Cross-Country Individual Participant Analysis of 4.1 Million Singleton Births in 5 Countries with Very High Human Development Index Confirms Known Associations but Provides No Biologic Explanation for 2/3 of All Preterm Births.

BACKGROUND: Preterm birth is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. Understanding of risk factors remains poor, and preventive interventions have only limited benefit. Large differences exist in preterm birth rates across high income countries. We hypothesized that understanding the basis for these wide variations could lead to interventions that reduce preterm birth incidence in countries with high rates. We thus sought to assess the contributions of known risk factors for both spontaneous and provider-initiated preterm birth in selected high income countries, estimating also the potential impact of successful interventions due to advances in research, policy and public health, or clinical practice. METHODS: We analyzed individual patient-level data on 4.1 million singleton pregnancies from four countries with very high human development index (Czech Republic, New Zealand, Slovenia, Sweden) and one comparator U.S. state (California) to determine the specific contribution (adjusting for confounding effects) of 21 factors. Both individual and population-attributable preterm birth risks were determined, as were contributors to cross-country differences. We also assessed the ability to predict preterm birth given various sets of known risk factors. FINDINGS: Previous preterm birth and preeclampsia were the strongest individual risk factors of preterm birth in all datasets, with odds ratios of 4.6-6.0 and 2.8-5.7, respectively, for individual women having those characteristics. In contrast, on a population basis, nulliparity and male sex were the two risk factors with the highest impact on preterm birth rates, accounting for 25-50% and 11-16% of excess population attributable risk, respectively (p<0.001). The importance of nulliparity and male sex on population attributable risk was driven by high prevalence despite low odds ratios for individual women. More than 65% of the total aggregated risk of preterm birth within each country lacks a plausible biologic explanation, and 63% of difference between countries cannot be explained with known factors; thus, research is necessary to elucidate the underlying mechanisms of preterm birth and, hence, therapeutic intervention. Surprisingly, variation in prevalence of known risk factors accounted for less than 35% of the difference in preterm birth rates between countries. Known risk factors had an area under the curve of less than 0.7 in ROC analysis of preterm birth prediction within countries. These data suggest that other influences, as yet unidentified, are involved in preterm birth. Further research into biological mechanisms is warranted. CONCLUSIONS: We have quantified the causes of variation in preterm birth rates among countries with very high human development index. The paucity of explicit and currently identified factors amenable to intervention illustrates the limited impact of changes possible through current clinical practice and policy interventions. Our research highlights the urgent need for research into underlying biological causes of preterm birth, which alone are likely to lead to innovative and efficacious interventions.

CDC Grand Rounds: Public Health Strategies to Prevent Preterm Birth.

Preterm birth (delivery before 37 weeks and 0/7 days of gestation) is a leading cause of infant morbidity and mortality in the United States. In 2013, 11.4% of the nearly 4 million U.S. live births were preterm; however, 36% of the 8,470 infant deaths were attributed to preterm birth (1). Infants born at earlier gestational ages, especially <32 0/7 weeks, have the highest mortality (Figure) and morbidity rates. Morbidity associated with preterm birth includes respiratory distress syndrome, necrotizing enterocolitis, and intraventricular hemorrhage; longer-term consequences include developmental delay and decreased school performance. Risk factors for preterm delivery include social, behavioral, clinical, and biologic characteristics (Box). Despite advances in medical care, racial and ethnic disparities associated with preterm birth persist. Reducing preterm birth, a national public health priority (2), can be accomplished by implementing and monitoring strategies that target modifiable risk factors and populations at highest risk, and by providing improved quality and access to preconception, prenatal, and interconception care through implementation of strategies with potentially high impact.

Fighting for the next generation: US Prematurity in 2030.

Preterm birth (PTB) is a serious problem, with >450 000 neonates born prematurely in the United States every year. Beginning in 1980, the United States experienced a nearly 3-decade rise in the PTB rate, peaking in 2006 at 12.8%. PTB has declined for 7 consecutive years to 11.4% in 2013, but it still accounts for 1 in 9 neonates born every year. In addition to elevated neonatal and infant mortality among those born preterm, many who survive will have lifelong morbidities and disabilities. Because of the burden of morbidity, disability, and mortality for PTB, as well as its impact more broadly on society, including excess annual costs estimated to be at least $26.2 billion by a committee for the Institute of Medicine, the March of Dimes initiated the Prematurity Campaign in 2003. In 2008 the March of Dimes established a goal of reducing the US PTB rate to 9.6% by 2020. However, the United States ranks extremely poorly for PTB rates among Very High Human Development Index (VHHDI) countries, subjecting untold numbers of neonates to unnecessary morbidity and mortality. Therefore, the March of Dimes proposes an aspirational goal of 5.5% for the 2030 US PTB rate, which would put the United States in the top 4 (10%) of 39 VHHDI countries. This 5.5% PTB rate is being achieved in VHHDI countries and by women from diverse settings receiving optimal care. This goal can be reached and will ensure a better start in life for many more neonates in the next generation.

Family support and family-centered care in the neonatal intensive care unit: origins, advances, impact.

