Extremely-low-birthweight infants: neurological, psychological, growth and health status beyond five years of age.

Of 60 consecutive survivors of birth weight 500-999 g, who were born in one tertiary perinatal centre from 1977 to 1980, 59 infants were assessed by a multidisciplinary team at two years of age (corrected for prematurity) and 58 children were evaluated when aged at least five years. At the latter examination, 9% of the 58 children who were assessed were severely disabled; 17% had a mild or moderate disability; and 74% had no important disability. For the 53 children who were tested, the means for the three scales of the Wechsler Preschool and Primary Scales of Intelligence were just above the test mean. The psychologist noted behavioural problems during her assessment in 50% of children, and 29% of mothers reported behavioural problems which could interfere with schooling. At the age of five years and over, five (9%) children had cerebral palsy and one child was deaf. Twenty-two (38%) children had a visual impairment, although only one child was blind; the detection of retinopathy of prematurity in the nursery was an important risk factor. Health problems with readmissions to hospital and suboptimal growth were present in many children at two years of age and frequently these problems persisted to five years of age. Although only four (7%) children were too disabled to attend a normal school, apprehension exists that many of the other children may later encounter educational difficulties. At the two-years' assessment, ascertainment of cerebral palsy had not been complete or entirely accurate and the Mental Developmental Index of the Bayley Scale tended to underestimate the later psychological performance.

Children of birth weight less than 1000 g: changing outcome between ages 2 and 5 years.

Of 55 consecutive long-term survivors of birth weight 500 to 999 g, complete psychologic and pediatric data were available for 54 children at 2 years corrected age and for 50 at age at least 5 1/2 years. At the latter age, 60% (30 of 50) were not impaired, 10% (five of 50) had severe sensorineural or intellectual impairments, 10% (five of 50) had mild to moderately impairment, and 20% (10 of 50) had minor neurobehavioural abnormalities. Sensorineural deafness in one child and bilateral blindness in one remained stable over time, but of six children with spastic cerebral palsy at 2 years, only three retained this diagnosis at 5 1/2 years. The mean Mental Developmental Index (MDI) on the Bayley Scales at 2 years was 91.1, significantly below the test mean; by 5 1/2 years the mean full scale of the Wechsler Preschool and Primary Scales of Intelligence (WPPSI) was 101.8. The MDI correlated highly with the full-scale WPPSI (r = 0.7), but for individual children it was not always an accurate predictor of 5-year ability. Between 2 and 5 1/2 years there was a substantial reordering within four categories of impairment: findings in 27 children were improved, four were judged to become more severely impaired over time, and 19 did not change. We conclude that our 2-year assessment often underrated the potential of the children as expressed at 5 1/2 years, and that 2 years is too early for reliable classification of children of birth weight 500 to 999 g.

Cerebral palsy in very low birthweight infants surviving to 2 years with modern perinatal intensive care.

The rate of cerebral palsy and factors associated with its occurrence were determined in surviving 2-year-old very low birthweight (VLBW) infants born during an era of modern perinatal intensive care. Of the survivors, 12.5% (52/416) of those traced had spastic cerebral palsy. Motor handicaps were mild in 42%, moderate in 25%, and severe in 33% of children with cerebral palsy. The prevalence of cerebral palsy was similar in all birthweight groups up to the upper limit of 1500 gm, and was considerably higher than in survivors born in the same hospital a decade earlier. Although several perinatal variables were associated with the occurrence of cerebral palsy, either singly or in combination, little statistical or clinical confidence would be placed in these associations. Moreover, although 77% of children with cerebral palsy had one or more commonly recognized perinatal risk factors, almost identical rates of risk factors were present in normal children. The advent of cranial ultrasonography during the time of the study was associated with an increase in mortality but no effect on the prevalence of cerebral palsy. Cerebroventricular hemorrhage correlated poorly with the presence of cerebral palsy. The prevalence of cerebral palsy in surviving VLBW infants is unacceptably high; however, no obvious preventable factors in its etiology could be identified.

