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ORIGINAL ARTICLE
Open Access

Evaluating WHO-Recommended Interventions for Preterm Birth: A Mathematical Model of the Potential Reduction of Preterm Mortality in Sub-Saharan Africa

Jennifer B. Griffin, Alan H. Jobe, Doris Rouse, Elizabeth M. McClure, Robert L. Goldenberg and Beena D. Kamath-Rayne
Global Health: Science and Practice June 2019, 7(2):215-227; https://doi.org/10.9745/GHSP-D-18-00402
Jennifer B. Griffin
aRTI International, Durham, NC, USA.
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Alan H. Jobe
bDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
cPerinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
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Doris Rouse
aRTI International, Durham, NC, USA.
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Elizabeth M. McClure
aRTI International, Durham, NC, USA.
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Robert L. Goldenberg
dDepartment of Obstetrics and Gynecology, Columbia University, New York, NY, USA.
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Beena D. Kamath-Rayne
bDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
cPerinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
eGlobal Child Health, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
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  • For correspondence: Beena.Kamath-Rayne@cchmc.org
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    FIGURE

    MANDATE Model Estimates of the Number of Preterm Deaths Associated With Subconditions Impacting Preterm Mortality, Sub-Saharan Africa, 2015

    Abbreviation: MANDATE, Maternal and Neonatal Directed Assessment of Technology.

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    TABLE 1.

    WHO Interventions and Recommendations to Improve Preterm Birth Mortality, With MANDATE Model Assumptions of Intervention Penetration, Utilization, and Efficacy in Sub-Saharan Africa, 2015

    InterventionRecommendation SummaryWHO Strength of Recommendation for ImplementationQuality of EvidenceBaseline Penetration in MANDATE Home/Clinic/Hospital, %Baseline Utilization in MANDATE Home/Clinic/Hospital, %Efficacy in MANDATE Model, %Key References
    Prenatal interventions for preterm
    Antenatal corticosteroidsFor women at risk of preterm birth (24–34 weeks gestation) under specific conditionsStrongModerate0/10/500/5/25RDS: 50
    IVH: 42
    NEC: 54
    16–18,28
    Antibiotics for preterm laborFor women with preterm prelabor rupture of membranesStrongModerateNot included in model
    Postnatal care
    Cord careDaily CHX application to the umbilicus for newborns born at home in settings with high neonatal mortality. Clean, dry cord care for newborns born in health facilities and at home in low neonatal mortality settings.StrongModerate0/0/00/0/05529–32
    Care of the preterm/LBW neonate
    Thermal care for preterm newbornsKMC for the routine care of newborns weighing ≤2,000 g at birth, and should be initiated in health care facilities as soon as the newborns are clinically stable.StrongModerate95/95/950/0/25115,33
    Unstable newborns weighing ≤2,000 g or stable newborns weighing ≤2,000 g who cannot be given KMC should be cared for in a thermo-neutral environment either under radiant warmers or in incubators.StrongVery low0/0/500/0/306034–36
    FeedingLBW infants, including those with very low birth weight, should be fed mother's own milk.StrongModerate99/99/9920/40/55Sepsis: 55
    LBW: 18
    37–39
    Management: newborn resuscitation
    Immediate drying and additional stimulationNewly born babies who do not breathe spontaneously after thorough drying should be stimulated by rubbing the back 2–3 times before cord clamping and PPV initiation.WeakNot graded50/85/9050/70/851540–42
    PPVIn newly born term or preterm (>32 weeks of gestation) babies requiring PPV, ventilation should be initiated with air.StrongModerate5/50/9520/40/604042–45
    Oxygen therapy for preterm newbornsVentilation of preterm babies born at or before 32 weeks of gestation with oxygen therapy with 30% oxygen or air (if blended oxygen is not available).StrongVery low0/15/600/50/75RDS: 25
    Asphyxia: 25
    46,47
    Management: RDS
    Continuous positive airway pressure for newborns with RDSContinuous positive airway pressure therapy is recommended for the treatment of preterm newborns with RDS.StrongLow0/2/200/50/70RDS: 50
    Asphyxia: 50
    46,47
    Surfactant administration for newborns with RDSSurfactant replacement therapy is recommended for intubated and ventilated newborns with RDS.Conditional (health care facilities only with intubation, ventilator care, blood gas analysis, newborn nursing care and monitoring)Moderate0/1/50/50/753546,48
    Management: neonatal sepsis
    Prophylactic antibiotics for prevention of sepsisA neonate with risk factors for infection (i.e., membranes ruptured > 18 hours before delivery, maternal fever > 38°C before delivery or during labor, or foul-smelling or purulent amniotic fluid) should be treated with the prophylactic antibiotics ampicillin and gentamicin for at least 2 days and reassessed if signs of sepsis or positive blood culture.WeakVery lowNot modeled
    Empirical antibiotics for suspected neonatal sepsisNeonates with signs of sepsis should be treated with antibiotic treatment for at least 10 days.StrongLow10/85/9520/65/757249,50
    Management: NEC
    Antibiotics for treatment of NECYoung neonates with suspected NEC should be treated with intravenous or intramuscular ampicillin (or penicillin) and gentamicin as first-line antibiotic treatment for 10 days.StrongLowNot modeled
    • Abbreviations: CHX, chlorhexidine; KMC, kangaroo mother care; IVH, intraventricular hemorrhage; LBW, low birth weight; MANDATE, Maternal and Neonatal Directed Assessment of Technology; NEC, necrotizing enterocolitis; PPV, positive pressure ventilation; RDS, respiratory distress syndrome; WHO, World Health Organization.

