Deficiency in SLC25A1, encoding the mitochondrial citrate carrier, causes combined D-2- and L-2-hydroxyglutaric aciduria.

The Krebs cycle is of fundamental importance for the generation of the energetic and molecular needs of both prokaryotic and eukaryotic cells. Both enantiomers of metabolite 2-hydroxyglutarate are directly linked to this pivotal biochemical pathway and are found elevated not only in several cancers, but also in different variants of the neurometabolic disease 2-hydroxyglutaric aciduria. Recently we showed that cancer-associated IDH2 germline mutations cause one variant of 2-hydroxyglutaric aciduria. Complementary to these findings, we now report recessive mutations in SLC25A1, the mitochondrial citrate carrier, in 12 out of 12 individuals with combined D-2- and L-2-hydroxyglutaric aciduria. Impaired mitochondrial citrate efflux, demonstrated by stable isotope labeling experiments and the absence of SLC25A1 in fibroblasts harboring certain mutations, suggest that SLC25A1 deficiency is pathogenic. Our results identify defects in SLC25A1 as a cause of combined D-2- and L-2-hydroxyglutaric aciduria.

Nordic pulse oximetry screening--implementation status and proposal for uniform guidelines.

AIM: Pulse oximetry screening of newborn infants increases early detection of critical congenital heart disease and minimises the risk of circulatory collapse before surgery. This study provides an update on the implementation of pulse oximetry screening in the Nordic countries and proposes standardised guidelines. METHODS: A questionnaire exploring pulse oximetry screening, clinical examination routines and availability of echocardiography was distributed to all 157 delivery units in the Nordic countries in June 2013. RESULTS: We received responses from 156 of the 157 delivery units, and 116 (74%) were using pulse oximetry screening by September 2013. Preductal and postductal screening were both used in 59 of 116 units (51%), with just postductal screening in 51 of 116 (44%) and just preductal screening alone in 6 of 116 (5%). Screening was performed before 24 h in 105 of 116 units (91%). The implementation of screening was highest in Finland (29/30, 97%), Sweden (42/46, 91%) and Norway (43/48, 90%) and lowest in Denmark (2/24, 8%) and Iceland (0/8 units). CONCLUSION: In Sweden, Norway and Finland, the implementation of pulse oximetry screening is currently the highest in the world and coverage will be close to 100% in 2014. We propose uniform Nordic guidelines using preductal and postductal screening before 24 h of age.

Neonatal family care for 24 hours per day: effects on maternal confidence and breast-feeding.

In family care (FC) program for neonatal intensive care units (NICUs), parents are encouraged to reside together with their infant for 24 hours a day to actively be involved in the care. The aim of this study was to assess the impact of FC on maternal confidence and breast-feeding. Maternal confidence and rate of breast-feeding were assessed in 31 mothers offered FC that included special family rooms in the NICU, and in 30 mothers from a comparable NICU providing traditional care without such facilities. One week prior to hospital discharge, mothers in the FC group felt better informed regarding nursing issues and had more confidence in interpretation of the infants regarding feeding issues and in caregiving without staff attendance (P < .05). They also reported a higher level of empowerment (P < .05). Three months after discharge, the mothers in the FC group had a higher self-reported skill level for interpretation of the infant's signals and knowledge about breast-feeding (P < .05). Despite similar rate of breast-feeding at discharge, more infants in the FC group were breastfed 3 months after discharge (P < .05). An FC program in the NICU promoted better maternal confidence during the hospital stay and 3 months after discharge compared with traditional care.

[Malpositioning of umbilical vessel catheters]. / Feilplassering av navlekatetre.

BACKGROUND: Catheterization of umbilical veins and arteries is a common intervention in newborns. Malpositioning of catheters is associated with complications. The objective of this study was to evaluate catheter positions after insertion. MATERIAL AND METHODS: The study is based on retrospective evaluation of all relevant X-ray images of newborns admitted to the neonatal intensive care unit, Vestfold Hospital, Norway in the period 1.06.98 - 28.02.10. Accurate localization of the catheter tip was determined in all images. In term infants, acceptable positioning for venous catheters was defined as

[Trends in the diagnosis and management of neonatal hyperbilirubinaemia]. / Endring i diagnostikk og behandling av hyperbilirubinemi hos nyfødte.