Improved outcome to two years of very low-birthweight infants: fact or artifact?

In 1966-70, the survival rate for very low-birthweight (VLBW) children born in a tertiary perinatal centre was 37.1 per cent but by 1980-82 it had increased to 68.3 per cent. The latter cohort had a significantly reduced prevalence of strabismus, myopia and a head circumference under the 10th percentile, but a significantly increased prevalence of cerebral palsy compared with the 1966-70 VLBW children. Survivors born in 1980-82 had a significantly increased mean Mental Development Index (MDI) on the Bayley Scales compared with the sub-group of survivors born in 1968-70 but there was also a significant improvement in mean MDI over time for a group of normal-birthweight children. No improvement of MDI scores of VLBW survivors in the 1980-82 cohort could be attributed solely to perinatal care. The two-year-old VLBW children in the 1980-82 cohort had similar rates of sensorineural impairments, disabilities and mean MDI to those who would have survived with the care available in 1966-70. It is concluded that survival of VLBW infants has improved in recent times but that neurodevelopmental outcome still lags behind that of normal-birthweight peers.

Very low birthweight and normal birthweight infants. A comparison of continuing morbidity.

One hundred and forty-eight (95.5%) of 155 consecutive two-year survivors of 227 very low birthweight (VLBW, less than 1501 g) infants and 50 (83.3%) of 60 infants of normal birthweight who were selected at random, all of whom were born at the Royal Women's Hospital, Melbourne from October 1980 to March 1982, were seen at the age of two years. Social, psychological and health data were compared between the groups. The mean Bayley Mental Developmental Index scores of VLBW children were significantly lower; the prevalence of major handicaps and poor growth (height and weight below the 10th percentile), and the number of hospital readmissions, wheezing episodes, major and minor congenital anomalies and postnatally-acquired malformations (for example, abnormally shaped skull) were significantly greater in VLBW children. There was a trend for a greater number of episodes of otitis media, lower respiratory tract infections and surgical procedures per child in VLBW children. Extremely low birthweight children (birthweight less than 1000 g) contributed significantly to this morbidity. Parents of VLBW children perceived significantly more problems with infant vomiting and behavioural disturbances at two years of age. The children of mothers of limited education, or immigrant status and non-fee paying or lower socioeconomic families had lower mean Bayley Mental Developmental Index scores but similar handicap rates and health status in both weight cohorts.

Relationship of growth and psychoneurologic status of 2-year-old children of birthweight 500-999 g.

There were 257 liveborn infants of birthweight 500-999 g born in one tertiary centre in the 5 1/4 years commencing January 1977; 86 (33.5%) survived to 2 years of age, corrected for prematurity and 83/86 (96.5%) were fully assessed. The prevalence of cerebral palsy was 10/83 (12%) and 17/83 (20%) had a major impairment. The distribution of weights and heights for 2-year-old boys and girls was significantly lower than for the standard population, as was the head circumference distribution for boys; the distribution of the Mental Developmental Index (Bayley Scales) was not related to the head circumference or body weight at two years or to head-circumference/bodyweight or height ratios. At birth measurements of weight, length and head circumference were under the 3rd percentile for 13/86 (15%), 9/86 (10.5%) and 9/86 (10.5%) respectively. By 2 years of age, weight, length and head circumference were under the 3rd percentile in 23/83 (27.7%), 26/83 (31.3%) and 4/83 (4.8%) respectively. 12 children who were SGA at birth were fully assessed at 2 years; the group of 6, who continued with poor postnatal weight gains (under the 3rd percentile) had the highest rate of major impairment but included were the only extremely SGA twins and the only two major malformations in the study. We found no association of other health problems or unfavourable social factors with poor postnatal growth or impaired outcome.

Effects of antenatal steroid therapy on mortality and morbidity in very low birth weight infants.

