[Substitution treatment of drug addicts during pregnancy: consequences for the children?]. / Har legemiddelassistert rehabilitering i svangerskapet konsekvenser for barna?

BACKGROUND: Substitution treatment of opioid-dependent addicts was introduced in Norway in 1998. During the last 10 years, approximately 150 infants have been born to mothers taking part in this programme. MATERIAL AND METHODS: 10 mothers, who took part in the substitution treatment programme, gave birth to 15 infants at Haukeland University Hospital in the period 1999-2005. The infants were observed and monitored at the Department of Pediatrics, Haukeland University Hospital. RESULTS: During pregnancy, six of the infants were only exposed to opiates, i.e methadone or buprenorphine. Eight infants were also exposed to heroine, benzodiazepines or cannabis. As a group, these infants had lower birth weight than the national average. 14 of the 15 children developed neonatal abstinence syndrome (NAS), 10 needed treatment and two children died from sudden infant death syndrome (SIDS). Long-term follow-up showed that six of 13 children had normal psychomotor development, five had various degrees of delayed psychomotor development and two children had symptoms indicating a hyperkinetic disorder. Five children were in foster care. INTERPRETATION: Infants of women included in substitution treatment programmes for drug addicts are at high risk compared to infants of women without such addiction. For the newborn, NAS was a frequent complication. The study also showed that symptoms of hyperkinetic disorder and delayed psychomotor development were common. Children who had been exposed to opiates in combination with additional drugs seemed to have a high risk of delayed development and behaviour disorders. As they get older many were placed in foster care, despite well-coordinated, multidisciplinary treatment for the mother.

POLG1 mutations cause a syndromic epilepsy with occipital lobe predilection.

The epileptic semiology of 19 patients (from 15 families) with mitochondrial disease due to mutations in the POLG1 gene is presented. The patients were either homozygous for the 1399G > A (p.A467T) or 2243G > C (p.W748S) mutations or compound heterozygotes for these two mutations. While the clinical features have been reviewed, detailed analysis of their epilepsy is presented for the first time. Irrespective of genotype, patients developed an epileptic syndrome with initial features of occipital lobe epilepsy. Occipital seizure phenomena included flickering coloured light, sometimes persisting for weeks, months or even years, ictal visual loss, horizontal/vertical nystagmus or oculoclonus, dysmorphopsia, micro-/macropsia and palinopsia. Most patients developed simple partial seizure phenomena with motor symptoms suggesting frontal lobe seizure initiation or spread. Simple and complex partial seizures, clonic- and/or myoclonic seizures with epilepsia partialis continua and frequent convulsive status epilepticus were observed in this syndrome that appears to be a symptomatic and secondary generalized or multifocal epilepsy with focal occipital predilection. The mean age of seizure presentation was 18.4 years (6-58 years). All patients developed status epilepticus and 11 patient deaths were, all related to prolonged convulsive status epilepticus, including two with liver failure apparently precipitated by treatment with sodium valproate.

Radiation doses to children with shunt-treated hydrocephalus.

BACKGROUND: Children with shunt-treated hydrocephalus are still followed routinely with frequent head CT scans. OBJECTIVE: To estimate the effective dose, brain and lens doses from these examinations during childhood, and to assess dose variation per examination. MATERIALS AND METHODS: All children born between 1983 and 1995 and treated for hydrocephalus between 1983 and 2002 were included. We retrospectively registered the number of examinations and the applied scan parameters. The effective dose was calculated using mean conversion factors from the CT dose index measured free in air, while doses to the lens and brain were estimated using tabulated CT dose index values measured in a head phantom. RESULTS: A total of 687 CT examinations were performed in 67 children. The mean effective dose, lens dose and brain dose to children over 6 months of age were 1.2 mSv, 52 mGy and 33 mGy, respectively, and the corresponding doses to younger children were 3.2 mSv, 60 mGy and 48 mGy. The effective dose per CT examination varied by a factor of 64. CONCLUSION: None of the children was exposed to doses known to cause deterministic effects. However, since the threshold for radiation-induced damage is not known with certainty, alternative modalities such as US and MRI should be used whenever possible.

