Table 1

Study characteristics of studies assessing neonatal mortality

Author (year)+CountryStudy designDuration of study (months)Study participants and sample sizeSettingInterventionControlMortality as primary outcomeStudy definition of mortality
Antenatal corticosteroidsAlthabe et al20 (2015), Garces et al36 (2016) Klein et al39 (2016)
Argentina, Zambia, Guatemala, India, Pakistan, Kenya
Cluster RCT18Women at risk of preterm birth* from 24+0 to 35+6/7 weeks of gestation/intervention: 2520, control: 2258709 health facilities: 520 clinics and 189 primary health centres, community health clinics or dispensariesMultifaceted: 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 birthStandard careYes≤28 days post birth
<5th percentile birth weight births/intervention: 3268, control: 2997
Rasool et al43 (2017)
RCT1Pregnant 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 hospitalFour 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)NoNeonatal death
Maintenance tocolysisAggarwal et al21 (2018)
RCT18Pregnant 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 hospitalMaintenance tocolysis with oral nidefipine 20 mg 8 hourly for 12 days in established preterm labourStandard careNoPerinatal mortality
Feeding interventions
Donor human milkAdhisivam et al25 (2018)
RCTNAPreterm neonates/intervention: 40, control: 40NICU of a tertiary hospitalFortified pasteurised donor human milk (PDHM)Unfortified PDHMNo≤28 days post birth or discharge whichever was earlier
Formula feedingNandakumar et al42 (2020)
RCT21Preterm neonates born between 27 and 32 weeks of gestation; and birth weight <1500 g/intervention: 62, control: 59Level II NICU of a referral hospitalHybrid milk feeds: mother’s milk supplemented with formula milkMother’s milk aloneNoMost likely simultaneously measured with oxygen dependency at 28 days. (author did not respond)
Infection prevention
Cord cleansing with chlorhexidineArifeen et al27 (2012)
Cluster RCT28LBW† live births/intervention: 3374 (multiple), 3173 (single), control: 3058Three 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 careYes≤28 days post birth
Preterm live births/intervention: 2188 (multiple), 1933 (single), control: 2073
Skin cleansing with chlorhexidineTielsch et al46 (2007)
Cluster RCT31All live births in the study area
Birth weight <2500 g/intervention: 2448, control: 2491
A rural district where >95% of births occur at homeWiping of the total body excluding the eyes and ears with infant wipes that released a 0.25% free chlorhexidine solutionPlaceboYes≤28 days post birth
Topical emollient ointment therapyDarmstadt et al34 (2004)
RCTNAPreterm infants with gestational age <34 weeks/intervention: 51, control: 52NICU of a tertiary hospitalThree times daily topical application of sunflower seed oil (SSO) for the first 14 days, then twice daily until 28 days post birthStandard skin careNoBeyond 2 days post birth until 28 days or discharge.
Darmstadt et al35 (2008)
RCT68Preterm infants ≤72 hours after birth ≤33 weeks of gestation/intervention: 157 Aquaphor, 159 SSO, control: 181Special care nursery of a children’s hospital(1) Topical high-linoleate SSO.
(2) Aquaphor original emollient topical ointment.
