Elín Bjarnadóttir - Academia.edu (original) (raw)
Papers by Elín Bjarnadóttir
JAMA, Jan 26, 2016
IMPORTANCE Observational studies have suggested that increased dietary vitamin D intake during pr... more IMPORTANCE Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to pregnant women is unknown. OBJECTIVE To determine whether supplementation of vitamin D 3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring. DESIGN, SETTING, AND PARTICIPANTS A double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. Enrollment began March 2009 with a goal of 708 participants, but due to delayed ethical approval, only 623 women were recruited at 24 weeks of pregnancy. Follow-up of the children (N = 581) was completed when the youngest child reached age 3 years in March 2014. INTERVENTIONS Vitamin D 3 (2400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D 3 as part of usual pregnancy care. MAIN OUTCOMES AND MEASURES Age at onset of persistent wheeze in the first 3 years of life. Secondary outcomes included number of episodes of troublesome lung symptoms, asthma, respiratory tract infections, and neonatal airway immunology. Adverse events were assessed. RESULTS Of the 581 children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D 3 group and 57 children (20%) in the control group. Vitamin D 3 supplementation was not associated with the risk of persistent wheeze, but the number of episodes of troublesome lung symptoms was reduced, and the airway immune profile was up-regulated (principal component analysis, P = .04). There was no effect on additional end points. Intrauterine death was observed in 1 fetus (<1%) in the vitamin D 3 group vs 3 fetuses (1%) in the control group and congenital malformations in 17 neonates (5%) in the vitamin D 3 group vs 23 neonates (8%) in the control group. End Point Vitamin D 3 Control Estimate (95% CI) P Value Persistent wheeze, No. (%) 47 (16) 57 (20) Hazard ratio (HR), 0.76 (0.52-1.12) .16 Episodes of troublesome lung symptoms, mean (95% CI) 5.9 (5.2-6.6) 7.2 (6.4-8.1) Incidence risk ratio (IRR), 0.83 (0.71-0.97) .02 Asthma at 3 y, No. (%) 32 (12) 47 (14) Odds ratio, 0.82 (0.50-1.36) .45 Respiratory tract infections Upper, annual mean (95% CI) 5.2 (4.8-5.5) 5.3 (4.9-5.6) IRR, 0.99 (0.90-1.09) .84 Lower, No. (%) 94 (32) 95 (33) HR, 0.96 (0.72-1.27) .76 CONCLUSIONS AND RELEVANCE The use of 2800 IU/d of vitamin D 3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years. However, interpretation of the study is limited by a wide CI that includes a clinically important protective effect.
Child Development, Jan 28, 2021
A double‐blind randomized controlled trial of n‐3 long‐chain polyunsaturated fatty acid (n‐3 LCPU... more A double‐blind randomized controlled trial of n‐3 long‐chain polyunsaturated fatty acid (n‐3 LCPUFA) supplementation or matching placebo during third trimester of pregnancy was conducted within the COPSAC2010 mother‐child cohort consisting of 736 women and their children. The objective was to determine if maternal n‐3 LCPUFA pregnancy supplementation affects offspring neurodevelopment until 6 years. Neurodevelopment was evaluated in 654 children assessing age of motor milestone achievement, language development, cognitive development, general neurodevelopment, and emotional and behavioral problems. Maternal n‐3 LCPUFA supplementation during pregnancy improved early language development and reduced the impact of emotional and behavioral problems. The n‐3 LCPUFA supplementation was in boys associated with the earlier achievement of gross motor milestones, improved cognitive development, and a reduced impact of emotional and behavioral problems.
JAMA network open, Dec 8, 2020
IMPORTANCE Observational studies have reported an association between high maternal vitamin D lev... more IMPORTANCE Observational studies have reported an association between high maternal vitamin D levels and improved neurodevelopment in offspring, but no randomized clinical trial (RCT) has investigated these observations. OBJECTIVE To determine whether high-dose vitamin D supplementation during pregnancy improves offspring neurodevelopment from birth to age 6 years. DESIGN, SETTING, AND PARTICIPANTS This prespecified secondary analysis of a double-blinded, placebo-controlled RCT of high-dose vitamin D 3 supplementation vs standard dose during the third trimester of pregnancy was conducted in the unselected prospective mother-child birth cohort at a single-center research unit in Denmark as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC-2010). Participants included pregnant women; women with vitamin D intake greater than 600 IU/d or an endocrine, heart, or kidney disorder, and those who did not speak Danish fluently were excluded. Neurodevelopmental assessments for offspring of these women were performed at ages 0 to 6 years. Children born prematurely (gestational week <37), with low birth weight (<2500 g), or with a neurological disease affecting neurodevelopment were excluded. Data were analyzed from August 2019 to February 2020. INTERVENTIONS High-dose (ie, 2800 IU/d) vs standard dose (ie, 400 IU/d) vitamin D 3 supplementation from pregnancy week 24 until 1 week after birth. MAIN OUTCOMES AND MEASURES The primary outcome of interest was cognitive development assessed at 2.5 years using the Bayley Scales of Infant and Toddler Development. Other neurodevelopmental outcomes included age of motor milestone achievement (Denver Developmental Index and World Health Organization milestone registration), language development (MacArthur-Bates Communicative Development Inventories), general neurodevelopment at age 3 years (Ages and Stages Questionnaire), and emotional and behavioral problems at age 6 years (Strengths and Difficulties Questionnaire). RESULTS Among 623 women randomized, 315 were randomized to high-dose vitamin D 3 and 308 were randomized to standard dose placebo. A total of 551 children were evaluated from birth to age 6 years, (282 [51.2%] boys; 528 [95.8%] White), with 277 children in the high-dose vitamin D 3 group and 274 children in the standard dose group. There was no effect of the high-dose compared with standard dose of vitamin D 3 supplementation during pregnancy on offspring achievement of motor milestones (β = 0.08 [95% CI, −0.26 to 0.43]; P = .64), cognitive development (score difference: 0.34 [95% CI, −1.32 to 1.99]; P = .70), general neurodevelopment (median [IQR] communication (continued) Key Points Question Does maternal high-dose vitamin D supplementation in the third trimester of pregnancy improve offspring neurodevelopment in the first 6 years of life? Findings This prespecified secondary analysis of a randomized clinical trial of vitamin D 3 supplementation during pregnancy and offspring neurodevelopment among 551 children showed no effect on neurodevelopment in the first 6 years of life, except for an isolated negative effect on language development at age 2 years in the highdose compared with standard dose group. Meaning This secondary analysis of a randomized clinical trial found that maternal high-dose vitamin D 3 supplementation during pregnancy did not improve neurodevelopmental outcomes in the offspring during the first 6 years of life compared with the standard recommended dose of vitamin D.
