Ronald E. Hoekstra

Survival and follow-up of infants born at 23 to 26 weeks of gestational age: Effects of surfactant therapy

Abstract Little information is available regarding the effect of surfactant on outcome for infants born at or before 26 weeks of gestation. We addressed this issue by reviewing records of 310 infants born at gestational ages of 23 through 26 weeks who were admitted to our nursery from 1986, when surfactant was introduced, through 1990. Surfactant was administered to 154 infants (5 during a single-dose prevention study, 25 during a multiple-dose prevention study, 124 while receiving a Food and Drug Administration treatment investigational new drug); 156 infants were not treated with surfactant. Seventy-three percent of the treated infants survived, compared with 55% of the nontreated infants. Increased survival occurred at all gestational ages between 23 and 26 weeks but were greatest in infants born at 23 and 24 weeks. At follow-up, no differences in neurologic outcome were detected between surfactant-treated and nontreated infants. We conclude that surfactant use in extremely premature infants improves survival rates without increasing the proportion of impaired survivors. (J P EDIATR 1994;124: 119-24)

Effects of exogenous surfactant therapy on dynamic compliance during mechanical breathing in preterm infants with hyaline membrane disease

In a prospective, randomized, controlled clinical trial, the immediate and the longitudinal effects of exogenous surfactant therapy on pulmonary mechanics were evaluated in extremely premature infants during mechanical respiration. Ninety-four infants weighing between 600 and 1250 gm received either exogenous surfactant or sham (air) therapy in the delivery room and up to three additional doses in the first 48 hours of life if they were ventilator-dependent, had fractional inspiratory oxygen requirements greater than or equal to 0.30, and radiographic findings consistent with hyaline membrane disease. Each infant underwent pulmonary mechanics assessment (dynamic compliance, total pulmonary resistance, tidal volume) immediately before and 1 hour after each dose, and at 24, 48, and 72 hours and 7 days of age. There were no significant differences in dynamic compliance, total pulmonary resistance, and tidal volume in the surfactant (n = 47) and control (n = 47) groups before and 1 hour after each dose. However, dynamic compliance was 50% greater in the surfactant group at 24 hours of age (p less than or equal to 0.009); this difference steadily increased to 94% at 7 days of age (p less than or equal to 0.009). Oxygenation, assessed by the ratio of alveolar to arterial oxygen pressure, was significantly greater in the surfactant group during the first 72 hours of life; the greatest difference was noted at 24 hours (p less than or equal to 0.001). Mean airway pressure requirements in the surfactant group were significantly less than in the control group at all times during the first week. We conclude that exogenous surfactant therapy, administered at birth and during the first 48 hours of life in extremely premature infants with hyaline membrane disease, improves dynamic compliance and gas exchange during mechanical breathing.

Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema

We studied 50 preterm infants who had multiple or traumatic endotracheal intubations, or whose duration of endotracheal intubation was > or = to 14 days, and who were considered at high risk for airway edema. These infants were enrolled in a prospective, randomized, controlled clinical trial to assess whether prophylactic dexamethasone therapy would be effective in the prevention of postextubation stridor and respiratory distress. At study entry, both groups had similar weights, postnatal ages, methylxanthine use, ventilator settings, blood gas values, and pulmonary function test results (dynamic compliance, total respiratory resistance, tidal volume, peak-to-peak transpulmonary pressure, minute ventilation, and peak inspiratory and expiratory flow rates). Patients underwent blood gas studies, physical examinations, and pulmonary function testing at baseline (4 hours before extubation) and again 2 to 4 hours and 18 to 24 hours after extubation. Twenty-seven infants received dexamethasone, 0.25 mg/kg per dose, at baseline, and then every 8 hours for a total of three doses; 23 infants received saline solution at corresponding times. Eighteen to twenty-four hours after extubation, total pulmonary resistance increased by 225% from baseline in the control group compared with 33% in the dexamethasone group (p < 0.006), and the dexamethasone group had a greater tidal volume, a greater dynamic compliance, and a lower arterial carbon dioxide pressure. Of 23 control infants, 10 had postextubation stridor compared with 2 of 27 dexamethasone-treated patients (p < 0.006). Of the 23 control patients, 4 required reintubation compared with none of the treated group (p < 0.05). We conclude that the prophylactic use of corticosteroids for the prevention of postextubation stridor and respiratory distress is efficacious in low birth weight, high-risk preterm infants.

