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

A randomized clinical trial of the use of bovine surfactant for the prevention of neonatal respiratory distress syndrome was completed at our Institution in 1984 (Pediatrics 1985;76:145-153). All infants entering the trial were enrolled in our follow-up clinic and seen at regular intervals for assessment of growth and development, neurologic and sensory status, and incidence of respiratory disease and allergic conditions. Infants have now been followed-up for at least 2 years. Of those infants for whom follow-up is complete, two of 32 (6.3%) surfactant-treated infants died, five (15.6%) had major neuro-developmental handicaps, and five had minor neurodevelopmental handicaps. In the control group, eight of 33 (24%) infants died, whereas only two (6.1%) survived with major neurodevelopmental handicaps, and four (12.1%) were left with minor handicaps. Except for an increased neonatal death rate in the control group, other differences were not statistically significant. The groups were also comparable in terms of the incidence of late respiratory or allergic disease as assessed by history. Treatment with bovine surfactant at birth of premature infants at high risk for respiratory distress syndrome appears to be safe and of short-term benefit, although no decrease in neurodevelopmental handicap at 2 years' follow-up can be demonstrated.

Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period.

The follow-up records of 605 infants with birth weights of less than 1,500 g, with data available for 2 years after birth, were examined for evidence of abnormal pulmonary signs or symptoms. A total of 119 infants were identified and the neonatal oxygen requirements of these infants were compared with those of 486 infants who had normal pulmonary function. A requirement for oxygen at 28 days of life had a positive predictive value for abnormal pulmonary findings at the time of follow-up of only 38%, whereas 31% of those with normal pulmonary findings at the time of follow-up were still receiving oxygen at this age. The need for oxygen at 28 days was a good predictor of abnormal findings in infants of greater than or equal to 30 weeks' gestational age at birth but became increasingly less useful as gestational age decreased. It was found that, irrespective of gestational age at birth, the requirement for additional oxygen at 36 weeks' corrected postnatal gestational age was a better predictor of abnormal outcome, increasing the positive predictive value to 63%. The prediction of a normal outcome remained 90% for infants not receiving oxygen at this corrected gestational age.

Etiological factors associated with the development of periventricular leukomalacia.

Prenatal, intrapartum and postnatal factors are compared between 15 preterm infants, known to have periventricular leukomalacia (PVL) on ultrasound and 15 infants of similar birthweight and gestation who ultrasonographically showed no evidence of cystic lesions, and who are known to be neurologically normal at follow up. Prenatally, the incidence of antepartum haemorrhage was significantly higher in the PVL group. Intrapartum factors were similar between the two groups but postnatally, the PVL group had significantly lower PaCO2 readings during the first 72 h of life. It is postulated that a severe maternal bleed in late pregnancy and neonatal hypocarbia could significantly decrease cerebral perfusion and cause areas of ischaemia and infarction resulting in periventricular leukomalacia.

Periventricular leukomalacia: ultrasonic diagnosis and neurological outcome.

The ultrasonographic findings and neurological development of 15 preterm infants, born between August 1981 and July 1984, who developed periventricular leukomalacia (P.V.L.) are described. The incidence of P.V.L. in infants with a birth weight less than 1 500 g was 2.3%. Nine of the 15 infants demonstrated areas of increased echogenicity in the periventricular regions prior to the development of cystic changes. The mean age for the appearance of cysts was 26 days. At follow-up 14 infants showed evidence of abnormal motor development and 8 infants had visual defects. All infants appear to have normal hearing, but 3 infants show signs of delayed speech. To date, only 2 infants demonstrate signs of mental retardation, but many of the infants are too young to assess intelligence accurately.

Perinatal factors associated with death or handicap in very preterm infants.

That death or major developmental handicap is associated with prematurity and low birth weight is well recognized. The importance of other perinatal factors related to presentation and management, however, is far from certain. In an attempt to elucidate the importance of some of these factors, data from 383 live-born infants delivered at 26 to 30 weeks' gestation were analyzed. All infants were born in a tertiary perinatal unit and long-term follow-up had been carried out on the survivors for at least 1 year. A group of 39 infants who died in the neonatal period and 34 infants with long-term handicap were compared with matched normal control infants. Perinatal factors related to outcome were analyzed and it was found that, while initial poor condition at birth was correlated with death, there were few predictors of subsequent handicap. More refined methods of both prenatal and neonatal assessment are required to define these factors.

Perinatal intensive care: where and how to draw the line.