Acta Paediatrica, Mar 21, 2019
The objective of this study was to identify possible pre-and postnatal factors influencing neurod... more The objective of this study was to identify possible pre-and postnatal factors influencing neurodevelopment of the young child. Methods: We used data from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC 2010) mother-child cohort, but excluded those with a neurological diagnosis, born <37 weeks of gestation and birthweights <2500 g, resulting in 650 children analysed. Neurodevelopment was assessed as age of achievement of early milestones, language scores at 1 and 2 years and cognitive score at 2 ½ years of age. Results: Neurodevelopmental scores were not associated with breastfeeding, persistent wheeze, eczema and number of sick days (p > 0.05 in all tests). Early age at milestone achievement was associated with male sex (p = 0.05), lower maternal age (p = 0.02), higher gestational age (p < 0.001) and paternity leave (p = 0.01). A higher 1-year language score was associated with female sex (p = 0.02) and maternal smoking during pregnancy (p = 0.01) and a higher 2-year language score with female sex (p < 0.001) and being first born (p = 0.01). A higher cognitive score was associated with female sex (p = 0.02). Conclusion: Neurodevelopmental scores were unrelated to breastfeeding, persistent wheeze, eczema and number of sick days. Neurodevelopment in early childhood was mostly associated with gender.
sveit fái síður ofnaemi en börn alin upp í þéttbýli (11-13). Flest bendir til þess að breyting á ... more sveit fái síður ofnaemi en börn alin upp í þéttbýli (11-13). Flest bendir til þess að breyting á lífsháttum með aukinni velferð og baettum efnahag eigi með einhverjum haetti sök á þessari óheillaþróun. Fáar rannsóknir hafa verið gerðar til að varpa ljósi á tengsl efnahags við hana. Í tveimur nýlegum rannsóknum frá Ítalíu og Þýskalandi hefur þó verið sýnt fram á meira ofnaemi meðal barna þeirra sem betur voru staeðir (14,15). Almennt er talið að fólki með langskólanám að Ágrip
PLOS ONE
Background Otitis media with middle ear effusion (MEE) can be treated with ventilation tubes (VT)... more Background Otitis media with middle ear effusion (MEE) can be treated with ventilation tubes (VT) insertion, and it has been speculated that prolonged MEE in childhood can affect neurological development, which in turn may be important for later academic achievements. Objective To investigate the association between middle ear effusion (MEE), treatment with ventilation tubes (VT) and childhood neurological development. Study design We examined 663 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) unselected mother-child cohort study. Children were followed by study pediatricians with regular visits from pregnancy until 3 years of age. MEE was diagnosed using tympanometry at age 1, 2 and 3 years. Information regarding VT from age 0–3 years was obtained from national registries. We assessed age at achievement of gross motor milestones from birth, language scores at 1 and 2 years, cognitive score at 2.5 years and general development score at age ...
The Lancet Respiratory Medicine, 2016
Background Bacteria and viruses are equally associated with the risk of acute episodes of asthma-... more Background Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like symptoms in young children, suggesting antibiotics as a potential treatment for such episodes. We aimed to assess the eff ect of azithromycin on the duration of respiratory episodes in young children with recurrent asthma-like symptoms, hypothesising that it reduces the duration of the symptomatic period. Methods In this randomised, double-blind, placebo-controlled trial, we recruited children aged 1-3 years, who were diagnosed with recurrent asthma-like symptoms from the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort; a birth cohort consisting of the general Danish population of Zealand, including Copenhagen. Exclusion criteria were macrolide allergy, heart, liver, neurological, and kidney disease, and, before each treatment, one or more clinical signs of pneumonia (respiratory frequency of ≥50 breaths per min; fever of ≥39°C; C-reactive protein concentration of ≥476•20 nmol/L [≥50 mg/L]). Each episode of asthma-like symptoms lasting at least 3 days was randomly allocated to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo after thorough examination by a study physician at the Copenhagen Prospective Studies on Asthma research unit. Each episode was randomly allocated independently of previous treatment from a computer-generated list of random numbers in blocks of ten (generated at the Pharmacy of Glostrup). Investigators and children were masked until the youngest child turned 3 years of age and throughout the data validation and analysis phases. The primary outcome was duration of the respiratory episode after treatment, verifi ed by prospective daily diaries and analysed with Poisson regression. Analyses were per protocol (excluding those without a primary outcome measure or who did not receive treatment). This trial is registered with ClinicalTrials.gov, number NCT01233297.
sveit fái síður ofnaemi en börn alin upp í þéttbýli (11-13). Flest bendir til þess að breyting á ... more sveit fái síður ofnaemi en börn alin upp í þéttbýli (11-13). Flest bendir til þess að breyting á lífsháttum með aukinni velferð og baettum efnahag eigi með einhverjum haetti sök á þessari óheillaþróun. Fáar rannsóknir hafa verið gerðar til að varpa ljósi á tengsl efnahags við hana. Í tveimur nýlegum rannsóknum frá Ítalíu og Þýskalandi hefur þó verið sýnt fram á meira ofnaemi meðal barna þeirra sem betur voru staeðir (14,15). Almennt er talið að fólki með langskólanám að Ágrip
The New England journal of medicine, Dec 29, 2016
Background Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contri... more Background Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring. Methods We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respirat...
Acta Paediatrica, 2019
The objective of this study was to identify possible pre-and postnatal factors influencing neurod... more The objective of this study was to identify possible pre-and postnatal factors influencing neurodevelopment of the young child. Methods: We used data from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC 2010) mother-child cohort, but excluded those with a neurological diagnosis, born <37 weeks of gestation and birthweights <2500 g, resulting in 650 children analysed. Neurodevelopment was assessed as age of achievement of early milestones, language scores at 1 and 2 years and cognitive score at 2 ½ years of age. Results: Neurodevelopmental scores were not associated with breastfeeding, persistent wheeze, eczema and number of sick days (p > 0.05 in all tests). Early age at milestone achievement was associated with male sex (p = 0.05), lower maternal age (p = 0.02), higher gestational age (p < 0.001) and paternity leave (p = 0.01). A higher 1-year language score was associated with female sex (p = 0.02) and maternal smoking during pregnancy (p = 0.01) and a higher 2-year language score with female sex (p < 0.001) and being first born (p = 0.01). A higher cognitive score was associated with female sex (p = 0.02). Conclusion: Neurodevelopmental scores were unrelated to breastfeeding, persistent wheeze, eczema and number of sick days. Neurodevelopment in early childhood was mostly associated with gender.
