Neuropsychiatric disorders in newborn infants with very low birth weight (VLBW infants)--before and following introduction of modern perinatal medicine. 1. Overview of the problem, criteria for quality of survival, major CNS disorders (major handicap)

The survival quality of very low birthweight infants (VLBW infants) is highly actual just even in the time of modern perinatal medicine. Through the development and permanent improvement of the perinatal intensive therapy the survival chances of VLBW infants could be improved significantly in the last 25 years. In the 70's survival rates of 60-84 per cent were achieved in VLBW infants, in the leading centers even rates of 86 and 90.5 percent, respectively. In the 70's an enormous improvement in the survival rates from 20-45 per cent was achieved in tiny premature infants (birth weight 1,000 gm and less), too. However, the efforts of gynecologists and neonatologists to reduce the mortality of low birth-weight infants are again and again blamed for possibly obtaining successes with an increase in CNS morbidity. The parallel analysis of some brain damage groups in VLBW infants seems suitable to gain a clear statement if modern perinatal medicine contributes to reduce the frequency of early infantile cerebral damages and their consecutive handicaps altogether. In an extensive review of literature it is tried to prove this for the major CNS handicaps altogether and separately for the infantile cerebral palsies, epilepsies and mental retardations (oligophrenias). Simultaneously with an average increase from 29.7 to 69.5 per cent of the healthy surviving children, there was a reduction of major CNS handicaps on the average from 36 to 12 per cent.     

Neuropsychiatric disorders in newborn infants with very low birth weight (VLBW infants)--before and following introduction of modern perinatal medicine. 2. Infantile cerebral palsy, epilepsy and mental handicap (oligophrenia)

Simultaneously with the introduction of modern perinatal intensive therapy the infantile cerebral palsies (ICP) of VLBW infants dropped on the average from 23 to 5.9 per cent. In Swedish and West-Australian ICP studies a considerable decrease in the ICP incidence was found in the 60's, but there was again a slight increase in the 70's. A decrease in the epilepsies was found on an average from 9 to 1.6 per cent, whereby in 10 of 16 actual studies mostly performed at early follow-up age no epilepsies were reported. A decrease in the mental retardations (oligophrenias) was found on an average from 22 to 10.6 per cent. There was especially noteworthy a reduction of the severe mental retardations from 8 to 10 per cent to an average of 2.3 per cent.     

Parameters of cellular adaptation in newborn infants in health and in perinatal injuries of the CNS

A study was made of the level of compensatory and adaptive reactions in red blood cells (intensity of membranous metabolism, lipid peroxidation, malonic dialdehyde (MDA) metabolism, changes in the correlation of lipid fractions) in the newborn in health and in perinatal CNS injuries within the first days of life. Changes in the indicated parameters were examined after preincubation of red blood cells under physiologic conditions and by means of MDA addition to the incubation medium. It is concluded that the newborn with perinatal CNS injuries are marked by metabolic inertness and reduced cellular adaptation in red blood cells preincubated under physiologic conditions as well as by pronounced disadaptation under the conditions of excess MDA.     

Incidence of and risk factors for neonatal morbidity after active perinatal care: extremely preterm infants study in Sweden (EXPRESS)

Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004–2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long‐term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage ≥3. Eighty‐five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty‐seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long‐term health of survivors are warranted.     

Mortality and morbidity of newborn infants in intensive care (birth weight less than 1,501 grams)

A comparative analysis of the mortality and morbidity of premature infants with a birthweight below 1.501 g, born in the years 1974, 1978 and 1981, is given. The mortality rate has remained unchanged in the years 1974 (when a neonatal intensive care unit was installed at the University Children's Hospital Graz) and 1981 with 33% and 32% respectively. The total number of admissions rose from 36 (1974) to 67 (1978) and 91 (1981). Simultaneously the number of patients, who needed neonatal intensive care increased. Whilst in 1974 only 2 of 24 surviving infants needed artificial ventilation, in 1978 19 of 38 patients had respirator therapy. Despite the increasing severity of neonatal affections the number of severe handicaps caused by perinatal complications remained constantly low with altogether 5 cases in the years 1978 and 1981. Two children had a spastic tetraplegia, two others had a posthaemorrhagic hydrocephalus and one child was blind due to bilateral septic abscesses of the vitreous body. Only two of these children had long time artificial ventilation. Approximately 80% of the surviving children exhibited normal psychomotor development and showed no neurological sequelae. This rate was unchanged in the investigated periods.     

Acute neonatal morbidity and long-term central nervous system sequelae of perinatal asphyxia in term infants.

Twenty-eight term neonates with severe perinatal asphyxia were referred to a tertiary neonatal intensive care unit (NICU). The morbidity of asphyxia included involvement of the pulmonary (n = 24 infants), central nervous system (n = 22), renal (n = 15), cardiac (n = 14), metabolic (n = 13) and hematologic (n = 10) systems. The majority of neonates had more than three organ systems involved. Twenty-four neonates survived the neonatal course and at NICU discharge all system effects other than the central nervous system had resolved. At 5 years (60 months), 14 children had a normal neurologic examination, 9 had spastic quadriplegia and one had hemiplegia. Nine children had a McCarthy General Cognitive Index (GCI) greater than or equal to 84, 3 had a GCI between 68 and 83 and 12 scored less than 67. Neonatal seizures, renal problems, microcephaly at 3 months, and post-neonatal seizures were associated with an abnormal neurologic outcome or a GCI less than 67. A neurologic examination during the first year of life may reveal whether children with birth asphyxia will be relatively normal at age 5 years or whether they will show considerable delay.     

