In 2010, many research gaps in the care of preterm and low birth weight (LBW) infants were identified.1 Important questions about the efficacy and effectiveness of interventions for preterm and LBW infants have been answered over the last 10 years,2 yet gaps in the global evidence base remain. A framework of care needed for preterm and LBW infants was developed at a World Health Organization (WHO) guideline development group expert meeting in December 2020.3 Thirty-eight interventions were identified (Tables 1 and 2). Thirty interventions had already been included in other WHO guidelines. Eight interventions with 24 research questions had not been addressed by other WHO guidelines (Table 3).
TABLE 1
Framework for Care of the Preterm or LBW Infant
| Components . | Scope . |
|---|---|
| Target population | Preterm (<37 wk gestation) or LBW (<2.5kg) infants |
| Setting | Care of the infant in both the health facility and the home |
| Focus is low- and middle-income country settings, but the guidelines can be used in all settings | |
| Intervention type | Preventive and promotive care from birth, care for complications |
| Emphasis on (1) the care that all infants need that may have a special impact on preterm and LBW infants and (2) the special care that only preterm and LBW infants need | |
| Intervention period | From birth to 24 mo of life |
| Outcome type | Mortality, morbidity, growth, neurodevelopment |
| Outcome period | At latest follow-up and specific for intervention |
| Important strata and subgroups | <32 wk gestation, ≥32 wk gestation, <1.5kg birth wt, ≥1.5kg birth wt, and specific for intervention |
| Components . | Scope . |
|---|---|
| Target population | Preterm (<37 wk gestation) or LBW (<2.5kg) infants |
| Setting | Care of the infant in both the health facility and the home |
| Focus is low- and middle-income country settings, but the guidelines can be used in all settings | |
| Intervention type | Preventive and promotive care from birth, care for complications |
| Emphasis on (1) the care that all infants need that may have a special impact on preterm and LBW infants and (2) the special care that only preterm and LBW infants need | |
| Intervention period | From birth to 24 mo of life |
| Outcome type | Mortality, morbidity, growth, neurodevelopment |
| Outcome period | At latest follow-up and specific for intervention |
| Important strata and subgroups | <32 wk gestation, ≥32 wk gestation, <1.5kg birth wt, ≥1.5kg birth wt, and specific for intervention |
TABLE 2
Interventions for Care of the Preterm or LBW Infant
| Domain . | Intervention . |
|---|---|
| Preventive and promotive care of the infant from birth | |
| Delivery management | Early identification of preterm and LBW infants |
| Cord clamping | |
| Infection prevention | Infection prevention |
| Vaccination | |
| Thermal care | Kangaroo mother care |
| Thermal care if kangaroo mother care cannot be done | |
| Responsive care | Responsive caregiving |
| Positioning during care | |
| Sleep positioning | |
| Prevention of injury and pain | Injury prevention |
| Pain management | |
| Nutrition | Milk feeding |
| Micronutrients | |
| Probiotics | Probiotics |
| Skin, cord, eye care and bathing | Emollients |
| Cord care | |
| Eye care | |
| Bathing | |
| Congenital and metabolic screening | Metabolic screening |
| Congenital abnormality screening | |
| Discharge and postdischarge care | Discharge preparedness |
| Hearing, vision, growth, neurodevelopment | |
| Management of respiratory complications | |
| Respiratory distress and apnea | Oxygen |
| Surfactant | |
| Continuous positive airway pressure | |
| Methylxanthines | |
| Chronic lung disease | Bronchopulmonary dysplasia |
| Management of other preterm and LBW complications | |
| Growth and neurodevelopment | Growth failure |
| Encephalopathy | |
| Neurodisability, hearing, vision, retinopathy | |
| Gastrointestinal | Necrotizing enterocolitis |
| Metabolic | Hypoglycemia |
| Hyperbilirubinemia | |
| Anemia | |
| Polycythemia | |
| Management of other neonatal problems | |
| Including sepsis, respiratory, diarrhea | |
| Family care | |
| Family involvement | |
| Family support |
| Domain . | Intervention . |
|---|---|
| Preventive and promotive care of the infant from birth | |
| Delivery management | Early identification of preterm and LBW infants |
| Cord clamping | |
| Infection prevention | Infection prevention |
| Vaccination | |
| Thermal care | Kangaroo mother care |
| Thermal care if kangaroo mother care cannot be done | |
| Responsive care | Responsive caregiving |
| Positioning during care | |
| Sleep positioning | |
| Prevention of injury and pain | Injury prevention |
| Pain management | |
| Nutrition | Milk feeding |
| Micronutrients | |
| Probiotics | Probiotics |
