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

doi:10.9745/GHSP-D-18-00402

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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

Intervention	Recommendation Summary	WHO Strength of Recommendation for Implementation	Quality of Evidence	Baseline Penetration in MANDATE Home/Clinic/Hospital, %	Baseline Utilization in MANDATE Home/Clinic/Hospital, %	Efficacy in MANDATE Model, %	Key References
Prenatal interventions for preterm
Antenatal corticosteroids	For women at risk of preterm birth (24–34 weeks gestation) under specific conditions	Strong	Moderate	0/10/50	0/5/25	RDS: 50 IVH: 42 NEC: 54	16–18,28
Antibiotics for preterm labor	For women with preterm prelabor rupture of membranes	Strong	Moderate	Not included in model
Postnatal care
Cord care	Daily 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.	Strong	Moderate	0/0/0	0/0/0	55	29–32
Care of the preterm/LBW neonate
Thermal care for preterm newborns	KMC 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.	Strong	Moderate	95/95/95	0/0/2	51	15,33
	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.	Strong	Very low	0/0/50	0/0/30	60	34–36
Feeding	LBW infants, including those with very low birth weight, should be fed mother's own milk.	Strong	Moderate	99/99/99	20/40/55	Sepsis: 55 LBW: 18	37–39
Management: newborn resuscitation
Immediate drying and additional stimulation	Newly 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.	Weak	Not graded	50/85/90	50/70/85	15	40–42
PPV	In newly born term or preterm (>32 weeks of gestation) babies requiring PPV, ventilation should be initiated with air.	Strong	Moderate	5/50/95	20/40/60	40	42–45
Oxygen therapy for preterm newborns	Ventilation 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).	Strong	Very low	0/15/60	0/50/75	RDS: 25 Asphyxia: 25	46,47
Management: RDS
Continuous positive airway pressure for newborns with RDS	Continuous positive airway pressure therapy is recommended for the treatment of preterm newborns with RDS.	Strong	Low	0/2/20	0/50/70	RDS: 50 Asphyxia: 50	46,47
Surfactant administration for newborns with RDS	Surfactant 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)	Moderate	0/1/5	0/50/75	35	46,48
Management: neonatal sepsis
Prophylactic antibiotics for prevention of sepsis	A 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.	Weak	Very low	Not modeled
Empirical antibiotics for suspected neonatal sepsis	Neonates with signs of sepsis should be treated with antibiotic treatment for at least 10 days.	Strong	Low	10/85/95	20/65/75	72	49,50
Management: NEC
Antibiotics for treatment of NEC	Young neonates with suspected NEC should be treated with intravenous or intramuscular ampicillin (or penicillin) and gentamicin as first-line antibiotic treatment for 10 days.	Strong	Low	Not 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

Assumptions	Value
Preterm births in sub-Saharan Africa, N	3,988,000
Delivery location in sub-Saharan Africa, %
Home	50
Clinic	35
Hospital	15
Antenatal care location in sub-Saharan Africa, %
Home	30
Clinic	65
Hospital	5
Preterm subconditions contributing to preterm mortality, Prevalence \| Case fatality rate,^a %
Respiratory distress	20 \| 35
Intraventricular hemorrhage	7 \| 7.5
Necrotizing enterocolitis	1 \| 25
Sepsis	9 \| 40
Birth asphyxia	20 \| 20
Preterm with no other conditions	43 \| 2.1
Diagnostics, Baseline penetration \| Baseline utilization \| Efficacy for Home/Clinic/Hospital, %
Preterm labor⁵¹^–⁵³	50/85/90 \| 5/20/35 \| 25/80/80
Respiratory distress syndrome⁴⁶^,⁵⁴	50/85/90 \| 40/60/95 \| 75/95/95
Intraventricular hemorrhage⁵⁴	50/85/90 \| 5/40/70 \| 25/45/45
Necrotizing enterocolitis⁵⁴^–⁵⁶	50/85/90 \| 5/40/70 \| 25/85/85
Sepsis⁴⁹^,⁵⁷^,⁵⁸	95/85/90 \| 75/80/90 \| 75/95/95
Low birth weight⁵⁹	50/85/90 \| 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 Interventions^a to Prevent Preterm Mortality From RDS, IVH, and NEC, Sub-Saharan Africa, 2015

