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Newborn-Care Training and Perinatal Mortality in Developing Countries Waldemar A. Carlo, M.D., Shivaprasad S. Goudar M.D., M.H.P.E., Imtiaz Jehan, F.C.P.S., M.Sc., Elwyn Chomba, M.D., Antoinette Tshefu, M.D., Ana Garces, M.D., Sailajanandan Parida, M.D., Fernando Althabe, M.D., Elizabeth M. McClure, M.Ed., Richard J. Derman, M.D., M.P.H., Robert L. Goldenberg, M.D., Carl Bose, M.D., Nancy F. Krebs, M.D., Pinaki Panigrahi, M.D., Ph.D., Pierre Buekens, M.D., Ph.D., Hrishikesh Chakraborty, Dr.P.H., Tyler D. Hartwell, Ph.D., Linda L. Wright, M.D., and the First Breath Study Group*

A BS T R AC T Background From the University of Alabama at Birmingham, Birmingham (W.A.C.); Centre for Infectious Disease Research in Zambia (W.A.C., E.C.) and University Teaching Hospital (E.C.) — both in Lusaka, Zambia; Jawaharlal Nehru Medical College, Belgaum (S.S.G.), and Sriramchandra Bhanja Medical College, Cuttack, Orissa (S.P.) — both in India; Aga Khan University, Karachi, Pakistan (I.J.); Kinshasa School of Public Health, Kinshasa, Democratic Republic of Congo (A.T.); San Carlos University, Guatemala City, Guatemala (A.G.); Institute for Clinical Effectiveness and Health Policy, Buenos Aires (F.A.); RTI International, Durham (E.M.M., H.C., T.D.H.), and University of North Carolina at Chapel Hill, Chapel Hill (C.B.) — both in North Carolina; University of Missouri at Kansas City School of Medicine, Kansas City (R.J.D.); Drexel University College of Medicine, Philadelphia (R.L.G.); University of Colorado Health Sciences Center, Denver (N.F.K.); University of Maryland School of Medicine, Baltimore (P.P.), and Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda (L.L.W.) — both in Maryland; and Tulane School of Public Health and Tropical Medicine, New Orleans (P.B.). Address reprint requests to Dr. Carlo at the University of Alabama at Birmingham, 525 New Hillman Bldg., 619 S. 20th St., Birmingham, AL 35233, or at [email protected]. *Members of the First Breath Study Group are listed in the Appendix. N Engl J Med 2010;362:614-23. Copyright © 2010 Massachusetts Medical Society.

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Of the 3.7 million neonatal deaths and 3.3 million stillbirths each year, 98% occur in developing countries. An evaluation of community-based interventions designed to reduce the number of these deaths is needed. Methods

With the use of a train-the-trainer model, local instructors trained birth attendants from rural communities in six countries (Argentina, Democratic Republic of Congo, Guatemala, India, Pakistan, and Zambia) in the World Health Organization Essential Newborn Care course (which focuses on routine neonatal care, resuscitation, thermoregulation, breast-feeding, “kangaroo” [skin-to-skin] care, care of the small baby, and common illnesses) and (except in Argentina) in a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (which teaches basic resuscitation in depth). The Essential Newborn Care intervention was assessed among 57,643 infants with the use of a before-and-after design. The Neonatal Resuscitation Program intervention was assessed as a cluster-randomized, controlled trial involving 62,366 infants. The primary outcome was neonatal death in the first 7 days after birth. Results

The 7-day follow-up rate was 99.2%. After birth attendants were trained in the Essential Newborn Care course, there was no significant reduction from baseline in the rate of neonatal death from all causes in the 7 days after birth (relative risk with training, 0.99; 95% confidence interval [CI], 0.81 to 1.22) or in the rate of perinatal death; there was a significant reduction in the rate of stillbirth (relative risk with training, 0.69; 95% CI, 0.54 to 0.88; P = 0.003). In clusters of births in which attendants had been randomly assigned to receive training in the Neonatal Resuscitation Program, as compared with control clusters, there was no reduction in the rates of neonatal death in the 7 days after birth, stillbirth, or perinatal death. Conclusions

The rate of neonatal death in the 7 days after birth did not decrease after the introduction of Essential Newborn Care training of community-based birth attendants, although the rate of stillbirths was reduced. Subsequent training in the Neonatal Resuscitation Program did not significantly reduce the mortality rates. (ClinicalTrials .gov number, NCT00136708.) n engl j med 362;7  nejm.org  february 18, 2010

