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Optimising outcomes for preterm infants is a priority for those providing neonatal care. Active care for infants as low as 22–23 weeks of gestational age (GA) is increasing, although outcomes for this population are variable depending on the region where they are born and the enthusiasm of the responsible physician for active care in this high-risk population []. For infants 24 weeks of GA and above, there is a shift towards less invasive management with protocols for management of respiratory distress syndrome (RDS) centred on protecting the delicate lungs from injury. Data on nearly 60,000 babies born at <1,500 g from the Vermont Oxford Network and admitted to NICUs show that in 2024, around 75% of 24–26 weeks of gestation babies survive, although rates of bronchopulmonary dysplasia (BPD) remain stubbornly high at 60%. In 2024, nearly 90% of 24–26-week infants received surfactant, dropping to 65% at 27–29 weeks and 32% for 30–32 weeks of GA. Nearly 90% of 24–26-week infants were mechanically ventilated, dropping to 55% at 27–29 weeks and 25% at 30–32 weeks of GA (data available on Nightingale). There is now good evidence that a gentler approach aimed at minimising exposure to the harmful effects of positive pressure ventilation may result in greater numbers of survivors without BPD, but clearly, there is more work to be done in terms of convincing clinicians to change practice.

The “European Consensus Guidelines on the Management of RDS” were first published in 2007 [], primarily intended for use in Europe, but with evidence-based recommendations that could potentially be used anywhere, provided that clinicians had access to the resources needed to deliver modern neonatal intensive care. The guidelines have been updated every 3 years since 2010 with previous versions collectively being cited over 4,400 times, and this being the 7th version, using data from clinical research studies to 2025.

RDS is a disorder of surfactant deficiency resulting in clinical signs of respiratory distress from soon after birth that may impact the ability to transition smoothly from intrauterine to extrauterine life. Defining RDS is challenging, with classical definitions such as “ground glass and air bronchograms” on X-ray being late signs which can be avoided by early non-invasive respiratory support (NRS) and surfactant replacement therapy. Clinical judgement on work of breathing and oxygen requirements in the delivery room is subjective, but often the only way to decide if surfactant is needed, and babies will be coded as having RDS if they have received surfactant. Therefore, it is difficult to be certain how many infants who receive surfactant genuinely have RDS. The aim of management of RDS is to maximise the numbers of infants who survive without lung injury. Given that manual lung inflations or mechanical ventilation (MV) have the potential to cause lung injury, there is a delicate balance to be struck. Thankfully, many of the interventions employed are studied in randomised trials, and many of these are also subjected to systematic reviews. These guidelines update the previous six versions after critical examination of the most recent evidence up to autumn 2025. As before, we have used a format of summarising the issues in the text followed by evidence-based recommendations according to the GRADE system, to reflect the authors’ consensus view of both the strength of the evidence supporting each recommendation, and the strength of the recommendation []. Quality of evidence and strength of recommendation are summarised in . Summary of the recommendations is shown in online supplementary Material 1 (for all online suppl. material, see https://doi.org/10.1159/000551062 ).

Prenatal management remains largely unchanged, perhaps with more emphasis on confirming preterm labour, to allow more judicious use of antenatal steroids. In the delivery room, we suggest physiologically-based cord clamping rather than time-based approach, with an emphasis on strategies for managing thermal care if equipment is available before the cord is cut. Starting FiO 2 of 0.6 rather than 0.3 at birth should reduce bradycardia and need for chest compressions and adrenaline for infants born <29 weeks of GA, albeit with no differences in other outcomes. Surfactant prophylaxis has reappeared for extremely preterm infants in the current era of less invasive surfactant administration (LISA), with an emphasis on use of videolaryngoscopy for LISA catheter placement or intubation because of greater first pass success for intubations. Nasal ventilation rather than continuous positive airways pressure (CPAP) now seems the most potent mode of NRS, both after initial stabilisation and when coming off MV, although there is no unified approach as to how best to provide it. For babies who have not received prophylactic surfactant, the treatment thresholds of FiO 2 0.3 are unchanged, but with more emphasis on using ultrasound where possible to diagnose RDS regardless of FiO 2 requirements in babies with signs of respiratory distress.

