[Sickle cell disease ­ clinical manifestations and diagnostics]. / Sigdcellesykdom ­ kliniske manifestasjoner og diagnostikk.

Sickle cell disease is a group of diseases presenting with a set of characteristic acute and chronic manifestations. Sickle cell disease has traditionally been uncommon in the Northern European population; however, due to demographic changes, it is increasingly also something that Norwegian clinicians should be cognisant of. In this clinical review article we wish to present a brief introduction to sickle cell disease, with an emphasis on its aetiology, pathophysiology, clinical manifestation and how the diagnosis is established based on laboratory testing.

Introduction of a high dependency unit at a large paediatric and adolescent medicine department. / Innføring av barneovervåkningsenhet ved en stor barne- og ungdomsklinikk.

BACKGROUND: A goal has been set to establish paediatric high dependency units (PHDUs) in Norwegian hospitals. We sought to describe the patient population in one such unit, and to investigate whether the need for admission to an intensive care unit (ICU) changed after the unit was established. MATERIAL AND METHOD: Information was obtained from electronic patient records, patient administration systems and the quality register for the PHDU at the Department of Paediatrics and Adolescent Medicine at Haukeland University Hospital. All patients admitted to the PHDU within five years of its opening in 2017 were included. A comparison was made between ICU patients in the five years before and the five years after the establishment of the PHDU. RESULTS: The PHDU had a total of 851 patient admissions in the period 2017-2021, increasing from 125 in 2017 to 247 in 2021. This accounted for 3.5 % and 7.6 % of the total number of patients admitted to the Department of Paediatrics and Adolescent Medicine in these years, respectively. The ICU had 185 paediatric patient admissions in the period 2012-2016 and 187 in the period 2017-2021, which constituted 0.9 % and 1.1 % of all patients admitted to the Department of Paediatrics and Adolescent Medicine during the periods, respectively. After the start-up of the PHDU, a lower proportion of patients were admitted to the ICU in the diagnostic groups diabetic ketoacidosis (15 % in 2017-2021 versus 20 % in 2012-2016) and sepsis (12 % in 2017-2021 versus 19 % in 2012-2016). INTERPRETATION: The introduction of a PHDU was not associated with a simultaneous reduction in the number of ICU admissions overall. For diabetic ketoacidosis and sepsis, however, the proportion of transfers to the ICU was reduced.

An apathetic child with hallucinations. / Et apatisk barn med hallusinasjoner.

BACKGROUND: Lysergic acid diethylamide (LSD) is a potent, hallucinogenic substance that distorts the perception, state of consciousness and behaviour of the user. LSD poisonings are rare in children and may be difficult to recognise based on clinical symptoms alone. CASE PRESENTATION: A young boy was admitted to the hospital because of bizarre behaviour and reduced responsiveness towards his parents. At first, he was agitated. Later he fell silent and became apathetic. He suffered from ataxia and showed signs of visual hallucinations. A conclusive diagnosis of LSD poisoning was made possible through targeted and specific laboratory testing of blood and urine samples. The patient recovered completely without any specific treatment. INTERPRETATION: We urge doctors who examine paediatric patients with acute and unexplained neuropsychiatric symptoms or abnormal behaviour to consider drug intoxication as a possible differential diagnosis. Blood and urine samples from such patients should be obtained as soon as possible and analysed for a broad spectrum of substances. No antidote exists for LSD. If sedation is required due to convulsions, tachycardia, agitation, or frightening hallucinations, treatment with a benzodiazepine, such as diazepam or midazolam, is recommended.

Intake of sucrose-sweetened soft beverages during pregnancy and risk of congenital heart defects (CHD) in offspring: a Norwegian pregnancy cohort study.

Studies report increased risk of congenital heart defects (CHD) in the offspring of mothers with diabetes, where high blood glucose levels might confer the risk. We explored the association between intake of sucrose-sweetened soft beverages during pregnancy and risk of CHD. Prospective cohort data with 88,514 pregnant women participating in the Norwegian Mother and Child Cohort Study was linked with information on infant CHD diagnoses from national health registers and the Cardiovascular Diseases in Norway Project. Risk ratios were estimated by fitting generalized linear models and generalized additive models. The prevalence of children with CHD was 12/1000 in this cohort (1049/88,514). Among these, 201 had severe and 848 had non-severe CHD (patent ductus arteriosus; valvular pulmonary stenosis; ventricular septal defect; atrial septal defect). Only non-severe CHD was associated with sucrose-sweetened soft beverages. The adjusted risk ratios (aRR) for non-severe CHD was 1.30 (95% CI 1.07-1.58) for women who consumed 25-70 ml/day and 1.27 (95% CI 1.06-1.52) for women who consumed ≥ 70 ml/day when compared to those drinking ≤ 25 ml/day. Dose-response analyses revealed an association between the risk of non-severe CHD and the increasing exposure to sucrose-sweetened soft beverages, especially for septal defects with aRR = 1.26 (95% CI 1.07-1.47) per tenfold increase in daily intake dose. The findings persisted after adjustment for maternal diabetes or after excluding mothers with diabetes (n = 19). Fruit juices, cordial beverages and artificial sweeteners showed no associations with CHD. The findings suggest that sucrose-sweetened soft beverages may affect the CHD risk in offspring.