Prophylactic indomethacin therapy in the first twenty-four hours of life for the prevention of patent ductus arteriosus in preterm infants treated prophylactically with surfactant in the delivery room

OBJECTIVE To determine whether a course of low-dose indomethacin therapy, when initiated within 24 hours of birth, would decrease ductal shunting in premature infants who received prophylactic surfactant in the delivery room. DESIGN Ninety infants, with birth weights of 600 to 1250 gm, were entered into a prospective, randomized, controlled trial to receive either indomethacin, 0.1 mg/kg per dose, or placebo less than 24 hours and again every 24 hours for six doses. Echocardiography was performed on day 1 before treatment and on day 7, 24 hours after treatment. A hemodynamically significant patent ductus arteriosus (PDA) was confirmed with an out-of-study echocardiogram, and the nonresponders were treated with standard indomethacin or ligation. RESULTS Forty-three infants received indomethacin (birth weight, 915 +/- 209 gm; gestational age, 26.4 +/- 1.6 weeks; 25 boys), and 47 received placebo (birth weight, 879 +/- 202 gm; gestational age, 26.4 +/- 1.8 weeks; 22 boys) (P = not significant). Of 90 infants, 77 (86%) had a PDA by echocardiogram on the first day of life before study treatment; 84% of these PDAs were moderate or large in size in the indomethacin-treated group compared with 93% in the placebo group. Nine of forty indomethacin-treated infants (21%) were study-dose nonresponders compared with 22 (47%) of 47 placebo-treated infants (p < 0.018). There were no significant differences between both groups in any of the long-term outcome variables, including intraventricular hemorrhage, duration of oxygen therapy, endotracheal intubation, duration of stay in neonatal intensive care unit, time to regain birth weight or reach full caloric intake, incidence of bronchopulmonary dysplasia, and survival. No significant differences were noted in the incidence of oliguria, elevated plasma creatinine concentration, thrombocytopenia, pulmonary hemorrhage, or necrotizing enterocolitis. CONCLUSION The prophylactic use of low doses of indomethacin, when initiated in the first 24 hours of life in low birth weight infants who receive prophylactic surfactant in the delivery room, decreases the incidence of left-to-right shunting at the level of the ductus arteriosus.

Effects of surfactant therapy on outcome of infants with birth weights of 600 to 750 grams

Replacement therapy with exogenous surfactant has been studied for both prevention and treatment of respiratory distress syndrome. Although reports demonstrate improved survival rates for surfactant-treated infants with RDS, the impact of this therapy on outcome of extremely low birth weight infants is unknown. TM Previous studies have not reported outcome after surfactant treatment for the subset of premature infants who are born at ELBWs and who are at the highest risk for complications of prematurity. We report the outcome of infants born with birth weights between 600 and 750 gm who underwent prospective random selection to receive either surfactant or placebo as part of a multidose prevention study.

Effects of surfactant therapy on outcome of extremely premature infants.

