Evaluation of screening procedures for congenital cataracts.

AIM: To evaluate the efficacy of two different Swedish screening procedures for early detection of congenital cataracts in comparison with no screening. METHODS: Children born between January 1992 and December 1998 in Swedish regions with an established eye-screening routine procedure, diagnosed with congenital cataract, and operated on before 1 y of age, were included in a retrospective study. Age at referral and age at time of the operation were compared between regions using different screening procedures: screening in the maternity wards (Region 1), at the well-baby clinics (Region 2) and one region without any screening (Region 3). RESULTS: Seventy-two children were included in the study. Concerning early diagnosis and surgery, Region 1 differed significantly from Regions 2 and 3, which were more similar and were combined for further analysis. The difference in detected cases was greatest at 21 d of age (55% vs 18%; p < 0.001), but persisted even at 100 d of age (78% vs 64%; p < 0.02). Region 1 screening resulted in more and earlier cases detected than the other two regions (22 vs 15 per 100,000 births). In 72% of all cases, surgery was performed in response to referrals from either the maternity wards (36%), or the well-baby clinics (36%). However, half of the cases from the well-baby clinics were detected too late, i.e. at > 100 d. CONCLUSION: Eye screening in the maternity ward is preferable to well-baby clinic screening and to no screening at all, since it leads to early detection. Screening should also be performed routinely at well-baby clinics within the period when successful treatment is possible.

Preterm infants with low immunoglobulin G levels have increased risk of neonatal sepsis but do not benefit from prophylactic immunoglobulin G.

OBJECTIVE: In a prospective, randomized, placebo-controlled, multicenter study, we evaluated the prevention of neonatal infections with intravenous immunoglobulin G (IVIgG) prophylaxis for preterm infants (gestational age <33 weeks) with umbilical cord blood IgG levels < or =4 g/L. STUDY DESIGN: Intravenous IgG or placebo (albumin), 1 g/kg body weight, was given on days 0, 3, 7, 14, and 21 to 81 infants with umbilical cord blood IgG levels < or =4 g/L: (1) IVIgG group, n = 40, mean (SD) gestational age 27.5 (2.2) weeks and birth weight 1.06 (0.39) kg; (2) placebo group, n = 41, mean (SD) gestational age 27.7 (2.5) weeks and birth weight 1.13 (0.38) kg. Infants with umbilical cord blood IgG levels >4 g/L (n = 238) served as a separate comparison group. Neonatal infections according to European Society of Pediatric Infectious Disease criteria were monitored until 28 days of life. RESULTS: Infants with IgG levels < or =4 g/L at birth who received IVIgG had no significant reduction in infectious episodes or mortality rate when compared with those given placebo. However, infants with a serum concentration of IgG >4 g/L at birth had significantly fewer infectious episodes (culture-proven sepsis) than infants with low serum concentrations of IgG (< or =4 g/L) when compared at the same gestational ages (26 to 29 weeks, P <.003). CONCLUSIONS: Prophylactic immunotherapy with IVIgG did not improve the immune competence in preterm infants with low serum IgG concentrations at birth. We speculate that a spontaneously high serum IgG concentration at birth reflects placenta function and is an indicator of a more mature immune system capable of protecting the preterm infant against severe neonatal infections.

Neurosensory outcome and growth at three years in extremely low birthweight infants: follow-up results from the Swedish national prospective study.

A prospective national investigation comprising 633 extremely low birthweight (ELBW) infants born alive in the 2-y period 1990-1992 with a birthweight of < or = 1000 g and gestational age of > or = 23 completed weeks was conducted regarding neurosensory outcome and growth. Three-hundred and sixty-two (98%) surviving ELBW infants were assessed at a median age of 36 months, using a specially designed protocol. At follow-up, mean height, weight and head circumference in both boys and girls were significantly lower than the reference values. The incidence of cerebral palsy was 7% among all children and 14%, 10% and 3% in children born at 23-24, 25-26 and > or = 27 gestational weeks, respectively. At least one obvious handicap was present in 14%, 9% and 3% of these three groups of children, respectively. After adjustment for gestational age, a significantly increased risk of handicap was found in children with intraventricular haemorrhage grade > or = 3 and/or periventricular leucomalacia and in children with retinopathy of prematurity stage > or = 3. The results show that more than 90% of ELBW children born at > or = 25 completed gestational weeks were without neurosensory handicap at 36 months of corrected age. In infants born at 23-24 weeks of gestation, both survival and long-term outcome were less favourable.

