Author (year)+Country | Study design | Duration of study (months) | Study participants and sample size | Setting | Intervention | Control | Mortality as primary outcome | Study definition of mortality | |
ANTENATAL INTERVENTIONS | |||||||||
Antenatal corticosteroids | Althabe et al20 (2015), Garces et al36 (2016) Klein et al39 (2016) Argentina, Zambia, Guatemala, India, Pakistan, Kenya | Cluster RCT | 18 | Women at risk of preterm birth* from 24+0 to 35+6/7 weeks of gestation/intervention: 2520, control: 2258 | 709 health facilities: 520 clinics and 189 primary health centres, community health clinics or dispensaries | Multifaceted: health-provider training, posters, pregnancy disc and uterine height tape to facilitate identification of women at risk of preterm birth, one course of four doses of 6 mg of dexamethasone intramuscular every 12 hours, referral recommendation for women identified as at high risk of preterm birth | Standard care | Yes | ≤28 days post birth |
<5th percentile birth weight births/intervention: 3268, control: 2997 | |||||||||
Rasool et al43 (2017) Pakistan | RCT | 1 | Pregnant women 28– 36 weeks of gestation, admitted to the hospital because of premature contractions or risk of preterm delivery/intervention: 25 (analysed: 24), control: 25 (analysed: 24) | NICU of a teaching hospital | Four doses of 6 mg dexamethasone 12 hours apart (route of admission not reported) | Two doses of 12 mg of dexamethasone 24 hours apart (route of admission not reported) | No | Neonatal death | |
Maintenance tocolysis | Aggarwal et al21 (2018) India | RCT | 18 | Pregnant women between 26 and 33+6/7 weeks of gestation and arrested preterm labour/intervention: 25, control: 25 Preterm deliveries/intervention: 18 control: 23 | Tertiary hospital | Maintenance tocolysis with oral nidefipine 20 mg 8 hourly for 12 days in established preterm labour | Standard care | No | Perinatal mortality |
POSTNATAL INTERVENTIONS | |||||||||
Feeding interventions | |||||||||
Donor human milk | Adhisivam et al25 (2018) India | RCT | NA | Preterm neonates/intervention: 40, control: 40 | NICU of a tertiary hospital | Fortified pasteurised donor human milk (PDHM) | Unfortified PDHM | No | ≤28 days post birth or discharge whichever was earlier |
Formula feeding | Nandakumar et al42 (2020) India | RCT | 21 | Preterm neonates born between 27 and 32 weeks of gestation; and birth weight <1500 g/intervention: 62, control: 59 | Level II NICU of a referral hospital | Hybrid milk feeds: mother’s milk supplemented with formula milk | Mother’s milk alone | No | Most likely simultaneously measured with oxygen dependency at 28 days. (author did not respond) |
Infection prevention | |||||||||
Cord cleansing with chlorhexidine | Arifeen et al27 (2012) Bangladesh | Cluster RCT | 28 | LBW† live births/intervention: 3374 (multiple), 3173 (single), control: 3058 | Three rural subdistricts of northern Bangladesh | (1) Single cleansing on the cord: 4% aqueous chlorhexidine solution once at birth. (2) Multiple cleansing: at birth plus daily for 7 days. | Dry cord care | Yes | ≤28 days post birth |
Preterm live births/intervention: 2188 (multiple), 1933 (single), control: 2073 | |||||||||
Skin cleansing with chlorhexidine | Tielsch et al46 (2007) Nepal | Cluster RCT | 31 | All live births in the study area Birth weight <2500 g/intervention: 2448, control: 2491 | A rural district where >95% of births occur at home | Wiping of the total body excluding the eyes and ears with infant wipes that released a 0.25% free chlorhexidine solution | Placebo | Yes | ≤28 days post birth |
Topical emollient ointment therapy | Darmstadt et al34 (2004) Egypt | RCT | NA | Preterm infants with gestational age <34 weeks/intervention: 51, control: 52 | NICU of a tertiary hospital | Three times daily topical application of sunflower seed oil (SSO) for the first 14 days, then twice daily until 28 days post birth | Standard skin care | No | Beyond 2 days post birth until 28 days or discharge. |
Darmstadt et al35 (2008) Bangladesh | RCT | 68 | Preterm infants ≤72 hours after birth ≤33 weeks of gestation/intervention: 157 Aquaphor, 159 SSO, control: 181 | Special care nursery of a children’s hospital | (1) Topical high-linoleate SSO. (2) Aquaphor original emollient topical ointment. | Standard skin care | No | ≤28 days post birth | |
Erdemir et al 23 (2015) Turkey | RCT | 24 | Preterm infants ≤34 weeks of gestation/intervention: 100, control: 97 | Level III NICU of a tertiary hospital | Aquaphor original emollient topical ointment | Standard skin care | No | Not reported. The infants were studied for a period of 3 weeks | |
Feeding supplements | Aggarwal et al26 (2016) India | RCT | 14 | VLBW‡ infants with gestational age <32 weeks/intervention: 49 (analysed: 45), control: 50 (analysed: 45) | Neonatology department of a tertiary hospital | Supplementation with 10 µg selenium (SE) powder | 100 mg Glucon-D powder alone | No | ≤28 days post birth; during hospital stay or follow-up |
Kaur et al37 (2015) India | RCT | 15 | LBW neonates <2000 g/intervention: 65 (analysed: 63), control: 67 | Level III NICU of a tertiary hospital | Bovine lactoferrin supplementation | Placebo | No | After the first 72 hours up to 28 days post birth | |
BCG | Aaby et al 24 (2011) Guinea-Bissau | RCT | 39 | LBW infants/intervention: 1182 (analysed: 1168), control: 1161 (analysed: 1152) | Six districts with a population of around 102 000, including 30% of the inhabitants of the capital | Early BCG vaccine administered directly after birth | Late BCG (when a normal birth weight was obtained or with the first DTP vaccination at 6 weeks of age) | Yes | At 1 month of age |