Limits of viability of extremely premature infants have recently been addressed both in Europe and the United States. These reports, which demonstrate frequent adverse outcome of infants born before 26 weeks of gestation, have not considered the impact of surfactant therapy. We reviewed records of 445 infants born between 23 and 36 weeks gestation who were admitted to our nursery following the availability of surfactant treatment in 1986 through 1992. Two hundred and eighty-five infants were treated with surfactant (Survanta, Ross Laboratories) as part of controlled, prospective trials or as routine treatment under Food and Drug Administration approval. One hundred and fifty-six infants were unable to be treated with surfactant, as either they received placebo therapy during prospective trials or were born prior to approval of routine surfactant use in the United States. Four additional infants born following the commercial availability of surfactant did not receive surfactant therapy. Survival of untreated infants was 56% compared to 75% in treated infants (P<0.001). Infants born at all gestational ages between 23 and 26 weeks had an increased likelihood of survival as a result of surfactant treatment. No differences in neurologic outcome between surfactant treated and non-treated infants were demonstrated at subsequent follow-up. We conclude that survival of extremely premature infants is improved following surfactant therapy and that subsequent neurologic outcome is not compromised as a result of this therapy.

Early adult outcomes following delivery at 23–26 weeks of gestation

Objective. There are few reports of young adult outcomes of infants born at 23-26 weeks gestation. The objective of this study is to report educational, health, social, and employment outcomes of a large cohort of these infants born during an era when significant advances in neonatal care led to a marked increase in survival. Methods. Medical records of 316 infants who were born between January 1, 1986 and December 31, 1990, were analyzed retrospectively. Two hundred three (64%) infants survived to discharge home, and 5 died following discharge, leaving 198 young adults available for follow-up. One hundred sixty-two (82%) young adults responded to a 27 item telephone questionnaire designed to assess educational, health, social, and employment status at a mean age of 19.3 years. Parents of subjects were interviewed in cases where subjects could not be contacted or had cognitive issues which precluded their responding (19 subjects). Parent social and educational status was previously obtained by response to a phone survey at eight year follow-up and also by phone interview of parents of young adults previously not available for follow-up, but who were located for this report. Results. The only statistically significant differences between the 162 young adult responders and the 36 non-responders were a younger maternal age at delivery (28 ± 6 years vs 25 ± 6 years, respectively, p = 0.015) and race (91% of responders were white compared to 67% of the non-responders, p = 0.001). One hundred forty-three (88%) young adults had graduated from high school. Eighty-four (52%) required educational assistance in the form of special education, a tutor, or an Individual Education Plan (IEP). Ninety-one (56%) were currently enrolled in post-secondary education. These levels of educational achievement closely correspond to the 91% of their mothers who graduated from high school and the 57% who had completed some college level courses, including 30% with either four-year or advanced degrees. Twenty-nine (18%) of the young adults interviewed reported some problems with depression. Thirty subjects admitted to using alcohol socially, 11 reported tobacco use, and 3 admitted to using marijuana. One hundred forty-two have been or are currently employed. Conclusions. The majority of infants born at the lower limits of viability not only have the potential to survive, but with appropriate assistance and resources have the ability to successfully navigate the educational system and eventually be employed as productive members of society.

School Age Follow-up of Extremely Preinature Infants. ♦ 1175

Ninety-seven infants born between 1/86 and 12/89 at gestational ages between 23-26 wks were followed at a mean age of 8.5 yrs, after completion of grades 1-3. Included were 39 M and 58 F with BW 787 ± 82 gm and GA 25.2± 0.8 weeks. Early assessment (<36 mo.) included physical examination with Bayley Scales of Infant Development. Evaluation at 3-5 years included Denver Development testing with Early Language Milestone Screen and Zimmerman preschool articulation test. Five year examination included Stanford-Binet assessment, and school age F/U was based on the Univ.of Vermont Achenbach Child Behavior Checklist and the Achenbach Teacher Report. Outcome of all 97 infants is summarized as follows: normal - 61(63%) mild - 21(22%) severe - 15(15%) Of the severely affected children, 11 had cerebral palsy, one had ADD, and three were in the appropriate class but were far below average in two subjects. Longitudinal F/U data were available on 83 infants. Change in classification after 6 - 12 mo is identified as + or - 1 or 2 categories followed by (# of infants). Table