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    TABLE 2.

    Additional MANDATE Model Assumptions, Sub-Saharan Africa, 2015

    AssumptionsValue
    Preterm births in sub-Saharan Africa, N3,988,000
    Delivery location in sub-Saharan Africa, %
    Home50
    Clinic35
    Hospital15
    Antenatal care location in sub-Saharan Africa, %
    Home30
    Clinic65
    Hospital5
    Preterm subconditions contributing to preterm mortality, Prevalence | Case fatality rate,a %
    Respiratory distress20 | 35
    Intraventricular hemorrhage7 | 7.5
    Necrotizing enterocolitis1 | 25
    Sepsis9 | 40
    Birth asphyxia20 | 20
    Preterm with no other conditions43 | 2.1
    Diagnostics, Baseline penetration | Baseline utilization | Efficacy for Home/Clinic/Hospital, %
    Preterm labor51–5350/85/90 | 5/20/35 | 25/80/80
    Respiratory distress syndrome46,5450/85/90 | 40/60/95 | 75/95/95
    Intraventricular hemorrhage5450/85/90 | 5/40/70 | 25/45/45
    Necrotizing enterocolitis54–5650/85/90 | 5/40/70 | 25/85/85
    Sepsis49,57,5895/85/90 | 75/80/90 | 75/95/95
    Low birth weight5950/85/90 | 5/75/90 | 25/95/95
    • Abbreviation: MANDATE, Maternal and Neonatal Directed Assessment of Technology.

    • ↵a The prevalence and case fatality rates assume no preventive or treatment interventions.

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    TABLE 3.

    Impact of ANCS and Other WHO-Recommended Interventionsa to Prevent Preterm Mortality From RDS, IVH, and NEC, Sub-Saharan Africa, 2015

    Scenario No.ScenarioIncremental Change ModelbUniversal Coverage Modelc
    Preterm Deaths, No.dPreterm Deaths Prevented Compared With Current Level of Care, No. (%)Preterm Deaths, No.Preterm Deaths Prevented Compared With Current Level of Care, No. (%)
    1Current levels of prevention, diagnosis, and treatment303,400N/A303,400N/A
    Improved WHO single interventions
    2Increased surfactant in hospital settings for RDS303,300100 (<0.1)303,100300 (0.1)
    3Increased ANCS in hospital settings for RDS, IVH, and NEC302,3001,100 (0.4)298,4005,000 (1.7)
    4Increased oxygen/CPAP in hospital and clinical settings for RDS295,3008,100 (2.7)261,10042,300 (13.9)
    Improved diagnosis of preterm labor and transfer with current care
    5Increased diagnosis of preterm labor birth, with current levels of care for RDS, IVH, and NEC302,4001,000 (0.3)299,9003,500 (1.2)
    6Increased diagnosis of imminent preterm birth and transfer to hospitals, with current levels of care for RDS, IVH, and NEC301,3002,100 (0.7)287,10016,300 (5.4)
    Improved diagnosis and transfer with WHO single interventions
    7Increased diagnosis of respiratory distress, transfer, and surfactant (hospitals only) for RDS299,9003,500 (1.2)282,80020,600 (6.8)
    8Increased diagnosis of imminent preterm birth, transfer to hospitals, and ANCS (hospitals only) for RDS, IVH, and NEC298,6004,800 (1.6)236,70066,700 (22.0)
    9Increased diagnosis of respiratory distress, transfer, and oxygen/CPAP for preterm RDS287,40016,000 (5.3)176,100127,300 (42.0)
    Improved diagnosis and transfer with WHO packaged interventions
    10Improved diagnosis of imminent preterm birth, transfer to hospitals, ANCS (hospitals only), and treatment with surfactants (hospitals only) and oxygen/CPAP for RDS, IVH, and NEC289,70013,700 (4.5)191,300112,100 (37.0)
    11Increased diagnosis of respiratory distress, transfer to hospitals, and treatment, including surfactants (hospitals only) and oxygen/CPAP for RDS286,90016,500 (5.4)155,700147,711 (48.7)
    12Hospital delivery for all preterm birth, with ANCS (hospitals only), improved diagnosis and treatment of respiratory distress, including surfactants (hospitals only) and CPAP for RDS, IVH, and NEC223,30080,100 (26.4)112,800190,600(62.8)
    • Abbreviations: ANCS, antenatal corticosteroids; CPAP, continuous positive airway pressure; IVH, intraventricular hemorrhage; NEC, necrotizing enterocolitis; RDS, respiratory distress syndrome; WHO, World Health Organization.

    • ↵a Assumptions regarding baseline penetration and utilization of interventions including ANCS, surfactant, and CPAP as shown in Table 1. Assumptions regarding diagnostics and transfers found in Table 2.

