Perinatal Research and Obstetrics (PPRO) studies prenatal diagnosis of congenital anomalies, particularly congenital heart disease.

Research on Preterm Birth

NICHD supports and conducts research not only on ways to prevent preterm delivery, but also on ways to improve survival and outcomes for infants born preterm.

The Pregnancy and Perinatology Branch (PPB) supports research to understand preterm birth, prevent it, and improve outcomes for infants born preterm. Much of the PPB's support for research on preterm birth comes through the Maternal-Fetal Medicine Units (MFMU) Network. For instance, one ongoing trial conducted through this collaborative research network examines whether antenatal steroids can reduce the need for respiratory support to the infant after a late preterm birth. Besides the MFMU Network, researchers in the PPB-funded Neonatal Research Network (NRN) also carry out trials relevant to preterm birth. The NRN is a collaborative network of neonatal intensive care units across the United States whose current trials study common causes of neonatal morbidity and mortality. Examples of recent NRN findings include:

• The long-term benefits of hypothermia treatment for intrapartum asphyxia (PMID: 22646631)
• The ideal oxygen-saturation targets in extremely preterm infants (PMID: 20472937)
• The benefits of prenatal steroids in improving preterm infants' survival (PMID: 22147379)
• The particular mortality risks of extremely low birth weight triplets (PMID: 21357334)

Outside of the PPB, PPRO scientists have made major contributions to our understanding of the mechanisms of disease in preterm labor and delivery. For example, a 2011 study carried out by PPRO scientists and their collaborators found that administration of a vaginal progesterone gel reduced the rate of preterm birth before the 33rd week of pregnancy by 45% among women with a short cervix, a known risk factor for preterm labor. The treated women's newborns were also less likely to develop respiratory distress syndrome. (PMID: 21472815)

Besides preterm birth, NICHD-supported research has also documented the risks associated with birth during the early term period. In fact, PPB-supported research has found that these births carry significant risks of infant mortality. Researchers in the MFMU Network found that infants delivered by a repeat elective cesarean section at or after 37 weeks, and before 39 weeks, are at significantly increased risk of suffering complications similar to those of infants born preterm, such as breathing problems and sepsis. The study findings continue to support recommendations that clinicians avoid elective delivery before 39 weeks of pregnancy. (PMID: 19129525)

Similarly, other PPB-supported researchers reviewed linked birth–death records compiled by the Centers for Disease Control and Prevention from more than 46 million infants born in the United States between 1995 and 2006. They found that between 1995 and 2006, infants born at 37 weeks were twice as likely to die before their first birthday as those born at 40 weeks. Common causes of death included congenital anomalies; Sudden Infant Death Syndrome (SIDS); lack of oxygen, either in the womb or during birth; and accidents. They also found that although the infant mortality rate for infants born during the entire term period (then defined as 37 to 40 completed weeks of gestation) fell over this time period, there were large differences in the decline in the infant death rate between racial and ethnic groups during the early term period. (PMID: 21606738)

For more information on NICHD research on preterm labor and birth, visit the Preterm Labor and Birth: NICHD Research Information page.

Research on Sudden Infant Death Syndrome (SIDS)

NICHD has been a leader in SIDS research for decades. NICHD has been the primary federal resource for research on SIDS since the passage of the SIDS Act of 1974.

The Institute's efforts include studies on the causes and mechanisms of SIDS and research on the incidence and prevalence of SIDS, especially among certain portions of the U.S. population. NICHD also conducts outreach designed to educate parents and caregivers about ways to reduce SIDS risk, especially among those populations with a higher incidence of SIDS. For additional information about the history of NICHD's SIDS research and activities in risk reduction, visit Safe to Sleep^®: Key Moments in Campaign History.

Two major, PPB-funded SIDS studies that have shaped ongoing outreach and risk-reduction efforts are the National Infant Sleep Position (NISP) Study and the Collaborative Home Infant Monitoring Evaluation (CHIME). Both studies have completed data collection, but their datasets are available to researchers interested in conducting their own analyses. These datasets continue to yield important results, including a recent finding related to bed sharing.