Lack of antenatal care increases risk of death or severe morbidity []. General measures to prevent preterm birth include prevention of teenage pregnancies, adequate pregnancy spacing, prevention of unnecessary caesarean sections (CSs), early screening for preeclampsia, and treatment with low-dose aspirin in women at risk, and single embryo transfer when in vitro fertilisation is used [].

In asymptomatic pregnant women at risk of spontaneous preterm birth, due to either previous preterm birth or where a shortened cervix by the end of the first half of pregnancy has been identified, use of progesterone is associated with a reduced rate of preterm birth and lowered perinatal mortality [, ]. The efficacy of progesterone in pregnant women with previous preterm birth, who do not have short cervix, has been questioned []. In twin pregnancies with short cervix, progesterone may decrease risk of very preterm births []. Cervical cerclage may also reduce preterm birth in high-risk singleton pregnancies [, ]. The present challenge is to identify the high-risk pregnancies early and to aim for effective prevention of preterm birth. The same holds for omega-3 fatty acid supplementation, which may also reduce preterm delivery [], but likely only in populations with poor nutrition.

Interventions to improve outcomes and prevent RDS begin before birth. There is often warning of impending preterm delivery, and there is a need to consider interventions to prolong gestation or to reduce risk of an adverse outcome by “preparing” the foetus. Cervical length measurement, possibly in combination with a biomarker [], may determine which women are actually at risk of delivery within 7 days, perhaps allow more judicious use of antenatal treatments. Preterm foetuses with expected delivery before 28–30 weeks of gestation should, where possible, be transported in utero to tertiary centres where appropriate skills are available; best outcomes are achieved for immature infants born in high throughput perinatal centres []. In cases of prenatal pre-labour rupture of membranes, antibiotics can delay preterm delivery and reduce neonatal morbidity, although co-amoxiclav (amoxicillin/cluvulanic acid 4:1) should be avoided because of its association with increased risk of NEC [].

Magnesium sulphate, given to women with imminent preterm delivery before 32 weeks, reduces the incidence of cerebral palsy at 2 years of age by about 30%, although longer term benefits are less clear [, ]. A reduction of cerebral palsy may be obtained if magnesium sulphate is given as little as 4 h before delivery, so advanced dilation is not a contraindication to treatment []. Overdosing must be avoided given the maternal side effects such as vasodilatation with hypotension and neuromuscular blockage. Tocolytic drugs can be used in the short term to delay birth, allow safe transfer to a perinatal centre, and allow prenatal corticosteroids time to take effect, although beneficial effects on perinatal outcome are uncertain []. Of the tocolytic drugs oxytocin antagonists and Ca channel blockers are quite safe to both the foetus and the mother and should be used rather than indomethacin. There is little evidence that delivering preterm infants by CS rather than allowing vaginal delivery improves outcome, although it may help around assembling appropriate team for stabilisation when planned electively [].

A single course of antenatal corticosteroids (ANCS) given to mothers with anticipated preterm delivery before 34 weeks of gestation improves survival reduces risk of RDS, NEC, and IVH and does not appear to be associated with any significant maternal or short-term foetal adverse effects []. Even with modern neonatal care, ANCS are beneficial. The beneficial effects are also evident in low-resource countries when the indications are defined []. ANCS therapy is recommended in all pregnancies with threatened preterm birth before 34 weeks of gestation where active care of the newborn is anticipated. Although RCT data are limited in babies at <25 weeks of gestation, observational studies support the concept that ANCS, together with other active management practices, reduce mortality even down to 22 weeks [, ]. The decision to administer ANCS should be concordant with neonatal treatment plans and informing the mother or parents of their desire for either intensive care or palliative care after birth and decisions should always be taken only after full discussion with mothers and partners of potential benefits and risks. [, ]. ANCS are associated with a decrease in the early mortality of infants born at 22–25 weeks in US academic centres. Death or neurodevelopmental impairment at 18–22 months was lower for the ANCS-exposed infants born at 23–25 weeks [].

In pregnancies between 34 and 37 weeks of gestation, ANCS reduce risk of short-term respiratory morbidity, but not mortality, and there is increased risk of neonatal hypoglycaemia []; with increasing gestation, the benefits decrease, whereas the incidence of hypoglycaemia increases [, ]. In women in spontaneous preterm labour after 34 weeks, the use of ANCS is therefore controversial and not advisable [, ]. The situation may be different in CS without labour in between 34 and 37 weeks, where ANCS are possibly indicated.

