Review
Respiratory consequences of late preterm birth

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Summary

In developed countries most preterm births occur between 34 and 37 weeks’ gestation. Deliveries during this ‘late preterm’ period are increasing and, since even mild prematurity is now recognised to be associated with adverse health outcomes, this presents healthcare challenges. Respiratory problems associated with late preterm birth include neonatal respiratory distress, severe RSV infection and childhood wheezing. Late preterm birth prematurely interrupts in utero lung development and is associated with maternal and early life factors which adversely affect the developing respiratory system. This review considers 1) mechanisms underlying the association between late preterm birth and impaired respiratory development, 2) respiratory morbidity associated with late preterm birth, particularly long-term outcomes, and 3) interventions which might protect respiratory development by addressing risk factors affecting the late preterm population, including maternal smoking, early life growth restriction and vulnerability to viral infection.

Introduction

Babies born between 34 and 37 weeks of gestation have, until recently, been considered sufficiently mature to be treated similarly to term infants. Whilst for many of these infants outcomes are good, it is now recognised that significant maturation occurs during the last weeks of gestation, placing late preterm infants at increased risk of adverse health outcomes in the neonatal period and beyond [1], [2]. Late preterm delivery interrupts normal in utero respiratory development and relative immaturity is compounded by associated adverse perinatal factors. These include increased rates of caesarean delivery [3], and increased rates of intrauterine growth retardation[4] and associated maternal factors, including hypertensive disorders, diabetes and smoking [5], [6]. Additionally, morbidities incurred during the early postnatal period, including neonatal respiratory distress [1], poor feeding and growth [7], and vulnerability to respiratory viruses [8] have lasting consequences for respiratory development. (Figure 1) This is significant since early life lung development is increasingly recognised as a determinant of later respiratory health [9]. Moreover, following temporal changes in maternal age, infertility treatments, multiple birth prevalence, and obstetric interventions [10], [11], late preterm deliveries now account for the largest and most rapidly increasing proportion of preterm births [12], [13], [14].

Section snippets

Mechanisms

Normal lung development proceeds from the embryonic period (day 26-52) through pseudoglandular (day 52-week 16), canalicular (17-26 weeks) and saccular periods (24-36 weeks to term) to the alveolar period; during which alveolar development commences at 36 weeks’ gestation and continues into postnatal life [15], [16]. Extreme preterm (< 28 weeks) and very preterm birth (28-32 weeks) occur, respectively, during the canalicular period; characterised by precapillary and bronchiole formation, and

Neonatal

A 2011 systematic review and meta-analysis concluded that late preterm infants are more likely to need mechanical ventilation (RR 4.9; 95% CI, 2.8–8.6), and are at higher risk of neonatal respiratory morbidities, including respiratory distress syndrome (RDS) (RR 17.3; 95% CI, 9.8–30.6), transient tachypnoea of the newborn (RR 7.5, 95% CI 5.0–11.2), persistent pulmonary hypertension (RR 4.9, 95% CI 3.8–6.3), apnoea (RR 15.7, 95% CI 11.8–20.9), pneumothorax (RR 3.4, 95% CI 1.8–6.4) and pneumonia

Respiratory physiology

Studies evaluating the effects of prematurity independent from those of neonatal respiratory disease or its treatments have largely recruited late preterm infants since these infants generally require less intervention than those born at earlier gestations. Reduced expiratory flows at a year of age were reported in a study of 24 healthy preterm infants born at 29-36 weeks’ gestation [49]. (Table 2) This study used the rapid thoracoadominal compression technique to measure maximal forced

Obstetric interventions

Preterm delivery may be spontaneous or indicated in response to adverse maternal or fetal conditions. Spontaneous premature deliveries continue to outnumber those attributable to obstetric indications, particularly after 34 weeks of gestation where spontaneous deliveries account for 80% of births; [57] nevertheless, prematurity due to obstetric intervention is increasing [58]. Whilst this increase has been associated with a decrease in stillbirths and likely reflects higher rates of maternal or

Conclusion

Babies born late preterm are at increased risk of respiratory morbidity. Late preterm delivery interrupts normal lung development and is associated with obstetric complications and neonatal morbidities which compound the adverse developmental consequences of preterm birth. Infants born late preterm have poorer lung function from birth than infants born at term. Relative lung function deficits persist through infancy and late preterm birth appears to be associated with an increased risk of

Educational aims

  • To review the evidence for respiratory morbidity, in particular long-term adverse outcomes, associated with late preterm birth.

  • To consider the mechanisms by which late preterm birth impacts upon respiratory development.

  • To recognise interventions which might protect respiratory development and improve outcomes for this patient group.

Future research directions

  • The potential for catch-up lung growth in late preterm infants is not fully understood and requires careful study in animal models as well as prospective clinical studies.

  • Interventions based upon maximising and protecting lung growth should also be evaluated.

  • Useful areas for further exploration include, timing of obstetric intervention, effects of nutrition and growth upon respiratory development and benefits associated with RSV prophylaxis.

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