Two cheap newborn interventions, and where they work

Chlorhexidine applied to the umbilical cord cuts cord infection from 87 to 62 per 1000 newborns, a 29% reduction (RR 0.71; 95% CI 0.60–0.85) ¹. That is the headline of the March 2026 Cochrane review. Chlorhexidine and antenatal corticosteroids are both cheap. The 15-year review includes both positive trials and failed implementation strategies, showing why low price alone does not establish where either intervention should be used.

This article looks at both. For each, it sets out the burden they address, how they work, the key trials, where they failed, and what to watch next.

The burden

In 2022, 2.3 million newborns died in their first 28 days. That is 47% of all deaths in children under five ¹⁷. Newborn deaths have fallen from 5.0 million in 1990, but progress has slowed a lot since 2010 ¹⁷.

The main causes are preterm birth, complications during birth, neonatal infections and congenital anomalies ¹⁷. Sub-Saharan Africa has the highest neonatal mortality rate, at 27 per 1000 live births. Central and southern Asia follows at 21 per 1000 ¹⁷.

Infection. Neonatal infections are among the major causes of newborn death ¹⁷. The umbilical cord stump is one way in. After birth, bacteria can enter through the stump and cause local infection (omphalitis), sepsis and death, most often in low- and middle-income countries (LMICs) ¹.

Preterm birth. An estimated 13.4 million babies were born preterm in 2020, before 37 completed weeks ¹⁸. Complications of preterm birth caused about 900,000 deaths in 2019 ¹⁸. Most preterm births happen in southern Asia and sub-Saharan Africa ¹⁸.

The survival gap is stark. In low-income settings, half of babies born at or before 32 weeks die from lack of basic care. In high-income countries, almost all of them survive ¹⁸. Preterm birth complications are the leading cause of newborn and under-5 deaths ⁶.

How it works

Chlorhexidine

Chlorhexidine is a broad-spectrum antiseptic ². For cord care, a 4% solution or gel is put on the cord stump after birth ¹. As an antiseptic, it stops germs growing on the stump, which is a possible entry point for infection ¹.

In the trials, the schedule varied. In Nepal, field workers cleaned the cord at home on days 1–4, 6, 8 and 10 ¹⁰. In Bangladesh, one arm tested a single cleansing as soon as possible after birth, and another daily cleansing for 7 days ¹¹. In Pakistan, traditional birth attendants applied it at birth and families then applied it daily for up to 14 days ¹².

The alternative is "dry cord care": keeping the stump clean and dry with nothing applied. In many communities, families put substances on the cord that can cause infection. Replacing those with chlorhexidine is part of the goal ⁴.

Antenatal corticosteroids

Antenatal corticosteroids are steroid injections, usually dexamethasone or betamethasone, given to a woman at risk of giving birth early ⁷. They speed up the maturing of the baby's lungs before birth ⁷.

Experimental and human pharmacokinetic studies suggest the lungs mature in response to sustained low steroid levels in the baby, not high peaks ⁷. The standard 24 mg regimen was introduced more than five decades ago and has never gone through a formal dose-finding study ⁷.

The benefit depends on getting the timing and the woman right. WHO recommends the injections from 24 to 34 weeks only when five conditions are met ¹⁶:

• gestational age can be assessed accurately;
• preterm birth is likely within 7 days;
• there is no clinical sign of infection in the mother;
• adequate childbirth care is available, including the ability to manage preterm labour and birth;
• adequate care for the preterm newborn is available, including resuscitation, warmth, feeding support, infection treatment and safe oxygen use ¹⁶.

The reason is simple. Steroids given to a woman who will not deliver early, or whose baby cannot get basic newborn care, can do harm without benefit ⁸.

What the evidence shows

Earlier background: chlorhexidine in Nepal (Lancet 2006)

This trial predates the September 2011 start of the review and is retained as historical context. It was run in Sarlahi, southern Nepal. It randomised 413 communities to 4% chlorhexidine, soap and water, or dry cord care. It included 4,934 infants in the chlorhexidine arm ¹⁰.

Severe omphalitis fell by 75% with chlorhexidine (incidence rate ratio 0.25; 95% CI 0.12–0.53) ¹⁰. Neonatal mortality was 24% lower (RR 0.76; 0.55–1.04), which was not significant overall ¹⁰. In infants enrolled within the first 24 hours, mortality was 34% lower (RR 0.66; 0.46–0.95) ¹⁰. Soap and water did not help ¹⁰.

Chlorhexidine: Bangladesh (Lancet 2012)

In Sylhet, Bangladesh, a cluster trial divided the area into 133 clusters and enrolled 29,760 newborns from 2007 to 2009 ¹¹. Local female village health workers delivered the cord care ¹¹.

