Ragnhild Støen

Prediction of Neurodevelopmental and Sensory Outcome at 5 Years in Norwegian Children Born Extremely Preterm

OBJECTIVE: To examine the prevalence of neurodevelopmental disability and the predictive value of pre-, peri-, and postnatal data on neurologic, sensory, cognitive, and motor function in children born extremely preterm. METHODS: This was a prospective observational study of all infants born in Norway between 1999 and 2000 with gestational ages between 22 and 27 weeks or birth weights between 500 and 999 g. Cognitive function was assessed with the Wechsler Preschool and Primary Scale of Intelligence–Revised, motor function with the Movement Assessment Battery for Children, and severity of cerebral palsy with the Gross Motor Function Classification for Cerebral Palsy. Disabilities were described as mild, moderate, or severe. RESULTS: Of 371 eligible children, 306 (82%) were examined at a mean (SD) age of 5 years and 10 (4) months. For gestational age less than 28 weeks (n = 239), 26 (11%) children had cerebral palsy alone (n = 21) or in combination with blindness (n = 3) or deafness (n = 2); 1 was blind and 1 was deaf. Of the remaining children, the mean full-scale IQ was 94 ± 15, and significant predictors were (values given as the difference in IQ points [95% confidence intervals]) high maternal education (9.6 [5.7–13.4]), preeclampsia (−7.7 [−12.7 to −2.7]), and retinopathy of prematurity higher than grade 2 (−17.5 [−27.1 to −8.0]). Movement Assessment Battery for Children scores were positively associated with gestational age and prenatal steroids and negatively associated with being small for gestational age, male gender, and having retinopathy of prematurity. Moderate to severe neurodevelopmental disability was more common for gestational ages 25 weeks or less (28 of 87 children) than for 26 to 27 weeks (12 of 152 children; P < .001) and 28 weeks or more (7 of 67 children; P = .001). CONCLUSIONS: The outcome was poorer for children with gestational ages of 25 weeks or less compared with those with gestational ages between 26 and 27 weeks. For those without cerebral palsy, blindness, or deafness, however, gestational age had a limited association with cognitive and motor function.

Early prediction of cerebral palsy by computer-based video analysis of general movements: a feasibility study

Aim  The aim of this study was to investigate the predictive value of a computer‐based video analysis of the development of cerebral palsy (CP) in young infants.

Neonatal mortality and morbidity in extremely preterm small for gestational age infants: a population based study

Aim: To assess if growth restricted (small for gestational age, SGA) extremely preterm infants have excess neonatal mortality and morbidity. Methods: This was a cohort study of all infants born alive at 22–27 weeks’ post menstrual age in Norway during 1999–2000. Outcomes were compared between those who were SGA, defined as a birth weight less than the fifth percentile for post menstrual age, and those who had weights at or above the fifth percentile. Results: Of 365 infants with a post menstrual age of <28 weeks, 31 (8%) were SGA. Among infants with a post menstrual age of <28 weeks, only chronic lung disease was associated with SGA status (OR 2.7, 95% CI 1.0 to 7.2). SGA infants with a post menstrual age of 26–27 weeks had excess neonatal mortality (OR 3.8, 95% CI 1.3 to 11), chronic lung disease and a significantly higher mean number of days (age) before tolerating full enteral nutrition. SGA infants with a post menstrual age of 22–25 weeks had an excess risk of necrotising enterocolitis. Conclusion: Extremely preterm SGA infants had excess neonatal mortality and morbidity in terms of necrotising enterocolitis and chronic lung disease.

Predicting neurosensory disabilities at two years of age in a national cohort of extremely premature infants.

BACKGROUND Extreme prematurity carries a high risk of neurosensory disability. AIMS Examine which information obtained pre-, peri- and postnatally may be predictive of neurosensory disabilities at 2 years of age. STUDY DESIGN Prospective observational study of all infants born in Norway in 1999 and 2000 with gestational age (GA) 22-27 completed weeks or birth weight (BW) of 500-999 g. OUTCOME MEASURES Incidence of neurosensory disabilities. RESULTS Of 373 surviving children, 30 (8%) had major neurosensory disabilities (26 CP, 6 blind, 3 deaf), and a further 46 (12%) had minor visual or hearing disabilities. The rate of major neurosensory disabilities was 19 of 99 (19%) for children with GA 23-25 vs. 8 of 189 (4%) for GA 26-27 weeks (p<0.001). In a multivariable model, only morbidities detected in the neonatal intensive care unit (NICU) were associated with major neurosensory disabilities; adjusted odds ratios (95% confidence intervals) were 68.6 (18.7, 252.2) for major abnormalities on cerebral ultrasound, 6.8 (1.7, 27.4) for retinopathy of prematurity (ROP) grade>2, 3.2 (1.0, 9.7) for ROP grade 1-2, 6.5 (1.9, 22.3) for prolonged use (> or = 21 days) of steroid treatment for lung disease and 3.1 (1.0, 9.4) for clinical chorioamnionitis. The visual outcome was strongly related to the degree of ROP (p<0.001), and all who had a normal hearing screen in the NICU had normal hearing at 2 years. CONCLUSION NICU morbidities, rather than GA or intrauterine growth are the significant predictors of major neurosensory disabilities among extreme prematurity surviving to discharge from the NICU.