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Tr aining of birth attendants in developing countries

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nnually, there are approximately 3.7 million neonatal deaths and 3.3 million stillbirths worldwide.1 Approximately 38% of deaths among children younger than 5 years of age occur during the first 28 days of life, and 75% of the neonatal deaths occur within the first 7 days.1-3 Without a major reduction in neonatal deaths in the first 7 days after birth, achievement of the United Nations’ Millennium Development Goal 4 — a reduction in mortality by two thirds among children younger than 5 years of age2 — is unlikely to be realized. In areas of the world with high rates of home delivery, stillbirths are prevalent, but they are difficult to distinguish from early neonatal deaths.4,5 Therefore, examining both stillbirths and early neonatal deaths is important in an evaluation of perinatal programs that are designed to reduce mortality.4 Major global causes of perinatal mortality are asphyxia at birth, low birth weight, and prematurity. Low-cost interventions, including training in neonatal resuscitation6 and “kangaroo” (skinto-skin) care,7 may effectively reduce deaths from these causes; it has been estimated that introducing these interventions as a package might decrease perinatal deaths by 50% or more.8,9 A recent study that used a “before-and-after” implementation design showed that training in the World Health Organization (WHO) Essential Newborn Care course10 improved midwives’ skill and knowledge11 and reduced neonatal deaths in the first 7 days after birth among low-risk women who delivered in first-level clinics in Zambia.12 A systematic review of the literature suggests that perinatal mortality may be decreased by training birth attendants.13 Thus, wide-scale implementation and evaluation of evidence-based interventions are needed to improve perinatal outcomes, particularly in rural settings, where more than 50% of neonatal deaths occur. The First Breath study was designed to test the primary hypothesis that training birth attendants in the WHO Essential Newborn Care course and in a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program would reduce the rate of death from all causes in the first 7 days after birth, among infants with birth weights of at least 1500 g who were born in rural communities in developing countries.

ME THODS Study Sites and Study Populations

We conducted the before-and-after study of training in Essential Newborn Care in rural communities in seven sites of the Global Network for Women’s and Children’s Health Research in six countries (Argentina, Democratic Republic of Congo, Guatemala, India, Pakistan, and Zambia) from March 2005 through February 2007 (Fig. 1) with the use of an active baseline design.14 This design requires the protocol to be initiated before data collection is started. (In the case of this study, all training except for training in the Essential Newborn Care intervention was conducted before the initiation of data collection.) The cluster-randomized trial of training in the Neonatal Resuscitation Program was conducted in 88 communities in five countries (the same as those in the Essential Newborn Care study, except for Argentina) from July 2006 through August 2008 (Fig. 2). The communities were selected to represent rural areas, to be geographically distinct, and to have at least 300 births per year. Most communities had poor health systems and a high rate of home births assisted by traditional birth attendants. Government officials and community leaders facilitated the training of all birth attendants in the two courses and in the collection of data. The studies were approved by the institutional review board at each participating site in the developing countries and in the United States. An independent data and safety monitoring committee reviewed recruitment, outcomes, and adverse events. Additional monitoring included site visits by local and central personnel and monthly recruitment reports. Maternal and neonatal data were collected for all births with a gestation period that was considered to have been 28 weeks or longer (on the basis of the mother’s last menstrual period and other clinical information) and a birth weight of 1500 g or more (including stillbirths). We excluded fetuses and neonates with a birth weight of less than 1500 g because advanced medical care for very-low-birth-weight infants was not available in most of the study communities. In cases in which the birth weight was not measured, infants were included if the birth weight was

n engl j med 362;7  nejm.org  february 18, 2010

The New England Journal of Medicine Downloaded from nejm.org on January 14, 2017. For personal use only. No other uses without permission. Copyright © 2010 Massachusetts Medical Society. All rights reserved.

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cal practice sessions and demonstrations to train all birth attendants in the study procedures and Baseline data collection before Essential Newborn Care Intervention in the implementation of the two programs. These 96 Clusters participating courses were first tested in a clinic-based study 23,137 Mothers screened (23,248 infants) in Zambia11,12,15 and were modified for the current study so that they would also be appropriate 124 Mothers declined participation for use by community-based birth attendants; modifications included the development of mate23,013 Mothers consented (23,123 infants) rials for illiterate participants. During a 3-day course before the baseline data collection, three 498 Infants excluded experienced trainers trained two master trainers 364 Live births