Groundbreaking global studies on preterm birth and disability carried out by almost 50 researchers at 35 institutions and launched in association with World Prematurity Day finds baby boys are at a higher risk of death and disability due to preterm birth than baby girls. These disabilities range from learning problems and blindness to deafness and motor problems, including cerebral palsy.
The six major papers in Pediatric Research, published by Nature, show that boys are 14 percent more likely to be born preterm than girls.
"Baby boys have a higher likelihood of infections, jaundice, birth complications, and congenital conditions but the biggest risk for baby boys is due to preterm birth. For two babies born at the same degree of prematurity, a boy will have a higher risk of death and disability compared to a girl. Even in the womb, girls mature more rapidly than boys, which provides an advantage, because the lungs and other organs are more developed," says Professor Joy Lawn, M.D., PhD, a neonatologist and epidemiologist at the London School of Hygiene & Tropical Medicine (LSHTM) and team leader of the new research.
"One partial explanation for more preterm births among boys is that women pregnant with a boy are more likely to have placental problems, pre-eclampsia, and high blood pressure, all associated with preterm births."
However, after the first month of life, in some societies where girls receive less nutrition and medical care, the girls are more likely to die than boys, despite this biological survival advantage for girls.
Preterm birth-tiny babies, but a big global health problem
These are just a few of the new and confirmed findings on the death and disability of premature infants, a massive global health problem. Of the 15.1 million born too soon, some 1 million die due to prematurity, accounting for one-third of the world's 2.9 million newborn deaths, a huge impact for families, societies and economies in both high and low-income countries. Newborn conditions, especially premature birth, are responsible for almost 10 percent of the global burden of disease for all ages and all countries.
In the last three years, some $25 billion in new funds have been spent on maternal, newborn and child health, according to a 2013 report by The Partnership for Maternal, Newborn & Child Health (PMNCH). Low- and middle-income countries, as well as private foundations, non-government organizations, and the private sector have raised about 40 percent of this. However less than 1 percent is specifically directed at premature or newborn care.
Improving prematurity prevention and care is a key part of a wider drive to reduce newborn deaths and improve quality care at the time of birth, when risks are highest for both women and their babies.
"Three quarters of the 1 million babies who die each year from complications associated with prematurity could have been saved with cost-effective interventions, even without intensive care facilities," says UN Secretary General Ban Ki-moon, whose Every Woman Every Child movement has provided major worldwide impetus for women and children. "World Prematurity Day is an opportunity to mobilize partners to improve the care available to all women and children."
More than 50 partners, convened by UNICEF and WHO, are developing a major new global plan to improve newborn health. The plan will focus on improving the quality of care for women and children during labor and delivery, as well as the critical few days before and after birth, when risks are highest. The Every Newborn plan will be launched during the World Health Assembly, in May 2014.
Outcomes for 15 million preterm babies
The studies, funded through the Bill & Melinda Gates Foundation, present the first systematic estimates of disability in preterm babies. Worldwide, of the 15.1 million preterm babies, 13 million survived beyond the first month of life. Of the survivors, 345,000 (2.7 percent) had moderate or severe impairment and 567,000 (4.4 percent) had mild impairment.
Risks for disabilities or impairments are affected by where a preterm baby is born:
In upper income countries, more than 80 percent of babies born under 37 weeks survive and thrive. Risk of death and disability is greatest for those born at less than 28 weeks. Infants who survive preterm birth face lifelong physical and intellectual disabilities. Even babies born just a few days early are more likely to be re-hospitalized and have learning and behavioral challenges.
In middle-income countries, great progress has been made in reducing deaths. For example, Turkey has more than halved preterm and newborn deaths in the last two decades. But, in middle-income countries, the risk of disability for babies born at 28-32 weeks is double that of high-income countries. For these countries, learning from past experiences is essential to improve quality of care.
In low-income countries, preterm babies are 10 times more likely to die than those in high-income countries. Without basic care, few survive even with severe disabilities. Death is twice as likely as disability in these countries.
Eye problems for premature babies
Preterm babies are vulnerable to eye complications. Of the estimated 185,000 newborns affected by retinopathy of prematurity, an abnormal blood vessel development in the retina of the eye in some premature infants, about 20,000 suffered moderate to severe disabilities, including blindness, and another 12,000 had other visual problems.
"There is a risk of repeating the epidemic of blindness in preterm survivors seen in the US and Europe in the 1940s and 1950s," says Professor Clare Gilbert, a physician at LSHTM and world expert on retinopathy of prematurity. "Much can be done to reduce blindness from retinopathy of prematurity by improving quality of neonatal care, including safer use of oxygen, and by detecting retinopathy early. Preterm infants must be followed up and their eyes must be checked."
Important conditions causing deaths and disability for full term newborns
In addition to preterm birth, the six papers published in Pediatric Research present analyses regarding other newborn conditions that also occur in full term babies and account for death and disability:
Birth "asphyxia" complications. Some 10 million babies are not breathing at birth, mainly due to brain injury. This is caused by obstructed labor or acute hemorrhage during birth. More than 700,000 term newborns died of birth complications. Among survivors, 233,000 had moderate or severe disability and another 181,000 had learning problems.
Of the 200,000 newborns estimated to suffer from neonatal meningitis, almost 112,000 died, 22,000 survived with severe disabilities, and 9,000 had minor impairments. Disability from sepsis, which may present like meningitis, could not be estimated due to the very few studies that have examined this, despite it being a very common and serious condition.