Acetylcholine-induced vasodilation may depend entirely upon NO in the femoral artery of young piglets

To characterize agonist‐induced relaxation in femoral artery rings from young piglets, we compared the effect of a NOS‐inhibitor Nω‐nitro‐L‐arginine (L‐NOARG), an NO‐inactivator oxyhaemoglobin (HbO) and a soluble guanyl cyclase(sGC)‐inhibitor 1H‐[1,2,4]Oxadiazolo‐[4,3,‐α]quinoxalin‐1‐one (ODQ) on acetylcholine(ACh)‐induced relaxation. The involvement of K+ channel activation was studied on relaxations induced by ACh, the two NO donors sodium nitroprusside (SNP) and diethylamine (DEA) NONOate, and the cell membrane permeable guanosine 3′5′ cyclic monophosphate (cGMP) analogue 8‐Br‐cGMP. Full reversal of phenylephrine‐mediated precontraction was induced by ACh (1 nM–1 μM) (pD2 8.2±0.01 and Rmax 98.7±0.3%). L‐NOARG (100 μM) partly inhibited relaxation (pD2 7.4±0.02 and Rmax 49.6±0.8%). The L‐NOARG/indomethacin(IM)‐resistant response displayed characteristics typical for endothelium‐derived hyperpolarizing factor (EDHF), being sensitive to a combination of the K+ channel blockers charybdotoxin (CTX) (0.1 μM) and apamin (0.3 μM). ODQ (10 μM) abolished relaxations induced by ACh and SNP. L‐NOARG/IM‐resistant relaxations to ACh were abolished by HbO (20 μM). Ouabain (1 μM) significantly inhibited ACh‐induced L‐NOARG/IM‐resistant relaxations and relaxations induced by SNP (10 μM) and 8‐Br‐cGMP (0.1 mM). A combination of ouabain and Ba2+ (30 μM) almost abolished L‐NOARG/IM‐resistant ACh‐induced relaxation (Rmax 7.7±2.5% vs 23.4±6.4%, with and without Ba2+, respectively, P<0.05). The present study demonstrates that in femoral artery rings from young piglets, despite an L‐NOARG/IM‐resistant component sensitive to K+ channel blockade with CTX and apamin, ACh‐induced relaxation is abolished by sGC‐inhibition or a combination of L‐NOARG and HbO. These findings suggest that relaxation can be fully explained by the NO/cGMP pathway.

Postnatal changes in mechanisms mediating acetylcholine-induced relaxation in piglet femoral arteries

We studied the nitric oxide-cGMP pathway in endothelium-dependent relaxation in femoral arterial rings from piglets at different postnatal ages. Responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined in phenylephrine-precontracted rings from newborn (10-22-h) and 7 d(7-10-d)-old piglets. Relaxant responses were investigated in endothelium-denuded rings and endothelium-intact controls, and in endothelium-intact rings incubated with the nitric oxide synthase (NOS) inhibitor NG-monomethyl-L-arginine acetate (L-NMMA), indomethacin, or the superoxide anion generator 6-anilinoquinoline-5,8-quinone(LY83583). Arterial rings from both age groups relaxed to a similar degree in response to ACh. Relaxation in rings from newborn piglets was insensitive to NOS inhibition by L-NMMA, whereas in artery rings from 7-d-old piglets, the relaxant response was significantly inhibited by L-NMMA. Incubation with LY83583 gave an inhibition of ACh-induced relaxation very similar to that of L-NMMA. Incubation with indomethacin had no significant effect on ACh-induced relaxation in either age group. Artery rings from both age groups relaxed 100% to SNP; the 7-d-old group was more sensitive than the newborn. NOS inhibition potentiated SNP-induced relaxation in both groups, but the potentiating effect was of greater magnitude in the newborn. Our results indicate a difference in the mechanism(s) underlying ACh-induced relaxation in the femoral artery from newborn and 7-d-old piglets, with an intact relaxant response in rings from the newborn despite NOS inhibition. The SNP results indicate a down-regulated soluble guanylate cyclase in the newborn, possibly related to a difference in basal NO release between the two age groups.