A cohort of 678 consecutive very low birth weight infants, liveborn in one tertiary institution during a 63-month period, was studied to investigate whether antenatal steroid therapy had any beneficial or harmful effects on mortality or morbidity over the first 2 years of life. Comparing the 244 babies who received treatment with the 434 controls, 195 (79.9%) and 265 (61.1%), respectively, were discharged home (P less than 0.001). Mortality in the treated group remained substantially lower and was almost halved after adjustment for birth weight, extreme immaturity, lethal malformations, and confounding obstetric variables (P = 0.001). Fatal cases of respiratory distress syndrome were less common in the treated group (P = 0.044). Of in-hospital survivors, those in the treated group required less positive pressure respiratory support (P = 0.003) and fewer days in oxygen (P = 0.018), and the incidences of bronchopulmonary dysplasia (P = 0.003) and patent ductus arteriosus (P = 0.002) were lower. Two-year survivors who had received treatment were heavier (P = 0.016) and had larger head circumferences (P = 0.029). These beneficial associations in the treated group were not at the expense of increased rates of infection or adverse neurologic outcome. We did not detect any adverse effects of antenatal steroid therapy on any relevant aspect of mortality or morbidity in infancy under circumstances in which the chances of finding substantial differences were high.

Mortality and two year outcome of infants of birthweight 500-1500 g: relationship with neonatal cerebral ultrasound data.

Cranial ultrasounds were performed on 218 (96%) of 227 liveborn infants of birthweight 500-1500 g delivered in the Royal Women's Hospital, Melbourne, Australia, in an 18-month period concluding in March 1982. Seventy-two (31.7%) of the children died; 28 children (38.9%) had cerebroventricular haemorrhage, 35 (48.6%) showed no bleeding and there were nine (12.5%) with no data. Paired necropsy and ultrasound data were congruent in 22 (88%) of 25 children. One hundred and forty-eight (95.5%) of 155 survivors were seen at 2 years of age. Forty-one (28%) had cerebroventricular haemorrhage; nine children (6%) had both ventricular dilatation and haemorrhage and two had ventricular dilatation alone. Apart from a marginal advance in gestation and higher number of immigrant and less educated mothers in children without cerebroventricular haemorrhage, all other perinatal, biographical and social variables between those with haemorrhage and those without were similar. The major handicap rate overall was 14.2% (21 patients). The children with cerebroventricular haemorrhage had a trend for greater prevalence of handicap and lower mean Bayley psychological scores. This was even more evident with ventricular dilatation being present. Of children with major handicap 57.1% (12/21) had normal serial ultrasound findings during their primary hospitalization. Major handicap occurred in 15% (3/20) of children with grade 1 haemorrhage, 23.5% (4/17) with grade 2 or 3 bleeds and 25% (1/4) of those with grade 4 haemorrhage. Laterality of cerebral palsy did not correlate with ultrasound findings. Ultrasound findings did not improve statistical prediction of deaths or major handicap.

Cesarean section or vaginal delivery at 24 to 28 weeks' gestation: comparison of survival and neonatal and two-year morbidity.

A large cohort of consecutive live births with gestational ages assessed antenatally from 24 to 28 weeks from one tertiary center was studied to determine the association between mode of delivery and in-hospital mortality and morbidity and morbidity at two years of age. Between 1 January 1977 and 31 March 1982, 52.8% (172 of 326) of such infants survived their primary hospitalization. Obstetric factors independently associated with improved survival were increasing gestational age (P less than .0001), the absence of maternal hypertension (P = .007), singleton pregnancy (P = .007), and antenatal steroid therapy (P = .018). Although 62.7% (32 of 51) of infants delivered by cesarean section survived compared with 50.9% (140 of 275) of infants delivered vaginally, the increased survival was not statistically significant (X 2 = 1.97). Moreover, the trend favoring cesarean section disappeared after adjustment for confounding obstetric factors. In univariate analyses cesarean births more frequently required ventilatory support and there was a trend toward a lower incidence of cerebroventricular hemorrhage; again, however, when adjusted for extraneous factors these associations disappeared. Of the 172 in-hospital survivors, five died at home unexpectedly; 162 of the remaining 167 were traced; 18 (11.1%) had cerebral palsy and two (1.2%) were deaf. Of the 111 children who were fully assessed, 13.5% had major handicaps, 23.4% were suspect, and 63.1% were free of handicap at two years' corrected age. There was no association between mode of delivery and frequency of handicap. Little evidence was found from mortality or morbidity data to support routine delivery of infants of borderline viability by cesarean section.

