Pamela M Fitzhardinge

INTRAUTERINE GROWTH RETARDATION (IUGR): AN ADDED RISK TO THE PRETERM INFANT

In order to determine the dual effects of IUGR and premature birth, a prospective study of growth and development was done in a group of preterm small-for-gestational age infants (SGA). All were ≤ 32 weeks gestation with hirth weights more than 2 standard deviations below the mean for gestation. During 1974, 60 infants meeting these criteria were referred to our neonatal intensive care unit. Twenty-six of the 29 survivors were followed to age 18 months post-term. Mean birth weight was 988±152 g, gestation 30.5±1.7 weeks. Each infant was randomly paired with a surviving infant of appropriate weight for gestation (AGA) who matched for birth weight, sex, and type of ventilatory support (birth weight 999±129 g, gestation 27.8±1.5 weeks). The SGA infants were significantly smaller at 18 months post-term than the AGA controls with a mean difference in weight of 0.8 kg, length 2.2 cm, head circumference 1.3 cm (p<0.005). Eight of the 26 SGA children had major neurological defects: 1 with microcephaly, 2-hydrocephaly, 4-cerebral palsy, 1-seizure disorder. None of the controls were so affected (p<0.005). The Bayley developmental indices (corrected for gestation) were significantly lower than those of the controls: mental 88±15, mean difference 10 (p<0.02); motor 79±21, mean difference 11 (p<0.05).The results suggest that the complication of IUGR significantly increases the risk of serious sequelae in the tiny premature Infants.

Perinatal Damage to the Developing Brain

Prevention of perinatal damage to the developing brain is a major problem of modern neonatal intensive care. Our approach to this problem in the 1980s is aided by a considerable body of knowledge that has accumulated from diverse investigations over the past 20 years. Follow—up studies have documented the improvements in survival of infants of varying gestational ages and have identified with increasing accuracy those surviving neonates at highest risk of long—term neuro—developmental defects. Correlations between neonatal disease states and outcome have provided information on the relative importance of each neonatal complication in terms of brain damage. Recently, develop—mental neuroanatomy has given much needed information about the vulnerable areas of the neonatal brain at various stages of gestation. Human adult, neonatal, and experimental animal studies have provided additional valuable insights into the pathophysiology of the cerebral lesions seen in neonates. In the last few years, the development of radionucleotide, computed tomography, and ultrasound scans of the brain have enabled localization of at least some neonatal cerebral lesions in the living infant.

1597 DIAGNOSTIC ACCURACY OF NEONATAL BRAIN IMAGING: A POST-MORTEM CORRELATION

During an 11 month period of a prospective study of < 1250 gm appropriate for gestational age infants, 31/87 (36%) died. Autopsies were performed on 24 and revealed 2 (8%) with germinal layer hemorrhage only, 15 (63%) with intraventricular±germinal layer hemorrhage and 7 (29%)without either hemorrhage. During life all infants were scanned through the skull in coronal and axial planes using real-time linear array ultrasound (U/S). Transfontanelle static sector U/S and CT studies were done after death prior to autopsy. The table shows correlation of autopsy findings with these scans.Although the differences are not statistically significant, the results suggest that greatest accuracy is obtained by ultrasound imaging through the fontanelle. It is noteworthy that no method of brain imaging was 100% accurate in detecting hemorrhage.

SEOUELAE OF EARLY-ONSET GBS NEONATAL MENINGITIS

Early onset group B streptococcal (GBS) meningitis is reputed to have a high mortality rate of 58%. Outcome data have been reported on only very small samples. From 1974-82 27 infants with early onset GBS meningitis (≤7 days) were referred shortly after birth to our hospital. Diagnosis depended upon positive CSF culture. Six (22%) infants died. Prospective studies on 20 survivors included full neurological, visual and psychometric evaluations. Bayley scores were obtained on 14 at 18 mos.; Wechsler on 4 at 5 years. Two were assessed clinically at 12 mos. Seven were preterm; 14 were male. The outcome is not related to gestational age, sex, or neonatal course.The mortality rate is lower than previously reported with a combined mortality and morbidity rate of 46%. Only 3 (15%) of the survivors were severely handicapped.

1126 FOLLOW-UP STUDIES OF INFANTS WITH ABNORMAL NEONATAL COMPUTED TOMOGRAPHY (CT) RESULTING FROM ASPHYXIA

20 full term infants had abnormal CT during the neonatal period. All had histories of peripartum asphyxia followed by seizures. Bleeding into the ventricles and/or adjoining brain tissue was present in 7 and was extensive in 5. Areas of decreased cortical density secondary to anoxia were present in the remaining 13. In 3, these changes were confined to one hemisphere with a pattern suggesting infarction of the middle cerebral artery. Severe edema obliterating the ventricles was present in 2 others.All patients have been followed for a minimum of 9 mo with a repeat CT done at 6-12 mo in 18. 12 of the 20 have severe neurological abnormalities: 2 hydrocephalus; 7 cerebral palsy; 3 microcephaly with retardation. All 18 follow-up CT show brain atrophy with localization and extent corresponding to the neonatal CT. The 5 children with extensive intracranial bleeding are severely defective; the other 2 have minimal dystonia and developmental delay. All 3 patients with unilateral changes are hemiplegic. The 2 patients with severe neonatal edema have central atrophy on follow-up CT and spastic quadriplegia with retardation.These results show that CT in the asphyxiated neonate is highly predictive of the type and severity of later neurologic deficits, especially in cases showing severe edema, major vessel infarction, or extensive intracranial hemorrhage.