BACKGROUND: The guidelines for diagnosis and treatment of neonatal hyperbilirubinaemia were changed at Vestfold Hospital, Norway in 1994 and 2007. Universal screening for ABO-immunization was implemented in 2006. This article describes effects of these changes. MATERIAL AND METHODS: Blood-type immunization, phototherapy and exchange transfusions were prospectively recorded in the 21-year period 1988-2008. Three cohorts comprised the basis for the analyses: infants born in the time-periods 1988-93, 1994-2006 or 2007-2008. RESULTS: 6.2 % of the infants born 1988-93 and 6.7 % born 1994-2006 received phototherapy. Physiological hyperbilirubinaemia in term infants was the main reason for phototherapy in the first cohort, while it was hyperbilirubinemia in preterm infants in the second cohort. 4.8 % of the infants born 2007-8 received phototherapy. Exchange transfusion was performed in 0.02 % born 1994-2008 and 0.2 % born 1988-93. Such transfusions were undertaken more frequently in cases with RhD-immunization (7.8 %) than in those with ABO-immunization (2.0 %). Universal screening for ABO-immunization increased the percentage of diagnosed cases in the population from 2.1 % to 3.6 %. No case of kernicterus was diagnosed. INTERPRETATION: Fewer term infants were treated with phototherapy for hyperbilirubinaemia after the changes of therapeutic guidelines in 1994, while more preterm infants were treated after this change. Far less exchange transfusions are performed nowadays than before 1994. ABO-immunization has been diagnosed more often after implementation of universal screening.

Is breech presentation a risk factor for cerebral palsy? A Norwegian birth cohort study.

AIM: To study whether breech presentation is a risk factor for cerebral palsy (CP). METHODS: Perinatal data from 177 272 children born in breech or vertex presentation in Norway during 1996 to 1998 were retrieved from the Medical Birth Registry of Norway. Data were collected between 1 January 2003 and 31 March 2006. Data on 245 children with CP were recorded in the Norwegian Cerebral Palsy Registry. Odds ratios (OR) with 95% confidence intervals (CI) for CP among children born in breech compared with vertex presentation were calculated. Confounding was addressed in logistic regression and stratified analyses. RESULTS: Among the 245 children with CP (46.5% females and 53.5% males), 31% had unilateral, 49% bilateral, 7% dyskinetic, and 5% the ataxic subtype, and 8% of cases were unclassified. Among children born in breech, the OR for CP was 3.6 (95% CI 2.4-5.3). The increased risk was reduced when adjusted for preterm birth, plurality, and smallness for gestational age. Among singletons born in breech by vaginal delivery at term, the OR for CP was 3.9 (95% CI 1.6-9.7). Severity or subtype of CP did not differ between breech and vertex presentation. INTERPRETATION: Breech delivery is a significant risk factor for CP, in particular among singletons born by vaginal delivery at term.

Pulse oximetry screening as a complementary strategy to detect critical congenital heart defects.

OBJECTIVE: To compare strategies with and without first-day of life pulse oximetry screening to detect critical congenital heart defects (CCHDs). STUDY DESIGN: Population based study including all live born infants in Norway in 2005 and 2006 (n = 116 057). Postductal (foot) arterial oxygen saturation (SpO(2)) was measured in apparently healthy newborns after transferral to the nursery, with SpO(2) < 95% as cut-off point. Out of 57 959 live births in the hospitals performing pulse oximetry screening, 50 008 (86%) were screened. RESULTS: A total of 136 CCHDs (1.2 per 1000) were diagnosed, 38 (28%) of these prenatally. Of the CCHDs detected after birth, 44/50 (88%) were detected before discharge in the population offered pulse oximetry screening (25 by pulse oximetry), compared to 37/48 (77%) in the non-screened population (p = 0.15). Median times for diagnosing CCHDs in-hospital before discharge were 6 and 16 h after birth respectively (p < 0.0001). In the screened population 6/50 (12%) CCHDs were missed and recognized after discharge because of symptoms. Two of the six missed cases failed the pulse oximetry screening, but were overlooked (echocardiography not performed before discharge). If these cases had been recognized, 4/50 (8%) would have been missed compared to 11/48 (23%) in the non-screened population (p = 0.05). Of the cases missed, 14/17 (82%) had left-sided obstructive lesions. CONCLUSION: First-day of life pulse oximetry screening provides early in-hospital detection of CCHDs and may reduce the number missed and diagnosed after discharge.