Handicaps and health problems in 2 year old children of birth weight 500 to 1500 g.

Fifty-nine infants of birthweight 500 to 999 g born in 1977 to 1980 and 132 infants of birthweight 1000 to 1500 g born in 1977 to 1978 were reviewed at two years corrected age. For the whole cohort, cerebral palsy was found in 12.6%, bilateral deafness in 1%, blindness in 1% and severe developmental delay in 12%. There was no significant difference in these disabilities between the groups of larger and smaller infants; 37.7% of the cohort was readmitted to hospital on at least one occasion, 35.6% of children had wheezing episodes and/or lower respiratory tract infections which together accounted for 51% of hospitalizations. The infants of birthweight 500 to 999 g tended to require more frequent and prolonged hospitalizations. Dolicocephalic head shape, chest deformities, iatrogenic sequelae from intensive care, poor growth and cicatricial retrolental fibroplasia were significantly more frequent in children of birthweight 500 to 999 g. Parents reported that 39% of their children had 'colic', 31.6% had sleep disturbance and 25% had multiple behavioural problems. Low frustration tolerance, inability to wait, hypo- or hyperactivity and an inappropriate relationship with the mother as measured by the psychologist all occurred significantly more frequently in children of birthweight of less than 1000 g. This report confirms the belief that a comprehensive follow-up is required for very low birthweight (VLBW) children because significant health problems continue after primary hospitalization.

Live-born infants of 24 to 28 weeks' gestation: survival and sequelae at two years of age.

The survival rate of infants born alive between 24 and 28 weeks of gestation has increased significantly in this tertiary care centre, from about 9% in the first cohort studied (1966-1970), to 19.5% in the second cohort (1971-1974) and 50.3% in the third cohort (1977-1982); the borderline of practical viability decreased from 27 to 24 weeks over the years of the study. The number of mothers with a history of prior termination of pregnancy increased about sixfold from the second to the third cohorts but the rate of premature births increased by only 50%. The augmented survival rate was accompanied by an increase in the prevalence and total number of children with cerebral palsy, but bilateral blindness due to retinopathy of prematurity and severe sensorineural deafness were reduced. When 96% of children in the third cohort were assessed at two years of age. 13% had severe handicaps, 59% were considered normal and in 24% some handicap was suspected. The serious handicap rate was 28% for children born at 24-26 weeks compared with 8.5% for those born at 27-28 weeks of gestation.

Collaborative study of very-low-birth-weight infants. Correlation of handicap with risk factors.

Two large maternity services studied consecutive inborn infants (birth weight range, 500 to 1,500 g) born between 1977 and 1978. The multidisciplinary team members used identical assessment methods and documentation. Of 259 long-term survivors, 252 (97.3%) were seen at 2 years of age. Survival rates for hospitals 1 and 2 were 68.5% and 69.0%, respectively. Cerebral palsy rates for hospitals 1 and 2 were 11.8% and 11.2%, respectively. Major handicaps (cerebral palsy, mental developmental index [MDI] on the Bayley scales less than 69, epilepsy, deafness, or blindness) occurred in 30 (18.6%) and 17 (17.3%) of hospitals 1 and 2 survivors, respectively. Both cerebral palsy and developmental delay (MDI below 75 without severe or moderate cerebral palsy) were significantly correlated with a number of perinatal variables, but none were common to the two hospitals. Of the 30 children with cerebral palsy, 15 (50%) were not ventilated, and 28 (93%) had a five-minute Apgar score greater than 4; there was no indication that selective treatment to prevent cerebral palsy was possible.

Infants born before 29 weeks gestation: survival and morbidity at 2 years of age.