The optimal treatment to delivery interval is more than 24 h and less than 7–10 days, for maximising the beneficial effects. Beyond 7–10 days, benefits are diminished. According to a cohort study, the beneficial effect of the first dose of ANCS starts within the first day, so advanced dilatation should not be a reason not to treat []. There is still debate as to whether ANCS should be repeated 1 to 2 weeks after the first course for women with threatened very preterm labour. A repeat course reduces the requirement of transient respiratory support; however, it does not further reduce mortality or other serious health outcomes, while multiple courses reduces birth weight and head circumference []. None of the clinical trials showed any improved outcomes when the repeat course had been given after 32 weeks; a single repeat course should therefore be restricted to a GA <32 weeks []. Data on ANCS in multiple gestations are scarce but suggest that they also reduce morbidity and mortality in very preterm birth.

Steroids are potent drugs with many unwanted effects. When given appropriately, they improve outcome. If not, then side effects, such as dose-dependent impaired foetal length and head circumference, impaired placental growth, brain apoptosis, and increased infection risk may prevail. Long-term follow-up of children from trials conducted in the 1970s has been reassuring. However, when ANCS were given <34 weeks and delivery takes place at or near term, the neurodevelopmental outcome may be disturbed [, ]. Data from sibling pairs in Finland raise concerns that any ANCS has a negative effect on neurological, cognitive, and behavioural disorders, especially for infants who are born at term []. However, the outcomes could have been influenced by the occurrence of preterm contractions, which, in themselves may be a risk factor for neurodevelopmental impairment [].

ANCS should only be given to women who are highly likely to deliver preterm. This continues to be a challenge since 40–50% of women receiving ANCS deliver at term with possible adverse outcomes [, ]. Unnecessary use of ANCS might be reduced by adequate dating of gestation, preterm birth risk assessment, restriction of repeated courses to a single course before 32 weeks, avoidance of ANCS in women at risk of late preterm delivery, and avoidance of unnecessary early elective CS. The current ANCS dosage appears to be high; betamethasone phosphate results in excessive peak concentrations and the release of betamethasone acetate proceeds slowly for 1–2 weeks []. A recent RCT from France compared a single betamethasone phosphate/acetate injection to the regular two injections 24 h apart. The half dosage resulted in a higher risk of need for surfactant treatment within 48 h: surfactant treatment occurred in 20.0% in the half dosage and in 17.5% of the full dosage group. There were no between-group differences in the rates of mortality, rates of surfactant therapy, risk of BPD, or other important outcomes []. Pharmacodynamic studies continue. Maternal BMI and multiple pregnancies might need to be factored in []. The same holds for studies in early foetal growth restriction, as ANCS are widely used without focusing on this high-risk group.

Mothers at high risk of preterm birth <28–30 weeks of gestation should be transferred to perinatal centres with experience in management of RDS (B1). Ultrasound screening of cervix in high-risk pregnancies, and for women with a short cervix in mid-pregnancy, guides vaginal progesterone treatment in singleton pregnancies to increase GA at delivery and to reduce perinatal mortality and morbidity (A1). In women with symptoms of preterm labour, cervical length and accurate biomarker measurements should be considered to prevent unnecessary use of tocolytic drugs and/or antenatal steroids (B2). Clinicians should offer a single course of ANCS to all women at high risk of preterm delivery, from when pregnancy is considered potentially viable up to 34 completed weeks of gestation, ideally at least 24 h before birth (A1). A single repeat course of steroids may be given in threatened preterm birth before 32 weeks of gestation if the first course was administered at least 1–2 weeks earlier (A2). MgSO 4 should be administered to women with imminent delivery before 32 weeks of gestation (A1). Clinicians should consider short-term use of oxytocin antagonists or Ca channel blockers for tocolysis in very preterm pregnancies to allow completion of a course of prenatal corticosteroids and/or in utero transfer to a perinatal centre (B1).

In the delivery room, timings begin when the foetus is fully expelled from the mother, rather than from when the cord is cut. Those attending birth should know how to identify sick infants who require urgent airway management and lung inflation to establish gas exchange and restore cardiac output.

European Resuscitation Guidelines [] focus on strategies for how to intervene when infants are born in poor condition secondary to hypoxia, with emphasis on airway opening and lung inflation. However, most babies at risk of RDS will try to breathe on their own. Experimental and clinical studies show that laryngeal closure during apnoea and in between breathing can impede attempts to inflate lungs artificially in infants []. It is therefore important to focus on gentle approaches that encourage spontaneous breathing and support normal transition.