A single cleansing cut neonatal mortality from 28.3 to 22.5 per 1000 live births (RR 0.80; 0.65–0.98) ¹¹. Daily cleansing for 7 days did not significantly reduce mortality (RR 0.94; 0.78–1.14), but it did cut severe cord infection (RR 0.35; 0.15–0.81) ¹¹. The trial was funded by USAID and Save the Children's Saving Newborn Lives programme ¹¹.

Chlorhexidine: Pakistan (Lancet 2012)

In Dadu, a rural district of Sindh province, a factorial trial tested chlorhexidine and handwashing promotion in 187 clusters ¹². The chlorhexidine was delivered in birth kits through traditional birth attendants. The trial included 9,741 newborns ¹².

Chlorhexidine cut omphalitis (RR 0.58; 0.41–0.82) and neonatal mortality (RR 0.62; 0.45–0.85) ¹². Handwashing promotion had no measurable effect on either ¹². No serious adverse events were recorded ¹².

Chlorhexidine: Zambia (ZamCAT, Lancet Global Health 2016)

The Zambia Chlorhexidine Application Trial (ZamCAT) ran in Southern Province with 90 health-facility clusters. It enrolled 39,679 women with 37,856 live births, from 2011 to 2013 ¹³. Most births, 63.8%, happened in facilities ¹³.

Neonatal mortality was 15.2 per 1000 live births with chlorhexidine and 13.6 with dry cord care (RR 1.12; 0.88–1.44) ¹³. There was no benefit. The authors conclude that chlorhexidine does not seem to give clear benefit where most births are in facilities and mortality is lower ¹³.

Chlorhexidine: Tanzania (Pemba, Lancet Global Health 2016)

On Pemba Island, Zanzibar, 36,911 newborns from hospital and community births were randomised individually to chlorhexidine or dry cord care from 2011 to 2014 ¹⁴.

Mortality was 10.5 per 1000 live births with chlorhexidine and 11.7 with dry cord care (RR 0.90; 0.74–1.09; p = 0.27) ¹⁴. The difference was not significant ¹⁴.

Chlorhexidine: the Cochrane review (2026)

The Cochrane review, led by Aamer Imdad with Zulfiqar Bhutta, pooled 18 trials with 143,150 participants ¹. It searched up to December 2025 ¹.

In LMICs, chlorhexidine likely reduces omphalitis from 87 to 62 per 1000 (RR 0.71; 0.60–0.85; 5 studies, 128,486 participants; moderate certainty) ¹. For deaths, it drew on 5 population-based trials with 2,280 deaths among 129,381 participants. Neonatal mortality fell from 18 to 15 per 1000 (RR 0.86; 0.73–1.01), with low certainty ¹.

Chlorhexidine: home versus facility births

A 2026 scoping review from India of 16 studies found that in home-birth settings, chlorhexidine cut omphalitis by 68–75% and mortality by 23–38% ². In facility settings, results varied more, with benefits mainly in high-risk groups ². Chlorhexidine skin cleansing for preterm and low-birthweight babies was linked to a 28% reduction in deaths ².

Home birth still carries extra risk where chlorhexidine is used. In Eastern Uganda, a cohort of 2,052 newborns nested in the BabyGel trial run from Busitema University and Mbale found an omphalitis rate of 3.0% (95% CI 1.9–4.4) among babies given chlorhexidine gel. Home-born babies had about twice the risk (aHR 1.99; 1.01–3.9) ³. The BabyGel trial is registered as PACTR202004705649428 ³.

Chlorhexidine: coverage

Using Demographic and Health Survey data from 2017–2018 in Bangladesh and 2016 in Nepal, UNC researchers found chlorhexidine coverage of 15.0% in Bangladesh and 50.7% in Nepal ⁴. Both countries have national policies promoting it ⁴. A harmful substance was put on the cord of 16.9% and 22.6% of newborns respectively ⁴.

Facility birth was the strongest predictor of getting chlorhexidine (Bangladesh OR 2.23; Nepal OR 5.01) ⁴. Poor families and less-educated mothers were not disadvantaged ⁴.

In Enugu, southeast Nigeria, a survey of 191 postpartum women at Poly General Hospital found 52.9% had poor knowledge of chlorhexidine gel for cord care. Only 25.7% had used it for their most recent child ¹⁹.

Antenatal corticosteroids: ACT, the warning before ACTION-I

The ACT cluster-randomised trial, first published online in 2014 and in a 2015 issue, tested a strategy to expand steroid use across six lower-resource countries. Mortality did not fall among the smallest babies used as a proxy for prematurity (risk ratio 0.96, 95% CI 0.87–1.06). Across all births, neonatal mortality increased from 23.9 to 27.4 per 1,000 (risk ratio 1.12, 1.02–1.22), and suspected maternal infection increased ²¹.