The five-year survival of children with Down syndrome in Norway 1994-2009 differed by associated congenital heart defects and extracardiac malformations.

AIM: We investigated the prevalence of Down syndrome in a nationwide birth cohort, focusing on congenital heart defects (CHDs), their associations with extracardiac malformations (ECM) and survival. METHODS: National registers were used to identify Norwegian births (1994-2009) and deaths (1994-2014) and updated with hospital diagnoses. We estimated birth defect frequencies in Down syndrome and the general population, the association between CHDs and ECM and hazard ratios for death from different combinations of CHDs and ECM. RESULTS: Down syndrome was found in 1672 of 953 450 births (17.6 per 10 000). Of the 1251 live births (13.3 per 10 000), 58% had CHD and 9% ECM. CHDs were associated with oesophageal atresia (p = 0.02) and Hirschsprung's disease (p = 0.03) but with no other malformations. The five-year survival for Down syndrome increased from 91.8% (1994-1999) to 95.8% (2000-2009) (p = 0.006), and overall survival was 92.0% with CHD and 97.4% without. Compared with Down syndrome children without CHD or ECM, the five-year mortality was similar for those with nonsevere CHDs, without or with ECM, but 4-7 times higher in those with severe CHDs without ECM and 13-28 times higher in those with severe CHDs and ECM. CONCLUSION: Down syndrome childhood survival improved, but mortality remained high with severe CHDs and extracardiac defects.

Recurrence of congenital heart defects among siblings-a nationwide study.

Congenital heart defects (CHD) constitute the largest group of congenital malformations. In most families, only one person has CHD; however, the risk of CHD increases for children born into families already affected. In this study, all births from 1994 through 2009 were identified in the Medical Birth Registry of Norway, including supplemental information on CHD from clinical and administrative registers, as part of the CVDNOR project. By using the unique personal identification number of each parent we were able to link 16,078 pairs of twins, 445,584 pairs of full siblings, and 106,840 pairs of half-siblings. Sibling recurrence risk ratio (RRR) was calculated using CHD status in the oldest sibling as exposure and CHD status in the younger sibling as outcome, adjusted for year of birth, maternal age, and maternal diabetes. Among full sibling pairs with CHD in the older sibling, the younger sibling had CHD in 4.1% compared to 1.1% of the pairs without CHD in the older sibling (adjusted RRR 3.6; 95% confidence interval (CI) 3.1-4.1). In same-sex twins the RRR was 14.0 (95% CI 10.6-18.6), and in opposite-sex twins the RRR was 11.9 (95% CI 7.1-19.9). For half-siblings the RRR was 1.5 (95% CI 0.8-2.8). When restricting to severe types of CHD, the RRR was 6.9 (95% CI 4.9-9.8) for full siblings. In 50% of the pairs with recurrent CHD, the siblings had similar types of CHD. The high relative risk of recurrence indicates that familial risk factors are important in the etiology of CHD.

Possible Common Aetiology behind Maternal Preeclampsia and Congenital Heart Defects in the Child: a Cardiovascular Diseases in Norway Project Study.

