Very preterm born children at early school age: Healthcare therapies and educational provisions.

AIM: To explore changes in motor and cognitive outcomes in very preterm (VP; gestational age<30weeks) born children between ages five and six years, and to determine whether changes in these outcomes were associated with the use of healthcare therapies and educational provisions. STUDY DESIGN: Single-center observational cohort study. Five-year-old VP born children of a one-year-cohort of our neonatal follow-up program (N=90) were invited for re-assessments at age six. Use of healthcare therapies and educational provisions was registered at ages five and six years. Motor function (Movement Assessment Battery for Children-2 [M-ABC-2]; higher scores indicate better functioning) and IQ (Wechsler Preschool and Primary Scale for Intelligence [WPPSI-III-NL]) were assessed at both ages. RESULTS: Sixty-four VP born children were seen at ages five and at six years. In this year, 61% received healthcare therapies and/or educational provisions. M-ABC-2 scores of VP born children who received healthcare therapy and/or educational provisions were significantly higher (M=8.9 [SD=3.2]) at age six years than at age five years (M=7.5 [SD=3.3]); p<0.00). M-ABC-2 scores remained stable in the average range in VP born children without any support. IQ scores remained stable irrespective of received support. CONCLUSIONS: Improvements in motor outcomes are associated with the use of healthcare therapies and/or educational support between ages five and six years in VP born children. Future studies need to determine the efficacy of existing interventions, and to develop tailored interventions to support VP born children in the transfer period from preschool to primary education.

Development and growth in very preterm infants in relation to NIDCAP in a Dutch NICU: two years of follow-up.

AIM: To study development and growth in relation to newborn individualized developmental and assessment program (NIDCAP) for infants born with a gestational age of less than 30 weeks. METHODS: Developmental outcome of surviving infants, 25 in the NIDCAP group and 24 in the conventional care group, in a prospective phase-lag cohort study performed in a Dutch level III neonatal intensive care unit (NICU) was compared. Main outcome measure was the Bayley scales of infant development-II (BSID-II) at 24 months corrected age. Secondary outcomes were neurobehavioral and developmental outcome and growth at term, 6, 12 and 24 months. RESULTS: Accounting for group differences and known outcome predictors no significant differences were seen between both care groups in BSID-II at 24 months. At term age NIDCAP infants scored statistically significant lower on neurobehavioral competence; motor system (median [IQR] 4.8 [2.9-5.0] vs. 5.2 [4.3-5.7], p = 0.021) and autonomic stability (median [IQR] 5.7 [4.8-6.7] vs. 7.0 [6.0-7.7], p = 0.001). No differences were seen in other developmental outcomes. After adjustment for background differences, growth parameters were comparable between groups during the first 24 months of life. CONCLUSION: At present, the strength of conclusions to be drawn about the effect of NIDCAP on developmental outcome or growth at 24 months of age is restricted. Further studies employing standardized assessment approaches including choice of measurement instruments and time points are needed.

Family-based transmission disequilibrium test (TDT) and case-control association studies reveal surfactant protein A (SP-A) susceptibility alleles for respiratory distress syndrome (RDS) and possible race differences.

A key cause of respiratory distress syndrome (RDS) in the prematurely born infant is deficiency of pulmonary surfactant, a lipoprotein complex. Both low levels of surfactant protein A (SP-A) and SP-A alleles have been associated with RDS. Using the candidate gene approach, we performed family-based linkage studies to discern linkage of SP-A to RDS and identify SP-A susceptibility or protective alleles. Moreover, we performed case-control studies of whites and blacks to detect association between RDS and SP-A alleles. Transmission disequilibrium test (TDT) analysis revealed that the frequency of transmission (from parent to the offspring with RDS) of alleles 6A(2) and 1A(0) and of 1A(0)/6A(2) haplotype in RDS was increased, whereas transmission of alleles 1A(5) and 6A(4) and of haplotype 1A(5)/6A(4) was decreased. Extended TDT analysis further strengthened the observations made. The case-control studies showed that in whites or blacks with RDS the frequencies of specific genotypes, 1A(0) and 6A(2) or 1A(0), were increased, respectively, but the frequency of specific 6A(3) genotypes was increased in certain white subgroups and decreased in blacks. Regression analysis revealed gestational age (GA) and 6A(3) genotypes are significant factors in blacks with RDS. In whites with RDS, GA and antenatal steroids are important factors. The data together indicate linkage between SP-A and RDS; certain SP-A alleles/haplotypes are susceptibility (1A(0), 6A(2), 1A(0)/6A(2)) or protective (1A(5), 6A(4), 1A(5)/6A(4)) factors for RDS. Some differences between blacks and whites with regard to SP-A alleles may exist.