JAMA, 2016
IMPORTANCE Observational studies have suggested that increased dietary vitamin D intake during pr... more IMPORTANCE Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to pregnant women is unknown. OBJECTIVE To determine whether supplementation of vitamin D 3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring. DESIGN, SETTING, AND PARTICIPANTS A double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. Enrollment began March 2009 with a goal of 708 participants, but due to delayed ethical approval, only 623 women were recruited at 24 weeks of pregnancy. Follow-up of the children (N = 581) was completed when the youngest child reached age 3 years in March 2014. INTERVENTIONS Vitamin D 3 (2400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D 3 as part of usual pregnancy care. MAIN OUTCOMES AND MEASURES Age at onset of persistent wheeze in the first 3 years of life. Secondary outcomes included number of episodes of troublesome lung symptoms, asthma, respiratory tract infections, and neonatal airway immunology. Adverse events were assessed. RESULTS Of the 581 children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D 3 group and 57 children (20%) in the control group. Vitamin D 3 supplementation was not associated with the risk of persistent wheeze, but the number of episodes of troublesome lung symptoms was reduced, and the airway immune profile was up-regulated (principal component analysis, P = .04). There was no effect on additional end points. Intrauterine death was observed in 1 fetus (<1%) in the vitamin D 3 group vs 3 fetuses (1%) in the control group and congenital malformations in 17 neonates (5%) in the vitamin D 3 group vs 23 neonates (8%) in the control group. End Point Vitamin D 3 Control Estimate (95% CI) P Value Persistent wheeze, No. (%) 47 (16) 57 (20) Hazard ratio (HR), 0.76 (0.52-1.12) .16 Episodes of troublesome lung symptoms, mean (95% CI) 5.9 (5.2-6.6) 7.2 (6.4-8.1) Incidence risk ratio (IRR), 0.83 (0.71-0.97) .02 Asthma at 3 y, No. (%) 32 (12) 47 (14) Odds ratio, 0.82 (0.50-1.36) .45 Respiratory tract infections Upper, annual mean (95% CI) 5.2 (4.8-5.5) 5.3 (4.9-5.6) IRR, 0.99 (0.90-1.09) .84 Lower, No. (%) 94 (32) 95 (33) HR, 0.96 (0.72-1.27) .76 CONCLUSIONS AND RELEVANCE The use of 2800 IU/d of vitamin D 3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years. However, interpretation of the study is limited by a wide CI that includes a clinically important protective effect.
Icelandic Medical Journal
To compare the prevalence of IgE-mediated sensitization, allergic disorders and possible risk fac... more To compare the prevalence of IgE-mediated sensitization, allergic disorders and possible risk factors for atopic sensitization among Icelandic medical students (n=113) to a randomly chosen age matched group previously investigated in the Icelandic part of the European Community Respiratory Health Survey. Altogether 100 medical students participated and 102 in the control group. They were skin prick tested and they answered questions about respiratory symptoms, smoking habits, family history and home environment in childhood. Only 4% of medical students reported daily smoking compared to 27% of the controls. The medical students also had a significantly lower number (mean +/- SD) of siblings (2.2+/-1.3) compared to the controls (3.9+/-1.7). The controls also shared bedrooms with older siblings in childhood three times as often. Atopic sensitization, defined as a positive (3 mm or more) reaction to at least one of nine common airborne allergens used in testing, was found in 41% of the...
13). Flest bendir til þess að breyting a lifshattum með aukinni velferð og baettum efnahag eigi m... more 13). Flest bendir til þess að breyting a lifshattum með aukinni velferð og baettum efnahag eigi með einhverjum haetti sok a þessari oheillaþroun. Faar rannsoknir hafa verið gerðar til að varpa ljosi a tengsl efnahags við hana. I tveimur nýlegum rannsoknum fra Italiu og Þýskalandi hefur þo verið sýnt fram a meira ofnaemi meðal barna þeirra sem betur voru staeðir (14,15). Almennt er talið að folki með langskolanam að Agrip
Child development, 2021
A double-blind randomized controlled trial of n-3 long-chain polyunsaturated fatty acid (n-3 LCPU... more A double-blind randomized controlled trial of n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation or matching placebo during third trimester of pregnancy was conducted within the COPSAC2010 mother-child cohort consisting of 736 women and their children. The objective was to determine if maternal n-3 LCPUFA pregnancy supplementation affects offspring neurodevelopment until 6 years. Neurodevelopment was evaluated in 654 children assessing age of motor milestone achievement, language development, cognitive development, general neurodevelopment, and emotional and behavioral problems. Maternal n-3 LCPUFA supplementation during pregnancy improved early language development and reduced the impact of emotional and behavioral problems. The n-3 LCPUFA supplementation was in boys associated with the earlier achievement of gross motor milestones, improved cognitive development, and a reduced impact of emotional and behavioral problems.
IMPORTANCE Observational studies have reported an association between high maternal vitamin D lev... more IMPORTANCE Observational studies have reported an association between high maternal vitamin D levels and improved neurodevelopment in offspring, but no randomized clinical trial (RCT) has investigated these observations. OBJECTIVE To determine whether high-dose vitamin D supplementation during pregnancy improves offspring neurodevelopment from birth to age 6 years. DESIGN, SETTING, AND PARTICIPANTS This prespecified secondary analysis of a double-blinded, placebo-controlled RCT of high-dose vitamin D3 supplementation vs standard dose during the third trimester of pregnancy was conducted in the unselected prospective mother-child birth cohort at a single-center research unit in Denmark as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC-2010). Participants included pregnant women; women with vitamin D intake greater than 600 IU/d or an endocrine, heart, or kidney disorder, and those who did not speak Danish fluently were excluded. Neurodevelopmental asse...
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 2013
We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutritio... more We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. Pregnant women from eastern Denmark were invited during 2008-2010 to a novel unselected 'COPSAC2010 ' cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and c...
