Landmark Articles In Neonatology: Basis For Current Clinical Practice Smeeta Sardesai, MD, Ms Ed, FAAP Associate Professor of Pediatrics Associate Professor of Pediatrics Associate Director Neonatal-Perinatal Medicine Fellowship Program Keck School of Medicine University of Southern California
Disclosure Who’s hiding what? “ I have nothing to hide!”
Key Areas That Provide The Basis For The Care of All Neonates • Thermoregulation • Respiratory Support • Nutrition
“If we can just maintain these weaklings warm from the time they are born we will be able to save a great majority of them, leaving the warmth of their mother’s womb is the greatest challenge they face…..” Dr. Stephane Tarnier, 1880. • Tarnier’s (1880) most important contribution was introduction of incubators. introduction of incubators. • He compared premature infant mortality before and after the introduction of the device in a large case series (500 infants). • Mortality of infants in the1200 to 2000gm range fell from 66% to 38%.
Thermoregulation in Preterm Infants • Blackfan and Yaglou in 1933 made serial observations of body temperature and outcomes of preterm infants. • The authors concluded that subnormal temperature is characteristic of prematurity which should be preserved. • This paper led to preterm babies being nursed in inappropriately low environmental temperatures. Blackfan KD, et al. The premature infant: a study of the effects of atmospheric • conditions on growth and development. Am J Dis Child 1933;46:1175–1236.
Landmark Article on Thermoregulation in Neonates • In 1958, Silverman et al. in a randomized controlled trial observed that prematurely born infants nursed in incubators maintained at a temperature of 31.7°C during the first 5 days of life had a better survival rate than those nursed at 28.9°C (84% versus 68%). • The beneficial effect was observed in all birthweight categories. Silverman W.A., et al. Pediatrics 1958; 22: 876-886. Optimizing the thermal environment has proven significant for improving the chances of survival for small infants.
• Remarkable progress has been made in the production of infant incubators, which are currently highly technological devices. The most important thing: Infants should be nursed in the neutral thermal environment and have a core body temperature between 36.5 – 37.2 0 Celsius. 125 years Later…..
Temperature in Preterm Infants in 21 st Century • Admission temperature (<35°C) was inversely related to mortality, with a 28% increase in death and 11% increase in late onset sepsis for every 1°C decrease in temperature. Laptook AR, et al. Admission Temperature of Low Birth Weight Infants: • Predictors and Associated Morbidities. Pediatrics 2007:119;e643-e649. • Retrospective observational study, at 29 NICUs in the Canadian Retrospective observational study, at 29 NICUs in the Canadian Neonatal Network of 9,833 inborn infants born at <33 weeks' gestation found that the relationship between admission temperature and adverse neonatal outcomes was U-shaped. • The lowest rates of adverse outcomes were associated with admission temperatures between 36.5°C and 37.2°C. Lyu Y, et al. JAMA Pediatr. 2015;169(4): e150277. •
Implications for Practice • Key interventions that reduce heat loss after birth: • Increasing ambient temperature in the delivery room. • Use of heated humidified gases. • Use of exothermic or thermal mattresses. • Use of heat loss barriers: head covers or plastic body covers. • Skin-to-skin kangaroo mother care. • Skin-to-skin kangaroo mother care. Knobel-Dail, RB. Role of effective thermoregulation in preterm neonates. Research and Reports in Neonatology 2014, 4:147-156. • Implementation of a multidisciplinary guideline improves preterm infant admission temperatures. J Perinatol. (Virginia) 2017 Jul 20. doi:10.1038/jp.2017.112. J Pediatr (Rio J). 2017 Sep 6. pii: S0021-7557
Key Areas That Provide The Basis For The Care of All Neonates • Thermoregulation • Respiratory Support: • Supplemental O 2 . • Surfactant. • Surfactant. • Mechanical Ventilation. • Non Invasive ventilation. • Antenatal steroids. • Nutrition
Supplemental Oxygen for Preterm Infants • 1902: Budin recommended O 2 inhalation for cyanotic episodes in premature infants. • 1917: Ylppö advised that O 2 be introduced into the stomach by a tube as a means of resuscitating premature infants and to manage apnea. • 1922: Hess recommended continuous or intermittent showers of O 2 in the attempt to ward off cyanotic attacks. • 1923: Bakwin noted that when O 2 was administered early, subsequent cyanotic attacks were fewer in number and more readily amenable to treatment. • To reap full benefit from treatment, Bakwin recommended that O 2 be given over a long period of time, preferably in a closed chamber.