ACT tested an implementation strategy, not the same carefully selected hospital population as ACTION-I. Read together, the trials explain why gestational dating, imminent preterm birth and adequate maternal and newborn care are conditions for use, rather than optional additions ¹⁶²¹.

Antenatal corticosteroids: ACTION-I (NEJM 2020)

The WHO ACTION-I trial is the main evidence for steroids in low-resource settings. It falls within the expanded window and should be read alongside ACT.

It enrolled 2,852 women at 26 to 33 weeks and 6 days of gestation, in 29 hospitals across Bangladesh, India, Kenya, Nigeria and Pakistan ¹⁵. Women got intramuscular dexamethasone or placebo. The trial was stopped early for benefit ¹⁵.

Neonatal death occurred in 19.6% of babies with dexamethasone and 23.5% with placebo (RR 0.84; 0.72–0.97) ¹⁵. Stillbirth or neonatal death was 25.7% against 29.2% (RR 0.88; 0.78–0.99) ¹⁵. Possible maternal bacterial infection was 4.8% against 6.3% (RR 0.76; 0.56–1.03), so there was no increase ¹⁵.

Antenatal corticosteroids: WHO 2022 recommendations

WHO updated its recommendations in 2022, drawing on 27 efficacy trials including ACTION-I ¹⁶. Before 34 weeks, there is "compelling evidence" of fewer perinatal and neonatal deaths and less breathing-related illness ¹⁶.

After 34 weeks, the picture is different. There is no difference in mortality, a modest reduction in breathing problems, and more low blood sugar in newborns ¹⁶. WHO limited use to before 34 weeks until there is better evidence of benefit over risk, especially from low-resource countries ¹⁶. That is the gap ACTION-III is designed to fill.

Antenatal corticosteroids: reassurance on the brain

A University of British Columbia review pooled 14 studies: 8 randomised trial follow-ups (n=2,233) and 6 quasi-experimental studies (n=277,679) ⁵. For 19 of 23 outcomes, there was no association with later neurodevelopment ⁵. Among studies at low or moderate risk of bias, there was no link to adverse neurodevelopment ⁵. This helps balance observational alarm about long-term harm.

Antenatal corticosteroids: readiness in facilities

A study using Service Provision Assessments from nine LMICs asked whether facilities could give steroids safely ⁸. Across eight countries with comparable sampling, a median of only 10.7% of facilities had ever given antenatal corticosteroids (range 6.7–35.2%) ⁸. Only a quarter (median 25.3%) had injectable steroids in stock on the day of the survey ⁸.

Overall readiness ranged from 8.1% in Bangladesh to 32.9% in Senegal ⁸. The weakest step was accurate dating of the pregnancy, met by only 7.3% ⁸. Ability to identify maternal infection was 24.8%, adequate preterm newborn care 31.3% and adequate childbirth care 32.9% ⁸.

Results table

LimitsWhat didn't work (or the limits)

Chlorhexidine's effect on deaths is borderline. The pooled mortality result (RR 0.86; 0.73–1.01) crosses 1, and certainty is low ¹. The trials that showed a mortality benefit were in South Asian home-birth settings [10,11,12]. Trials in Zambia and Tanzania were null [13,14]. In high-income countries, the evidence is very uncertain ¹.

It delays cord separation. Cord separation took 1.85 days longer with chlorhexidine in the pooled LMIC trials ¹. In the earlier, pre-window Nepal trial, the mean was 5.32 days with chlorhexidine against 4.24 days with dry cord care ²⁰. Parents and health workers should be told to expect this. The Nepal authors argue the delay should not stop use where infection risk is high ²⁰.

More is not always better. In Bangladesh, a single cleansing cut deaths, but daily cleansing for 7 days did not significantly do so ¹¹. The best frequency is still not settled ¹¹.

Alcohol is not a substitute. For 70% alcohol in LMICs, the Cochrane review found the evidence on infection prevention very uncertain ¹.

Broad steroid rollout caused harm in ACT. The increased neonatal mortality in ACT is a randomised finding about an implementation strategy ²¹. It does not negate benefit in the selected hospital population of ACTION-I ¹⁵.

Steroids depend on the facility. Surveys of facilities in 8 countries found a median of only 10.7% had given antenatal corticosteroids, and readiness ranged from 8.1% in Bangladesh to 32.9% in Senegal ⁸. Without accurate gestational age and care for preterm newborns, steroids cannot be targeted to the babies who benefit ⁸. The authors note that giving steroids in poorly equipped settings can cause harm ⁸.

