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Allbrand, M., Åman, J., Nilsson, K., Cao, Y. & Lodefalk, M. (2019). Expression of genes involved in inflammation and growth: does sampling site in human full-term placenta matter?. Journal of Perinatal Medicine, 47(5), 539-546
Open this publication in new window or tab >>Expression of genes involved in inflammation and growth: does sampling site in human full-term placenta matter?
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2019 (English)In: Journal of Perinatal Medicine, ISSN 0300-5577, E-ISSN 1619-3997, Vol. 47, no 5, p. 539-546Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate the placental gene expression of substances in the inflammatory cascade and growth factors at nine different well-defined sampling sites in full-term placentas from 12 normal weight healthy non-smoking women with an uncomplicated singleton pregnancy.

Methods: All placentas (six girls and six boys) were delivered vaginally. Quantitative real-time polymerase chain reaction was used to analyze toll receptor-2 and -4, interleukin-6 and -8, tumor necrosis factor-α, leptin, ghrelin, insulin-like growth factor-1 and -2, hepatocyte growth factor, hepatocyte growth factor receptor and insulin receptor (IR).

Results: The leptin gene and the IR gene showed higher expression in lateral regions near the chorionic plate compared to central regions near the basal plate (P = 0.028 and P = 0.041, respectively).

Conclusion: Our results suggest that the sampling site may influence the gene expression for leptin and IR in placental tissue obtained from full-term normal pregnancies. We speculate that this may be due to differences in placental structure and perfusion and may be important when future studies are designed.

Place, publisher, year, edition, pages
Walter de Gruyter, 2019
Keywords
Cytokines, gene expression, growth factors, placenta, sampling
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-73427 (URN)10.1515/jpm-2018-0290 (DOI)000473532900008 ()30920955 (PubMedID)2-s2.0-85063721684 (Scopus ID)
Note

Funding Agencies:

Research Committee of Region Örebro County  

Nyckelfonden, Örebro University Hospital  

Available from: 2019-04-04 Created: 2019-04-04 Last updated: 2019-08-08Bibliographically approved
Östling, H., Kruse, R., Helenius, G. & Lodefalk, M. (2019). Placental expression of microRNAs in infants born small for gestational age. Placenta, 81, 46-53
Open this publication in new window or tab >>Placental expression of microRNAs in infants born small for gestational age
2019 (English)In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 81, p. 46-53Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: The molecular mechanisms behind poor foetal growth are not fully known. The aim of this study was to explore global microRNA expression in placentas of infants born small for gestational age (SGA) compared to infants with a normal birth weight (NBW).

METHODS: Placental biopsies from term infants were identified in a biobank and divided into four groups: infants born SGA with (n = 13) or without (n = 9) exposure to low maternal gestational weight gain (GWG) and infants born with NBWs with (n = 20) or without (n = 26) exposure to low GWG. All women and infants were healthy, and no woman smoked during pregnancy. Only vaginal deliveries were included. Next-generation sequencing was performed with single read sequencing of >9 million reads per sample. Differential microRNA expression was analysed using ANOVA for unequal variances (Welch) with multiple testing corrections through the Benjamini-Hochberg method. A fold change >2 and a corrected p value < 0.05 were considered significant. Adjustments for possible confounding factors were made using a linear regression model.

RESULTS: A total of 1870 known, mature human microRNAs were detected in the sample. MiR-3679-5p and miR-193b-3p were significantly upregulated, and miR-379-3p, miR-335-3p, miR-4532, miR-519e-3p, miR-3065-5p, and miR-105-5p were significantly downregulated after adjustment for potential confounding factors in SGA infants with normal GWG compared to infants with NBWs and normal GWG.

DISCUSSION: Infants born unexplained SGA show differential microRNA expression in their placenta. Important pathways for the differentially expressed microRNAs include inflammation and the insulin-IGF system.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Foetal growth, Inflammation, Placenta, RNA-Sequencing, Small for gestational age, microRNA
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-74556 (URN)10.1016/j.placenta.2019.05.001 (DOI)000468874700007 ()31138431 (PubMedID)2-s2.0-85065481896 (Scopus ID)
Note

Funding Agency:

Research Committee of Region Örebro County and ALF funding Region Örebro County

Available from: 2019-06-05 Created: 2019-06-05 Last updated: 2019-06-14Bibliographically approved
Rodanaki, M., Lodefalk, M., Forssell, K., Arvidsson, C.-G., Forssberg, M. & Åman, J. (2019). The Incidence of Childhood Thyrotoxicosis Is Increasing in Both Girls and Boys in Sweden. Hormone Research in Paediatrics, 91(3), 195-202
Open this publication in new window or tab >>The Incidence of Childhood Thyrotoxicosis Is Increasing in Both Girls and Boys in Sweden
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2019 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 91, no 3, p. 195-202Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: We found an increase in the incidence rate (IR) of childhood thyrotoxicosis (CT) during the 1990s in central Sweden. The optimal treatment method for CT is a subject that is still debated upon.