Postnatal growth and health in children born after cryopreservation as embryos.

BACKGROUND: There is uncertainty about the health of children born from in-vitro fertilisation (IVF) with cryopreserved embryos. We investigated the postnatal growth and health (up to 18 months) of these children compared with those born after standard IVF with fresh embryos and those from spontaneous pregnancies. METHODS: 255 children from cryopreserved embryos were matched by maternal age, parity, single or twin pregnancy, and date of delivery with 255 children born after IVF with fresh embryos, and 252 children from spontaneous pregnancies. The main endpoint was growth; secondary endpoints were the prevalence of chronic illness, major malformations, cumulative incidence of common diseases, and development during the first 18 months. Growth was assessed by comparison with standard Swedish growth charts and by standard deviation scores. FINDINGS: Growth features were similar for both singletons and twins in the three groups. There were 6 (2.4%) of 255, 9 (3.5%) of 255, and 8 (3.2%) of 252 major malformations in the cryopreserved group, standard IVF, and spontaneous groups, respectively (p=0.6 between the cryopreserved and standard IVF group). The prevalence of chronic diseases did not differ between the three groups, with 18.0%, 15.3%, and 16.7% of children with a chronic illness in the cryopreserved group, standard IVF, and spontaneous groups, respectively. INTERPRETATION: The cryopreservation process does not adversely affect the growth and health of children during infancy and early childhood. Minor handicaps, behavioural disturbances, learning difficulties, and dysfunction of attention and perception cannot be ruled out at this age.

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 < or = 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 > or = 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 IIa (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 IIb 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.

Changes in prevalence, aetiology, age at detection, and associated disabilities in preschool children with hearing impairment born in Göteborg.

The prevalence of hearing impairment (HI) in preschool children born in Göteborg in 1980 to 1984 was 2.0 per 1000. This was significantly lower than the 3.8 per 1000 found in a previous study for 1970 to 1974. The decrease took place in the moderate to severe range of HI, while deafness and mild HI remained unchanged during the period. The cause was considered to be prenatal in 58% with heredity in 33% as the main causative factor. Following the introduction of the MPR (Morbilli-Parotitis-Rubella) vaccination programme in Sweden, no cases of rubella- or mumps-induced HI could be found. The number of HI of perinatal origin decreased by half, in spite of the fact that the figures for preterm baby survival almost doubled during the period. Associated disabilities were diagnosed in 62% of the children with HI; speech retardation in 33%, visual abnormalities in 30%, mental retardation in 12% and neuropsychiatric disorders in 9% of the cases. The importance of collaborative efforts between the otolaryngologist and the neurologically and neuropsychiatrically interested paediatrician in the complete evaluation of additional difficulties in the HI child is emphasized.

Birth asphyxia: incidence, clinical course and outcome in a Swedish population.

A total of 42,203 live infants were born in Göteborg in 1985-1991, and 292 term infants had Apgar scores < 7 at 5 min. Infants with congenital malformations, infections and opioid-induced respiratory depression were excluded and thus 227 infants were included in the birth asphyxia group, which formed the basis of this retrospective study. Clinical signs of mild, moderate or severe hypoxic-ischemic encephalopathy (HIE) were present in 65 infants, and in another 10 infants, sedated and on controlled ventilation, HIE was assumed but grading was not possible. The incidences of Apgar scores < 7 at 5 min, birth asphyxia and birth asphyxia with HIE were 6.9, 5.4 and 1.8 per 1,000 live born infants: 95% of infants resuscitated with bag and mask ventilation only, did well, compared with 1 of 11 in whom resuscitation included adrenaline. Seizures occurred in 27 of 227 infants, beginning in 18 infants within 12 h of birth. Small-for-gestational-age (SGA) infants were overrepresented in the birth asphyxia group but not in the birth asphyxia-HIE group. All infants with severe HIE died or developed neurological damage. Half of the infants with moderate, and all of the infants with mild, HIE were reported to be normal at 18 months of age. A total of 0.3 per 1,000 live born infants died and 0.2 per 1,000 developed a neurological disability related to birth asphyxia. The disabilities were dyskinetic (4), tetraplegic (2), spastic diplegic (2), cerebral palsy and mild neuromotor dysfunction (1). The relatively low incidences of birth asphyxia and HIE were probably due to effective antenatal care.