Severe neonatal jaundice affected an estimated 588,000 newborns, with 114,000 dying and at least 63,000 surviving with moderate or severe disability. These numbers are likely to be an underestimate, especially as no estimates were made for survivors with mild disability. Many jaundice cases were due to Rhesus incompatibility and could be prevented with Rhesus immunoglobulin injections after pregnancy for women who are Rhesus negative.
Better care needed at birth and especially for sick and small newborns
"Essential newborn care is especially important for all babies born preterm," says Elizabeth Mason, M.D., Director of WHO's Department of Maternal, Newborn, Child and Adolescent Health. "This means keeping them warm, clean, initiating breastfeeding, and ensuring that babies who have difficulty breathing get immediate attention. There is a golden minute after birth that counts for every newborn."
Most newborn deaths can be prevented without intensive care. Low-cost interventions that are very effective, but are not commonly used in the highest burden countries include:
Antenatal corticosteroids given to mothers in preterm labor. These are injections of dexamethosone, a steroid used to treat asthma, which helps speed up the development of the baby's lungs. At a cost of about US$1, two shots can help stop premature babies from going into respiratory distress when they are born. More widely used, corticosteroid injections could prevent 400,000 deaths annually.
Kangaroo Mother Care, a technique where the infant is held skin-to-skin on the mother's chest, keeps the baby warm and facilitates breastfeeding. Keeping preterm babies warm is especially important because tiny bodies lose heat rapidly, making these babies highly vulnerable to illness, infection and death. Kangaroo Mother Care could prevent 450,000 deaths annually.
Antibiotics, such as amoxicillin, to treat pneumonia, and gentamicin and penicillin to fight serious infections, could save over half a million lives each year.
Continuous positive airways pressure ventilation system helps preterm babies with breathing difficulties.
"Using an essential package of pregnancy, childbirth, and postnatal care that includes these interventions will save more than three-quarters of preterm babies from death without expensive, high-tech intensive care," says Carole Presern, PhD, Executive Director of PMNCH and a midwife. "Most of these infants can grow up healthy and without lifelong disabilities, but the message needs to get out there."
This is especially true in the poorest countries. "We need to increase training and support for all those who are delivering the babies -- from obstetricians and pediatricians to midwives and nurses," said Mickey Chopra, M.D., PhD, UNICEF Chief of Health.
"Better access to family planning, particularly for adolescent girls, could save an estimated 230,000 babies, if family planning were scaled up to 60 percent coverage," Dr. Presern says.
Better care for children with disability and their families
For many children with disabilities, exclusion begins in the first days of life with their birth going unregistered. Lacking official recognition, they are cut off from the social services and legal protections that are crucial to their survival and prospects. Their marginalization only increases with discrimination.
"For children with disabilities to count, they must be counted – at birth, at school and in life," says Dr. Chopra.
In The State of the World's Children 2013: Children with Disabilities, UNICEF urges governments to ratify and implement the Convention on the Rights of Persons with Disabilities and the Convention on the Rights of the Child, to save more newborn lives and to support families to meet the costs of caring for children with disabilities.
Differences for countries around the world
Broken down by region, most of the problems were reported in low-income countries in South Asia and sub-Saharan Africa, where 2.2 million newborns died, and more than 606,000 had some degree of impairment following newborn complications.
Of the 11.7 million births in high-income countries, including the United States, Canada, Australia and most of Europe, 40,035 preterm babies died due to birth complications and infections, and another 147,000 were impaired. Major disability is most common for babies born at less than 28 weeks, and especially in those born under 25 weeks.
A country-by country analysis shows that India (3,277,200) and China (1,315,000), because of their size, had the greatest numbers of preterm births, followed by Nigeria (831,100), Pakistan (757,900), Indonesia (748,500), United States (497,600), Bangladesh (435,500), Philippines (343,400), Democratic Republic of the Congo (323,100), Ethiopia (305,900), Brazil (266,500) and Tanzania (210,300).
Rates of preterm births differed from absolute numbers, with Malawi topping the list with a rate of 18.1 per thousand live births, followed by Comoros (16.7), Zimbabwe (16.6), Equatorial Guinea (16.5), Mozambique (16.4), Gabon (16.3), Pakistan (15.8), Indonesia (15.5), and Mauritania (15.4).
These studies, based on more than 1,000 data sources, reveal significant data gaps, especially in most low-income and many middle-income countries. For instance, basic information on the number of preterm births and deaths is missing in areas where many babies are delivered at home. Follow-up information does not exist for much of the world, a crucial deficiency because many disabilities -- cerebral palsy and learning difficulties among them -- may not be apparent for several years.
The findings also expose the need for more research to find ways to prevent preterm birth and improve the long-term outlook for all survivors of preterm birth. "We need research to inform us about what we don't understand, such as what causes preterm labor, and to find other things to improve the outcome for survivors," says Edward R.B. McCabe, M.D., Chief Medical Officer of the March of Dimes Foundation and a pediatrician. "But we also need to use what we know already so we can prevent more preterm births."
Leading researchers and global health organizations issued a new call-to-action on a research agenda to address preterm birth. This "Solution Pathway," published today in The Lancet Global Health, was developed by more than 30 scientific experts at a meeting convened by the Bill & Melinda Gates Foundation; the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS), an initiative of Seattle Children's; and the March of Dimes Foundation.
"With this comprehensive, priority research agenda, we have the roadmap to advance discovery, find new solutions to the problem of preterm birth, and evaluate effective strategies to scale up what we know can save lives of newborns," says Eve Lackritz, M.D., a pediatrician and a researcher at GAPPS.