OBJECTIVES: To investigate whether the increase in IR of CT in Sweden persists and to study the treatment outcome.

METHOD: Children <16 years of age diagnosed with CT during 2000-2009 and living in 1 of 5 counties in central Sweden were identified retrospectively using hospital registers. Data on clinical and biochemical characteristics and outcomes of treatment were collected from medical records. The corresponding data from 1990 to 1999 were pooled with the new data.

RESULTS: In total, 113 children were diagnosed with CT during 1990-2009 in the study area. The overall IR was 2.2/100,000 person-years (95% CI 1.2-2.5/100,000 person-years). The IR was significantly higher during 2000-2009 than during 1990-1999 (2.8/100,000 [2.2-3.6] vs. 1.6/100,000 person-years [1.2-2.2], p = 0.006). The increase was significant for both sexes. Seventy percent of the patients who completed the planned initial treatment with antithyroid drugs (ATDs) and were not lost to follow-up relapsed within 3 years. Boys tended to relapse earlier than girls (6.0 months after drug withdrawal [95% CI 1.9-10.0] vs. 12.0 months [95% CI 6.8-17.3], p = 0.074).

CONCLUSIONS: The IR of CT is increasing in both girls and boys. Relapse rate after withdrawal of ATD treatment is 70%. Boys tend to relapse earlier than girls, and this needs to be further investigated.

Place, publisher, year, edition, pages
S. Karger, 2019
Keywords
Children, Hyperthyroidism, Incidence rate, Relapse, Thyrotoxicosis
National Category
Pediatrics Endocrinology and Diabetes
Identifiers
urn:nbn:se:oru:diva-74317 (URN)10.1159/000500265 (DOI)000476517300005 ()31096231 (PubMedID)2-s2.0-85065962578 (Scopus ID)
Note

Funding Agency:

ALF funding at Region Örebro County, Sweden

Available from: 2019-05-20 Created: 2019-05-20 Last updated: 2019-08-12Bibliographically approved
Rodanaki, M., Lodefalk, M. & Åman, J. (2018). Incidence and Treatment Outcome of Childhood Thyrotoxicosis. Paper presented at 57th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE 2018), Athens, Greece, September 27-29, 2018. Hormone Research in Paediatrics, 90(Suppl.1), 90-91, Article ID RFC5.3.
Open this publication in new window or tab >>Incidence and Treatment Outcome of Childhood Thyrotoxicosis
2018 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 90, no Suppl.1, p. 90-91, article id RFC5.3Article in journal, Meeting abstract (Refereed) Published
Abstract [en]

Aim: To study the incidence of childhood thyrotoxicosis in five counties in central Sweden during 1990–2009 and to study the treatment outcome.

Methods: Children below the age of 16 years diagnosed with thyrotoxicosis during the 20-years period and living in the study area were identified retrospectively. Data on the total number of children below 16 years of age living in the area during the study period was collected from the National Board of Statistics, Sweden. Data regarding clinical and biochemical characteristics and the outcome of the treatment were collected from medical records.

Results: 113 patients were identified. The annual incidence was 2.2/100,000 children during the whole study period. The incidence was higher during the last ten studied years as compared to the first ten studied years (2.8 vs. 1.6/100,000, p = 0.006). The increase in incidence was seen in both girls and boys (p = 0.041 and p = 0.038, respectively). Treatment with antithyroid drugs (ATD) was the first hand choice, but 69% of the patients relapsed within three years after the planned discontinuation of the ATD treatment. Boys relapsed more often than girls (p = 0.013), but we could not identify any other significant predictor for relapse.

Conclusion: Thyrotoxicosis is uncommon in pediatric patients but the incidence seems to be increasing. The outcome of the initial treatment with ATD is poor with high relapse rates. Boys seems to have an increased risk for relapse compared to girls. More studies are needed to identify an optimal treatment protocol for each individual.