[Fetal injury and alcohol drinking during pregnancy]. / Fosterskade ved alkoholbruk i svangerskap.

BACKGROUND: There is still an ongoing discussion whether moderate alcohol consumption during pregnancy is harmful to the fetus. In most western countries, however, total abstinence is recommended. MATERIAL AND METHODS: Over the last five years we have seen 64 infants and children with alcohol-related disorders. We present the clinical records of one alcohol-damaged child, and present the latest recommended categorisation of alcohol-related disorders in infants and children. RESULTS: In our experience, some women with heavy alcohol consumption are allowed to continue their abuse without interference from health professionals. Children of women with moderate alcohol consumption may be seriously damaged. Updated research on pregnancy and alcohol that we have reviewed provide clear evidence that brain structure as well as brain function are affected by heavy prenatal alcohol exposure. INTERPRETATION: Use of alcohol in pregnancy, also in moderate amounts, is a serious risk factor for fetal damage. Therefore complete abstinence from alcohol during pregnancy should be recommended. For the alcohol-damaged children, early recognition and appropriate treatment will give the child a better opportunity for future optimal development.

Extended phenotype of pontocerebellar hypoplasia with infantile spinal muscular atrophy.

Pontocerebellar hypoplasia (PCH) is rarely associated with anterior horn cell disease and designated as PCH-1. This phenotype is characterized by severe muscle weakness and hypotonia starting prenatally or at birth with a life span not exceeding a few months in most cases. Milder disease courses with later onset and longer survival are normally not diagnosed as PCH-1. We describe the clinical and neuroradiological findings in nine patients out of six siblingships with evidence of cerebellar defects and early onset spinal muscular atrophy (SMA), representing a broad spectrum of clinical variability. In all patients, the diagnosis of SMA (Werdnig-Hoffmann disease) was made on the basis of electrophysiological data and muscle biopsy; however, genetic testing failed to confirm the diagnosis of infantile SMA with a gene defect on chromosome 5q and resulted in clinical reevaluation. Age at onset was after a normal period in the first months of life in three siblingships and pre- and postnatally in the other three families. Life span was 2-4 years in patients with later onset, and age at death occurred after birth or within months in the more severe group. Two siblingships showed discordant ages at death despite similar treatment. In contrast to the previous definition of PCH-1, our observations suggest the existence of milder phenotypes with pontocerebellar hypoplasia or olivopontocerebellar atrophy in combination with anterior horn cell loss. A pontine involvement is not necessarily seen by neuroimaging methods. The genetic basis of PCH-1 remains to be determined. The gene locus for infantile SMA on chromosome 5q could be excluded by linkage studies. Parental consanguinity and affected siblings make autosomal recessive inheritance most likely.

[Intravenous enzyme substitution therapy in children with Fabry's disease]. / Intravenøs enzymsubstitusjonsbehandling ved Fabrys sykdom hos barn.

BACKGROUND: Fabry's disease is a X-linked lysosomal storage disorder with accumulation of globotriaosylceramide primarily in vascular endothelial cells, affecting mainly skin, kidney, heart and brain. Symptoms may appear in 7-8-year-old children as burning pain in hands and feet; organ damage usually becomes evident in adult age. Intravenous enzyme replacement therapy has recently become available. PATIENTS: Two brothers, 13.5 and 15 years old, had typical symptoms with acroparesthesia, fever, abdominal pain and diarrhoea. There were high levels of urinary globotriaosylceramide, low levels of alfagalactosidase A in leukocytes, and a single-nucleotide deletion in position 10671 of the alfagalactosidase gene (GLA). Both brothers showed slightly abnormal echocardiography and one had typical changes on cerebral MRI. Enzyme replacement therapy with alfagalactosidase A (Replagal) was started in November 2001. After one year of therapy there was clearly clinical improvement with no fever and diarrhoea and less pain. The urinary excretion of globotriaosylceramide was reduced. No adverse effects were recorded. INTERPRETATION: During 12 months of intravenous enzyme replacement therapy in two adolescent subjects with Fabry's disease we observed clinical improvement and no adverse effects. We recommend greater awareness of Fabry's disease in paediatrics as well as in adult medicine.