Hydrocholecystitis in children and newborn infants. Apropos of 3 cases

We report two cases of hydrocholecystitis in children and one in a neonate. One child had hepatitis A and the other had typhoid fever. A beta-hemolytic group B streptococcal infection was found in the neonate. In all three cases, the first manifestation was an abdominal mass and treatment of the causative disease ensured recovery. These three observations provided us with the opportunity for reviewing the literature. Isolated hydrocholecystitis is distinguished from hydrocholecystitis as a symptom. The clinical evaluation and diagnostic investigations are described in detail; special attention is given to abdominal ultrasonography. Etiology and pathophysiology, as well as management are discussed. Our three cases and the review of the literature confirm the benign prognosis of this condition.     

Leukocyte transforming agent (Epstein-Barr virus) in newborn infants and older individuals.

The lymphocyte transforming agent, associated with Epstein-Barr virus, was sought in the oropharynx and other clinical sites of 443 individuals in the following groups: premature and term neonates; infants with congenital malformations or with suspected TORCH syndrome; children with various illnesses; pregnant and postpartum women; healthy adults; and patients with infectious mononucleosis. Evidence of intrauterine infection was found in one newborn infant and LTA was demonstrated in a 16-day-old infant who developed transient hepatosplenomegaly. LTA was not detected in 96 other newborn infants and 57 infants with various anomalies or illnesses; nor was it found in the cervix of 125 pregnant or postpartum women. LTA was demonstrated in varying frequency in ill children, healthy adults, and those with infectious mononucleosis. It is suggested that the clinicoepidemiologic patterns of EBV infection in newborn infants and children will best be established by prospective studies.     

ATP-binding cassette member A3 (E292V) gene mutation and pulmonary morbidity in very-low-birth-weight infants

Aim: ATP‐binding cassette member A 3 (ABCA3) plays a critical role for the transport of surfactant phospholipids into the lamellar bodies of type II alveolar epithelial cells. Term infants carrying the E292V missense mutation of the gene encoding ABCA3 are likely to develop respiratory distress syndrome, and the mutation has also been linked to interstitial lung disease in paediatric patients. The aim of this study was to investigate the association of the E292V genotype with pulmonary morbidity in a large cohort of very‐low‐birth‐weight (VLBW) infants. Methods: We performed a genetic association study with a prospective, population‐based multi‐centre cohort of 3177 VLBW infants born in 16 German study centres between 2003 and 2009 (German Neonatal Network). The ABCA3 genotype was determined by restriction fragment length polymorphism–PCR in genomic DNA samples derived from buccal swabs. Results: In a large cohort of 3177 VLBW infants, 11 individuals were found to be heterozygote for the E292V mutation (0.34%). After stratification according to ABCA3 genotype, no differences were noted for clinical characteristics, necessary treatments and neonatal pulmonary outcomes. Conclusions: Within the size limits of our study cohort, the ABCA3 missense mutation E292V had no remarkable effect on pulmonary outcome in VLBW infants. Present results do not rule out the possibility that E292V phenotype is associated with minor difference in the morbidity.     

The Swedish national prospective study on extremely low birthweight (ELBW) infants. Incidence, mortality, morbidity and survival in relation to level of care

In a 2-year (1990-92) prospective national investigation, comprising all stillborn and live-born ELBW infants with a birthweight of ≤1000 g born at 23 completed weeks of gestation or more, we examined the incidence, neonatal mortality, major morbidity and infant survival in relation to level of care and place of residence. A total of 633 ELBW infants were live-born, i.e. 0.26% of all live-born infants, and 298 were stillborn. The average neonatal mortality was 37% and 91% at 23 weeks, 70% at 24 weeks, and 40% at 25 weeks of gestation. Of neonatal survivors, 8% had intraventricular haemorrhage grade 3,10% retinopathy of prematurity of stage ≥3, 2% necrotizing enterocolitis, and 28% were oxygen-dependent at a time corresponding to 36 weeks of gestation. In all, 77% were treated with mechanical ventilation, whereas 19% survived without, almost all of them being CPAP treated. Infant mortality among infants born at level III (tertiary centres) was 30%, at level Ha (with full perinatal service) 46% and at level IIb (with basic neonatal service) 55 %. Only 1 % was born at hospital level I. Regarding the relation to place of residence, the mortality rates among infants residing in the areas served by levels III, IIa and lib hospitals were 36%, 45% and 41%, respectively. The referral system thus functioned well, but can be improved, and increased perinatal referral, at borderline perinatal viability, might provide a better quality of care and a better chance of survival.     

Persistent HBsAg antigenemia in newborn infants following intrauterine HBV infection. Cause for the failure of the prevention of perinatal HBV transmission

In areas with high carrier rates for hepatitis B the combination of hepatitis B immune globulin and hepatitis B vaccine prevent perinatal infection in 90-95% of the newborn infants. Since 1979 the failure of perinatal prevention of hepatitis B infection was observed in only two cases. Evidence of intrauterine infection is presented in these two cases.