BACKGROUND: The aetiology of congenital heart defects (CHD) is mostly unknown, but maternal factors may modify the infant risk of CHD. We investigated the association between maternal preeclampsia and offspring risk of severe CHD in a nation-wide cohort study. METHODS: Information on all births registered in the Medical Birth Registry of Norway, 1994-2009, was completed with information on CHD diagnoses from national health registries and the Cardiovascular Diseases in Norway Project (CVDNOR). RESULTS: Among 914 703 singleton births without chromosomal abnormalities, 32 864 (3.6%) were born after a pregnancy with preeclampsia. The preeclampsia was diagnosed before the 34th week of pregnancy (early-onset preeclampsia) in 2618 (8.0% of preeclamptic pregnancies). CHDs were diagnosed in 10 691 infants; of these, 2473 had severe CHD. The risk of severe CHD was compared between births with and without maternal preeclampsia and estimated with binomial log-linear regression. When adjusting for year of birth, maternal age, parity, and pregestational diabetes, the risk ratio (RR) for severe CHD in offspring of mothers with any preeclampsia was 1.3 [95% confidence interval (CI) 1.1, 1.5], and in pregnancies with early-onset preeclampsia, the RR was 2.8 (95% CI 1.8, 4.4). The association between early-onset preeclampsia and specific types of severe CHD was stronger for atrioventricular septal defects (AVSD), with adjusted RR 13.5 (95% CI 6.8, 26.8). CONCLUSIONS: Early-onset preeclampsia was strongly associated with infant risk of severe CHD, specifically; the risk of AVSD was 15-fold higher if the mother was diagnosed with early-onset preeclampsia, suggesting common aetiological factors for early-onset preeclampsia and erroneous fetal heart development.

Periconceptional Folic Acid Supplementation and Infant Risk of Congenital Heart Defects in Norway 1999-2009.

BACKGROUND: The birth prevalence of congenital heart defects (CHDs) has decreased in Canada and Europe. Recommended intake of folic acid in pregnancy is a suggestive risk-reducing factor for CHDs. We investigated the association between periconceptional intake of folic acid supplements and infant risk of CHDs. METHODS: Information on maternal intake of folic acid supplements before and during pregnancy in the Medical Birth Registry of Norway 1999-2009 was updated with information on CHD diagnoses from national health registers and the Cardiovascular Diseases in Norway Project. The association between folic acid intake and infant risk of CHD was estimated as relative risk (RR) with binomial log linear regression. RESULTS: Among 517 784 non-chromosomal singleton births, 6200 children were identified with CHD and 1153 with severe CHD. For all births, 18.4% of the mothers initiated folic acid supplements before pregnancy and 31.6% during pregnancy. The adjusted RR for severe CHD was 0.99 [95% confidence interval [CI] 0.86, 1.13] comparing periconceptional intake of folic acid with no intake. Specifically, RR for conotruncal defects was 0.99 [95% CI 0.80, 1.22], atrioventricular septal defects 1.19 [95% CI 0.78, 1.81], left ventricular outflow tract obstructions 1.02 [95% CI 0.78, 1.32], and right ventricular outflow tract obstructions 0.97 [95% CI 0.72, 1.29]. Birth prevalence of septal defects was higher in the group exposed to folic acid supplements with RR 1.19 [95% CI 1.10, 1.30]. CONCLUSIONS: Periconceptional folic acid supplement use showed no association with severe CHDs in the newborn. An unexpected association with an increased risk of septal defects warrants further investigation.

Birth prevalence of congenital heart defects in Norway 1994-2009--a nationwide study.

BACKGROUND: The reasons for decreasing birth prevalence of congenital heart defects (CHDs) in several European countries and Canada are not fully understood. We present CHD prevalence among live births, stillbirths, and terminated pregnancies in an entire nation over a period of 16 years. METHODS: Information on all births in the Medical Birth Registry of Norway, 1994-2009, was updated with information on CHD from the hospitals' Patient Administrative Systems, the National Hospital's clinical database for children with heart disease, and the Cause of Death Registry. Individuals with heart defects were assigned specific cardiac phenotypes. RESULTS: Among 954,413 births, 13,081 received a diagnosis of CHD (137.1 per 10,000 births, 133.2 per 10,000 live births). The prevalence per 10,000 births was as follows: heterotaxia, 1.6; conotruncal defects, 11.6; atrioventricular septal defects, 5.6; anomalous pulmonary venous return, 1.1; left outflow obstructions, 8.7; right outflow obstructions, 5.6; septal defects, 65.5; isolated patent ductus arteriosus, 24.6; and other specified or unspecified CHD, 12.7. Excluding preterm patent ductus arteriosus, the CHD prevalence was 123.4 per 10,000; per year, the prevalence increased with 3.5% (95% CI 2.5-4.4) in 1994-2005 and declined with 9.8% (-16.7 to -2.4) from 2005 onwards. Severe CHD prevalence was 30.7 per 10,000; per-year increase was 2.3% (1.1-3.5) in 1994-2004, and per-year decrease was 3.4% (-6.6 to -0.0) in 2004-2009. Numbers included severe CHD in stillbirths and terminated pregnancies. CONCLUSIONS: The birth prevalence of CHD declined from around 2005. Specifically, the prevalence of severe CHD was reduced by 3.4% per year from 2004 through 2009.