| Skin, cord, eye care and bathing | Emollients |
| Cord care | |
| Eye care | |
| Bathing | |
| Congenital and metabolic screening | Metabolic screening |
| Congenital abnormality screening | |
| Discharge and postdischarge care | Discharge preparedness |
| Hearing, vision, growth, neurodevelopment | |
| Management of respiratory complications | |
| Respiratory distress and apnea | Oxygen |
| Surfactant | |
| Continuous positive airway pressure | |
| Methylxanthines | |
| Chronic lung disease | Bronchopulmonary dysplasia |
| Management of other preterm and LBW complications | |
| Growth and neurodevelopment | Growth failure |
| Encephalopathy | |
| Neurodisability, hearing, vision, retinopathy | |
| Gastrointestinal | Necrotizing enterocolitis |
| Metabolic | Hypoglycemia |
| Hyperbilirubinemia | |
| Anemia | |
| Polycythemia | |
| Management of other neonatal problems | |
| Including sepsis, respiratory, diarrhea | |
| Family care | |
| Family involvement | |
| Family support |
TABLE 3
Prioritized Interventions (n = 8) and PICO Questions (n = 24) for Care of the Preterm or LBW Infant
| Interventions . | PICO . |
|---|---|
| Thermal care | |
| Kangaroo mother care | In preterm or LBW infants (P), what is the effect of KMC (I) compared with conventional neonatal care (C) on critical outcomes (O)? If KMC is effective, then what is the effect of early‐onset KMC (I) compared with late‐onset KMC (C) on critical outcomes (O)? What is the effect of short (I) compared with longer (C) durations of KMC on critical outcomes (O)? |
| Milk feeding | |
| Mother’s own milk | In preterm or LBW infants (P), what is the effect of feeding mother's own milk (I) compared with feeding infant formula (C) on critical outcomes (O)? |
| Donor human milk | In preterm or LBW infants who cannot be fed mother's own milk (P), what is the effect of feeding donor human milk (I) compared with feeding infant formula (C) on critical outcomes (O)? |
| Fortification | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of multicomponent fortification of milk (I) compared with no fortification (C) on critical outcomes (O)? |
| Infant formula | In preterm or LBW infants who cannot be fed mother's own milk or donor human milk (P), what is the effect of feeding nutrient enriched (“preterm”) infant formula (I) compared with feeding standard infant (“term”) formula (C) on critical outcomes (O)? |
| Initiation of enteral feeding | In preterm or LBW infants (P), what is the effect of early initiation of enteral feeding (I) compared with delayed feeding (C) on critical outcomes (O)? If early, then when should feeding be initiated? Does this effect differ in infants given full enteral feeding compared with infants given restricted volumes, including minimal enteral feeding? |
| Responsive feeding | In preterm or LBW infants who receive any enteral feeding (P), what is the effect of responsive feeding based on infants’ cues (I) compared with scheduled feeding (C) on critical outcomes (O)? |
| Volume advancement | In preterm or LBW infants who receive any enteral feeding (P), what is the effect of fast advancement of enteral feeds (I) versus slower rates of feed advancement (C) on critical outcomes (O)? |
| Duration of exclusive breastfeeding | In preterm or LBW infants (P), what is the effect of exclusive breastfeeding for <6 mo (I) compared with exclusive breastfeeding for 6 mo (C) on critical outcomes (O)? If <6 mo, then what is the optimal duration? |
| Micronutrients | |
| Iron | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of enteral iron supplementation (I) compared with no iron supplementation (C) on critical outcomes (O)? |
| Zinc | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of enteral zinc supplementation (I) compared with no zinc supplementation (C) on critical outcomes (O)? |
| Vitamin D | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of enteral vitamin D supplementation (I) compared with no vitamin D supplementation (C) on critical outcomes (O)? |
| Vitamin A | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of enteral vitamin A supplementation (I) compared with no vitamin A supplementation (C) on critical outcomes (O)? |
| Calcium and phosphorous | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of enteral calcium and phosphorous supplementation (I) compared with no supplementation (C) on critical outcomes (O)? |
| Multiple micronutrient supplements | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of enteral multiple micronutrient supplements (I) compared with no enteral multiple micronutrient supplements (C) on critical outcomes (O)? |
| Probiotics | In preterm or LBW infants who receive any enteral feeding (P), what is the effect of probiotics (I) versus no probiotics (C) on critical outcomes (O)? |