Standard skin careNo≤28 days post birth
Erdemir et al 23 (2015)
RCT24Preterm infants ≤34 weeks of gestation/intervention: 100, control: 97Level III NICU of a tertiary hospitalAquaphor original emollient topical ointmentStandard skin careNoNot reported. The infants were studied for a period of 3 weeks
Feeding supplementsAggarwal et al26 (2016)
RCT14VLBW‡ infants with gestational age <32 weeks/intervention: 49 (analysed: 45), control: 50 (analysed: 45)Neonatology department of a tertiary hospitalSupplementation with 10 µg selenium (SE) powder100 mg Glucon-D powder aloneNo≤28 days post birth; during hospital stay or follow-up
Kaur et al37 (2015)
RCT15LBW neonates <2000 g/intervention: 65 (analysed: 63), control: 67Level III NICU of a tertiary hospitalBovine lactoferrin supplementationPlaceboNoAfter the first 72 hours up to 28 days post birth
BCGAaby et al 24 (2011)
RCT39LBW 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 capitalEarly BCG vaccine administered directly after birthLate BCG (when a normal birth weight was obtained or with the first DTP vaccination at 6 weeks of age)YesAt 1 month of age
Biering-Sørensen et al31 (2017)
RCT79LBW 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 capitalEarly BCG vaccine administered directly after birthLate BCGYes≤28 days post birth
Antifungal therapyKirpal et al38 (2016)
RCT19VLBW neonates receiving broad spectrum IV antibiotics for >3 days/ intervention: 40 (analysed: 38), control: 40 (analysed: 37)NICU of a tertiary hospitalIntravenous fluconazole (6 mg/kg) every other day for 7 days, then daily until day 28 post birth or dischargePlaceboNo≤28 days post birth
Strategies of newborn care
Kangaroo mother careNagai et al41 (2010)
RCT14LBW neonates/intervention: 37, control: 36A university referral hospitalEarlier kangaroo mother care (KMC): begin as soon as possible within 24 hours post birthConventional careYes≤28 days post birth
Worku et al47 (2005)
RCT12Neonates with birth weight <2000 g/intervention: 62, control: 61Neonatal unit of a tertiary university hospitalEarlier KMC: begin as soon as possible within 24 hours post birthConventional careYesNot 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)
RCT39Neonates 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 districtsCommunity-based KMCStandard home-based careYes≤28 days post birth
Sloan et al45 (2008)
Cluster RCT15All women aged 12–50 years/intervention: 20 516, control: 19 337Four rural subdistrictsCommunity-based KMCStandard home-based careYes≤28 days post birth
Live births ≤2500 g/intervention: 408, control: 333
Live births ≤2000 g/intervention: 95, control: 71
Home-based neonatal careBang et al29 (1999)
Pre–post intervention trial60LBW live births/observation year: 320, last intervention year: 321A rural, underdeveloped subdistrict of IndiaPackage of home-based neonatal care including management of sepsisPreintervention periodYes≤28 days post birth
Preterm births/observation year: 75, last intervention year: 93
Bang, Baitule et al28 (2005)
Pre–post intervention trial108LBW live births/observation year: 320, last three intervention years: 825A rural, underdeveloped subdistrict of IndiaPackage of home-based neonatal care including management of sepsisPreintervention periodYes≤28 days post birth
Preterm neonates/observation year: 75, last three intervention years: 226
Bang, Reddy et al30 (2005)
Pre–post intervention trial120Preterm neonates/observation year: 75, last two intervention years: 142A rural, underdeveloped subdistrict of IndiaPackage of home-based neonatal care including management of sepsisPreintervention periodYes≤28 days post birth
Training of traditional birth attendantsCarlo et al22 (2010)
Argentina, Democratic Republic of Congo, Guatemala, India, Pakistan, Zambia
ENC: pre–post intervention trial, NRP: cluster RCT24 (ENC)/26 (NRP)VLBW infants/ENC pre-trial: 169, post-trial: 359
NRP intervention: 273, control: 295
ENC: 96 rural communities, NRP: 88 rural communitiesEssential Newborn Care (ENC) training and Neonatal Resuscitation Programme (NRP) trainingENC: preintervention period, NRP: no additional trainingYes7-day neonatal mortality, perinatal mortality and stillbirths
DCCChopra et al33 (2018)
RCT16Pregnant women with gestational age at delivery of ≥35 weeks and an SGA infant <10th percentile/intervention: 55, control: 58Tertiary hospitalDCC after 60 sECC immediately after birthNoNeonatal mortality
Hypothermia preventionSarman et al44 (1989)
RCT10Neonates weighing between 1000 and 2000 g, <7 days of age/intervention: 28, control: 32Neonatal care unit of a university hospitalHypothermia prevention with heated, water-filled mattressAir-heated incubatorsNoNeonatal death
Quality improvement interventionCavicchiolo et al32 (2016)
Pre–post intervention trial24All newborns admitted to the NICU
admission for prematurity/preintervention: 447, postintervention: 605
Obstetrical department and NICU of a large public hospitalQuality improvement intervention focused on infrastructure, equipment and clinical protocolsPreintervention periodYesNeonatal 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.