1118 HANDICAP IN THE PRETERM SMALL-FOR-GESTATION (SGA) INFANT

Reports on incidence of central nervous system (CNS) sequelae in term SGA infants have been generally encouraging. This paper presents results of a follow-up study of preterm SGA infants (birthweight > SD below mean) born at 33-36 wk. gestation. 41 infants meeting these criteria were admitted to the neonatal unit in 1974, 75. 30/35 survivors were followed for at least 2 yrs and were tested by the Bayley Developmental Scales at 18 mo from term. The Bayley scores were low - mean 83±15 - with 12 (40%) scoring <80. Cerebral palsy occurred in 6 children, 5 of whom were diplegic. 4 of the 6 scored <80 on the Bayley.Bayley scores were not related to either the degree of intrauterine head growth restriction or the rate of early postnatal head growth. They did not correlate with gestation, complications of pregnancy/delivery, asphyxia or hypoglycemia. However, 6 of the 12 with Bayley <80 had asphyxia or hypoglycemia that was accompanied by seizures or apnea. Only 1/18 with Bayley >80 was so affected (p=< 0.02).The results show that, unlike the full term SGA, the preterm SGA is at a high risk for serious CNS handicap and that this risk increases if asphyxia or hypoglycemia is accompanied by seizures or apnea.

982 MASK VENTILATION IN PREMATURE NEONATES IS ASSOCIATED WITH SEVERE RETARDATION

Autopsy studies of infants with birthweights ≥1500g have shown significantly more cerebellar and intraventricular hemorrhage in neonates dying after ventilation via a face mask compared with those ventilated via an endotracheal tube (ETT)1. The intracranial hemorrhage (ICH) has been attributed to severe occipital compression and head molding from the velcro band attachment for the mask. The 99 survivors (birthweight ≥1500g) who were ventilated during the same time period have been followed prospectively for two years to determine the incidence of central nervous system sequelae.The differences in psychometric scoring were independent of birthweight or duration of ventilation. Five of the six severely retarded mask survivors had either cerebral palsy or hydrocephalus. All six had ICH as neonates. It is our conclusion, that the use of mask ventilation, compared to ETT ventilation, is associated with an unacceptably high incidence of severe retardation and that these defects are related to ICH.1. Pape, K. et al. Pediatrics, 58:473, 1976.

PERIPHERAL MEDIAN NERVE DAMAGE SECONDARY TO BRACHIAL ARTERIAL BLOOD GAS SAMPLING

In 1974, 252 infants with birth weights < 1501 g were referred to our neonatal intensive care unit. Arterial blood gases were monitored frequently to avoid the complications of hypo- and hyperoxia. Umbilical catheters were removed after 4 to 5 days; further arterial sampling was obtained preferentially from the right brachial artery. Eighty-nine percent (146/167) of the survivors have been examined prospectively to the age of 18 months post-term. Evidence of peripheral median nerve damage with mild to moderate impairment of the pincer grasp was found in 18 infants (12%). All had visually obvious scarring in the antecubital fossa secondary to arterial punctures. The right median nerve alone was affected in 13 cases; bilateral damage occurred in 5. The incidence of this lesion varied directly with the frequency of peripheral arterial punctures and indirectly with birth weight. An examination of autopsy tissue blocks of the antecubital fossa taken from 6 similarly treated infants revealed 4 with varying degrees of hemorrhage dissecting tissue planes. The most severe lesion demonstrated repeated extensive bleeding, muscle necrosis and a traumatic neuroma. A well defined pincer grasp is expected to be present by 12 months post-term; by 18 months post-term all peripheral regeneration of damaged nerve fibers should be completed. These results suggest that brachial arterial punctures may be associated with median nerve damage in the pre-term infant.

THE 1000 GRAM INFANT AT 18 MONTHS

During 1974, 97 infants with birth weights < 1001 g. were referred to our neonatal intensive care unit from outlying hospitals. Forty-five (46%) survived. Forty-two (93%), 14 of whom were small for gestational age, have been studied prospectively and the results analyzed at age 18 months post-term. Eleven of the 42 had major developmental sequelae. Nine had a developmental index (D.I.) less than 70; 4 of these and 2 others had major neurological defects (cerebral palsy, hydrocephaly, microcephaly). The median D.I. for these 11 with severe handicap was 64 mental, 57 motor. The remaining 31 infants (74%) were free of major handicap although 19 had evidence of minor dystonia or speech delay. The median D.I. for these 31 children was 96 mental, 90 motor. The average D.I. for the entire sample was 89±25 for mental, 81±22 for psychomotor.Retrolental fibroplasia was diagnosed in 6/42; 3 had less than 10% vision. None of the survivors had impaired hearing. Wilson-Mikity Syndrome or bronchopulmonary dysplasla occurred in 7; 4 were still symptomatic.Major developmental handicap at follow-up was most closely related to the complication of severe intrauterine growth retardation ( p< 0.005) or to the occurrence of neonatal intracranial hemorrhage or seizures ( p<0.005).