Not clamping the umbilical cord before the lungs are aerated is an important first aim. Avoiding immediate clamping of the cord reduces in-hospital mortality and the combined outcome of death or disability by 2 years of age []. The duration of deferred cord clamping may also be important, with longer deferrals >2 min being associated with the lowest risk of mortality []. Physiologically based cord clamping (PBCC) describes a strategy of only clamping the cord when the infant has achieved respiratory stability rather than a time-based approach. Specially adapted heated trolleys can facilitate full stabilisation with intact cord close to the mother before the placenta is delivered. Alternatively, delivering the placenta and holding it above baby during stabilisation with the cord intact also shows improved cerebral and peripheral oxygenation, although there are no large trials of this method []. The largest trial of PBCC versus time-based clamping using a specialised trolley showed that there was less need for subsequent top-up transfusions, less late-onset sepsis, and parents were more content and less anxious when PBCC was performed. Although no overall differences in rates of intact survival were found, there was a significant increase in intact survival in centres with the most use, suggesting a learning curve with the new technique []. In a time-based clamping study, where preterm infants were supported by deliberately providing CPAP or manual breaths before the cord was clamped at 120 s, rather than just waiting for 60 s and then starting stabilisation, did not appear to result in improved outcomes []. Umbilical cord milking is an alternative to delayed cord clamping which results in extra blood volume, however with concerns about increased intraventricular haemorrhage for infants less than 28 weeks of gestation []. Recent clinical trials suggest that it is a safe alternative for infants 28–32 weeks and could be used in infants born depressed, for whom deferred cord clamping is not feasible [].

Repetitive tactile stimulation is a well-established method for promoting spontaneous breathing and appears to show some benefit in reducing the need for intubation in an observational study []; however, further randomised trials are underway to determine if it really works ( NCT05942924 ). Very early caffeine increases tidal and minute volumes [], but it is not known whether efforts to secure IV access for caffeine immediately at birth will result in any meaningful difference to outcomes. Delivery room enteral caffeine may be a solution; however, further dosing and safety studies are needed before recommendations can be made [].

For preterm babies who are breathing, CPAP is considered the best early respiratory support resulting in less lung injury and BPD than intubation []. Heated humidified high-flow oxygen has also been used in more mature preterm infants in some centres, but switching to manual ventilation if needed is more challenging []. The use of positive end-expiratory pressure (PEEP) during resuscitation reduces mortality in preterm babies []. T-pieces are better than self-inflating bags for delivering controlled PEEP levels and consistent tidal volumes if ventilation is needed []. If lung inflation is needed, a peak pressure of 25 rather than 20 cm/H 2 O is most likely to achieve the desired tidal volume []. Peak pressure may require adjustment depending on the infant’s response, as recognised by HR increase and SpO 2 trajectory. Face mask application, but also binasal prongs, may induce apnoea due to stimulation of the trigeminocardiac reflex []. A recent randomised trial suggests that nasal interfaces in the delivery room reduced the risk of PPV compared to face masks but made no difference to the need for intubation []. Respiratory function monitoring in the delivery room will improve ventilation parameters but at present not widely available and there is uncertainty that it improves outcomes []. Choosing a delivery room CPAP system that can be secured easily to the infant’s head without the need to hold it in place will allow time (after stabilisation) for delivery room skin-to-skin [, ] and surfactant administration if indicated. Good manual ventilation practice, including ensuring that head position is neutral, avoidance of mask leak and airway obstruction, will decrease the proportion of infants requiring intubation []. A suggested starting CPAP level of 6 cm/H 2 O allows for the CPAP to be titrated either upwards or downwards if needed. Individualised dynamic PEEP strategies are being explored as an alternative to a set CPAP level for very preterm babies to prevent lung injury (POLAR trial NCT04372953 ).

The World Health Organization (WHO) recommends that the temperature of newborn infants is maintained between 36.5 and 37.5°C after birth. Delivery room gases should be heated and humidified, and preterm babies ≤32 weeks should be stabilised inside plastic bags under pre-heated radiant warmers in warm delivery rooms (≥23°C) to maintain a normal body temperature []. A hat should be placed immediately after birth; however, it makes no difference whether the bag is placed before or after the cord is clamped [].

