Lex W. Doyle

An overview of mortality and sequelae of preterm birth from infancy to adulthood.

Survival rates have greatly improved in recent years for infants of borderline viability; however, these infants remain at risk of developing a wide array of complications, not only in the neonatal unit, but also in the long term. Morbidity is inversely related to gestational age; however, there is no gestational age, including term, that is wholly exempt. Neurodevelopmental disabilities and recurrent health problems take a toll in early childhood. Subsequently hidden disabilities such as school difficulties and behavioural problems become apparent and persist into adolescence. Reassuringly, however, most children born very preterm adjust remarkably well during their transition into adulthood. Because mortality rates have fallen, the focus for perinatal interventions is to develop strategies to reduce long-term morbidity, especially the prevention of brain injury and abnormal brain development. In addition, follow-up to middle age and beyond is warranted to identify the risks, especially for cardiovascular and metabolic disorders that are likely to be experienced by preterm survivors.

Bronchopulmonary dysplasia in very low birth weight subjects and lung function in late adolescence.

OBJECTIVES. The purpose of this work was to determine the relationship between lung function in late adolescence and bronchopulmonary dysplasia, to establish whether lung function changed more from earlier in childhood in those with bronchopulmonary dysplasia, and to assess the effect of different definitions of bronchopulmonary dysplasia on respiratory outcome. METHODS. Subjects were composed of 147 survivors of birth weight <1500 g from the Royal Womens Hospital (Melbourne, Australia) born during 1977–1982 and who had lung function tests at a mean age of 18.9 years. Of the 147 subjects, 33 (22%) had bronchopulmonary dysplasia in the newborn period. Lung function was measured according to American Thoracic Society guidelines. RESULTS. All of the lung function variables reflecting airflow were substantially diminished in the bronchopulmonary dysplasia group, but lung volumes were not significantly different. More subjects in the bronchopulmonary dysplasia group had reductions in airflow in the clinically significant range (eg, forced expired volume in 1 second/forced vital capacity ratio <75%; bronchopulmonary dysplasia: 42.4% [14 of 33]; and no bronchopulmonary dysplasia: 16.4% [18/114]). Results were not substantially affected after adjustment for confounding variables, including intrauterine growth restriction or birth weight. Compared with earlier in childhood, the forced expired volume in 1 second/forced vital capacity ratio deteriorated more in bronchopulmonary dysplasia subjects between 8 and 18 years. Lung function results varied little with different definitions of bronchopulmonary dysplasia. CONCLUSIONS. Subjects of very low birth weight with bronchopulmonary dysplasia in the newborn period have poorer lung function in late adolescence than those without bronchopulmonary dysplasia, and their lung function may be deteriorating at a more rapid rate.

Adverse neurodevelopment in preterm infants with postnatal sepsis or necrotizing enterocolitis is mediated by white matter abnormalities on magnetic resonance imaging at term.

OBJECTIVES To test the hypothesis that the impact of postnatal sepsis/necrotizing enterocolitis (NEC) on neurodevelopment may be mediated by white matter abnormality (WMA), which can be demonstrated with magnetic resonance imaging (MRI). STUDY DESIGN A prospective cohort of 192 unselected preterm infants (gestational age <30 weeks), who were evaluated for sepsis and NEC, underwent imaging at term-equivalent age and neurodevelopmental outcome at 2 years corrected age with the Bayley Scales of Infant Development. RESULTS Sixty-eight preterm (35%) infants had 100 episodes of confirmed sepsis, and 9 (5%) infants had confirmed NEC. Coagulase-negative staphylococci accounted for 73% (73/100) of the episodes of confirmed sepsis. Infants with sepsis/NEC had significantly more WMA on MRI at term compared with infants in the no-sepsis/NEC group. They also had poorer psychomotor development that persisted after adjusting for potential confounders but which became nonsignificant after adjusting for WMA. CONCLUSIONS Preterm infants with sepsis/NEC are at greater risk of motor impairment at 2 years, which appears to be mediated by WMA. These findings may assist in defining a neuroprotective target in preterm infants with sepsis/NEC.

