Seventy-five yeas ago, Franklin D. Roosevelt’s personal struggle with polio, changed the lives of babies forever when he formed the March of Dimes Foundation around the fight against childhood polio. That mission accomplished, the foundation turned its focus to preventing birth defects and reducing infant mortality. In 2003, the March of Dimes joined a worldwide campaign in the fight against preterm births that had risen at an alarming rate in the prior decade. In fact, preterm birth (birth prior to 37 completed weeks of gestation) was becoming the most common cause of infant mortality and loss of human potential worldwide. Today, preterm birth is the most common cause of neonatal deaths (infants aged 0-27 days of age) and the second largest cause of infant deaths (under the age of one year) second only to congenital malformations and chromosomal abnormalities.
While advances in obstetrical and neonatal care over the last 20 years have dramatically improved the survival of premature infants, significant numbers still suffer from conditions related to preterm birth. Moreover, despite the increasing prevalence of diseases unique to preterm infants, many still lack known cures. One such disease is necrotizing enterocolitis (NEC). NEC is diagnosed in up to 5% of admissions to the neonatal intensive care unit and accounts for nearly 10,000 infants yearly in the United States. In addition, the overall mortality for patients with NEC ranges from 10%-50%, approaching 100% in infants with rapidly progressive disease, which typically includes the smallest and most premature infants.
Despite state of the art medical and surgical management in neonatal intensive care units, infants who recover from NEC still face long hospitalizations and disease related complications, shortening long-term survival, and negatively impacting growth and development. Infants with NEC are also at increased risk for poor neurodevelopmental outcomes.
Research supported by the March of Dimes and other national funding agencies shows that inflammation in the intestine of infants with NEC is triggered by the hypoxic (low oxygen) state around the time of birth, irreversibly weakening the lining of the bowel. When formula feeds are initiated, pathogenic bacteria resident in the gut proliferate in response to substrates from formula feeding, further injuring the intestinal lining and allowing pathogenic bacteria and their products into the infant’s blood stream. Translocation of bacteria and their products from the gut into the blood stream leads to systemic infections such as sepsis, meningitis, and pneumonia.
While prompt diagnosis and intervention are desirable tenants of disease management in NEC, there is no clear evidence that early diagnosis and interventions after the development of NEC alter patient outcome. Therefore, prevention of preterm birth primarily and developing novel treatment modalities for NEC secondarily, are paramount.
While the pathophysiology of NEC is multi-factorial and complex, the only consistent epidemiological risk factor for NEC in addition to prematurity, is a history of formula feeding which is thought to promote the growth of opportunistic and pathogenic bacteria in the gut. Breast milk feeding, by contrast, which is also known to reduce bacterial infections in infants, is the only known preventative measure to specifically to reduce the incidence of NEC among preterm infants. Whether breast milk feeding facilitates colonization by probiotic bacterial flora that effectively compete for niches normally occupied by pathogenic bacteria thereby protecting infants from the development of NEC is not known.
Neonatal intensive care hospitalization of premature infants is known to alter the composition of gastrointestinal flora. Moreover, these infants are routinely treated with broad-spectrum antibiotics further enhancing colonization with potentially pathogenic bacteria. Sensitive molecular techniques are now available to determine the composition (microbiome) of the birth canal and its relationship to the fore- and hind- gut premature newborns with and without NEC. Identification of a pathogenic bacterial microbiome may allow earlier identification of infants at risk for NEC aiding in its prevention.
Previous research supported by the March of Dimes studied the use of surfactant therapy in the successful reduction of respiratory distress syndrome. Bringing other novel and cutting edge therapies safely from bench to bedside will be paramount to improving disease-free survival and outcome of premature infants from many diseases like NEC over the next decades.
According to the March of Dimes, over 7 million babies in the United States are born prematurely, including more than 30,000 infants in Florida alone. During Prematurity Awareness Month this last November, every state received a letter “A-F” for the percentage of premature births relative to the Healthy People 2020 goals of reducing the premature birth to 9.6%. While the United States collectively received a letter grade of “C”, Florida with a 13.0% prematurity rate, received a letter grade of “D”, one of the highest rates in the nation. Although preterm birth rates have improved in Florida over the last five years, they are nearly twice the rate in Western Europe (8%)!
The disproportionate rates of premature births across central Florida, from a peak in Orange County of 14.7%, to 13.6 % in Osceola County, 13.2 % in Seminole County and a low of 12.4% in Volusia County suggest that efforts must be uniquely tailored to the needs of our individual communities.
The March of Dimes’ Prematurity Campaign seeks to raise awareness, find the causes of prematurity and to refine the treatment of diseases unique to premature newborns. Our community can raise awareness and generate support for research, clinical care and education by participating in the March for Babies. Last year nearly four thousand people gathered in Orlando to help support the March for Babies in central Florida. This walk supports treatment, research and programs that promote healthy pregnancies and supports the birth of healthy babies.
There are many ways to improve the health and strength of mothers and their babies in our community. Fortunately, the March of Dimes continues to partner with families and the health care community in central Florida like Nemours Children’s Hospital whereby community outreach, education, clinical care and research are tailored to conquering the impact of prematurity on infants and families and society.
Victoria Niklas, MD is Division Chief of Neonatal Medicine at Nemours Children’s Hospital in Orlando.Dr. Niklas received her medical degree from the Harvard Medical School. She completed her residency in Pediatrics at Children’s Hospital Los Angeles and a fellowship in Perinatal and Neonatal Medicine at the University of California, Los Angeles. She joined Nemours Children’s Hospital from Children’s Hospital Los Angeles and Keck School of Medicine of the University of Southern California.
By Victoria Niklas, MD