With the rapid advances in perinatal intensive care and resultant changes in neonatal prognosis, it is often difficult for the medical personnel involved to know where application of such care is justified, whether major intervention for fetal reasons is warranted, or what information to give parents as to probable outcome. To aid in developing guidelines for these areas of concerns, 730 consecutive live births that occurred in a perinatal unit between 23 and 32 weeks' gestation were analyzed for mortality and long-term morbidity by gestational age at birth. Probability of a normal outcome varies considerably according to which method of analyzing outcome is used. With a greater than 50% probability of intact survival from 25 weeks' gestation and above, intervention for fetal reasons seems to be justified if indicated on purely medical grounds, although prolonged use of restricted resources at or below 25 weeks remains a concern.

Diagnosis and evolution of periventricular leukomalacia: a study with real-time ultrasound.

Periventricular leukomalacia is an ischemic lesion in periventricular white matter of premature infants. Hemorrhage into the ischemic area occurs in up to 25% of cases. We report two cases in which the diagnosis of periventricular leukomalacia was made during life with real-time ultrasound scanning. In one case, serial scans demonstrated the evolution of echodense regions, observed in the first 3 days of life, to cystic echolucent areas at 4 weeks. In the second case, periventricular echodense areas did not precede the occurrence of cystic echolucent lesions. This may reflect a more chronic ischemic cerebral insult (consistent with recurrent apnea and bradycardia) rather than a presumed acute episode of cerebral ischemia (with or without secondary hemorrhage) sustained by the first case. Real-time ultrasound scanning is a simple, non-invasive technique with which to document the evolution of periventricular leukomalacia, and thus to define the clinical neurological correlates in the neonatal period.

Perinatal factors that influence the incidence of subependymal and intraventricular hemorrhage in low birthweight infants.

A total of 95 preterm infants, delivered consecutively in a perinatal center, over a 9-month period, were studied serially with real-time ultrasound for detection of subependymal/intraventricular hemorrhage (SEH/IVH); all infants were less than or equal to 32-week gestation and/or less than or equal to 1500 gm birthweight. Detailed statistical analysis was carried out to determine the influence of perinatal factors on the occurrence of SEH/IVH. The incidence of SEH/IVH was 34%; severe hemorrhage (Grade III-IV) occurred in only 13%. Gestational age was an important factor associated with SEH/IVH. Thus, the incidence in infants less than or equal to 29-weeks gestation was 45%, whereas in infants greater than 29-weeks gestation age, it was 19% (p less than 0.01). The overall incidence of SEH/IVH in the group which was less than or equal to 29-weeks gestation and delivered by cesarean section was 53%, whereas in those infants delivered vaginally it was 47%. In infants whose gestational age was less than or equal to 29-weeks, the incidence of hemorrhage was 47% if delivered vaginally and presenting as a vertex and 31% if delivered by cesarean section. In infants greater than 29-weeks gestation, the incidence of SEH/IVH was 42% in those delivered by the vaginal vertex route, 5% if presentation was vertex and delivered by cesarean section (p less than 0.05). In infants greater than 29-weeks gestation, cesarean section in vertex presentation decreased the incidence of SEH/IVH when compared with vaginal vertex delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence, severity, and timing of subependymal and intraventricular hemorrhages in preterm infants born in a perinatal unit as detected by serial real-time ultrasound.

Real-time ultrasound scans were performed on 66 low-birth-weight infants within the first six hours of life (mean, two hours), and then at 12, 24, 48, and 72 hours, and thereafter at weekly intervals. All of the infants were born in a perinatal unit. The incidence of intraventricular hemorrhage and subependymal hemorrhage was 31%. Eight of 20 infants had small hemorrhages (Papile, grades I and II); seven infants sustained grade III hemorrhages, and five infants sustained grade IV hemorrhages. All hemorrhages occurred in the first 72 hours of life; 25% were diagnosed with the first scan (ie, within the first six hours of life). The infants especially at risk were those less than 29 weeks' gestation. Five infants developed progressive posthemorrhagic ventriculomegaly that subsided spontaneously by age 8 weeks. The mortality in the study group was only 4.5%.

Outcome of very low-birth weight infants born at a perinatal center.

One hundred six infants with birth weights less than or equal to 1,000 gm were born at a Perinatal Center in 1979 and 1980. Eighty-three (78%) were born to women transferred to the Center because of antenatal problems. The most common obstetric problem was premature labor with or without premature rupture of the membranes. Seventy-two infants (68%) survived. The following perinatal factors were associated with increased survival: increased birth weight and gestational age, intrauterine growth retardation, antenatal steroids, absence of hyaline membrane disease, and absence of seizures or clinical signs of intraventricular hemorrhage. Of the 72 survivors, two were lost to follow-up and one died (sudden infant death syndrome). The most common general health problem was recurrent middle ear infection. Growth was satisfactory. Significant neurological or developmental handicap was found in nine infants (13% of the 69 evaluated).