Biering-Sørensen et al31 (2017) Guinea-Bissau | RCT | 79 | LBW infants/intervention: 2062 (analysed: 2059), control: 2071 (analysed: 2061) | Six districts with a population of around 102 000, including 30% of the inhabitants of the capital | Early BCG vaccine administered directly after birth | Late BCG | Yes | ≤28 days post birth | |
Antifungal therapy | Kirpal et al38 (2016) India | RCT | 19 | VLBW neonates receiving broad spectrum IV antibiotics for >3 days/ intervention: 40 (analysed: 38), control: 40 (analysed: 37) | NICU of a tertiary hospital | Intravenous fluconazole (6 mg/kg) every other day for 7 days, then daily until day 28 post birth or discharge | Placebo | No | ≤28 days post birth |
Strategies of newborn care | |||||||||
Kangaroo mother care | Nagai et al41 (2010) Madagascar | RCT | 14 | LBW neonates/intervention: 37, control: 36 | A university referral hospital | Earlier kangaroo mother care (KMC): begin as soon as possible within 24 hours post birth | Conventional care | Yes | ≤28 days post birth |
Worku et al47 (2005) Ethiopia | RCT | 12 | Neonates with birth weight <2000 g/intervention: 62, control: 61 | Neonatal unit of a tertiary university hospital | Earlier KMC: begin as soon as possible within 24 hours post birth | Conventional care | Yes | Not reported. The mean age at exit from the study was 4.6 days for KMC and 5.4 days for CMC | |
Mazumder et al40 (2019) India | RCT | 39 | Neonates weighing 1500–2250 g at home within 72 hours of birth, stable and feeding/intervention: 4480 (4470 analysed), control: 3922 (3914 analysed) | Rural and semiurban areas in two districts | Community-based KMC | Standard home-based care | Yes | ≤28 days post birth | |
Sloan et al45 (2008) Bangladesh | Cluster RCT | 15 | All women aged 12–50 years/intervention: 20 516, control: 19 337 | Four rural subdistricts | Community-based KMC | Standard home-based care | Yes | ≤28 days post birth | |
Live births ≤2500 g/intervention: 408, control: 333 | |||||||||
Live births ≤2000 g/intervention: 95, control: 71 | |||||||||
Home-based neonatal care | Bang et al29 (1999) India | Pre–post intervention trial | 60 | LBW live births/observation year: 320, last intervention year: 321 | A rural, underdeveloped subdistrict of India | Package of home-based neonatal care including management of sepsis | Preintervention period | Yes | ≤28 days post birth |
Preterm births/observation year: 75, last intervention year: 93 | |||||||||
Bang, Baitule et al28 (2005) India | Pre–post intervention trial | 108 | LBW live births/observation year: 320, last three intervention years: 825 | A rural, underdeveloped subdistrict of India | Package of home-based neonatal care including management of sepsis | Preintervention period | Yes | ≤28 days post birth | |
Preterm neonates/observation year: 75, last three intervention years: 226 | |||||||||
Bang, Reddy et al30 (2005) India | Pre–post intervention trial | 120 | Preterm neonates/observation year: 75, last two intervention years: 142 | A rural, underdeveloped subdistrict of India | Package of home-based neonatal care including management of sepsis | Preintervention period | Yes | ≤28 days post birth | |
Training of traditional birth attendants | Carlo et al22 (2010) Argentina, Democratic Republic of Congo, Guatemala, India, Pakistan, Zambia | ENC: pre–post intervention trial, NRP: cluster RCT | 24 (ENC)/26 (NRP) | VLBW infants/ENC pre-trial: 169, post-trial: 359 NRP intervention: 273, control: 295 | ENC: 96 rural communities, NRP: 88 rural communities | Essential Newborn Care (ENC) training and Neonatal Resuscitation Programme (NRP) training | ENC: preintervention period, NRP: no additional training | Yes | 7-day neonatal mortality, perinatal mortality and stillbirths |
Others | |||||||||
DCC | Chopra et al33 (2018) India | RCT | 16 | Pregnant women with gestational age at delivery of ≥35 weeks and an SGA infant <10th percentile/intervention: 55, control: 58 | Tertiary hospital | DCC after 60 s | ECC immediately after birth | No | Neonatal mortality |
Hypothermia prevention | Sarman et al44 (1989) Turkey | RCT | 10 | Neonates weighing between 1000 and 2000 g, <7 days of age/intervention: 28, control: 32 | Neonatal care unit of a university hospital | Hypothermia prevention with heated, water-filled mattress | Air-heated incubators | No | Neonatal death |
Quality improvement intervention | Cavicchiolo et al32 (2016) Mozambique | Pre–post intervention trial | 24 | All newborns admitted to the NICU admission for prematurity/preintervention: 447, postintervention: 605 | Obstetrical department and NICU of a large public hospital | Quality improvement intervention focused on infrastructure, equipment and clinical protocols | Preintervention period | Yes | Neonatal mortality |
*Preterm birth/neonate=<37 weeks of gestation.
†LBW=low birth weight (< 2500 g).
‡VLBW=very low birth weight (< 1500 g).
CMC, conventional method of care; DCC, delayed cord clamping; DTP, diphteria, tetanus, pertussis; ECC, early cord clamping; ENC, essential newborn care; IV, intravenous; KMC, kangaroo mother care; NICU, neonatal intensive care unit; NRP, neonatal resuscitation program; PDHM, pasteurised donor human milk; RCT, randomised controlled trial; Se, selenium; SGA, small for gestational age; SSO, sunflower seed oil.