Objective: To compare the prevalence of IgE-mediated sensitization, allergic disorders and possib... more Objective: To compare the prevalence of IgE-mediated sensitization, allergic disorders and possible risk factors for atopic sensitization among Icelandic medical students (n=113) to a randomly chosen age matched group previously investigated in the Icelandic part of the European Community Respiratory Health Survey. Material and methods: Altogether 100 medical students participated and 102 in the control group. They were skin prick tested and they answered questions about respiratory symptoms, smoking habits, family history and home environment in childhood. Results: Only 4% of medical students reported daily smoking compared to 27% of the controls. The medical students also had a significantly lower number (mean +/- SD) of siblings (2.2+/-1.3) compared to the controls (3.9+/-1.7). The controls also shared bedrooms with older siblings in childhood three times as often. Atopic sensitization, defined as a positive (3 mm or more) reaction to at least one of nine common airborne allergens used in testing, was found in 41% of the medical students compared to 26.5% of the controls. The prevalence of asthma and urticaria was also significantly higher among the medical students. Conclusions: Medical students have more often IgE-mediated sensitization and allergy related diseases than a controlgroup of the same age. A possible explanation to this is a lower number of siblings among medical students and a different household situation in childhood.
JAMA Network Open
IMPORTANCE Observational studies have reported an association between high maternal vitamin D lev... more IMPORTANCE Observational studies have reported an association between high maternal vitamin D levels and improved neurodevelopment in offspring, but no randomized clinical trial (RCT) has investigated these observations. OBJECTIVE To determine whether high-dose vitamin D supplementation during pregnancy improves offspring neurodevelopment from birth to age 6 years. DESIGN, SETTING, AND PARTICIPANTS This prespecified secondary analysis of a double-blinded, placebo-controlled RCT of high-dose vitamin D 3 supplementation vs standard dose during the third trimester of pregnancy was conducted in the unselected prospective mother-child birth cohort at a single-center research unit in Denmark as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC-2010). Participants included pregnant women; women with vitamin D intake greater than 600 IU/d or an endocrine, heart, or kidney disorder, and those who did not speak Danish fluently were excluded. Neurodevelopmental assessments for offspring of these women were performed at ages 0 to 6 years. Children born prematurely (gestational week <37), with low birth weight (<2500 g), or with a neurological disease affecting neurodevelopment were excluded. Data were analyzed from August 2019 to February 2020. INTERVENTIONS High-dose (ie, 2800 IU/d) vs standard dose (ie, 400 IU/d) vitamin D 3 supplementation from pregnancy week 24 until 1 week after birth. MAIN OUTCOMES AND MEASURES The primary outcome of interest was cognitive development assessed at 2.5 years using the Bayley Scales of Infant and Toddler Development. Other neurodevelopmental outcomes included age of motor milestone achievement (Denver Developmental Index and World Health Organization milestone registration), language development (MacArthur-Bates Communicative Development Inventories), general neurodevelopment at age 3 years (Ages and Stages Questionnaire), and emotional and behavioral problems at age 6 years (Strengths and Difficulties Questionnaire). RESULTS Among 623 women randomized, 315 were randomized to high-dose vitamin D 3 and 308 were randomized to standard dose placebo. A total of 551 children were evaluated from birth to age 6 years, (282 [51.2%] boys; 528 [95.8%] White), with 277 children in the high-dose vitamin D 3 group and 274 children in the standard dose group. There was no effect of the high-dose compared with standard dose of vitamin D 3 supplementation during pregnancy on offspring achievement of motor milestones (β = 0.08 [95% CI, −0.26 to 0.43]; P = .64), cognitive development (score difference: 0.34 [95% CI, −1.32 to 1.99]; P = .70), general neurodevelopment (median [IQR] communication (continued) Key Points Question Does maternal high-dose vitamin D supplementation in the third trimester of pregnancy improve offspring neurodevelopment in the first 6 years of life? Findings This prespecified secondary analysis of a randomized clinical trial of vitamin D 3 supplementation during pregnancy and offspring neurodevelopment among 551 children showed no effect on neurodevelopment in the first 6 years of life, except for an isolated negative effect on language development at age 2 years in the highdose compared with standard dose group. Meaning This secondary analysis of a randomized clinical trial found that maternal high-dose vitamin D 3 supplementation during pregnancy did not improve neurodevelopmental outcomes in the offspring during the first 6 years of life compared with the standard recommended dose of vitamin D.
The Lancet Respiratory Medicine, 2016
Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like sympto... more Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like symptoms in young children, suggesting antibiotics as a potential treatment for such episodes. We aimed to assess the effect of azithromycin on the duration of respiratory episodes in young children with recurrent asthma-like symptoms, hypothesising that it reduces the duration of the symptomatic period. In this randomised, double-blind, placebo-controlled trial, we recruited children aged 1-3 years, who were diagnosed with recurrent asthma-like symptoms from the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort; a birth cohort consisting of the general Danish population of Zealand, including Copenhagen. Exclusion criteria were macrolide allergy, heart, liver, neurological, and kidney disease, and, before each treatment, one or more clinical signs of pneumonia (respiratory frequency of ≥50 breaths per min; fever of ≥39°C; C-reactive protein concentration of ≥476·20 nmol/L [≥50 mg/L]). Each episode of asthma-like symptoms lasting at least 3 days was randomly allocated to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo after thorough examination by a study physician at the Copenhagen Prospective Studies on Asthma research unit. Each episode was randomly allocated independently of previous treatment from a computer-generated list of random numbers in blocks of ten (generated at the Pharmacy of Glostrup). Investigators and children were masked until the youngest child turned 3 years of age and throughout the data validation and analysis phases. The primary outcome was duration of the respiratory episode after treatment, verified by prospective daily diaries and analysed with Poisson regression. Analyses were per protocol (excluding those without a primary outcome measure or who did not receive treatment). This trial is registered with ClinicalTrials.gov, number NCT01233297. Between Nov 17, 2010, and Jan 28, 2014, we randomly allocated 158 asthma-like episodes in 72 children (79 [50%] to azithromycin and 79 [50%] to placebo). The mean duration of the episode after treatment was 3·4 days for children receiving azithromycin compared with 7·7 days for children receiving placebo. Azithromycin caused a significant shortening of the episode of 63·3% (95% CI 56·0-69·3; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0·0001). The effect size increased with early initiation of treatment, showing a reduction in episode duration of 83% if treatment was initiated before day 6 of the episode compared with 36% if initiated on or after day 6 (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0·0001). We noted no differences in clinical adverse events between the azithromycin (18 [23%] of 78 episodes included in final analysis) and placebo (24 [30%] of 79) groups (p=0·30), but we did not investigate bacterial resistance patterns after treatment. Azithromycin reduced the duration of episodes of asthma-like symptoms in young children, suggesting that this drug could have a role in acute management of exacerbations. Further research is needed to disentangle the inflammatory versus antimicrobial aspects of this relation. Lundbeck Foundation, Danish Ministry of Health, Danish Council for Strategic Research, Capital Region Research Foundation.