Neuron specific enolase in asphyxiated newborns: association with encephalopathy and cerebral function monitor trace.

Neuron specific enolase (NSE) in serum and cerebrospinal fluid (CSF) and glutamate in CSF were investigated in the immediate postasphyctic period in 22 term newborn infants. The cerebral function monitor (CFM) pattern was also assessed and hypoxic-ischaemic encephalopathy (HIE) was graded. NSE was significantly increased in the CSF of infants with HIE (median value 25.4 micrograms/l) compared with control infants (10.0 micrograms/l). Infants with the highest concentrations died. NSE in CSF correlated with the degree of asphyxial damage. Glutamate and NSE in CSF did not correlate, presumably due to the different time factors of the release after the insult. NSE in CSF corresponded well with the type of CFM pattern, which was also highly predictive of outcome.

Excitatory amino acids in the cerebrospinal fluid of asphyxiated infants: relationship to hypoxic-ischemic encephalopathy.

Asphyxiated (n = 27) and control infants (n = 25) were subjected to spinal taps. Amino acids were measured with liquid chromatography and the degree of hypoxic-ischemic encephalopathy was determined in each case. In asphyxiated infants, the concentrations of aspartate and glutamate were 286% and 387% (p < or = 0.01 and p < or = 0.05) of the control values, respectively. The cerebrospinal fluid aspartate levels were significantly (p < or = 0.05) higher in the group with severe (3.4 mumol/l) compared with the group with mild hypoxic-ischemic encephalopathy (1.0 mumol/l). Glutamate was also higher in the group with severe (12.3 mumol/l) than in the groups with mild (2.7 mumol/l) or moderate (3.2 mumol/l) hypoxic-ischemic encephalopathy (p < or = 0.05). High concentrations of excitatory amino acids were present in the CSF of asphyxiated infants which may exert excitotoxic effects.

Scavengers of free oxygen radicals in combination with magnesium ameliorate perinatal hypoxic-ischemic brain damage in the rat.

The effect of oxygen radical scavengers in combination with magnesium administered after a hypoxic-ischemic insult was evaluated in a model of perinatal brain damage. A mixture of scavengers of oxygen-derived free radicals (L-methionine, 0.2 g; mannitol, 0.5 g) and magnesium sulfate (0.3 g) per kg body weight was given to 34 1-wk-old rat pups immediately after a session of unilateral carotid artery ligation and 2 h of hypoxia (8% O2 in N2). Thirty-four littermates served as controls; they received a placebo. At 3 wk of age, there was a significantly smaller reduction of hemisphere weight ipsilateral to the ligation in the treated animals compared with the controls (0.7 versus 8.8% of contralateral hemisphere weight median values, p < 0.01). The difference was especially marked for the most severe degrees of brain damage. Only one of the 34 treated animals, compared with 13 of 34 control animals, had a reduction of ipsilateral hemisphere weight > 25%. The protection offered by the mixture used was larger than in previously published studies using this model and treatment after the hypoxic exposure with only one protective agent. It is concluded that a combination of oxygen radical scavengers and magnesium administered in the phase of resuscitation mitigates perinatal postasphyxial brain damage in the rat. An additive protective effect of different therapeutic strategies on the brain damage may be present in this situation.

Poliovirus antibody titres, relative affinity, and neutralising capacity in maternal milk.