Scenario No.	Scenario	Incremental Change Model^b		Universal Coverage Model^c
Scenario No.	Scenario	Preterm Deaths, No.^d	Preterm Deaths Prevented Compared With Current Level of Care, No. (%)	Preterm Deaths, No.	Preterm Deaths Prevented Compared With Current Level of Care, No. (%)
1	Current levels of prevention, diagnosis, and treatment	303,400	N/A	303,400	N/A
Improved WHO single interventions
2	Increased surfactant in hospital settings for RDS	303,300	100 (<0.1)	303,100	300 (0.1)
3	Increased ANCS in hospital settings for RDS, IVH, and NEC	302,300	1,100 (0.4)	298,400	5,000 (1.7)
4	Increased oxygen/CPAP in hospital and clinical settings for RDS	295,300	8,100 (2.7)	261,100	42,300 (13.9)
Improved diagnosis of preterm labor and transfer with current care
5	Increased diagnosis of preterm labor birth, with current levels of care for RDS, IVH, and NEC	302,400	1,000 (0.3)	299,900	3,500 (1.2)
6	Increased diagnosis of imminent preterm birth and transfer to hospitals, with current levels of care for RDS, IVH, and NEC	301,300	2,100 (0.7)	287,100	16,300 (5.4)
Improved diagnosis and transfer with WHO single interventions
7	Increased diagnosis of respiratory distress, transfer, and surfactant (hospitals only) for RDS	299,900	3,500 (1.2)	282,800	20,600 (6.8)
8	Increased diagnosis of imminent preterm birth, transfer to hospitals, and ANCS (hospitals only) for RDS, IVH, and NEC	298,600	4,800 (1.6)	236,700	66,700 (22.0)
9	Increased diagnosis of respiratory distress, transfer, and oxygen/CPAP for preterm RDS	287,400	16,000 (5.3)	176,100	127,300 (42.0)
Improved diagnosis and transfer with WHO packaged interventions
10	Improved diagnosis of imminent preterm birth, transfer to hospitals, ANCS (hospitals only), and treatment with surfactants (hospitals only) and oxygen/CPAP for RDS, IVH, and NEC	289,700	13,700 (4.5)	191,300	112,100 (37.0)
11	Increased diagnosis of respiratory distress, transfer to hospitals, and treatment, including surfactants (hospitals only) and oxygen/CPAP for RDS	286,900	16,500 (5.4)	155,700	147,711 (48.7)
12	Hospital 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 NEC	223,300	80,100 (26.4)	112,800	190,600(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.

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TABLE 4.

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

Scenario No.	Scenario	Incremental Change Model^b		Universal Coverage Model^c
Scenario No.	Scenario	Preterm Deaths, No.^d	Preterm Deaths Prevented Compared With Current Level of Care, No. (%)	Preterm Deaths, No.	Preterm Deaths Prevented Compared With Current Level of Care, No. (%)
1	Current levels of prevention, diagnosis, and treatment	198,400	N/A	198,400	N/A
Improved WHO single interventions
2	Oxygen/CPAP for birth asphyxia in clinics and hospitals	198,000	400 (0.2)	196,800	1,700 (0.9)
3	PPV for birth asphyxia in all settings	197,200	1,200 (0.6)	195,100	4,200 (2.1)
4	Drying and stimulation for birth asphyxia in all settings	196,486	1,900 (1.0)	195,400	3,000 (1.5)
5	Thermal care for LBW, including KMC in all settings and warmers in hospital settings	196,000	2,500 (1.3)	189,400	9,100 (4.6)
6	Antibiotics for suspected neonatal sepsis in all settings	192,100	6,300 (3.2)	180,300	18,200 (9.1)
7	Breastfeeding for sepsis and LBW in all settings	189,300	9,100 (4.6)	168,200	30,200 (15.2)
8	Chlorhexidine for sepsis in home settings and dry cord care in clinical settings	190,800	7,600 (3.8)	159,900	38,500 (19.4)
Improved diagnosis and transfer with current care
9	Diagnosis of birth asphyxia and need for postresuscitation care, with current levels of care	197,200	1,300 (0.7)	196,500	1,900 (1.0)
10	Diagnosis of birth asphyxia and need for postresuscitation care and improved transfer to hospitals, with current levels of care	197,000	1,400 (0.7)	196,200	2,200 (1.1)
11	Diagnosis of sepsis, with current levels of care	194,700	3,700 (1.9)	194,300	4,200 (2.1)
12	Diagnosis of sepsis and transfer to hospitals, with current levels of care	187,400	11,000 (5.5)	184,100	14,300 (7.2)
Improved diagnosis and transfer with WHO single treatment interventions
13	Diagnosis of birth asphyxia and need for postresuscitation care, transfer, and oxygen/CPAP	196,300	2,100 (1.1)	191,700	6,800 (3.4)
14	Diagnosis of birth asphyxia and need for postresuscitation care, transfer, and positive pressure ventilation	195,500	2,900 (1.5)	189,800	8,600 (4.3)
15	Diagnosis of sepsis, transfer, and antibiotics for suspected neonatal sepsis	180,800	17,600 (8.9)	169,800	28,600 (14.3)
Improved diagnosis and transfer with WHO-packaged interventions
16	Drying and stimulation, diagnosis of birth asphyxia and need for postresuscitation care, transfer to hospitals, and treatment, including PPV and oxygen/CPAP	188,057	10,400 (5.2)	172,200	26,200 (13.2)
17	Cord care and breastfeeding, diagnosis of sepsis, transfer, and antibiotics for suspected neonatal sepsis	169,200	29,200 (14.7)	139,400	59,100 (29.8)
18	Packaged interventions 16 and 17, with increased thermal care and breastfeeding for LBW	159,300	39,100 (19.7)	104,000	94,400 (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.