JAMA, Jan 26, 2016
IMPORTANCE Observational studies have suggested that increased dietary vitamin D intake during pr... more IMPORTANCE Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to pregnant women is unknown. OBJECTIVE To determine whether supplementation of vitamin D 3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring. DESIGN, SETTING, AND PARTICIPANTS A double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. Enrollment began March 2009 with a goal of 708 participants, but due to delayed ethical approval, only 623 women were recruited at 24 weeks of pregnancy. Follow-up of the children (N = 581) was completed when the youngest child reached age 3 years in March 2014. INTERVENTIONS Vitamin D 3 (2400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D 3 as part of usual pregnancy care. MAIN OUTCOMES AND MEASURES Age at onset of persistent wheeze in the first 3 years of life. Secondary outcomes included number of episodes of troublesome lung symptoms, asthma, respiratory tract infections, and neonatal airway immunology. Adverse events were assessed. RESULTS Of the 581 children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D 3 group and 57 children (20%) in the control group. Vitamin D 3 supplementation was not associated with the risk of persistent wheeze, but the number of episodes of troublesome lung symptoms was reduced, and the airway immune profile was up-regulated (principal component analysis, P = .04). There was no effect on additional end points. Intrauterine death was observed in 1 fetus (<1%) in the vitamin D 3 group vs 3 fetuses (1%) in the control group and congenital malformations in 17 neonates (5%) in the vitamin D 3 group vs 23 neonates (8%) in the control group. End Point Vitamin D 3 Control Estimate (95% CI) P Value Persistent wheeze, No. (%) 47 (16) 57 (20) Hazard ratio (HR), 0.76 (0.52-1.12) .16 Episodes of troublesome lung symptoms, mean (95% CI) 5.9 (5.2-6.6) 7.2 (6.4-8.1) Incidence risk ratio (IRR), 0.83 (0.71-0.97) .02 Asthma at 3 y, No. (%) 32 (12) 47 (14) Odds ratio, 0.82 (0.50-1.36) .45 Respiratory tract infections Upper, annual mean (95% CI) 5.2 (4.8-5.5) 5.3 (4.9-5.6) IRR, 0.99 (0.90-1.09) .84 Lower, No. (%) 94 (32) 95 (33) HR, 0.96 (0.72-1.27) .76 CONCLUSIONS AND RELEVANCE The use of 2800 IU/d of vitamin D 3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years. However, interpretation of the study is limited by a wide CI that includes a clinically important protective effect.
Child Development, Jan 28, 2021
A double‐blind randomized controlled trial of n‐3 long‐chain polyunsaturated fatty acid (n‐3 LCPU... more A double‐blind randomized controlled trial of n‐3 long‐chain polyunsaturated fatty acid (n‐3 LCPUFA) supplementation or matching placebo during third trimester of pregnancy was conducted within the COPSAC2010 mother‐child cohort consisting of 736 women and their children. The objective was to determine if maternal n‐3 LCPUFA pregnancy supplementation affects offspring neurodevelopment until 6 years. Neurodevelopment was evaluated in 654 children assessing age of motor milestone achievement, language development, cognitive development, general neurodevelopment, and emotional and behavioral problems. Maternal n‐3 LCPUFA supplementation during pregnancy improved early language development and reduced the impact of emotional and behavioral problems. The n‐3 LCPUFA supplementation was in boys associated with the earlier achievement of gross motor milestones, improved cognitive development, and a reduced impact of emotional and behavioral problems.
JAMA network open, Dec 8, 2020
IMPORTANCE Observational studies have reported an association between high maternal vitamin D lev... more IMPORTANCE Observational studies have reported an association between high maternal vitamin D levels and improved neurodevelopment in offspring, but no randomized clinical trial (RCT) has investigated these observations. OBJECTIVE To determine whether high-dose vitamin D supplementation during pregnancy improves offspring neurodevelopment from birth to age 6 years. DESIGN, SETTING, AND PARTICIPANTS This prespecified secondary analysis of a double-blinded, placebo-controlled RCT of high-dose vitamin D 3 supplementation vs standard dose during the third trimester of pregnancy was conducted in the unselected prospective mother-child birth cohort at a single-center research unit in Denmark as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC-2010). Participants included pregnant women; women with vitamin D intake greater than 600 IU/d or an endocrine, heart, or kidney disorder, and those who did not speak Danish fluently were excluded. Neurodevelopmental assessments for offspring of these women were performed at ages 0 to 6 years. Children born prematurely (gestational week <37), with low birth weight (<2500 g), or with a neurological disease affecting neurodevelopment were excluded. Data were analyzed from August 2019 to February 2020. INTERVENTIONS High-dose (ie, 2800 IU/d) vs standard dose (ie, 400 IU/d) vitamin D 3 supplementation from pregnancy week 24 until 1 week after birth. MAIN OUTCOMES AND MEASURES The primary outcome of interest was cognitive development assessed at 2.5 years using the Bayley Scales of Infant and Toddler Development. Other neurodevelopmental outcomes included age of motor milestone achievement (Denver Developmental Index and World Health Organization milestone registration), language development (MacArthur-Bates Communicative Development Inventories), general neurodevelopment at age 3 years (Ages and Stages Questionnaire), and emotional and behavioral problems at age 6 years (Strengths and Difficulties Questionnaire). RESULTS Among 623 women randomized, 315 were randomized to high-dose vitamin D 3 and 308 were randomized to standard dose placebo. A total of 551 children were evaluated from birth to age 6 years, (282 [51.2%] boys; 528 [95.8%] White), with 277 children in the high-dose vitamin D 3 group and 274 children in the standard dose group. There was no effect of the high-dose compared with standard dose of vitamin D 3 supplementation during pregnancy on offspring achievement of motor milestones (β = 0.08 [95% CI, −0.26 to 0.43]; P = .64), cognitive development (score difference: 0.34 [95% CI, −1.32 to 1.99]; P = .70), general neurodevelopment (median [IQR] communication (continued) Key Points Question Does maternal high-dose vitamin D supplementation in the third trimester of pregnancy improve offspring neurodevelopment in the first 6 years of life? Findings This prespecified secondary analysis of a randomized clinical trial of vitamin D 3 supplementation during pregnancy and offspring neurodevelopment among 551 children showed no effect on neurodevelopment in the first 6 years of life, except for an isolated negative effect on language development at age 2 years in the highdose compared with standard dose group. Meaning This secondary analysis of a randomized clinical trial found that maternal high-dose vitamin D 3 supplementation during pregnancy did not improve neurodevelopmental outcomes in the offspring during the first 6 years of life compared with the standard recommended dose of vitamin D.