Harm signals remain in weaker data. A 2026 meta-analysis in Pharmaceuticals reported a relative risk of 1.25 for autism spectrum disorders (95% CI 1.09–1.42) and 1.17 for suspected neurocognitive disorder ⁹. It pools observational data with trials and is lower quality than the UBC review [5,9]. Its own authors say the findings should be read with caution given the proven short-term benefits ⁹.

Late preterm use is not proven. WHO found no mortality benefit after 34 weeks and more low blood sugar in newborns ¹⁶. ACTION-III has no results yet. Only the protocol and dose rationale are published as of September 2026 [6,7].

Cost and scale

Both interventions are cheap. But the sources we reviewed for this article do not report a cost per dose or cost per life saved for either, so we do not quote one.

The real cost is in delivery. For chlorhexidine, the trials that worked used community workers: field workers in Nepal ¹⁰, female village health workers in Bangladesh ¹¹, and traditional birth attendants with birth kits in Pakistan ¹². Programmes that rely only on facility births will miss the home-born babies who benefit most [2,4].

For steroids, the constraint is facility readiness, not drug price. Only a quarter of surveyed facilities had injectable steroids in stock, and far fewer could date pregnancies accurately ⁸.

Coverage. Chlorhexidine reached 15.0% of newborns in Bangladesh and 50.7% in Nepal, despite national policies in both ⁴. In Enugu, Nigeria, 25.7% of mothers had used it for their last child ¹⁹. Steroid use is low: only 10.7% of facilities in the median country had ever given them ⁸.

Guideline status. WHO’s 2022 postnatal guideline recommends clean, dry cord care and limits daily 4% chlorhexidine in the first week to settings where harmful substances are commonly applied to the cord ²². Home birth or a mortality threshold alone is not that recommendation. For steroids, WHO’s 2022 recommendations support use from 24 to before 34 weeks when all five care conditions above are met ¹⁶.

What to watch

ACTION-III (ISRCTN11434567). The WHO ACTION-III trial is enrolling 13,500 women at 34+0 to 36+5 weeks, at seven sites in Bangladesh, India, Kenya, Nigeria and Pakistan ⁶. It compares dexamethasone 4×6 mg, a low-dose betamethasone 4×2 mg, and placebo ⁶. The primary outcome is stillbirth or neonatal death within 72 hours, or newborn respiratory support ⁶. It will also measure safety for women and newborns ⁶.

More than 85% of preterm births are late preterm, so this group matters ⁶. Modelling suggests 2 mg betamethasone every 12 hours for four doses reaches the target fetal level of 1–4 ng/mL without high peaks ⁷. A lower dose could reduce harm to babies who are then born at term ⁷. The trial was registered on 7 June 2021 ⁶.

Chlorhexidine where births are moving into facilities. As more births happen in facilities, the case for routine chlorhexidine gets weaker there [2,13]. The question is how to reach the babies still born at home. Uganda's BabyGel trial, which gave chlorhexidine in a birth kit, is one model ³.

Replacing harmful cord practices. In Nepal, using a harmful substance on the cord made chlorhexidine less likely ⁴. Work that replaces these practices is where chlorhexidine may save the most lives.

Gestational dating. Only 7.3% of facilities met the dating standard ⁸. Better dating would widen safe steroid use more than any change to the drug.

What it means

For ministries of health. The South Asian trials demonstrate potential benefit, but programme eligibility should follow the 2022 WHO guidance: target settings with harmful cord applications, alongside clean, dry cord care elsewhere ²². Coverage estimates in Nepal and Bangladesh describe delivery, not an instruction to treat every newborn ⁴.

In facility births, and in settings where trials were null, the mortality case is weaker [1,13,14]. That uncertainty is another reason to follow the setting-specific WHO recommendation ²².

Antenatal corticosteroids save early preterm babies only in facilities that can date the pregnancy and care for small newborns [8,16]. In ACTION-I, dexamethasone cut neonatal deaths by 16% in 29 secondary- and tertiary-level hospitals ¹⁵. The investment that unlocks this benefit is better gestational dating, such as ultrasound, and newborn care, not more steroid stock.

For clinicians. Give steroids from 24 to before 34 weeks when birth is likely within 7 days, the dates are reliable, there is no sign of maternal infection, and the facility can manage the birth and the baby ¹⁶. Do not give them routinely after 34 weeks outside a trial ¹⁶. For cord care, tell families to expect the cord to fall off about two days later with chlorhexidine ¹.

For funders. Support replacement of harmful cord practices in eligible settings and facility readiness for steroids ⁸²². The result to watch is ACTION-III ⁶. If a lower dose is safe and effective for late preterm birth, it could reach the largest group of preterm babies.