Varying titres of secretory IgA antibodies to poliovirus type 1 were found previously in the milk of unvaccinated, lactating Pakistani mothers during two different years, reflecting the antigenic exposure on mucosal membranes. To study further the changes in the extent and the form of antigenic exposure reflected in the human milk, human milk samples from Pakistani, Indian, Japanese, and Swedish mothers were collected. The quality and the neutralising capacity of the antibodies was also studied. Secretory IgA, IgG, and IgM antibodies to poliovirus type 1 were determined using enzyme linked immunosorbent assay (ELISA) and relative affinity was measured in ELISA by elution with potassium thiocyanide. Microneutralisation tests were also performed. The higher secretory IgA antibody titres to poliovirus type 1 in the unvaccinated, naturally exposed Pakistani and Indian mothers' milk, compared with the Swedish and Japanese mothers, presumably reflect the epidemiological situation in these countries. Neutralising capacity and the relative antibody affinity seemed to be higher both in the Pakistani mothers and the group without natural exposure but only given inactivated poliovirus vaccine, that is the Swedish mothers, than the group meeting only live vaccine strains, that is the Japanese mothers.

Isotype composition of antibodies to streptococcus group B type III polysaccharide and to tetanus toxoid in maternal, cord blood sera and in breast milk.

Neonates are protected against group B streptococcal (GBS) infections and tetanus by transplacentally transferred serum antibodies. Antibodies of the immunoglobulin (Ig) G, IgM and IgA classes and IgG subclasses to the capsular polysaccharide (CPS) of type III group B streptococci (GBS III) and to tetanus toxoid (TT) were measured in sera from healthy women of fertile age and in paired maternal and cord blood sera from term and preterm pregnancies. GBS III CPS antibodies of the IgG class were found in sera from 97 out of 100 women of fertile age, but only 15 of them had antibodies above the proposed protective level (greater than or equal to 2 micrograms/ml). TT IgG antibodies above the protective level (0.01 units/ml) were found in all sera. The IgG antibodies against GBS III CPS were mainly composed of the IgG2 subclass and to a lesser extent of IgG1. Almost all women had IgG1 antibodies against TT and 40% had IgG4 antibodies. Total IgG and IgG1 antibodies against GBS III CPS were higher in cord blood sera from 37 term neonates than in sera from their mothers whereas IgG2 antibody levels were similar. Total IgG and IgG1 antibodies against TT were also higher in the 20 term neonates tested than in their mothers. In contrast, total IgG and IgG1 to both GBS III CPS and TT and IgG2 to GBS III CPS were lower in cord blood sera from preterm neonates than in sera from their mothers. IgA antibodies to GBS III CPS were detected in 63% of breast milk samples while IgA antibodies against TT were detected in only 4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampicillin-aminoglycoside combinations as initial treatment for neonatal septicaemia or meningitis. A retrospective evaluation of 12 years' experience.

In a retrospective study covering the years 1975-1986, 341 episodes of invasive infections in 338 newborn infants were evaluated. Of the 365 pathogens isolated from blood and/or cerebrospinal fluid, 91% were sensitive to either ampicillin or aminoglycosides or both. Ampicillin resistance was mainly found in very low and low birthweight infants with late-onset infections, in which aerobic Gram-negative rods were common pathogens. In contrast, aminoglycoside resistance was common in early-onset infections, due to the dominance of group B streptococcal infections. The ampicillin-aminoglycoside combination had been given as initial treatment in 189 cases of septicaemia or meningitis. Treatment failed in 36 infections (20%), although all organisms were sensitive to one or both antibiotics. Treatment failed in 6 of 34 patients with meningitis but the failure was not related to ampicillin or aminoglycoside resistance. In conclusion, both in vitro and clinical results show that the ampicillin-aminoglycoside combination can be used as initial treatment of invasive infections in neonates.

Diameters of the common carotid artery and aorta change in different directions during acute asphyxia in the fetal lamb.

The aim of this experimental ultrasound study on six fetal lambs was to evaluate how blood flow variables and vessel diameters of the descending aorta and the common carotid artery change during fetal asphyxia in the acute preparation. When acute asphyxia was induced by obstructing the maternal aortic blood flow all fetuses reacted with significant decrease in the aortic diameter and blood flow. In the common carotid artery vessel diameter and the blood flow increased significantly. The results support the theory of a brain sparing effect during fetal distress with significant changes of blood vessel diameters occurring in opposite directions in the aorta and the common carotid artery, thereby contributing to the centralisation of circulation.