Identification of fidgety movements and prediction of CP by the use of computer-based video analysis is more accurate when based on two video recordings

This study evaluates the role of postterm age at assessment and the use of one or two video recordings for the detection of fidgety movements (FMs) and prediction of cerebral palsy (CP) using computer vision software. Recordings between 9 and 17 weeks postterm age from 52 preterm and term infants (24 boys, 28 girls; 26 born preterm) were used. Recordings were analyzed using computer vision software. Movement variables, derived from differences between subsequent video frames, were used for quantitative analysis. Sensitivities, specificities, and area under curve were estimated for the first and second recording, or a mean of both. FMs were classified based on the Prechtl approach of general movement assessment. CP status was reported at 2 years. Nine children developed CP of whom all recordings had absent FMs. The mean variability of the centroid of motion (CSD) from two recordings was more accurate than using only one recording, and identified all children who were diagnosed with CP at 2 years. Age at assessment did not influence the detection of FMs or prediction of CP. The accuracy of computer vision techniques in identifying FMs and predicting CP based on two recordings should be confirmed in future studies.

Neonatal Morbidity and 1-Year Survival of Extremely Preterm Infants.

This is a prospective, population-based cohort study comparing survival and neonatal morbidity in infants born at 22 to 26 weeks’ gestation in Norway in 2013–2014. OBJECTIVE: To determine 1-year survival and major neonatal morbidities (intracranial hemorrhage grade >2, cystic periventricular leukomalacia, retinopathy of prematurity grade >2, necrotizing enterocolitis, severe bronchopulmonary dysplasia) among extremely preterm infants in Norway in 2013–2014, and to compare the results to the first Norwegian Extreme Prematurity Study 1999–2000 and similar contemporary European population-based studies. METHODS: Population-based study of all infants born at 22 through 26 weeks’ gestation in Norway in 2013–2014. Prospectively collected data were obtained by linking data in the Norwegian Neonatal Network to the Medical Birth Registry of Norway. RESULTS: Of 420 infants (incidence 3.5 per 1000 births), 145 were stillborn (34.5%), 275 were live-born (82.3% of the 334 fetuses alive at admission for obstetrical care), and 251 (91.3% of live-born infants) were admitted to a neonatal unit. The survival among live-born infants was 18% at 22 weeks, 29% at 23 weeks, 56% at 24 weeks, 84% at 25 weeks and 90% at 26 weeks (for each week increment in gestational age: odds ratio 3.3; 95% confidence interval, 2.4–4.4). Among infants surviving to 1 year of age, major neonatal morbidity was diagnosed in 55%. Decreasing gestational age was moderately associated with rates of major morbidity (odds ratio 1.6; 95% confidence interval, 1.2–2.2). CONCLUSIONS: Compared to the previous 1999–2000 cohort, the rate of stillbirth before admission to an obstetrical unit increased, whereas the survival rate among live born infants was similar in our 2013–2014 cohort. Neonatal morbidity rates remain high among extremely preterm infants.

Relationship between white matter pathology and performance on the General Movement Assessment and the Test of Infant Motor Performance in very preterm infants

BACKGROUND Cerebral Magnetic Resonance Imaging, the General Movement Assessment, and the Test of Infant Motor Performance are all tools that can predict neurodevelopmental outcome in preterm infants. However, how these tests relate to each other is unclear. AIMS To examine the relationship between cerebral Magnetic Resonance Imaging measured at term age, and the General Movement Assessment and Test of Infant Motor Performance measured at 10-15 weeks post-term age. STUDY DESIGN Prospectively collected data in a sample of very preterm infants. SUBJECTS Fifty-three infants (23 female, 30 male) with a median gestational age of 28 weeks (range: 23-30 weeks) and a median birth weight of 1000 g (range: 515-1465 g). OUTCOME MEASURES Test of Infant Motor Performance, General Movement Assessment. RESULTS Infants with abnormal white matter were significantly more likely to have both abnormal general movements (p=0.01) and abnormal Test of Infant Motor Performance scores (p=0.001). Infants with abnormal general movements were significantly more likely to have lower Test of Infant Motor Performance Scores (p=0.01). CONCLUSIONS Abnormal white matter is related to motor deviations as measured by the General Movement Assessment and the Test of Infant Motor Performance as early as 3 months post-term age in a cohort of preterm infants.

Bifidobacterium longum Subspecies infantis Bacteremia in 3 Extremely Preterm Infants Receiving Probiotics.

To the Editor: Metaanalysis of randomized trials that tested different probiotics showed a reduction of ≈50% in necrotizing enterocolitis and all-cause deaths in preterm infants (1). Use of probiotics is increasing worldwide (2,3), and cases of probiotic sepsis were not reported among >5,000 infants in an updated review (1).