Prematurity (or Pre-term) describes infants delivered before 37 weeks of gestation. Pre-term birth is a leading cause of morbidity and mortality in children under 5 years globally, associated with early and long term complications.

The Word Health Organisation (WHO) estimates that 13.4 million infants were born prematurely in 2020 across the world with rates of premature births ranging from 4-16% [1]. According to the UK National Screening committee, 8.3% of infants were born preterm in 2020 [2].

Definitions:

Premature infants can be categorised according to gestational age and/or birthweight

WHO categories premature infants according to gestational age [1]:

Birthweight can also be used to categorise premature infants [3]:

Risk factors:

Risk factors that increase chances of preterm birth can be divided into modifiable and non-modifiable

Non-modifiable risk factors include:

• Previous preterm birth
• Multiple gestations
• Anomalies of reproductive organs
• Maternal age (<18 years and >35 years)
• Placenta previa
• Vaginal bleeding
• Foetal anomalies
• Preterm premature rupture of membranes

Modifiable risk factors include:

• Blood clotting disorders
• Diabetes
• Hypertension
• Infections: Urinary tract infections, sexually transmitted infections, vaginal infections like bacterial vaginosis
• In vitro fertilisation
• Pre-pregnancy weight (underweight or obesity)
• Lifestyle factors: smoking, alcohol, illicit drugs [4]

Prognosis:

Despite technological and medical advances in the fields of neonatology, the mortality remains a significant risk in extreme preterm infants.

According to the 2024 Child Death Review by the National Child Mortality Database (NCMD), the estimated neonatal death rate for infants born >24 weeks gestation has remained the same for the last three years at 11.6 deaths per 1000 live births. Of these neonatal deaths, 80% were preterm, which is greater than prior years with the NCMD recording 614 death notifications in infants <24 weeks [5]. The proportions are shown in the figure below

Figure 1: Proportion of neonatal deaths according to gestational age (NCMD 2024) [5]

Complications:

There are a number of complications associated with prematurity, of which the severity and incidence is associated with birthweight and gestational age.

• Respiratory: respiratory distress syndrome, chronic lung disease, apnoea, bronchopulmonary dysplasia
• Cardiovascular: patent ductus arteriosus, hypotension, bradycardia
• Neurological: intraventricular haemorrhage, cerebral palsy, neurodevelopmental delay
• Gastrointestinal: necrotising enterocolitis (NEC), feeding intolerance
• Hypothermia
• Immature skin barrier
• Metabolic: hyper/hypoglycaemia, jaundice
• Infections: sepsis, meningitis
• Ophthalmic: retinopathy of prematurity, visual impairment
• Auditory impairments
• Renal complications: metabolic acidosis, growth failure [6] [3]

Figure 2: Chart representing complications of prematurity

General management of pre-terms:

Management of pre-terms places an emphasis on thermoregulation, early respiratory care and fluid/nutritional support.

Thermoregulation:

Pre-term infants are at high risk of abnormal body temperature, particularly hypothermia, therefore WHO recommends that after birth infants’ body temperature is maintained at 36.5 – 37.5 °C.

Mortality increases by 28% with each 1 degree drop below 36.5 according to a retrospective cohort study by Laptook et al in 2007.

A larger surface area to mass ratio, immature skin and poor control of blood flow to the skin all make pre-terms more vulnerable to temperature fluctuations. Therefore, heat loss through evaporation after birth, convection and conduction heat loss in cold delivery rooms can lead to temperature drops.

However, it is important that in the effort of increasing body temperature, hyperthermia is avoided. This is important because abnormal temperature is an independent mortality risk factor.

Temperature can be regulated by:

• Managing the environment – limiting drafts, regulating delivery room temperature to be 25-35°C.
• Pre-warm towels and prevent heat loss with hat or polythene bag, recommended for infants <32 weeks [7], as shown in the image
• Use a radiant warmer, exothermic mattress, heated and humidified gases [8].
• Once admitted to NICU these babies are kept warm in an incubator with high humidity to prevent water loss from the skin

Figure 3: Image showing polythene bag and hat [9]

Early respiratory care:

Due to lung immaturity, and surfactant deficiency in pre-term infants, there is a high risk of acute respiratory failure. Therefore these infants will often require respiratory support, including supplementary oxygen, non-invasive or invasive ventilation. Providing respiratory support increases the possibility of bronchopulmonary dysplasia, as preterm lungs are vulnerable to barotrauma and volutrauma.