| Skin care | |
| Emolients | In preterm or LBW infants (P) what is the effect of topical ointment, cream or oil applied to the skin (I) compared with routine skin care (C) on critical outcomes (O)? |
| CPAP respiratory support | |
| CPAP for respiratory distress | In preterm infants with respiratory distress syndrome (P), what is the effect of any CPAP therapy (I) versus supportive care with oxygen therapy by head box, face mask, or nasal cannula (C) on critical outcomes (O)? |
| Early CPAP | In preterm infants with respiratory distress syndrome (P), what is the effect of early CPAP (I) versus late CPAP(C) on critical outcomes (O)? |
| CPAP prophylaxis | In preterm infants <32 wks, regardless of respiratory status (P), what is the effect of CPAP started immediately after birth (I) compared with supportive care with oxygen therapy by head box, face mask, or nasal cannula (C) on critical outcomes (O)? What is the effect of CPAP started immediately after birth (I) compared with mechanical ventilation (C) on critical outcomes (O)? |
| CPAP pressure source | In preterm infants with respiratory distress syndrome, what is the effect of bubble (I) compared with other forms of CPAP (C) on critical outcomes (O)? |
| Methylxanthine respiratory management | In preterm infants, what is the effect of any methylxanthine compared with no methylxanthine on critical outcomes? What is the effect by indication (any, prevention, treatment), by type of methylxanthine (eg, caffeine, theophylline) and by gestational age or birth wt? |
| Family care | |
| Family involvement | In hospitalized preterm or LBW infants (P), do interventions to involve families in the infant’s routine health care (family involvement strategies) (I) compared with standard hospital or NICU care (C) improve critical outcomes (O)? |
| Family support | In preterm or LBW infants (P), do interventions to support the family to care for the infant in the home (I) compared with no or different interventions (C) improve critical outcomes (O)? |
| Interventions . | PICO . |
|---|---|
| Thermal care | |
| Kangaroo mother care | In preterm or LBW infants (P), what is the effect of KMC (I) compared with conventional neonatal care (C) on critical outcomes (O)? If KMC is effective, then what is the effect of early‐onset KMC (I) compared with late‐onset KMC (C) on critical outcomes (O)? What is the effect of short (I) compared with longer (C) durations of KMC on critical outcomes (O)? |
| Milk feeding | |
| Mother’s own milk | In preterm or LBW infants (P), what is the effect of feeding mother's own milk (I) compared with feeding infant formula (C) on critical outcomes (O)? |
| Donor human milk | In preterm or LBW infants who cannot be fed mother's own milk (P), what is the effect of feeding donor human milk (I) compared with feeding infant formula (C) on critical outcomes (O)? |
| Fortification | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of multicomponent fortification of milk (I) compared with no fortification (C) on critical outcomes (O)? |
| Infant formula | In preterm or LBW infants who cannot be fed mother's own milk or donor human milk (P), what is the effect of feeding nutrient enriched (“preterm”) infant formula (I) compared with feeding standard infant (“term”) formula (C) on critical outcomes (O)? |
| Initiation of enteral feeding | In preterm or LBW infants (P), what is the effect of early initiation of enteral feeding (I) compared with delayed feeding (C) on critical outcomes (O)? If early, then when should feeding be initiated? Does this effect differ in infants given full enteral feeding compared with infants given restricted volumes, including minimal enteral feeding? |
| Responsive feeding | In preterm or LBW infants who receive any enteral feeding (P), what is the effect of responsive feeding based on infants’ cues (I) compared with scheduled feeding (C) on critical outcomes (O)? |
| Volume advancement | In preterm or LBW infants who receive any enteral feeding (P), what is the effect of fast advancement of enteral feeds (I) versus slower rates of feed advancement (C) on critical outcomes (O)? |
| Duration of exclusive breastfeeding | In preterm or LBW infants (P), what is the effect of exclusive breastfeeding for <6 mo (I) compared with exclusive breastfeeding for 6 mo (C) on critical outcomes (O)? If <6 mo, then what is the optimal duration? |
| Micronutrients | |
| Iron | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of enteral iron supplementation (I) compared with no iron supplementation (C) on critical outcomes (O)? |
| Zinc | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of enteral zinc supplementation (I) compared with no zinc supplementation (C) on critical outcomes (O)? |