Acta Paediatrica, Mar 21, 2019
The objective of this study was to identify possible pre-and postnatal factors influencing neurod... more The objective of this study was to identify possible pre-and postnatal factors influencing neurodevelopment of the young child. Methods: We used data from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC 2010) mother-child cohort, but excluded those with a neurological diagnosis, born <37 weeks of gestation and birthweights <2500 g, resulting in 650 children analysed. Neurodevelopment was assessed as age of achievement of early milestones, language scores at 1 and 2 years and cognitive score at 2 ½ years of age. Results: Neurodevelopmental scores were not associated with breastfeeding, persistent wheeze, eczema and number of sick days (p > 0.05 in all tests). Early age at milestone achievement was associated with male sex (p = 0.05), lower maternal age (p = 0.02), higher gestational age (p < 0.001) and paternity leave (p = 0.01). A higher 1-year language score was associated with female sex (p = 0.02) and maternal smoking during pregnancy (p = 0.01) and a higher 2-year language score with female sex (p < 0.001) and being first born (p = 0.01). A higher cognitive score was associated with female sex (p = 0.02). Conclusion: Neurodevelopmental scores were unrelated to breastfeeding, persistent wheeze, eczema and number of sick days. Neurodevelopment in early childhood was mostly associated with gender.
sveit fái síður ofnaemi en börn alin upp í þéttbýli (11-13). Flest bendir til þess að breyting á ... more sveit fái síður ofnaemi en börn alin upp í þéttbýli (11-13). Flest bendir til þess að breyting á lífsháttum með aukinni velferð og baettum efnahag eigi með einhverjum haetti sök á þessari óheillaþróun. Fáar rannsóknir hafa verið gerðar til að varpa ljósi á tengsl efnahags við hana. Í tveimur nýlegum rannsóknum frá Ítalíu og Þýskalandi hefur þó verið sýnt fram á meira ofnaemi meðal barna þeirra sem betur voru staeðir (14,15). Almennt er talið að fólki með langskólanám að Ágrip
PLOS ONE
Background Otitis media with middle ear effusion (MEE) can be treated with ventilation tubes (VT)... more Background Otitis media with middle ear effusion (MEE) can be treated with ventilation tubes (VT) insertion, and it has been speculated that prolonged MEE in childhood can affect neurological development, which in turn may be important for later academic achievements. Objective To investigate the association between middle ear effusion (MEE), treatment with ventilation tubes (VT) and childhood neurological development. Study design We examined 663 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) unselected mother-child cohort study. Children were followed by study pediatricians with regular visits from pregnancy until 3 years of age. MEE was diagnosed using tympanometry at age 1, 2 and 3 years. Information regarding VT from age 0–3 years was obtained from national registries. We assessed age at achievement of gross motor milestones from birth, language scores at 1 and 2 years, cognitive score at 2.5 years and general development score at age ...
The Lancet Respiratory Medicine, 2016
Background Bacteria and viruses are equally associated with the risk of acute episodes of asthma-... more Background Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like symptoms in young children, suggesting antibiotics as a potential treatment for such episodes. We aimed to assess the eff ect of azithromycin on the duration of respiratory episodes in young children with recurrent asthma-like symptoms, hypothesising that it reduces the duration of the symptomatic period. Methods In this randomised, double-blind, placebo-controlled trial, we recruited children aged 1-3 years, who were diagnosed with recurrent asthma-like symptoms from the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort; a birth cohort consisting of the general Danish population of Zealand, including Copenhagen. Exclusion criteria were macrolide allergy, heart, liver, neurological, and kidney disease, and, before each treatment, one or more clinical signs of pneumonia (respiratory frequency of ≥50 breaths per min; fever of ≥39°C; C-reactive protein concentration of ≥476•20 nmol/L [≥50 mg/L]). Each episode of asthma-like symptoms lasting at least 3 days was randomly allocated to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo after thorough examination by a study physician at the Copenhagen Prospective Studies on Asthma research unit. Each episode was randomly allocated independently of previous treatment from a computer-generated list of random numbers in blocks of ten (generated at the Pharmacy of Glostrup). Investigators and children were masked until the youngest child turned 3 years of age and throughout the data validation and analysis phases. The primary outcome was duration of the respiratory episode after treatment, verifi ed by prospective daily diaries and analysed with Poisson regression. Analyses were per protocol (excluding those without a primary outcome measure or who did not receive treatment). This trial is registered with ClinicalTrials.gov, number NCT01233297.
sveit fái síður ofnaemi en börn alin upp í þéttbýli (11-13). Flest bendir til þess að breyting á ... more sveit fái síður ofnaemi en börn alin upp í þéttbýli (11-13). Flest bendir til þess að breyting á lífsháttum með aukinni velferð og baettum efnahag eigi með einhverjum haetti sök á þessari óheillaþróun. Fáar rannsóknir hafa verið gerðar til að varpa ljósi á tengsl efnahags við hana. Í tveimur nýlegum rannsóknum frá Ítalíu og Þýskalandi hefur þó verið sýnt fram á meira ofnaemi meðal barna þeirra sem betur voru staeðir (14,15). Almennt er talið að fólki með langskólanám að Ágrip
The New England journal of medicine, Dec 29, 2016
Background Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contri... more Background Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring. Methods We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respirat...
Acta Paediatrica, 2019
The objective of this study was to identify possible pre-and postnatal factors influencing neurod... more The objective of this study was to identify possible pre-and postnatal factors influencing neurodevelopment of the young child. Methods: We used data from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC 2010) mother-child cohort, but excluded those with a neurological diagnosis, born <37 weeks of gestation and birthweights <2500 g, resulting in 650 children analysed. Neurodevelopment was assessed as age of achievement of early milestones, language scores at 1 and 2 years and cognitive score at 2 ½ years of age. Results: Neurodevelopmental scores were not associated with breastfeeding, persistent wheeze, eczema and number of sick days (p > 0.05 in all tests). Early age at milestone achievement was associated with male sex (p = 0.05), lower maternal age (p = 0.02), higher gestational age (p < 0.001) and paternity leave (p = 0.01). A higher 1-year language score was associated with female sex (p = 0.02) and maternal smoking during pregnancy (p = 0.01) and a higher 2-year language score with female sex (p < 0.001) and being first born (p = 0.01). A higher cognitive score was associated with female sex (p = 0.02). Conclusion: Neurodevelopmental scores were unrelated to breastfeeding, persistent wheeze, eczema and number of sick days. Neurodevelopment in early childhood was mostly associated with gender.