Survival Without Disability to Age 5 Years After Neonatal Caffeine Therapy for Apnea of Prematurity

CONTEXT Very preterm infants are prone to apnea and have an increased risk of death or disability. Caffeine therapy for apnea of prematurity reduces the rates of cerebral palsy and cognitive delay at 18 months of age. OBJECTIVE To determine whether neonatal caffeine therapy has lasting benefits or newly apparent risks at early school age. DESIGN, SETTING, AND PARTICIPANTS Five-year follow-up from 2005 to 2011 in 31 of 35 academic hospitals in Canada, Australia, Europe, and Israel, where 1932 of 2006 participants (96.3%) had been enrolled in the randomized, placebo-controlled Caffeine for Apnea of Prematurity trial between 1999 and 2004. A total of 1640 children (84.9%) with birth weights of 500 to 1250 g had adequate data for the main outcome at 5 years. MAIN OUTCOME MEASURES Combined outcome of death or survival to 5 years with 1 or more of motor impairment (defined as a Gross Motor Function Classification System level of 3 to 5), cognitive impairment (defined as a Full Scale IQ<70), behavior problems, poor general health, deafness, and blindness. RESULTS The combined outcome of death or disability was not significantly different for the 833 children assigned to caffeine from that for the 807 children assigned to placebo (21.1% vs 24.8%; odds ratio adjusted for center, 0.82; 95% CI, 0.65-1.03; P = .09). The rates of death, motor impairment, behavior problems, poor general health, deafness, and blindness did not differ significantly between the 2 groups. The incidence of cognitive impairment was lower at 5 years than at 18 months and similar in the 2 groups (4.9% vs 5.1%; odds ratio adjusted for center, 0.97; 95% CI, 0.61-1.55; P = .89). CONCLUSION Neonatal caffeine therapy was no longer associated with a significantly improved rate of survival without disability in children with very low birth weights who were assessed at 5 years.

A systematic review of the clinimetric properties of neuromotor assessments for preterm infants during the first year of life

This systematic review evaluates assessments used to discriminate, predict, or evaluate the motor development of preterm infants during the first year of life. Eighteen assessments were identified; nine met the inclusion criteria. The Alberta Infant Motor Scale (AIMS), Bayley Scale of Infant and Toddler Development ‐ Version III, Peabody Developmental Motor Scales ‐ Version 2, Test of Infant Motor Performance (TIMP), and Toddler and Infant Motor Examination have good discriminative validity when examined in large populations. The AIMS, Prechtls Assessment of General Movements (GMs), Neuro Sensory Motor Development Assessment (NSMDA), and TIMP were designed for preterm infants and are able to detect more subtle changes in movement quality. The best predictive assessment tools are age dependent: GMs, the Movement Assessment of Infants, and TIMP are strongest in early infancy (age 4mo or less) and the AIMS and NSMDA are better at older ages (8‐12mo). The TIMP is the only tool that has demonstrated a difference between groups in response to intervention in two randomized controlled trials. The AIMS, TIMP, and GMs demonstrated the highest levels of overall reliability (interrater and intrarater intraclass correlation coefficient or κ>0.85). Selection of motor assessment tools during the first year of life for infants born preterm will depend on the intended purpose of their use for discrimination, prediction, and/or evaluation.

The Cost of Preterm Birth Throughout Childhood in England and Wales

BACKGROUND. Infants born preterm are at increased risk of adverse health and developmental outcomes. Mortality and morbidity after preterm birth impose a burden on finite public sector resources. This study considers the economic consequences of preterm birth from birth to adult life and compares the costs accruing to those born preterm with those born at term. METHODS. A decision-analytic model was constructed to estimate the costs to the public sector over the first 18 years after birth, stratified by week of gestational age at birth. Costs were discounted and reported in UK pounds at 2006 prices. Probabilistic sensitivity analysis was used to examine uncertainty in the model parameters and generate confidence intervals surrounding the cost estimates. RESULTS. The model estimates the costs associated with a hypothetical cohort of 669601 children and is based on live birth and preterm birth data from England and Wales in 2006. The total cost of preterm birth to the public sector was estimated to be £2.946 billion (US

Impact of Postnatal Systemic Corticosteroids on Mortality and Cerebral Palsy in Preterm Infants: Effect Modification by Risk for Chronic Lung Disease

4.567 billion), and an inverse relationship was identified between gestational age at birth and the average public sector cost per surviving child. The incremental cost per preterm child surviving to 18 years compared with a term survivor was estimated at £22885 (US

High-Flow Nasal Cannulae in Very Preterm Infants after Extubation

35471). The corresponding estimates for a very and extremely preterm child were substantially higher at £61781 (US

Cognition, academic progress, behavior and self-concept at 14 years of very low birth weight children.

95760) and £94740 (US

Do early intervention programmes improve cognitive and motor outcomes for preterm infants after discharge? A systematic review

146847), respectively. CONCLUSIONS. Despite concerns about ongoing costs after discharge from perinatal services, the largest contribution to the economic implications of preterm birth are hospital inpatient costs after birth, which are responsible for 92.0% of the incremental costs per preterm survivor.