Supplemental Oxygen for Preterm Infants • By the 1930’s, the notion of “if a little is good, a lot should be better” was espoused and liberal use of O 2 was the standard of treatment for cyanotic infants. That was the beginning of “ROUTINE” use of supplemental O 2 in the care of small or preterm infants.
Supplemental Oxygen for Preterm Infants • 1940s: Liberal use of O 2 , and inability to measure arterial O 2 tension, many preterm infants developed childhood blindness. • 1951: Kate Campbell described that the liberal use of O 2 was directly linked to ROP and blindness. Campbell K: Intensive oxygen therapy as a possible cause of retrolental • fibroplasia: a clinical approach. Med J Aust 1951;2:48–50. fibroplasia: a clinical approach. Med J Aust 1951;2:48–50. • First RCT of comparing routine O 2 (>50% for 28 days) with curtailed O 2 (<50% only for cyanosis or respiratory difficulty) showed: • No appreciable increase in mortality with curtailed oxygen • Two thirds reduction in the rate of cicatricial ROP. • Bolton DP, Cross KW. Further observations on cost of preventing • retrolental fibroplasia. Lancet. 1974;1(7855):445–448.
Effect of Restrictive Use of Oxygen • O 2 concentrations > 40% were considered dangerous and incubators were designed so that no more than 40% O 2 could be delivered. • Increased mortality of infants with respiratory distress syndrome (RDS). syndrome (RDS). • Increase in cerebral palsy in surviving preterm infants. It has been estimated that EACH SIGHTED INFANT GAINED, MAY HAVE COST SOME 16 DEATHS Avery ME.: J Pediatr 1960;57:553–559. McDonald AD: Arch Dis Child 1963; 38:579–588.
Use of Oxygen in Current Practice • There are two opposing concerns. • Lower O 2 levels (targeting SpO ₂ at < 90%) may impair neurodevelopment or result in death. • Higher O 2 levels (targeting SpO ₂ > 90%) may increase Higher O levels (targeting SpO ₂ > 90%) may increase severe ROP or chronic lung disease. Oxygen Use in Neonatal Care: A TWO-EDGED SWORD
In Search of Optimal Oxygen Saturations • Systematic reviews and metanalysis of 5 trials. Canadian Oxygen Trial [COT] 1. Surfactant, Positive Pressure, and Oxygenation 2. Randomized Trial [SUPPORT] Benefits of Oxygen Saturation Targeting trial 3. [BOOST-II ] (Australia, New Zealand and UK) Askie LM, et al. Cochrane Database Syst Rev. 2017;4: • CD011190. Epub 2017 Apr 11. Manja V, et al. Pediatrics. 2017;139(1). • Stenson BJ. Neonatology. 2016;109(4):352-8. •
Effects of Targeting Lower Versus Higher Arterial Oxygen Saturations • Low SpO ₂ at < 90% target range: • Higher rate of mortality at 18 to 24 months corrected age. • Higher incidence of NEC. • Lower incidence of ROP requiring treatment. • No difference in the: No difference in the: • Combined outcome of death and major disability at 24 months corrected age. • Neurodevelopmental outcome, blindness, severe hearing loss, or cerebral palsy. Askie LM, et al. Cochrane Database Syst Rev. 2017;4: CD011190. Epub 2017 Apr 11. • Manja V, et al. Pediatrics. 2017;139(1). • Stenson BJ. Neonatology. 2016;109(4):352-8. •
Supplemental Oxygen for Preterm Infants 115 Years Later… • We still don’t know the target range of oxygen saturations in very preterm infants to ensure optimal survival without disability and the lowest possible rate of ROP. • AAP Clinical Report states that targeted SpO 2 range of 90% to 95% may be safer than 85% to 89% at least for 90% to 95% may be safer than 85% to 89% at least for some infants. Committee on Fetus and Newborn. Pediatrics 2016;138(2):e20161576. Avoid Hyperoxia Without Permitting Hypoxemia
Artificial Surfactant Therapy • The clinical era of surfactant replacement opened with the seminal article by Fujiwara. – Demonstrated the acute beneficial effects of natural surfactant in 10 preterm infants with RDS to a bolus of modified bovine surfactant given endo-tracheally. Fujiwara T, et al. Lancet 1980, 315:55–59. Fujiwara T, et al. Lancet 1980, 315:55–59. • The introduction of surfactant treatment was associated with overall decrease in neonatal mortality in the USA. • Considered a cost-effective therapy for RDS compared with other therapeutic interventions in premature infants. Surfactant therapy has been a major contribution to care of the preterm newborn during the past 35 years
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