Outcome at twelve months of adjusted age in very low birth weight infants with lung immaturity: A randomized, placebo-controlled trial of human surfactant

doi:10.1016/S0022-3476(05)83505-X

The Journal of Pediatrics

Volume 122, Issue 1, January 1993, Pages 126-132

https://doi.org/10.1016/S0022-3476(05)83505-X Get rights and content

We compared the neurodevelopmental outcome of extremely premature, surfactant-deficlent infants who received either prophylactic surfactant at birth, “rescue” surfactant after the clinical diagnosis of respiratory distresses syndrome was established, or placebo. Infants studied were participants in a randomized, bicenter (San Diego, Calif., and Helsinki, Finland), controlled trial of human surfactant therapy. One hundred fifty Infants (prophylaxis group, 63 infants; rescue group, 57; placebo group, 30) were prospectively enrolled at 38 weeks of gestational age. There were no neonatal intergroup differences in the incidence or severity of sonographic central nervous system abnormality or retinopathy. One hundred forty-five infants were alive at 1 year of adjusted age, at which time growth, neurosensory, and neurologic outcome were similar in all three treatment groups at both centers. Cerebral palsy occurred in 20% overall. Five infants (3.5%) were functionally blind. However, infants treated at birth had lower mean mental and motorscores on the Bayley Scales of Infant Development compared with those of infants rescued with surfactant after the onset of respiratory distress syndrome (Mental Development Index: 78 vs 96, p=0.02; Psychomotor Development Index: 73 vs 87, p=0.04). Chronic lung disease occurred more frequently in the prophylactically treated group and contributed to the subjects' neurologic and developmental morbidity. Because prophylactic surfactant treatment offered no neurodevelopmental advantage and may contribute to poorer outcome, we currently recommend early surfactant replacement only for those infants who have postnatal evidence of respiratory distress syndrome.

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The ideal threshold at which surfactant administration in preterm neonates with respiratory distress syndrome (RDS) is most beneficial is contentious. The aim of this systematic review was to determine the optimal clinical criteria to guide surfactant administration in preterm neonates with RDS.
The systematic review was registered in PROSPERO (CRD42022309433). Medline, Embase, CENTRAL and CINAHL were searched from inception till 16th May 2023. Only randomized controlled trials (RCTs) were included. A Bayesian random effects network meta-analysis (NMA) evaluating 33 interventions was performed. The primary outcome was requirement of invasive mechanical ventilation (IMV) within 7 days of life.
58 RCTs were included. In preterm neonates ≤30 weeks after adjusting for the confounding factor of modality of surfactant administration, an arterial alveolar oxygen tension ratio (aAO₂) <0.36 (FiO₂: 37–55%) was ranked the best threshold for decreasing the risk of IMV, very low certainty. Further, surfactant administration at an FiO₂ 40–45% possibly decreased mortality compared to rescue treatment when respiratory failure was diagnosed, certainty very low. The reasonable inference that could be drawn from these findings is that surfactant administration may be considered in preterm neonates of ≤30 weeks’ with RDS requiring an FiO₂ ≥ 40%. There was insufficient evidence for the comparison of FiO₂ thresholds: 30% vs. 40%. The evidence was sparse for surfactant administration guided by lung ultrasound. For the sub-group >30 weeks, nebulized surfactant administration at an FiO₂ < 30% possibly increased the risk of IMV compared to Intubate-Surfactant-Extubate at FiO₂ < 30% and 40%, and less invasive surfactant administration at FiO₂ 40%, certainty very low.
Surfactant administration may be considered in preterm neonates of ≤30 weeks’ with RDS if the FiO₂ requirement is ≥40%. Future trials are required comparing lower FiO₂ thresholds of 30% vs. 40% and that guided by lung ultrasound.
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Germinal matrix hemorrhage–intraventricular hemorrhage (GMH-IVH) is the most common variety of neonatal intracranial hemorrhage and is characteristic of the premature infant. This form of brain injury affects around 25% of all very low birthweight (<1500 g) premature infants, resulting in an increased risk for neurodevelopmental disability. Its occurrence can lead to impact on subsequent brain development because of destruction of the immature germinal cerebral region resulting in loss of progenitor cells, acceleration of white matter injury via pressure and oxidative stress, and direct parenchymal injury. Finally, hydrocephalus can complicate IVH, resulting in a further increased risk of neurodevelopmental disability. In this chapter, the neuropathology, pathogenesis, clinical features, diagnosis, prognosis, and management of IVH, and its complications will be reviewed. The prominent position of this lesion in neonatal medicine has been accompanied by a large increase in work from several disciplines. This chapter attempts to integrate this information in a meaningful way without oversimplifying a clearly complex problem.
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^*: Supported by National Institutes of Health grant No. HL/HD 35036, University of California, San Diego, General Clinical Research Center grant No. RR-00827, U.S. Food and Administration Office of Orphan Drug Products grant No. 000112, and Children's Hospital and Health Center, San Diego, California, Development grant (Dr. Merritt), and grants from the Finnish Academy and the Juselius Foundation (Dr. Hallman).

^*: Now at University of California, Davis, Medical Center, Sacramento, Calif.

^**: Now at University of California, Irvine, Medical Center.

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Outcome at twelve months of adjusted age in very low birth weight infants with lung immaturity: A randomized, placebo-controlled trial of human surfactant*

J Pediatr

J Pediatr

J Pediatr

Early Human Dev

J Pediatr

J Pediatr

J Pediatr

Surfactant replacement therapy with a single postventilatory dose of a reconstituted bovine surfactant in preterm neonates with respiratory distress syndrome: final analysis of a multicenter, double-blind, randomized trial and comparison with similar trials

Pediatrics

Improved neonatal survival following multiple doses of bovine surfactant in very premature neonates at risk for respiratory distress syndrome

Pediatrics

A comparison of surfactant as immediate prophylaxis and as rescue therapy in newborns of less than 30 weeks gestation

N Engl J Med

Reduction of neonatal mortality after multiple doses of bovine surfactant in low birth weight neonates with respiratory distress syndrome

Pediatrics

Prophylactic treatment of very premature infants with human surfactant

N Engl J Med

Surfactant replacement therapy for severe replacement therapy for severe respiratory distress syndrome: an international randomized trial

Pediatrics

Neurodevelopmental and respiratory outcome in early childhood after human surfactant treatment

Am J Dis Child

Two-year follow-up of infants enrolled in a randomized trial of surfactant replacement therapy for prevention of neonatal respiratory distress syndrome

Pediatrics

Two-year follow-up of infants enrolled in a randomized trial of surfactant replacement therapy: extension of original cohort due to concen about type ii error [Abstract]

Pediatr Res

Health and developmental outcomes of a surfactant controlled trial: follow-up at two years

Pediatrics