[Increased detection of malformations of kidneys and the urinary tract]. / Flere påviste misdannelser i nyrer og urinveier.

BACKGROUND: Congenital malformations of the kidneys and urinary tract may have changed over time. MATERIAL AND METHODS: Data for diagnosis, treatment and results were retrospectively recorded in children born in one of three Norwegian counties 1987-2006; their age at time of recording was from 1 to 21 years. RESULTS: 389 of 142 986 (2.7 per 1000) live born children had malformations of the kidneys and/or urinary tract. The prevalence was higher for children born in the period 1997-2006 (241/70 217; 3.4 per 1000) than in 1987-1996 (148/72 769; 2.0 per 1000), p< 0.0011. The percentage of children with anomalies diagnosed prenatally increased significantly from the first born 10-year cohort (35/148; 24 %) to the last (125/241; 52 %), p < 0.0011. Urosepsis occurred in 8 (1.1 per 1000) patients in the first 10-year cohort and in 9 (1.3 per 1000) patients in the last cohort (p = 0.75). 137 (35 %) patients had undergone surgery, of whom 68 (0.9 per 1000) were born 1987-96 and 69 (1 per 1000) were born 1997-2006. Chronic renal failure developed in 6 patients (0.1 per 1000) in each 10-year cohort; 4 (0.05 per 1000) and 11 (0.16 per 1000) patients died in the two cohorts (p = 0.07) respectively. INTERPRETATION: More frequent use of prenatal ultrasound screening has caused a 69 % increase in the prevalence of malformations in kidneys and the urinary tract. The number of patients treated by surgery, deaths and the prevalence of urosepsis and chronic renal failure has remained unchanged. This may indicate increased detection of less severe malformations.

First day of life pulse oximetry screening to detect congenital heart defects.

OBJECTIVE: To evaluate the efficacy of first day of life pulse oximetry screening to detect congenital heart defects (CHDs). STUDY DESIGN: We performed a population-based prospective multicenter study of postductal (foot) arterial oxygen saturation (SpO(2)) in apparently healthy newborns after transfer from the delivery suite to the nursery. SpO(2) < 95% led to further diagnostic evaluations. Of 57,959 live births, 50,008 (86%) were screened. In the screened population, 35 CHDs were [corrected] classified as critical (ductus dependent, cyanotic). CHDs were prospectively registered and diagnosed in 658/57,959 (1.1%) [corrected] RESULTS: Of the infants screened, 324 (0.6%) failed the test. Of these, 43 (13%) had CHDs (27 critical), and 134 (41%) had pulmonary diseases or other disorders. The remaining 147 infants (45%) were healthy with transitional circulation. The median age for babies with CHDs at failing the test was 6 hours (range, 1-21 hours). For identifying critical CHDs, the pulse oximetry screening had a sensitivity rate of 77.1% (95% CI, 59.4-89.0), specificity rate of 99.4% (95% CI, 99.3-99.5), and a false-positive rate of 0.6% (95% CI, 0.5-0.7). CONCLUSIONS: Early pulse oximetry screening promotes early detection of critical CHDs and other potentially severe diseases. The sensitivity rate for detecting critical CHDs is high, and the false-positive rate is low.

Cerebral palsy in Norway: prevalence, subtypes and severity.

BACKGROUND/AIM: To describe prevalence, subtypes and severity of cerebral palsy (CP) in Norway using criteria proposed by the Surveillance of Cerebral Palsy in Europe (SCPE) network. MATERIAL: All children in Norway with CP born in January 1996-December 1998 were registered in the Cerebral Palsy Registry of Norway. The Medical Birth Registry of Norway provided the perinatal data. RESULTS: A total of 374 children with CP were identified with a prevalence of 2.1 per 1000 live births. Detailed information was obtained from 294 (79%) children. Median age at clinical assessment was 6.9 years (range: 1.9-10.2 years). Thirty-three percent of the children had spastic unilateral CP, 49% spastic bilateral, 6% dyskinetic, 5% ataxic CP and 7% were not classified. Severely impaired vision and hearing were present in 5% and 4% of the children, respectively. Active epilepsy was present in 28%, mental retardation in 31% and severely impaired or no speech in 28% children. The most severe impairments in gross motor function were observed in children with low Apgar scores, and the most severe impairments in fine motor function in children born at term, with normal birth weight and low Apgar scores. CONCLUSION: Compared with other populations, the prevalence of CP as well as the proportions of subtypes and gross motor impairments were similar, whereas fine motor impairments and associated impairments were more common. The classification of children with mixed forms of CP is still a challenge. Children were more severely affected if Apgar scores were low, and if they were born at term.