Place, publisher, year, edition, pages
S. Karger, 2018
National Category
Pediatrics Endocrinology and Diabetes
Identifiers
urn:nbn:se:oru:diva-69441 (URN)000445204100176 ()
Conference
57th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE 2018), Athens, Greece, September 27-29, 2018
Available from: 2018-10-09 Created: 2018-10-09 Last updated: 2018-10-16Bibliographically approved
Rodanaki, M., Rask, E. & Lodefalk, M. (2018). Incidence of Delayed Puberty in Adolescents: A Population-Based Study in a County in Central Sweden. Paper presented at 57th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE 2018), Athens, Greece, September 27-29, 2018. Hormone Research in Paediatrics, 90(Suppl.1), 510-510, Article ID P2-P311.
Open this publication in new window or tab >>Incidence of Delayed Puberty in Adolescents: A Population-Based Study in a County in Central Sweden
2018 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 90, no Suppl.1, p. 510-510, article id P2-P311Article in journal, Meeting abstract (Refereed) Published
Abstract [en]

Introduction: Delayed puberty is defined as the absence of physical signs of puberty by the age of 14 years in boys and 13 years in girls. According to this definition, the prevalence of delayed puberty would be 2%, if the ages of pubertal onset were normally distributed in the population. However, the prevalence or incidence of delayed puberty has not been described before, as far as we know. Our aim was to study the incidence of delayed puberty in central Sweden.

Methods: In this population-based retrospective study all adolescents given the ICD-10 diagnosis “delayed puberty” in Örebro county during the period 2013-2015 were identified. Adolescents with other diagnoses potentially related to delayed puberty (e.g. short stature) were also identified to ensure that there were no additional cases. The medical records of these patients, except those not willing to participate, were systematically reviewed to ensure that the diagnosis was correct. The cases were then categorized into four groups depending on how accurate we found the diagnosis (certain, possible, wrong diagnosis, or unclear cases). Data on the total numbers of adolescents in Örebro county were obtained from the authority of statistics in Sweden.

Results: One hundred and twenty-eight of 180 eligible medical records were reviewed (response rate: 71 %). Nine boys and one girl were diagnosed with delayed puberty during the study time period and fulfilled our strict criteria for a certain diagnosis and 4 boys were classified as possible new cases. The total population in Örebro county for boys aged 14-18 years was on average 6,546 each year during the time period. The minimal annual incidence for boys was 46 per 100,000 (95% confidence interval (CI) 15-142 per 100,000). When possible cases were included, the annual incidence for boys increased to 66 (CI 26-170) per 100,000. Due to the low number of girls with delayed puberty no incidence for girls was calculated.

Discussion: This is, to our knowledge, the first study describing the incidence of delayed puberty in boys. We evaluated the accuracy of the diagnosis using strict criteria. The presented incidence should be regarded as the minimum incidence since some adolescents with delayed puberty may not seek medical advice or may be unrecognized by the health services in schools. Because of our small study population, larger studies are needed to confirm our findings and for calculation of the incidence in girls, where our data implies a much lower incidence.

Place, publisher, year, edition, pages
S. Karger, 2018
National Category
Pediatrics Endocrinology and Diabetes
Identifiers
urn:nbn:se:oru:diva-69442 (URN)000445204103277 ()
Conference
57th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE 2018), Athens, Greece, September 27-29, 2018
Available from: 2018-10-09 Created: 2018-10-09 Last updated: 2018-10-17Bibliographically approved
Östling, H., Kruse, R., Helenius, G. & Lodefalk, M. (2017). Infants born small-for-gestational age have different placental expression of microRNAs. Paper presented at 10th International Meeting of Pediatric Endocrinology, Washington D.C., USA, September 14-17, 2017. Hormone Research in Paediatrics, 88(Suppl. 1), 100-101, Article ID P1-508.
Open this publication in new window or tab >>Infants born small-for-gestational age have different placental expression of microRNAs
2017 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 88, no Suppl. 1, p. 100-101, article id P1-508Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
S. Karger, 2017
National Category
Endocrinology and Diabetes Pediatrics
Identifiers
urn:nbn:se:oru:diva-62072 (URN)10.1159/000481424 (DOI)000412595401195 ()
Conference
10th International Meeting of Pediatric Endocrinology, Washington D.C., USA, September 14-17, 2017
Available from: 2017-10-30 Created: 2017-10-30 Last updated: 2017-12-14Bibliographically approved
Allbrand, M., Åman, J. & Lodefalk, M. (2017). Placental ghrelin and leptin expression and cord blood ghrelin, adiponectin, leptin, and C-peptide levels in severe maternal obesity. The Journal of Maternal-Fetal & Neonatal Medicine, 31(21), 2839-2846
Open this publication in new window or tab >>Placental ghrelin and leptin expression and cord blood ghrelin, adiponectin, leptin, and C-peptide levels in severe maternal obesity
2017 (English)In: The Journal of Maternal-Fetal & Neonatal Medicine, ISSN 1476-7058, E-ISSN 1476-4954, Vol. 31, no 21, p. 2839-2846Article in journal (Refereed) Published
Abstract [en]