Family-centered care (FCC) has been increasingly emphasized as an important and necessary element of neonatal intensive care. FCC is conceptualized as a philosophy with a set of guiding principles, as well as a cohort of programs, services, and practices that many hospitals have embraced. Several factors drive the pressing need for family-centered care and support of families of infants in NICUs, including the increase in the number of infants in NICUs; growth in diversity of the population and their concurrent needs; identification of parental and familial stress and lack of parenting confidence; and gaps in support for families, as identified by parents and NICU staff. We explore the origins of and advances in FCC in the NICU and identify various delivery methods and aspects of FCC and family support in the NICU. We examine the research and available evidence supporting FCC in the NICU and offer recommendations for increased dissemination and for future study.

Cost of hospitalization for preterm and low birth weight infants in the United States.

OBJECTIVE: The objective of this study was to estimate national hospital costs for infant admissions that are associated with preterm birth/low birth weight. METHODS: Infant (<1 year) hospital discharge data, including delivery, transfers, and readmissions, were analyzed by using the 2001 Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project. The Nationwide Inpatient Sample is a 20% sample of US hospitals weighted to approximately >35 million hospital discharges nationwide. Hospital costs, based on weighted cost-to-charge ratios, and lengths of stay were calculated for preterm/low birth weight infants, uncomplicated newborns, and all other infant hospitalizations and assessed by degree of prematurity, major complications, and expected payer. RESULTS: In 2001, 8% (384,200) of all 4.6 million infant stays nationwide included a diagnosis of preterm birth/low birth weight. Costs for these preterm/low birth weight admissions totaled $5.8 billion, representing 47% of the costs for all infant hospitalizations and 27% for all pediatric stays. Preterm/low birth weight infant stays averaged $15,100, with a mean length of stay of 12.9 days versus $600 and 1.9 days for uncomplicated newborns. Costs were highest for extremely preterm infants (<28 weeks' gestation/birth weight <1000 g), averaging $65,600, and for specific respiratory-related complications. However, two thirds of total hospitalization costs for preterm birth/low birth weight were for the substantial number of infants who were not extremely preterm. Of all preterm/low birth weight infant stays, 50% identified private/commercial insurance as the expected payer, and 42% designated Medicaid. CONCLUSIONS: Costs per infant hospitalization were highest for extremely preterm infants, although the larger number of moderately preterm/low birth weight infants contributed more to the overall costs. Preterm/low birth weight infants in the United States account for half of infant hospitalization costs and one quarter of pediatric costs, suggesting that major infant and pediatric cost savings could be realized by preventing preterm birth.

Critical role of the March of Dimes in the expansion of newborn screening.

Expansion of newborn screening (NBS) has been driven primarily by a combination of advances in technology and medical treatment, and the sustained advocacy efforts of consumers and voluntary health organizations. The longstanding leadership of the March of Dimes has been credited by many as a critical factor in the expansion and improvement of state NBS programs. From the historic vantage point of four decades of March of Dimes involvement with newborn screening, this report reviews the unique origin of the first newborn screening test, and identifies from this point of origin several of the elements which still define the evolution of advocacy for NBS today. It also documents activities at the federal level and in seven states that have lead to expanded screening for newborns. Advances in NBS technology and medical treatment have informed policy development. Mobilization of volunteers and focused advocacy activities have brought about expansion of screening opportunities for newborns across the United States. But more work is needed. Continued application of the effective strategies identified in this report will help assure that all families have the best possible chance of assuring that their newborns do not have to suffer the complications of conditions that we know can be treated effectively.

Estimated effect of 17 alpha-hydroxyprogesterone caproate on preterm birth in the United States.

OBJECTIVE: A multicenter, randomized placebo-controlled trial among women with singleton pregnancies and a history of spontaneous preterm birth found that weekly injections of 17 alpha-hydroxyprogesterone caproate (17P), initiated between 16 and 20 weeks of gestation, reduced preterm birth by 33%. The current study estimated both preterm birth recurrence and the potential reduction in the national preterm birth rate. METHODS: Using 2002 national birth certificate data, augmented by vital statistics from 2 states, we estimated the number of singleton births delivered to women eligible for 17P through both a history of spontaneous preterm birth and prenatal care onset within the first 4 months of pregnancy. The number and rate of recurrent spontaneous preterm births were estimated. To predict effect, the reported 33% reduction in spontaneous preterm birth attributed to 17P therapy was applied to these estimates. RESULTS: In 2002, approximately 30,000 recurrent preterm births occurred to women eligible for 17P, having had a recurrent preterm birth rate of 22.5%. If 17P therapy were delivered to these women, nearly 10,000 spontaneous preterm births would have been prevented, thereby reducing the overall United States preterm birth rate by approximately 2%, from 12.1% to 11.8% (P < .001), with higher reductions in targeted groups of eligible pregnant women. CONCLUSION: Use of 17P could reduce preterm birth among eligible women, but would likely have a modest effect on the national preterm birth rate. Additional research is urgently needed to identify other populations who might benefit from 17P, evaluate new methods for early detection of women at risk, and develop additional prevention strategies. LEVEL OF EVIDENCE: III.