Surfactant treatment of neonates with respiratory failure and group B streptococcal infection. Members of the Collaborative European Multicenter Study Group.

OBJECTIVE: Connatal pneumonia caused by group B streptococcal (GBS) infection may be associated with surfactant dysfunction. We investigated the effects of surfactant treatment in term and preterm neonates with GBS infection and respiratory failure, in comparison with corresponding data from a control population of noninfected infants treated with surfactant for respiratory distress syndrome (RDS). DESIGN/METHODS: The study comprised 118 infants with respiratory failure, clinical and/or laboratory signs of acute inflammatory disease, and GBS infection proven by culture results. They were recruited retrospectively from a database of patients treated with surfactant at 28 neonatology units participating in European multicenter trials (1987-1993) and prospectively from the same units in the following years. A nonrandomized control group of 236 noninfected infants was selected from the same database. The primary parameters evaluated were oxygen requirement, ventilator settings, and incidence of complications. RESULTS: Median birth weight in the GBS study group was 1468 g (25th-75th percentiles: 1015-2170), and median gestational age was 30 (27-33) weeks. Thirty-one percent of the infants weighed >2000 g. Median age at surfactant treatment was 6 hours. The mean initial surfactant dose was 142 mg/kg (standard deviation: 53). Ninety of the infants were treated with Curosurf (Chiesi Farmaceutici, Parma, Italy), 13 with Survanta (Abboth GmbH, Wiesbaden, Germany), 12 with Alveofact (Dr Karl Thomae GmbH, Biberach, Germany), and 3 with Exosurf (Wellcome GmbH, Burgwedel, Germany). Within 1 hour of surfactant treatment, median fraction of inspiratory oxygen was reduced from .84 (25th-75th percentiles:.63-1.0) to.50 (.35-.80). The incidence of complications in the study group (mortality: 30%; pneumothorax: 16%; intracranial hemorrhage: 42%) was high, compared with infants with RDS. CONCLUSIONS: Surfactant therapy improves gas exchange in the majority of patients with GBS pneumonia. The response to surfactant is slower than in infants with RDS, and repeated surfactant doses are often needed. The mortality and morbidity are substantial, considering the relatively high mean birth weight of the treated infants.

Respiratory illness in families of preterm infants with chronic lung disease.

AIMS--To examine the relation, based on two types of questionnaires, between (1) chronic lung disease of the newborn (CLDN) and lower respiratory illness (LRI) in siblings, and between (2) CLDN and asthma, chronic obstruction pulmonary disease (COPD), or allergy in parents and grandparents. METHODS--Data from 209 children born before 32 weeks of gestation were randomly taken from the records of three neonatal units. Taking into account age and gender, the excess of LRI was calculated for each family compared with the average of all families. Subsequently whether CLDN was associated with an excess of LRI in the family was tested. RESULTS--Thirty one (14.8%) children were diagnosed as having CLDN. The family probability index for LRI did not differ between children with or without CLDN. The prevalence of COPD, asthma, and allergy in parents of children with CLDN was similar to that of children without CLDN. The prevalence of LRI was 18.1% in study children, 29.6% in children with CLDN, and 16.9% in children without CLDN (P < 0.01). These prevalences were higher compared with that of a group of term siblings (9.3%) (P = 0.05). CONCLUSIONS--These findings suggest that CLDN in preterm children is not related to a genetic or familial predisposition towards asthma, COPD, or allergy.