| Vitamin D | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of enteral vitamin D supplementation (I) compared with no vitamin D supplementation (C) on critical outcomes (O)? |
| Vitamin A | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of enteral vitamin A supplementation (I) compared with no vitamin A supplementation (C) on critical outcomes (O)? |
| Calcium and phosphorous | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of enteral calcium and phosphorous supplementation (I) compared with no supplementation (C) on critical outcomes (O)? |
| Multiple micronutrient supplements | In preterm or LBW infants who are fed mother's own milk or donor human milk (P), what is the effect of enteral multiple micronutrient supplements (I) compared with no enteral multiple micronutrient supplements (C) on critical outcomes (O)? |
| Probiotics | In preterm or LBW infants who receive any enteral feeding (P), what is the effect of probiotics (I) versus no probiotics (C) on critical outcomes (O)? |
| Skin care | |
| Emolients | In preterm or LBW infants (P) what is the effect of topical ointment, cream or oil applied to the skin (I) compared with routine skin care (C) on critical outcomes (O)? |
| CPAP respiratory support | |
| CPAP for respiratory distress | In preterm infants with respiratory distress syndrome (P), what is the effect of any CPAP therapy (I) versus supportive care with oxygen therapy by head box, face mask, or nasal cannula (C) on critical outcomes (O)? |
| Early CPAP | In preterm infants with respiratory distress syndrome (P), what is the effect of early CPAP (I) versus late CPAP(C) on critical outcomes (O)? |
| CPAP prophylaxis | In preterm infants <32 wks, regardless of respiratory status (P), what is the effect of CPAP started immediately after birth (I) compared with supportive care with oxygen therapy by head box, face mask, or nasal cannula (C) on critical outcomes (O)? What is the effect of CPAP started immediately after birth (I) compared with mechanical ventilation (C) on critical outcomes (O)? |
| CPAP pressure source | In preterm infants with respiratory distress syndrome, what is the effect of bubble (I) compared with other forms of CPAP (C) on critical outcomes (O)? |
| Methylxanthine respiratory management | In preterm infants, what is the effect of any methylxanthine compared with no methylxanthine on critical outcomes? What is the effect by indication (any, prevention, treatment), by type of methylxanthine (eg, caffeine, theophylline) and by gestational age or birth wt? |
| Family care | |
| Family involvement | In hospitalized preterm or LBW infants (P), do interventions to involve families in the infant’s routine health care (family involvement strategies) (I) compared with standard hospital or NICU care (C) improve critical outcomes (O)? |
| Family support | In preterm or LBW infants (P), do interventions to support the family to care for the infant in the home (I) compared with no or different interventions (C) improve critical outcomes (O)? |
PICO, population, intervention, comparator, outcome; KMC, kangaroo mother care.
An overview of the systematic reviews process was conducted (as outlined in paper 1 of this supplement),4 to understand which systematic reviews, if any, had addressed the 24 research questions in the last 3 years. Eight had already been addressed by published systematic reviews (donor human milk, multicomponent fortifier, formula milk, probiotics, emollients, use of continuous positive airways pressure [CPAP] in infants with respiratory distress syndrome, early initiation of CPAP, and prophylactic CPAP). Sixteen required new systematic reviews (kangaroo mother care, mother’s own milk, early initiation, responsive feeding, advancement of feeding, duration of exclusive breastfeeding, iron, zinc, vitamin A, vitamin D, calcium and phosphorous, multiple micronutrients, methylxanthines, family involvement, and family support).
The sixteen systematic reviews were subsequently completed. Four have been published elsewhere (kangaroo mother care, CPAP pressure source, methylxanthines, family support).5–8 Twelve are presented in this supplement. These reviews fill a much-needed gap in the evidence base. They can be used by the global public health community to (1) understand the impact, research priorities, and implementation considerations and (2) assist in the development of policies and programs to improve the care of these most vulnerable preterm and LBW infants.
Dr Edmond conceptualized and designed the study, drafted the initial manuscript, and approved the final manuscript as submitted.
FUNDING: No external funding.
CONFLICT OF INTEREST DISCLOSURES: The author has indicated they have no potential conflicts of interest relevant to this article to disclose.
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