JAMA, 2016
IMPORTANCE Observational studies have suggested that increased dietary vitamin D intake during pr... more IMPORTANCE Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to pregnant women is unknown. OBJECTIVE To determine whether supplementation of vitamin D 3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring. DESIGN, SETTING, AND PARTICIPANTS A double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. Enrollment began March 2009 with a goal of 708 participants, but due to delayed ethical approval, only 623 women were recruited at 24 weeks of pregnancy. Follow-up of the children (N = 581) was completed when the youngest child reached age 3 years in March 2014. INTERVENTIONS Vitamin D 3 (2400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D 3 as part of usual pregnancy care. MAIN OUTCOMES AND MEASURES Age at onset of persistent wheeze in the first 3 years of life. Secondary outcomes included number of episodes of troublesome lung symptoms, asthma, respiratory tract infections, and neonatal airway immunology. Adverse events were assessed. RESULTS Of the 581 children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D 3 group and 57 children (20%) in the control group. Vitamin D 3 supplementation was not associated with the risk of persistent wheeze, but the number of episodes of troublesome lung symptoms was reduced, and the airway immune profile was up-regulated (principal component analysis, P = .04). There was no effect on additional end points. Intrauterine death was observed in 1 fetus (<1%) in the vitamin D 3 group vs 3 fetuses (1%) in the control group and congenital malformations in 17 neonates (5%) in the vitamin D 3 group vs 23 neonates (8%) in the control group. End Point Vitamin D 3 Control Estimate (95% CI) P Value Persistent wheeze, No. (%) 47 (16) 57 (20) Hazard ratio (HR), 0.76 (0.52-1.12) .16 Episodes of troublesome lung symptoms, mean (95% CI) 5.9 (5.2-6.6) 7.2 (6.4-8.1) Incidence risk ratio (IRR), 0.83 (0.71-0.97) .02 Asthma at 3 y, No. (%) 32 (12) 47 (14) Odds ratio, 0.82 (0.50-1.36) .45 Respiratory tract infections Upper, annual mean (95% CI) 5.2 (4.8-5.5) 5.3 (4.9-5.6) IRR, 0.99 (0.90-1.09) .84 Lower, No. (%) 94 (32) 95 (33) HR, 0.96 (0.72-1.27) .76 CONCLUSIONS AND RELEVANCE The use of 2800 IU/d of vitamin D 3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years. However, interpretation of the study is limited by a wide CI that includes a clinically important protective effect.
Icelandic Medical Journal
To compare the prevalence of IgE-mediated sensitization, allergic disorders and possible risk fac... more To compare the prevalence of IgE-mediated sensitization, allergic disorders and possible risk factors for atopic sensitization among Icelandic medical students (n=113) to a randomly chosen age matched group previously investigated in the Icelandic part of the European Community Respiratory Health Survey. Altogether 100 medical students participated and 102 in the control group. They were skin prick tested and they answered questions about respiratory symptoms, smoking habits, family history and home environment in childhood. Only 4% of medical students reported daily smoking compared to 27% of the controls. The medical students also had a significantly lower number (mean +/- SD) of siblings (2.2+/-1.3) compared to the controls (3.9+/-1.7). The controls also shared bedrooms with older siblings in childhood three times as often. Atopic sensitization, defined as a positive (3 mm or more) reaction to at least one of nine common airborne allergens used in testing, was found in 41% of the...
13). Flest bendir til þess að breyting a lifshattum með aukinni velferð og baettum efnahag eigi m... more 13). Flest bendir til þess að breyting a lifshattum með aukinni velferð og baettum efnahag eigi með einhverjum haetti sok a þessari oheillaþroun. Faar rannsoknir hafa verið gerðar til að varpa ljosi a tengsl efnahags við hana. I tveimur nýlegum rannsoknum fra Italiu og Þýskalandi hefur þo verið sýnt fram a meira ofnaemi meðal barna þeirra sem betur voru staeðir (14,15). Almennt er talið að folki með langskolanam að Agrip
Child development, 2021
A double-blind randomized controlled trial of n-3 long-chain polyunsaturated fatty acid (n-3 LCPU... more A double-blind randomized controlled trial of n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation or matching placebo during third trimester of pregnancy was conducted within the COPSAC2010 mother-child cohort consisting of 736 women and their children. The objective was to determine if maternal n-3 LCPUFA pregnancy supplementation affects offspring neurodevelopment until 6 years. Neurodevelopment was evaluated in 654 children assessing age of motor milestone achievement, language development, cognitive development, general neurodevelopment, and emotional and behavioral problems. Maternal n-3 LCPUFA supplementation during pregnancy improved early language development and reduced the impact of emotional and behavioral problems. The n-3 LCPUFA supplementation was in boys associated with the earlier achievement of gross motor milestones, improved cognitive development, and a reduced impact of emotional and behavioral problems.
IMPORTANCE Observational studies have reported an association between high maternal vitamin D lev... more IMPORTANCE Observational studies have reported an association between high maternal vitamin D levels and improved neurodevelopment in offspring, but no randomized clinical trial (RCT) has investigated these observations. OBJECTIVE To determine whether high-dose vitamin D supplementation during pregnancy improves offspring neurodevelopment from birth to age 6 years. DESIGN, SETTING, AND PARTICIPANTS This prespecified secondary analysis of a double-blinded, placebo-controlled RCT of high-dose vitamin D3 supplementation vs standard dose during the third trimester of pregnancy was conducted in the unselected prospective mother-child birth cohort at a single-center research unit in Denmark as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC-2010). Participants included pregnant women; women with vitamin D intake greater than 600 IU/d or an endocrine, heart, or kidney disorder, and those who did not speak Danish fluently were excluded. Neurodevelopmental asse...
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 2013
We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutritio... more We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. Pregnant women from eastern Denmark were invited during 2008-2010 to a novel unselected 'COPSAC2010 ' cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and c...