Subependymal germinolytic cysts in Zellweger syndrome.

Ultrasonographic demonstration of periventricular cysts is usually associated with cystic periventricular leucomalacia due to necrosis of periventricular unmyelinated white matter. Cystic spaces with a similar appearance may also arise from prenatal lysis of fetal periventricular matrix tissue, rather than immature white matter. The resultant empty spaces are called "pseudocysts" or germinolytic cysts. Neuropathological studies have shown that germinolytic cysts may arise in Zellweger syndrome (generalized peroxisomal disorder). Here, we report their ultrasonographic demonstration in Zellweger syndrome, emphasizing the potential value of this sign in the diagnosis.

[3 examples of fetal genetic neuromuscular disorders which lead to hydramnion]. / Drie voorbeelden van genetische neuromusculaire aandoeningen bij de foetus die leiden tot hydramnion.

Causes of polyhydramnios include foetal neuromuscular disorders which cause inability of the foetus to swallow amniotic fluid. Three examples of such disorders are presented: X-linked myotubular myopathy, congenital myotonic dystrophy, and congenital nemaline myopathy. It is concluded that in case of polyhydramnios a search for foetal neuromuscular disease should be carried out. This implies ultrasound evaluation of the foetal movements, especially swallowing movements, neurological examination of the mother for myotonic dystrophy and examination of the newborn, which in selected cases includes muscle biopsy. Foetal neuromuscular disorders are usually genetic in origin. This adds to the need for accurate diagnosis and proper genetic counseling.

Immune response after surfactant treatment of newborn infants with respiratory distress syndrome.

We examined the sera of 68 newborn infants with respiratory distress syndrome; 49 were treated with a natural porcine-derived surfactant preparation and 19 were controls. Serum of the patients was collected before, 3 weeks and 3 months after surfactant treatment. To detect any antibody that had been raised, we applied diluted serum of the babies in an indirect immunoperoxidase staining technique on frozen pig lung tissue specimens. With light microscopy an immune response could be appreciated as a brown reddish deposit in the porcine lung tissue specimens in 4 out of the 49 surfactant-treated and not in the control babies.

A 2-year follow up of babies enrolled in a European multicentre trial of porcine surfactant replacement for severe neonatal respiratory distress syndrome. Collaborative European Multicentre Study Group.

The postnatal growth, respiratory status and neurodevelopmental outcome of surviving babies enrolled in the first European multicentre trial of porcine surfactant (Curosurf) replacement for severe neonatal respiratory distress syndrome, were assessed at corrected ages of 1 and 2 years. Follow up rates of survivors were 93% at 1 year and 89% at 2 years. Treated and control groups were similar at both 1 and 2 years in terms of physical growth, the prevalence of persistent respiratory symptoms and the occurrence of major and minor disability. Serum antibodies recognising Curosurf and surfactant-anti-surfactant immune complexes were detected in both treated and control babies, the titres showing no difference between groups. Examination of histological lung sections from non-survivors revealed a higher incidence of severe pulmonary interstitial emphysema in control babies than in those treated with surfactant. Surfactant treatment for severe respiratory distress syndrome reduces neonatal mortality and air leaks and is not associated with an increase in disability 2 years later.

Half-life of alpha-fetoprotein in patients with a teratoma, endodermal sinus tumor, or hepatoblastoma.

To evaluate the AFP-concentration postoperatively and/or during chemotherapy treatment, a retrospective study was carried out on 14 patients with a teratoma, endodermal sinus tumor (EST), or hepatoblastoma. Eleven patients were operated. Eight of the 11 patients showed postoperatively a linear decline in their AFP concentration. The half-life was about 6 days. In the group of patients that underwent a noncomplete resection, both a linear and a nonlinear declining pattern was seen. The patients that underwent a complete resection showed only a linear decline in the AFP concentration. No relationship was found between the reduction pattern of the AFP and the development of recurrences. The development of a recurrence was accompanied by an increasing AFP concentration.