In addition, several PPB-funded studies have linked SIDS to abnormalities in the serotonin system of the brainstem, which controls breathing and heart function during sleep.

Research on SIDS and its mechanisms has helped to inform the NICHD-led Safe to Sleep^® campaign (formerly Back to Sleep), which educates parents, caregivers, and healthcare providers about ways to reduce the risk of SIDS and other sleep-related causes of infant death. The messages communicated through the Safe to Sleep^® campaign are based on the recommendations from the American Academy of Pediatrics Task Force on SIDS, which reviews available research evidence on SIDS to compile its recommendations. Much of the evidence used by the Task Force resulted from NICHD-supported research.

Research on Infection

Maternal and pediatric infections that can cause infant death are also a focus of NICHD research support. Globally, infection is one of the principal causes of infant mortality. Researchers supported by the PPB recently reported that very low birth weight (VLBW) infants infected with methicillin-susceptible Staphylococcus aureus (MSSA) had similar morbidity and mortality rates to VLBW infants infected with methicillin-resistant Staphylococcus aureus (MRSA). These study findings suggest that clinicians may consider applying prevention and treatment approaches currently used for MRSA to MSSA among VLBW infants to improve the chances for survival and reduce complications. (PMID: 22412036)

Maternal and Pediatric Infectious Disease Branch (MPIDB)–supported research focuses primarily on the epidemiology, diagnosis, clinical manifestations, pathogenesis, transmission, treatment, and prevention of HIV, as well as on other infections and complications. The MPIDB has played a principal role in the development of an antiretroviral regimen that significantly lowers the risk of HIV transmission from mother to infant, and, thus, in preventing a large number of infant deaths from HIV. MPIDB-supported research continues to work on lowering the rate of mother-to-child transmission of HIV.

A study conducted by the MPIDB-funded International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Network recently found that treating the newborns of HIV-positive women with a particular multi-drug cocktail halves newborns' risk of contracting HIV (in this study, the women were not diagnosed in time to receive more effective, prenatal antiretrovirals; PMID: 22716975). MPIDB-supported research also studies the safety of these drugs for infants; for example, the MPIDB-funded Pediatric HIV/AIDS Cohort Study (PHACS) found recently that infants' size is not affected by their mothers' use of an anti-HIV drug during pregnancy (PMID: 22382151). Read more about NICHD's support for HIV-related research relevant to infant mortality at the HIV/AIDS: NICHD Research Information page.

In addition, the MPIDB funds research on malaria and other infectious diseases. For example, a large MPIDB-funded project in Uganda is evaluating regimens to prevent malaria among pregnant women and their children. Findings include confirmation of a preventive treatment for the very young that can be used year-round and a combination of anti-HIV medications that can help reduce malaria recurrence among HIV-positive infants. Infants are at greatest risk of severe malaria and death. (PMID: 23190222, PMID: 25093754)

Research on Other Causes and Contributors to Infant Mortality

The Population Dynamics Branch (PDB) supports research, research training, and data collection and archiving related to demographic and economic analysis of infant mortality, including methods of estimating infant mortality at the population level and examination of the causes and consequences of infant mortality.

• Branch-supported research has examined infant mortality rates within the context of air quality and environment. Several projects within this vein compare infant mortality rates before and after major regulatory changes, such as the Clean Air Act of 1970, showing reductions in infant mortality rates at the population level (National Bureau of Economic Research Working Papers 10053 and 7442 , and PMID: 19328569).
• Branch-supported research also evaluates the socioeconomic, demographic, and other factors that influence infant mortality rates and possible causes of or contributors to disparities in those rates in the United States and internationally. Poverty, violence, access to facilities and providers, maternal education level and age, rural versus urban community setting, and family structure are some of the factors related to infant mortality that PDB-supported studies address (PMIDs: 20444839, 23592326, 20093277, 23653129, 23073749, and 23055238).
• Also of interest to the Branch are factors that indirectly affect infant mortality rates. For example, improving consistent use of birth control increases the intrapartum period, which is associated with decreased infant mortality rates. Similarly, delaying first sex increases maternal age at delivery, which is also associated with reduced infant mortality. Studies on these types of issues are also important to the overall Branch portfolio on infant mortality.