Objective: To compare the prevalence of IgE-mediated sensitization, allergic disorders and possib... more Objective: To compare the prevalence of IgE-mediated sensitization, allergic disorders and possible risk factors for atopic sensitization among Icelandic medical students (n=113) to a randomly chosen age matched group previously investigated in the Icelandic part of the European Community Respiratory Health Survey. Material and methods: Altogether 100 medical students participated and 102 in the control group. They were skin prick tested and they answered questions about respiratory symptoms, smoking habits, family history and home environment in childhood. Results: Only 4% of medical students reported daily smoking compared to 27% of the controls. The medical students also had a significantly lower number (mean +/- SD) of siblings (2.2+/-1.3) compared to the controls (3.9+/-1.7). The controls also shared bedrooms with older siblings in childhood three times as often. Atopic sensitization, defined as a positive (3 mm or more) reaction to at least one of nine common airborne allergens used in testing, was found in 41% of the medical students compared to 26.5% of the controls. The prevalence of asthma and urticaria was also significantly higher among the medical students. Conclusions: Medical students have more often IgE-mediated sensitization and allergy related diseases than a controlgroup of the same age. A possible explanation to this is a lower number of siblings among medical students and a different household situation in childhood.
JAMA Network Open
IMPORTANCE Observational studies have reported an association between high maternal vitamin D lev... more IMPORTANCE Observational studies have reported an association between high maternal vitamin D levels and improved neurodevelopment in offspring, but no randomized clinical trial (RCT) has investigated these observations. OBJECTIVE To determine whether high-dose vitamin D supplementation during pregnancy improves offspring neurodevelopment from birth to age 6 years. DESIGN, SETTING, AND PARTICIPANTS This prespecified secondary analysis of a double-blinded, placebo-controlled RCT of high-dose vitamin D 3 supplementation vs standard dose during the third trimester of pregnancy was conducted in the unselected prospective mother-child birth cohort at a single-center research unit in Denmark as part of the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC-2010). Participants included pregnant women; women with vitamin D intake greater than 600 IU/d or an endocrine, heart, or kidney disorder, and those who did not speak Danish fluently were excluded. Neurodevelopmental assessments for offspring of these women were performed at ages 0 to 6 years. Children born prematurely (gestational week <37), with low birth weight (<2500 g), or with a neurological disease affecting neurodevelopment were excluded. Data were analyzed from August 2019 to February 2020. INTERVENTIONS High-dose (ie, 2800 IU/d) vs standard dose (ie, 400 IU/d) vitamin D 3 supplementation from pregnancy week 24 until 1 week after birth. MAIN OUTCOMES AND MEASURES The primary outcome of interest was cognitive development assessed at 2.5 years using the Bayley Scales of Infant and Toddler Development. Other neurodevelopmental outcomes included age of motor milestone achievement (Denver Developmental Index and World Health Organization milestone registration), language development (MacArthur-Bates Communicative Development Inventories), general neurodevelopment at age 3 years (Ages and Stages Questionnaire), and emotional and behavioral problems at age 6 years (Strengths and Difficulties Questionnaire). RESULTS Among 623 women randomized, 315 were randomized to high-dose vitamin D 3 and 308 were randomized to standard dose placebo. A total of 551 children were evaluated from birth to age 6 years, (282 [51.2%] boys; 528 [95.8%] White), with 277 children in the high-dose vitamin D 3 group and 274 children in the standard dose group. There was no effect of the high-dose compared with standard dose of vitamin D 3 supplementation during pregnancy on offspring achievement of motor milestones (β = 0.08 [95% CI, −0.26 to 0.43]; P = .64), cognitive development (score difference: 0.34 [95% CI, −1.32 to 1.99]; P = .70), general neurodevelopment (median [IQR] communication (continued) Key Points Question Does maternal high-dose vitamin D supplementation in the third trimester of pregnancy improve offspring neurodevelopment in the first 6 years of life? Findings This prespecified secondary analysis of a randomized clinical trial of vitamin D 3 supplementation during pregnancy and offspring neurodevelopment among 551 children showed no effect on neurodevelopment in the first 6 years of life, except for an isolated negative effect on language development at age 2 years in the highdose compared with standard dose group. Meaning This secondary analysis of a randomized clinical trial found that maternal high-dose vitamin D 3 supplementation during pregnancy did not improve neurodevelopmental outcomes in the offspring during the first 6 years of life compared with the standard recommended dose of vitamin D.
The Lancet Respiratory Medicine, 2016
Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like sympto... more Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like symptoms in young children, suggesting antibiotics as a potential treatment for such episodes. We aimed to assess the effect of azithromycin on the duration of respiratory episodes in young children with recurrent asthma-like symptoms, hypothesising that it reduces the duration of the symptomatic period. In this randomised, double-blind, placebo-controlled trial, we recruited children aged 1-3 years, who were diagnosed with recurrent asthma-like symptoms from the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort; a birth cohort consisting of the general Danish population of Zealand, including Copenhagen. Exclusion criteria were macrolide allergy, heart, liver, neurological, and kidney disease, and, before each treatment, one or more clinical signs of pneumonia (respiratory frequency of ≥50 breaths per min; fever of ≥39°C; C-reactive protein concentration of ≥476·20 nmol/L [≥50 mg/L]). Each episode of asthma-like symptoms lasting at least 3 days was randomly allocated to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo after thorough examination by a study physician at the Copenhagen Prospective Studies on Asthma research unit. Each episode was randomly allocated independently of previous treatment from a computer-generated list of random numbers in blocks of ten (generated at the Pharmacy of Glostrup). Investigators and children were masked until the youngest child turned 3 years of age and throughout the data validation and analysis phases. The primary outcome was duration of the respiratory episode after treatment, verified by prospective daily diaries and analysed with Poisson regression. Analyses were per protocol (excluding those without a primary outcome measure or who did not receive treatment). This trial is registered with ClinicalTrials.gov, number NCT01233297. Between Nov 17, 2010, and Jan 28, 2014, we randomly allocated 158 asthma-like episodes in 72 children (79 [50%] to azithromycin and 79 [50%] to placebo). The mean duration of the episode after treatment was 3·4 days for children receiving azithromycin compared with 7·7 days for children receiving placebo. Azithromycin caused a significant shortening of the episode of 63·3% (95% CI 56·0-69·3; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0·0001). The effect size increased with early initiation of treatment, showing a reduction in episode duration of 83% if treatment was initiated before day 6 of the episode compared with 36% if initiated on or after day 6 (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0·0001). We noted no differences in clinical adverse events between the azithromycin (18 [23%] of 78 episodes included in final analysis) and placebo (24 [30%] of 79) groups (p=0·30), but we did not investigate bacterial resistance patterns after treatment. Azithromycin reduced the duration of episodes of asthma-like symptoms in young children, suggesting that this drug could have a role in acute management of exacerbations. Further research is needed to disentangle the inflammatory versus antimicrobial aspects of this relation. Lundbeck Foundation, Danish Ministry of Health, Danish Council for Strategic Research, Capital Region Research Foundation.