Critical heart defects--the diagnostic challenge.

UNLABELLED: Infants with potentially life threatening congenital heart defects (CHDs) are discharged from hospital after birth with the condition unrecognized. Improved prenatal ultrasound imaging and universal pulse oximetry screening of babies in nurseries are strategies that probably most would contribute to avoid such defects to be missed. CONCLUSION: In general combining first day of life pulse oximetry, clinical examination and echocardiography before discharge in suspect cases is a rational strategy for early postnatal detection of heart defects. Universal echocardiography screening of newborns may be too resource consuming to be cost-effective.

[Pulmonary air-leakage in newborn infants]. / Pulmonal luftlekkasje hos nyfødte.

BACKGROUND: Pulmonary air-leakage (PAL), especially pneumothorax, is a potentially severe complication of pulmonary disease in newborn infants. It is often related to therapeutic procedures such as resuscitation and mechanical ventilation. MATERIAL AND METHODS: This is a prospective study of infants with PAL who were born in the period 1989-2006 and were hospitalised in an intensive care unit. RESULTS: PAL occurred in 54 of 39,101 (1.4 per 1000) live-born infants; 34/54 (63%) were boys and 34/54 (63%) were born at term. 38/54 (70%) PAL cases had asphyxia and different pulmonary diseases, 16/54 (30%) PAL-incidences occurred spontaneously and 23/54 (43%) were diagnosed < 1 hour after birth. PAL occurred during resuscitation for perinatal asphyxia or initiation of mechanical ventilation in 18/54 (33%) patients, during CPAP-treatment in 12/54 (22%), and during mechanical ventilation after the start-up phase in 8/54 (15%) patients. Of 271 infants treated with mechanical ventilation, 144 (53%) were preterm infants with RDS. 64/114 (born 1992-2006) of these received a porcine surfactant and 3/64 (5%) developed PAL. The remaining 50 ventilated RDS-patients born in the same time period had a milder disease; 3/50 (6%) of these developed PAL (p > 0.05). INTERPRETATION: PAL often occurred spontaneously and shortly after birth in connection with resuscitation and stabilization for respirator treatment. The risk for PAL in mechanically ventilated infants was lower once the start-up process had been completed. In infants who had received porcine surfactant for RDS the incidence of PAL during mechanical ventilation was low.

[Quality evaluation of neonatal transports]. / Kvalitetsvurdering av transport av syke nyfødte.

BACKGROUND: Neonatal transports carry risk of complications and technical mishaps which may cause deterioration of the patient's condition. MATERIAL AND METHODS: Prospective observational study on all transports from the subregional neonatal unit, Vestfold Hospital, Norway to other hospitals during the 23-year period 1982-2004. RESULTS: 396 transports were undertaken with a total of 359 patients, 0.7% of live born infants (n = 49,250). Indications were prematurity/respiratory distress syndrome (RDS) in 84 (21%), congenital malformations in 188 (47%), and other conditions in 124 (31%). After the establishment a local respirator programme 1989, transports for prematurity/RDS declined significantly from the 7-year period 1982 - 88 to the 16-year period 1989-2004 (3.4 vs. 1.0 per 1000 live born infants ;p < 0.0001). Night-time transports declined by 55 %. Technical mishaps occurred in 4% of the transports. No deaths occurred during transport; however, 10 infants (2.8%) died within 24 hours on arrival. INTERPRETATION: Neonatal transports were associated with risk of deterioration. High local competence and up-to-date technical equipment for neonatal intensive care improve the quality of transport, reduce the incidence of transports of premature infants with RDS, and of transports during night-time.