PURPOSE: The purpose of this study is to investigate placental ghrelin and leptin expression as well as cord blood ghrelin and adiponectin levels in maternal obesity and associations between placental ghrelin expression, cord blood ghrelin levels and maternal and infant variables.

MATERIALS AND METHODS: Placental ghrelin and leptin expression were analyzed by RT-PCR in 32 severely obese and 32 matched normal-weight women. Cord blood ghrelin, adiponectin, leptin, and C-peptide concentrations were analyzed by ELISA.

RESULTS: Neither ghrelin nor leptin expression and neither cord blood ghrelin nor adiponectin levels differed between the groups. Placental ghrelin expression was associated with BMI at delivery in the obese women (r = 0.424, p = .016) and in the infants born to normal-weight women with their weight z-scores at six (r = -0.642, p = .010), nine (r = -0.441, p = .015), and 12 months of age (r = -0.402, p = .028).

CONCLUSIONS: Placental ghrelin and leptin expression as well as cord blood ghrelin and adiponectin levels do not seem to be altered in severe maternal obesity. Placenta-derived ghrelin may influence the infants' postnatal weight gain, but possibly only when the mother has normal weight.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2017
Keywords
Adiponectin, birth weight, ghrelin, leptin, obesity, placenta
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-61734 (URN)10.1080/14767058.2017.1358262 (DOI)000440610300007 ()28783996 (PubMedID)2-s2.0-85027047254 (Scopus ID)
Note

Funding agencies:

Research Committee of Region Örebro County

Nyckelfonden, Örebro University Hospital

Available from: 2017-11-06 Created: 2017-11-06 Last updated: 2018-09-12Bibliographically approved
Lodefalk, M. & Nilsson, O. (2017). To Prime or Not to Prime - Is That Still a Question?: A Comment on the US Guidelines on Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents [Letter to the editor]. Hormone Research in Paediatrics, 88(2), 179-180
Open this publication in new window or tab >>To Prime or Not to Prime - Is That Still a Question?: A Comment on the US Guidelines on Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents
2017 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 88, no 2, p. 179-180Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
S. Karger, 2017
National Category
Pediatrics Endocrinology and Diabetes
Identifiers
urn:nbn:se:oru:diva-60875 (URN)10.1159/000475712 (DOI)000411496600009 ()28505613 (PubMedID)2-s2.0-85019911459 (Scopus ID)
Note

Funding Agencies:

Pfizer  

Merck Serono  

Novo Nordisk 

Available from: 2017-09-26 Created: 2017-09-26 Last updated: 2018-08-06Bibliographically approved
Lodefalk, M., Frykholm, C., Esbjörner, E. & Ljunggren, Ö. (2016). Hypercalcaemia in a Patient with 2p13.2-p16.1 Duplication. Hormone Research in Paediatrics, 85(3), 213-218
Open this publication in new window or tab >>Hypercalcaemia in a Patient with 2p13.2-p16.1 Duplication
2016 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 85, no 3, p. 213-218Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Partial duplication of 2p is a rare condition that causes facial anomalies, psychomotor delay, and growth failure. Hypercalcaemia is rare in children. So far, duplication of 2p has never been associated with hypercalcaemia.

METHODS: Here, we report a girl with a partial duplication of 2p presenting with moderate to severe hypercalcaemia at the age of 2 years. She also had hypercalciuria, nephrocalcinosis, decreased renal function, and secondary hyperparathyroidism at presentation. She was thoroughly investigated, including genetic testing of the CYP24A1, CASR, ALPL, and NOD2 genes, to determine the cause of hypercalcaemia.

RESULTS: 1,25-dihydroxyvitamin D levels were increased. Hypercalcaemia and hypercalciuria responded well to glucocorticoids but not to cinacalcet. Hyperparathyroidism resolved with improving renal function. Apart from the known duplication of 2p, no pathogenic variants were detected in the studied genes. The duplication of 2p contains the PPP3R1 gene, which encodes for the calcineurin B subunit.