Air oxygen blenders are necessary to allow titration of oxygen during stabilisation. For term babies, starting with air (21% oxygen) is best. Preterm babies achieve optimal saturations more quickly if higher concentrations of oxygen are used [], although there is a balance to be considered around avoiding oxygen toxicity. Although no clear differences in major outcomes are demonstrated whether higher (>0.6) vs. lower (<0.3) FiO 2 is initiated at birth [], data from recent clinical trials suggest less need for chest compressions and adrenaline if starting higher (0.6 vs. 0.3) in infants <29 weeks of gestation []. A recent updated systematic review using individual patient data from 1,055 babies <32 weeks in randomised trials also suggests starting at FiO 2 0.9 may be better than <0.3, but data are less clear about the difference between FiO 2 0.9 and 0.5–0.65 []. Oxygen levels should be titrated to achieve normal transitional saturations measured by pulse oximetry at the right hand aiming to achieve >80–85% within 5 min [], as this is associated with better outcomes at 2 years []. It is important to be aware that there is a significant time lag between changes in FiO 2 being made at the blender and these equilibrating within the mask, particularly with larger mask sizes in babies requiring small tidal volumes [].

Monitoring of infants during transition consists of assessment of adequate heart rate (HR) and oxygen saturations (SpO 2 ) that are improving in line with normal values, increasing from 60% to 90% over the first 10 min after birth. It may take up to a minute to have reliable pulse oximetry readings for HR and SpO 2 , or even longer in extremely preterm babies with low perfusion index. HR can be measured by auscultation, and although ECG is more accurate, it is uncertain whether routine addition of ECG in delivery room confers clinical benefit. Caregivers are usually capable of determining when HR <60 or above 100 bpm which is all that is required.

Once the infant is stable on CPAP, with saturations >90% and HR 120–140, for extremely preterm infants consider an early (selective prophylaxis) dose of surfactant by thin catheter if there are early signs of RDS such as chest retractions, to reduce the risk of needing MV. Some infants remain apnoeic and bradycardic and require intubation for stabilisation, although the number needing intubation can be reduced through quality improvement initiatives focused on delivering effective NRS []. Most extremely preterm infants 22–23 weeks will need intubation for effective stabilisation, and these or other urgent intubations can be done without sedation. Intubation experience is diminishing, although success rates can be improved through regular simulation training and the use of videolaryngoscopy [, ]. If intubation is required then confirmation that the tube is correctly placed should be done clinically by auscultation as well as using a colourimetric CO 2 detection device if available []. Surfactant can be administered prior to radiographic confirmation of tube position, and the infant should be ventilated using a lung protection strategy.

If clinical condition allows, defer clamping the umbilical cord for 60 s or longer (A1). If stabilisation with intact cord (PBCC) can be safely undertaken, longer deferred cord clamping is preferable, especially in infants <34 weeks (A1). If DCC is not feasible, consider umbilical cord milking in infants with GA ≥28 weeks (B2). T-piece devices should be used rather than self-inflating or flow-inflating bag and mask (B1). Breathing of preterm infants should be stimulated (C2) and supported with CPAP (A1). If spontaneous breathing does not occur within 30–60 s, start giving ventilation breaths. Expert consensus is to start with CPAP pressure at least 6 cm H 2 O and peak inspiratory pressures (PIPs) 25 cm H 2 O (D2). Oxygen for resuscitation should be controlled using a blender. Use starting FiO 2 of 0.6 for infants <29 weeks' gestation, ≥0.30 for babies 29–31 weeks', 0.21 for 32 weeks' gestation and above. FiO 2 adjustments up or down should be guided by pulse oximetry (B2). SpO 2 of 80% or more (and HR >100/min) should be achieved within 5 min for babies <32 weeks (C2). Intubation should be reserved for babies not responding to positive pressure ventilation via face mask or nasal prongs (A1). Use videolaryngoscope and colorimetric capnography if available (B1).

Room temperature (≥23°C), plastic bags, or occlusive wrapping under radiant warmers and humidified gas should be used during stabilisation for babies <32 weeks of gestation to reduce the risk of hypothermia. Additional measures during delayed cord clamping to ensure thermal stability (e.g., thermal mattress) are taken. Hyperthermia should also be avoided (A1).