Kristoffer Brodwall

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.

Maternal Diabetes, Birth Weight, and Neonatal Risk of Congenital Heart Defects in Norway, 1994-2009.

OBJECTIVE: To investigate the association between pregestational or gestational diabetes and offspring risk of congenital heart defects and the association between large-for-gestational-age birth weight and risk of cardiac defects in offspring of diabetic women. METHODS: Information on pregestational and gestational diabetes, cardiac defects, and birth weight among all births in Norway in 1994–2009 was ascertained from the Medical Birth Registry of Norway, national health registries, and the Cardiovascular Disease in Norway project. The relative risk (RR) compared offspring risk of cardiac defects for maternal diabetes with offspring risk in nondiabetic mothers adjusted for year of birth, maternal age, and parity. RESULTS: Among 914,427 births (live births, stillbirths, terminated pregnancies), 5,618 (0.61%) were complicated by maternal pregestational diabetes and 9,726 (1.06%) by gestational diabetes. Congenital heart defects were identified in 10,575 offspring. The prevalence of cardiac defects differed between groups: 344 of 10,000 births to women with pregestational diabetes, 172 of 10,000 to women with gestational diabetes, and 114 of 10,000 in women without diabetes (adjusted RRs 2.92, 95% confidence interval [CI] 2.54–3.36 and 1.47, 95% CI 1.26–1.71). During the study period, the adjusted RRs for congenital heart defects did not change. The risk of cardiac defects in neonates very large for gestational age (birth weight greater than 3 standard deviations above the mean) was compared with neonates with birth weight appropriate for gestational age. For pregestational diabetes, the prevalences of offspring cardiac defects were 561 compared with 248 per 10,000 births (adjusted RR 2.23, 95% CI 1.39–3.59) and for gestational diabetes 388 compared with 132 per 10,000 (adjusted RR 2.73, 95% CI 1.53–4.85). CONCLUSION: The increased risk of having a child with a congenital heart defect has not changed for diabetic women in Norway since 1994. Among women with pregestational or gestational diabetes, having a large-for-gestational-age neonate was associated with a two- to threefold increased risk of cardiac defects compared with neonates with normal birth weight.

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.

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.

Preeclampsia and Congenital Heart Defects

1 fell on 2 separate occasions, both times less than 24 hours after receiving lorazepam rescue medication for agitation. Nine of the 13 patients in the dextromethorphan-quinidine group who fell had a history of falls. More patients randomized to receive dextromethorphan-quinidine had a history of falls (17.2% for dextromethorphan-quinidine vs 12.6% for placebo). In addition, rerandomization of patients from placebo to active treatment at midpoint—as part of the sequential parallel comparison design—resulted in approximately 25% greater exposure-days for patients receiving dextromethorphan-quinidine than placebo. In the Citalopram for Agitation in Alzheimer Disease (CitAD) study, a 9-week, parallel-design, placebo-controlled study that enrolled patients with clinical characteristics comparable with our study in terms of age, severity of dementia, and agitation, falls were reported in 16.7% of patients receiving citalopram vs 11.6% of patients receiving placebo.1 The rate of falls with placebo in the CitAD study was higher than the rate with dextromethorphan-quinidine in our study. Newman and Steinman also compared the fall rate in our study against prior studies of dextromethorphanquinidine in patients with pseudobulbar affect. In the pivotal trial2 in patients with pseudobulbar affect secondary to amyotrophic lateral sclerosis or multiple sclerosis, 2 populations at risk of falling, the fall rate for patients receiving placebo (20%) was higher than the fall rate for patients receiving dextromethorphan-quinidine (13.1%; 20/10 mg twice a day), and was similar to rates for patients receiving dextromethorphan-quinidine (20.0%; 30/10 mg twice a day), the same dosages used in our study. In summary, no definitive conclusions can be reached regarding the risk of falls based on our study alone. The second comment by Newman and Steinman, regarding the ethics of patenting trial design, is a topic for discussion among the broader scientific community. We think it is important to note that the patent for the Trimentum method is not held by the study investigators or the study sponsor. The issue of high placebo response rates in studies of neuropsychiatric conditions has created a need to try new approaches, including enrichment designs. We used the innovative sequential parallel comparison design to mitigate the difficulty of interpreting treatment responses in trial populations with high rates of placebo response.

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

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.

Nytt legemiddel mot parasittsykdom i lever

Leverikte er en samlebetegnelse på parasittsykdommer forårsaket av trematoder som setter seg i lever og galleveier hos pattedyr. Sørøstasiatisk leverikte skyldes Opisthorchis viverrini, som kan forårsake alvorlig leversykdom, muligens også kreft i galleveiene. Sykdommen er utbredt i Thailand, Kambodsja og Laos med anslagsvis 10 millioner infiserte mennesker. Vanligste smittemåte er inntak av fisk.

Ebolavirusinfeksjon uten symptomer er sjeldent

I 2014 – 15 var det et stort ebolautbrudd i Vest-Afrika med over 28 000 syke mennesker (1). Ebolavirusets naturlige reservoar er ukjent, noe som gjør det vanskelig å forutsi og forebygge nye utbrudd. Enkelte eldre studier har antydet at asymptomatiske infeksjoner er vanlig, og noen eksperter har derfor fryktet at asymptomatiske bærere kan bidra til spredning av sykdommen. I en ny studie fra Sierra Leone kartlegges forekomsten av asymptomatiske ebolavirusinfeksjoner (2). Forfatterne validerte først en ny diagnostisk metode, ved å teste spytt for spesifikt IgG mot ebolavirus. Prøven var positiv for 93 av 97 personer som hadde overlevd PCR-bekreftet ebolavirusinfeksjon (sensitivitet 95,9 %) og negativ for alle 339 kontrollpersonene (spesifisitet 100 %).

[Trichorhinophalangeal syndrome--clinical presentation and genetics].

BACKGROUND The trichorhinophalangeal syndrome (TRPS) is a hereditary, skeletal dysplasia which has a characteristic clinical presentation and is classified in types 1, 2 and 3, based on phenotype and genotype. Typical findings may be mild and many patients probably remain undiagnosed. MATERIAL AND METHODS The paper is based on four case reports and provides a short review of the condition. RESULTS Our four patients all have typical facial features, such as a large nose and thin upper lip, thin hair and short curved fingers with characteristic radiological findings. The condition is autosomal dominant and caused by a mutation in the TRPS1 gene, which codes a gene-regulating protein involved in development of hair and modulation of chondrocytes. The diagnosis can be based on clinical findings, but DNA-analysis can be of help in unclear situations. Two of our patients were diagnosed from clinical and radiological findings, but for the two others genetic examinations were done as well. There is no causal treatment, but the diagnosis can give patients an explanation of their problems, and genetic counseling for the patient and family can be offered. Orthopedic surgery and cosmetic aids are valuable for many. INTERPRETATION In an increasingly technified medical daily life, the clinical view is still the most important tool in diagnosing patients with this condition.