Evaluation of brain damage in a rat model of neonatal hypoxic-ischemia.

In spite of improvements in obstetric and neonatal care, hypoxic-ischemic brain damage with severe neurologic disability is still a clinical reality. A model in 7-day-old rats has been introduced to study the pathophysiology of perinatal hypoxic-ischemic brain damage. Unilateral brain damage is produced in the cerebral cortex, striatum and hippocampus, i.e. a similar distribution as is often seen in human asphyxiated neonates. In the present investigation the model was evaluated further by comparing three different methods to assess the brain damage: weighing the hemispheres, morphometry and somatosensory evoked potentials. Seven-day-old rats were subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (7.7% O2 at 36 degrees C). After 2 h of hypoxic-ischemia pCO2 and pO2 decreased in mixed arterial/venous blood. The evaluation of the damage 2 weeks after the insult, demonstrated close correlation between morphometry and weighing (r = 0.836, P less than 0.01). The amplitude of evoked potentials correlated to the other parameters (r = 0.814, P less than 0.01 and r = 0.824, P less than 0.01 respectively) and displayed a greater relative attenuation than the other methods but with a more pronounced variability. These results indicate that the degree of brain damage can be assessed by weighing for screening purposes.

Incidence and etiology of neonatal septicaemia and meningitis in western Sweden 1975-1986.

In a retrospective study of neonatal septicaemia and meningitis in a defined region of western Sweden 1975-1986, 231 cases were identified. The incidence was 2.8/1000 live births. The case-fatality rate was 15%. thirty-three patients had meningitis. Only 55 patients (24%) had no known risk factors. Preterm delivery was a most important risk factor for both morbidity and mortality. The most common causative organisms were group B streptococci, Staphylococcus aureus and aerobic Gram-negative rods, together isolated from 82% of the patients. The cases were approximately equally divided between very early, early and late onset infections. Group B streptococci were over-represented in very early onset infections in all birthweight groups and aerobic Gram-negative rods were the most common isolates from low birthweight infants with late onset infections. However, group B streptococci, Staphylococcus aureus and Gram-negative rods were found in all birthweight and gestational age groups. Thus, initial antimicrobial therapy must be equally broad in all neonates with suspected septicaemia.

Normal pattern of the cerebral function monitor trace in term and preterm neonates.

Cerebral Function Monitor (CFM) recordings were performed on 10 term and 19 preterm healthy infants. Term infants were monitored once, while preterm infants were followed serially. Forty-six recordings were made on 7, 14, 16 and 9 occasions in the age groups 30-31, 32-33, 34-35 and 36-37 weeks. All infants were examined clinically at 18 months of age and found healthy. By drawing weighted lines derived from the lower and upper limits of the CFM traces, mean values of minimum and maximum cerebral activity were calculated for the different age groups. In the term infants different CFM traces were identified corresponding to quiet sleep and active sleep. In the preterm infants a similar cyclic variability of the CFM trace was noted. A gradual increase in the minimum cerebral activity was found with increasing gestational age, resulting in a gradual narrowing of the trace.

Concentrations of ceftazidime, tobramycin and ampicillin in the cerebrospinal fluid of newborn infants.

Thirty-five neonates with suspected septicaemia were randomized to treatment with tobramycin or ceftazidime, both in combination with ampicillin. Concentrations of antibiotics in the CSF were measured 1 h after the third, fourth or fifth injection. In 13 of 17 neonates tobramycin CSF concentrations were below 0.5 mg/l. Ceftazidime CSF concentrations ranged from 2.5 to 17 mg/l, which should be sufficient for treatment of infections with group B streptococci and most aerobic gram-negative bacilli but not all strains of Staphylococcus aureus. Ampicillin CSF concentrations ranged from 1 to 80 mg/l, which should be sufficient for treatment of meningitis caused by enterococci and Listeria monocytogenes, the most important neonatal pathogens not covered by ceftazidime.