The Pediatric Growth and Nutrition Branch (PGNB) supports research related to nutritional factors that affect infant mortality. Of particular relevance is the Branch's interest in studies of the complex nutritional relationships between the mother and her fetus, the placental transfer of nutrients, and the role of nutrition in infant development. This work includes projects focused in the United States and in resource-poor areas, where malnutrition is a major contributor to infant mortality. As a complement to research on nutrition, the PGNB also supports basic and clinical studies on the typical development of the infant gastrointestinal system and digestive function, in particular as it relates to necrotizing enterocolitis.

NICHD's Pediatric Trauma and Critical Illness Branch supports studies relevant to prevention, interventions, and treatments for critical illness and injuries in children, including infants. Its work encompasses clinical research on mortality due to severe infections in children and also includes studies of injuries due to car crashes, burns, drowning, poisoning, falls, suffocation, and child maltreatment, which are major causes of infant mortality in the United States (PMID: 19794321).

In addition to its work on congenital anomalies mentioned previously, the DiPHR Epidemiology Branch also studies other aspects of infant mortality. For example, the Consortium on Safe Labor (CSL) project, primarily a study on labor progression and timing of Cesarean delivery, also studies how maternal demographics and pregnancy complications affect the risk of infant mortality. The Air Quality and Reproductive Health study uses the CSL's data to look at how birth outcomes, including preterm birth, are related to maternal exposure to air pollution during pregnancy. The Branch's Fetal Growth Study, a large-scale observational epidemiology study of about 3,000 pregnant women, aims to determine optimal fetal growth rates and improved fetal growth estimation methodology. Findings from this study could help identify risk factors for adverse fetal growth outcomes that may further reduce infant mortality rates.

The Global Network for Women's and Children's Health Research is a partnership between NICHD and other organizations, including the Bill & Melinda Gates Foundation, that is committed to improving maternal and infant health outcomes and building health research capacity in resource-poor settings by testing cost-effective, sustainable interventions. One project the Global Network is involved with is Helping Babies Breathe , an inexpensive instructional program for birth attendants in resource-limited settings that teaches basic newborn care principles.

Other Activities and Advances

• As mentioned above, NICHD and several collaborators launched the Safe to Sleep^® Campaign (formerly the Back to Sleep campaign) to raise awareness about SIDS and to educate parents, caregivers, and healthcare providers on ways to reduce the risk of SIDS and other sleep-related causes of infant death. Since the campaign started in 1994, the U.S. SIDS rate has declined by 50%, and the percentage of infants placed on their backs to sleep has more than tripled.
• Research conducted by the PPB-funded MFMU Network is designed to answer clinical questions in maternal fetal medicine and obstetrics, particularly with respect to the continuing problem of preterm birth.
• The NRN is a collaborative network of neonatal intensive care units across the United States, supported by the PPB, whose current trials study common causes of neonatal morbidity and mortality.
• The mission of the Congenital Anomalies Initiative, supported in part by DBCAB, is to capitalize on genomic and other biomedical discoveries to further understanding of the mechanisms responsible for structural congenital anomalies, which affect almost 4% of all live births in the United States each year.
• The IMPAACT Network, funded in part by the MPIDB, is a cooperative group of institutions, investigators, and other collaborators focused on evaluating potential therapies for HIV infection and its related symptoms in infants, children, adolescents, and pregnant women, including clinical trials of HIV/AIDS interventions for and prevention of mother-to-child transmission.
• NICHD Domestic and International Pediatric and Maternal HIV Clinical Studies Network (NICHD Network), supported by the MPIDB, conducts trials related to preventing and treating HIV infection and its complications in newborns, infants, children, adolescents, and pregnant women.
• NICHD participates in the Federal Interagency Forum on Child and Family Statistics, which fosters coordination, collaboration, and integration of federal efforts to collect and report data on children and families. Each year, the forum releases a report, America's Children: Key National Indicators of Well-Being, which presents key indicators of children's wellbeing in seven domains: family and social environment, economic circumstances, healthcare, physical environment and safety, behavior, education, and health. Read more about the 2013 America's Children report.