The extent of respiratory support depends on the severity of respiratory failure:

• Supplementary oxygen, which is determined by the SpO2.
  • Target oxygen saturations are lower in preterm infants (88-92%) due to previous evidence demonstrating high oxygen saturations are associated with worse outcomes in the BOOST trial.
  • In the last few years this has been argued and the evidence currently shows that targets sats of 85-91% have lower risk of retinopathy of prematurity (ROP) but increased mortality while sats of 91-95% have lower mortality but increased rates of ROP.
• Non-invasive ventilation which provides constant airway pressure
  • Continuous positive airway pressure (CPAP)
  • High flow nasal cannula
• Non-invasive ventilation with variable pressures
  • Bilevel positive airway pressure (BiPAP) or Non-invasive posttive pressure ventialtion (NIPPV)
• Intubation may be necessary if there is apnoea or increasing oxygen requirement  [10].
• Surfactant can also be given in respiratory failure either via endotracheal tube (ETT) or with Less Invasive surfactant administration (LISA)/Minimally invasive surfactant therapy (MIST) for infants with high oxygen requirements.

IV access and fluid support:

Preterm infants <34 weeks need immediate IV access for IV fluids or IV parenteral nutrition.

Providing adequate nutrition is important for the development and growth of pre-term infants. This is because pre-term infants may have low nutritional reserves, low birth weight or gastrointestinal defects or disease.

Furthermore, the first 24-48 hours after birth is associated with a diuretic phase, as they excrete more fluid, following fluid shifts from extra to intravascular compartments. Therefore, regular weights are required with biochemistry (particularly sodium) and clinical assessment to assess the fluid status and electrolyte requirements of infants.

The nutritional needs of pre-term infants can be met using:

• Parenteral nutrition given via a long line or umbilical venous catheter (UVC)
• Enteral feeds – are started in a graded fashion due to risk of necrotising enterocolitis and feed intolerance.
• Fluid and electrolyte replacement [11]

Overall the field of neonatology has rapidly evolved in the last 2 decades with an increasingly better researched evidence base. This is associated with improved survival but also increasing morbidities which we require more evidence for in order to optimise management of the preterm infant.

Bibliography:

[1]           ‘Preterm birth’. Accessed: May 29, 2025. [Online]. Available: https://www.who.int/news-room/fact-sheets/detail/preterm-birth

[2]           ‘Preterm birth – UK National Screening Committee (UK NSC) – GOV.UK’. Accessed: May 29, 2025. [Online]. Available: https://view-health-screening-recommendations.service.gov.uk/preterm-birth/

[3]           ‘Preterm Infants – Pediatrics’, MSD Manual Professional Edition. Accessed: May 29, 2025. [Online]. Available: https://www.msdmanuals.com/professional/pediatrics/perinatal-problems/preterm-infants

[4]           ‘What are the risk factors for preterm labor and birth? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development’. Accessed: May 29, 2025. [Online]. Available: http://www.nichd.nih.gov/health/topics/preterm/conditioninfo/who_risk

[5]           N. Programme, ‘Child death data release 2024’, National Child Mortality Database. Accessed: May 29, 2025. [Online]. Available: https://www.ncmd.info/publications/child-death-review-data-release-2024/

[6]           R. E. Behrman, A. S. Butler, and I. of M. (US) C. on U. P. B. and A. H. Outcomes, ‘Mortality and Acute Complications in Preterm Infants’, in Preterm Birth: Causes, Consequences, and Prevention, National Academies Press (US), 2007. Accessed: May 29, 2025. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK11385/

[7]           V. V. Ramaswamy et al., ‘Maintaining normothermia immediately after birth in preterm infants <34 weeks’ gestation: A systematic review and meta-analysis’, Resuscitation, vol. 191, p. 109934, Oct. 2023, doi: 10.1016/j.resuscitation.2023.109934.

[8]           E. A. Dunne, C. P. F. O’Donnell, B. Nakstad, and L. K. McCarthy, ‘Thermoregulation for very preterm infants in the delivery room: a narrative review’, Pediatr. Res., vol. 95, no. 6, pp. 1448–1454, May 2024, doi: 10.1038/s41390-023-02902-w.

[9]           A. L. C. Possidente, I. G. M. Bazan, H. C. Machado, S. T. M. Marba, and J. P. S. Caldas, ‘Evaluation of two polyethylene bags in preventing admission hypothermia in preterm infants: a quasi-randomized clinical trial’, J. Pediatr. Engl. Ed., vol. 99, no. 5, pp. 514–520, Sep. 2023, doi: 10.1016/j.jped.2023.04.004.

[10]        M. Tana et al., ‘Respiratory Management of the Preterm Infant: Supporting Evidence-Based Practice at the Bedside’, Children, vol. 10, no. 3, p. 535, Mar. 2023, doi: 10.3390/children10030535.

[11]        J. Pichler, V. Horn, S. Macdonald, and S. Hill, ‘Intestinal failure-associated liver disease in hospitalised children’, Arch. Dis. Child., vol. 97, no. 3, pp. 211–214, Mar. 2012, doi: 10.1136/archdischild-2011-300274.

Written by Froher Yasin (FY1)

Edited by Dr Bex Evans, Senior Paediatric Registrar