In a collaborative study involving two hospitals with large maternity services, 166 liveborn infants of gestational age from 24 to 28 weeks were born in the calendar years 1977 and 1978. Of these infants, 75 (45.2%) died either in hospital or after discharge home. At the age of 2 years, 16 (9.6%) of the cohort had a major handicap [cerebral palsy, Mental Developmental Index (MDI) under 69, deafness or blindness]. An additional 20 children (12.0%) had significant developmental delay (MDI 69 to 84, -2 to -1 SD below mean) and 53 (31.9%) were considered to be free of these handicaps. Psychological assessments were not performed on two survivors (1.2%) but reliable reports indicated that they were free of major handicaps. Long-term survival increased in a stepwise fashion from 9.1% at 24 weeks to 68.5% at 28 weeks gestation, and there was a trend for major handicap and significant developmental delay to decrease in incidence with increasing maturity. Of the 58 children who had presented by the vertex 42 (72.4%) were free of significant handicap; however, of the 31 children in whom there had been either a breech presentation or a transverse lie, only 11 (35.5%) were free of significant handicap (chi 2 = 9.69, P less than 0.01). The mode of delivery (vaginal or caesarean section) did not significantly affect the handicap rate in the survivors.

Changing outcome over 13 years of very low birthweight infants.

The survival prospects for infants of birthweight less than or equal to 1500 g born in recent years have improved. Evidence for a corresponding decrease in long-term morbidity of survivors is conflicting but recent reports from some centers indicate that high morbidity rates are occurring. Until additional satisfactory reports are available on the outcome of very low birthweight (VLBW) infants born after 1975, preferably from a community or region, uncertainty will continue. The outcome of three cohorts of VLBW infants, born in the Royal Women's Hospital, Melbourne between 1966 and 1978 is reported; more than 90% of each cohort were fully assessed, aged 2-8 years. There were 169 long-term survivors from the first cohort (1966-1970 births) and 72 from the second cohort (1973-74 births); survival rates were 37.1% and 37.3% respectively; however, for the 1977-78 births, there were 161 survivors, a significant increase to 68.3%. In the first cohort, 32.7% had one or more visual defects and 3.9% were blind but visual morbidity decreased progressively in cohorts 2 and 3; 3% of the second cohort and 1.2% of the third cohort were blind. There was a trend for a decrease in severe sensorineural deafness. Cerebral palsy increased progressively, respectively 2.6%, 4.5% and 11.9% in the first, second and third cohorts. There was a significant increase in the mean Mental Developmental Index of the Bayley Scales at the age of 2 years from 75.38 for the 64 children born in 1966-70 compared with 90.96 for 150 children in the 1977-78 cohort. Although there had been an increase in upper social class families in the more recent cohort, improvement in test scores was still highly significant when higher social classes (1-3 Congalton Scale) were excluded. However, there was no significant improvement in the 6 year psychological test scores of the first and second cohorts. There was a steady increase in occurrence of cerebral palsy. Significance associations in the 1977-78 cohort were found with only 2 perinatal variables (use of theophylline and necrotizing entercolitis). Furthermore, 17 (89.5%) of children had a five-minute Apgar score greater than 5 and 14 (73.7%) did not require ventilatory support: Prevention of cerebral palsy by selective treatment in the delivery room or nursery was not feasible for prediction of this condition was not possible from perinatal risk factors.

Collaborative study of very-low-birthweight infants: Techniques of perinatal care and mortality.

The neonatal units in two large maternity hospitals collaborated in a study of 440 liveborn infants weighting 500-1500 g born in 1977 and 1978: 377 (85.7%) were born in hospital. The overall survival rate was 70.5%, with a range of 67.5% to 71.5% for the inborn and outborn categories of infants in each hospital. In hospital A the survival rate of infants weighing greater than or equal to 1100 g was higher than that in hospital b, whereas the survival rate of infants weighing less than 800 g was higher in hospital B. Obstetric risk factors and obstetric management differed little between the hospitals, but there were several important differences in paediatric management; in particular, hospital B (with a better survival rate of infants weighing under 800 g) used ventilatory support and parenteral feeding much more frequently.