    • ↵b The incremental change model assumes 20% increase from baseline penetration and utilization.

    • ↵c The universal coverage model assumes 98% penetration and utilization of interventions.

    • ↵d All estimates rounded to nearest 100.

    • View popup
    TABLE 4.

    Impact of WHO-Recommended Interventionsa to Prevent Preterm Mortality From Sepsis, Birth Asphyxia, and Low Birth Weight, Sub-Saharan Africa, 2015

    Scenario No.ScenarioIncremental Change ModelbUniversal Coverage Modelc
    Preterm Deaths, No.dPreterm Deaths Prevented Compared With Current Level of Care, No. (%)Preterm Deaths, No.Preterm Deaths Prevented Compared With Current Level of Care, No. (%)
    1Current levels of prevention, diagnosis, and treatment198,400N/A198,400N/A
    Improved WHO single interventions
    2Oxygen/CPAP for birth asphyxia in clinics and hospitals198,000400 (0.2)196,8001,700 (0.9)
    3PPV for birth asphyxia in all settings197,2001,200 (0.6)195,1004,200 (2.1)
    4Drying and stimulation for birth asphyxia in all settings196,4861,900 (1.0)195,4003,000 (1.5)
    5Thermal care for LBW, including KMC in all settings and warmers in hospital settings196,0002,500 (1.3)189,4009,100 (4.6)
    6Antibiotics for suspected neonatal sepsis in all settings192,1006,300 (3.2)180,30018,200 (9.1)
    7Breastfeeding for sepsis and LBW in all settings189,3009,100 (4.6)168,20030,200 (15.2)
    8Chlorhexidine for sepsis in home settings and dry cord care in clinical settings190,8007,600 (3.8)159,90038,500 (19.4)
    Improved diagnosis and transfer with current care
    9Diagnosis of birth asphyxia and need for postresuscitation care, with current levels of care197,2001,300 (0.7)196,5001,900 (1.0)
    10Diagnosis of birth asphyxia and need for postresuscitation care and improved transfer to hospitals, with current levels of care197,0001,400 (0.7)196,2002,200 (1.1)
    11Diagnosis of sepsis, with current levels of care194,7003,700 (1.9)194,3004,200 (2.1)
    12Diagnosis of sepsis and transfer to hospitals, with current levels of care187,40011,000 (5.5)184,10014,300 (7.2)
    Improved diagnosis and transfer with WHO single treatment interventions
    13Diagnosis of birth asphyxia and need for postresuscitation care, transfer, and oxygen/CPAP196,3002,100 (1.1)191,7006,800 (3.4)
    14Diagnosis of birth asphyxia and need for postresuscitation care, transfer, and positive pressure ventilation195,5002,900 (1.5)189,8008,600 (4.3)
    15Diagnosis of sepsis, transfer, and antibiotics for suspected neonatal sepsis180,80017,600 (8.9)169,80028,600 (14.3)
    Improved diagnosis and transfer with WHO-packaged interventions
    16Drying and stimulation, diagnosis of birth asphyxia and need for postresuscitation care, transfer to hospitals, and treatment, including PPV and oxygen/CPAP188,05710,400 (5.2)172,20026,200 (13.2)
    17Cord care and breastfeeding, diagnosis of sepsis, transfer, and antibiotics for suspected neonatal sepsis169,20029,200 (14.7)139,40059,100 (29.8)
    18Packaged interventions 16 and 17, with increased thermal care and breastfeeding for LBW159,30039,100 (19.7)104,00094,400 (47.6)
    • Abbreviations: CPAP, continuous positive airway pressure; KMC, kangaroo mother care; LBW, low birth weight; PPV, positive pressure ventilation; WHO, World Health Organization.

    • ↵a Assumptions regarding baseline penetration and utilization of interventions including ANCS, surfactant, and CPAP as shown in Table 1. Assumptions regarding diagnostics and transfers found in Table 2.

    • ↵b The incremental change model assumes 20% increase from baseline penetration and utilization.

    • ↵c The universal coverage model assumes 98% penetration and utilization of interventions.

    • ↵d All estimates rounded to nearest 100.

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Evaluating WHO-Recommended Interventions for Preterm Birth: A Mathematical Model of the Potential Reduction of Preterm Mortality in Sub-Saharan Africa
Jennifer B. Griffin, Alan H. Jobe, Doris Rouse, Elizabeth M. McClure, Robert L. Goldenberg, Beena D. Kamath-Rayne
Global Health: Science and Practice Jun 2019, 7 (2) 215-227; DOI: 10.9745/GHSP-D-18-00402

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Evaluating WHO-Recommended Interventions for Preterm Birth: A Mathematical Model of the Potential Reduction of Preterm Mortality in Sub-Saharan Africa
Jennifer B. Griffin, Alan H. Jobe, Doris Rouse, Elizabeth M. McClure, Robert L. Goldenberg, Beena D. Kamath-Rayne
Global Health: Science and Practice Jun 2019, 7 (2) 215-227; DOI: 10.9745/GHSP-D-18-00402
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