CONCLUSION: We conclude that partial duplication of 2p can be associated with hypercalcaemia and hypercalciuria and hypothesise that the underlying mechanism is an increased extra-renal, parathyroid hormone-independent 25-hydroxyvitamin D 1α-hydroxylase activity, leading to raised amounts of 1,25-dihydroxyvitamin D. The increased enzymatic activity could possibly be caused by calcineurin B subunit-related macrophage stimulation.

Place, publisher, year, edition, pages
Basel: S. Karger, 2016
Keywords
1, 25-dihydroxyvitamin D; 2p duplication; 25-hydroxyvitamin D 1 alpha-hydroxylase; Hypercalcaemia; Nephrocalcinosis
National Category
Pediatrics Endocrinology and Diabetes
Research subject
Pediatrics
Identifiers
urn:nbn:se:oru:diva-49857 (URN)10.1159/000442747 (DOI)000373926500007 ()26675490 (PubMedID)
Available from: 2016-04-18 Created: 2016-04-18 Last updated: 2018-07-10Bibliographically approved
Allbrand, M., Åman, J. & Lodefalk, M. (2015). Adipocytokines in placenta and cord blood in relation to maternal obesity, and foetal and postnatal growth of the child. Paper presented at 54th Annual ESPE (European Society for Paediatric Endocrinology) Meeting in Barcelona, Spain, 1-3 October 2015.. Hormone Research in Paediatrics, 82(Suppl. 1), 47-48
Open this publication in new window or tab >>Adipocytokines in placenta and cord blood in relation to maternal obesity, and foetal and postnatal growth of the child
2015 (English)In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 82, no Suppl. 1, p. 47-48Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background: The nutritional and hormonal state in utero may be a link between maternal obesity and obesity in the offspring. The gene expression in placentae in pregnancies complicated by diabetes is reduced for leptin, but increased for ghrelin. It is not known whether these genes’ expressions in placentae are altered in maternal obesity.

Objectives and hypotheses: To compare obese and normal-weight women and their children concerning gene expressions of leptin and ghrelin in placentae; leptin, ghrelin, adiponectin, and C-peptide levels in cord blood, birth size and postnatal growth. Changes in the expression of these adipocytokines may lead to an altered hypothalamic sensitivity to leptin and ghrelin resulting in an increased risk of obesity in the offspring.

Method: 32 women with pre-pregnancy obesity, but otherwise healthy, were compared to 32 matched, normal-weight controls. Full-term placenta biopsies were analysed with qPCR for leptin mRNA and ghrelin mRNA. Cord blood samples were examined with ELISA for leptin, ghrelin, adiponectin, and C-peptide concentrations. Birth size and postnatal growth of the children were collected from clinical registers at the Child Health Care Units.

Results: The leptin and ghrelin gene expressions in placentae did not differ between obese and normal-weight women. The leptin concentration in cord blood was higher in children of obese mothers (P=0.021). It correlated with birth weight Z-score (r=0.467, P<0.001) and C-peptide level in cord blood (r=0.446, P<0.001). Children of obese women were slightly heavier at birth, but postnatal growth did not differ between groups. Children with birth weight  ≤−0.67 Z-score had higher ghrelin levels in cord blood than heavier children (P=0.042). The leptin level in cord blood correlated negatively with weight gain at 6 months (r=−0.332, P=0.009). The ghrelin level in cord blood correlated with weight gain at 3 months in girls (r=0.611, P=0.001), but not in boys. The adiponectin level in cord blood correlated negatively with length gain at 3 years in the obese group (r=−0.571, P=0.033), but not in the normal-weight group.

Conclusion: Leptin and ghrelin placental gene expressions are not altered in obese women, but foetal adipocytokine production may influence early postnatal growth, possibly by influencing hunger signalling or insulin levels

Place, publisher, year, edition, pages
Basel, Switzerland: S. Karger, 2015
Keywords
Obesity, ghrelin, leptin, adipocytokines, growth
National Category
Medical and Health Sciences Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:oru:diva-49275 (URN)
Conference
54th Annual ESPE (European Society for Paediatric Endocrinology) Meeting in Barcelona, Spain, 1-3 October 2015.
Available from: 2016-03-11 Created: 2016-03-11 Last updated: 2017-11-30Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-5292-4913

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