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There is consensus about the positive effects of high quality Early Childhood Education and Care (ECEC) on children’s development, particularly for children from lower socioeconomic backgrounds. However, limited knowledge exists on the access to quality in ECEC in a universal context. This study investigates potential socioeconomic selection into ECEC of higher structural quality in the context of a universal, heavily subsidized, and regulated system in Norway, intended to provide equal access to high quality ECEC. Furthermore, we explore the impact of SES and structural quality in ECEC on student-teacher relationship quality. Our conceptual model takes into account how readily accessible information on different quality aspects is for parents. We use data from the Norwegian Mother, Father and Child Cohort Study linked with teacher-reported ECEC quality for children born in 2006–2009 (N 7,226), supplemented by registry data at ECEC and municipality level. We find that higher parental education, and to a lesser degree income, predict child attendance of ECEC with higher structural quality as rated by ECEC teachers. Further, higher parental SES and structural quality (i.e., developmental material, staff competence and stability) predict better student-teacher relationship quality in terms of higher level of closeness and less conflict. These findings suggest that ambitions of universal equal access to high quality ECEC are not entirely realized and more efforts are needed to ensure higher structural quality in ECEC and enhance relationship quality for children from less advantageous socioeconomic backgrounds.

The relationship between iodine intake and depression is unknown. The aim of the present study was to investigate whether iodine intake was associated with symptoms of perinatal emotional distress and depression in a mild- to moderately iodine deficient population.The study population comprised 67,812 women with 77,927 pregnancies participating in the Norwegian Mother, Father and Child Cohort Study. Self-reported emotional distress and depressive symptoms were reported in pregnancy and at six months postpartum. Iodine intake was assessed by a food frequency questionnaire in mid-pregnancy. Urinary iodine concentration (UIC) was available for 2792 pregnancies.The median iodine intake from food was 121 μg/day and the median UIC was 68 μg/L. The prevalence of high scores for emotional distress was 6.6 % in pregnancy and 5.8 % six months postpartum, and for high scores on postpartum depression it was 10.3 %. In non-users of iodine supplements (63 %), a low maternal iodine intake from food (lower than ~100-150 μg/day) was associated with increased risk of high scores of emotional distress and depression both in pregnancy and six months postpartum (p 0.001). Iodine supplement use was associated with increased risk of high scores of emotional distress in pregnancy compared to no supplement use or use of supplements without iodine.Observational design, self-report information, and short scales to assess symptoms of emotional distress and depression.A low habitual iodine intake was associated with increased prevalence of perinatal emotional distress and depression. The potential non-beneficial effect of iodine supplements may have biological explanations. More studies are needed.

Background: Female educational advantage is evident from elementary school and throughout the education system. Understanding the gender differences that precede school entry might provide important insight as to why girls outperform boys later in their educational careers. Aims: The aim of this study was to explore gender differences in early literacy and numeracy skills, as well as a range of neurodevelopmental and behavioral domains between the age of five and six years. Methods: We used questionnaire data from preschool teachers in the Norwegian Mother, Father and Child Cohort Study reported for 7467 children attending the final year in preschool, to explore gender differences and age patterns by fitting flexible regression models predicting pre-academic, behavioral and neurodevelopmental outcomes. Results: We found gender differences favoring girls for all outcomes except internalizing behavior. For neurodevelopment and behavior, differences in adjusted standardized scores ranged from 46% of a standard deviation (95% confidence interval (CI) 0.41, 0.50) in overall school readiness to 31% of a standard deviation difference in externalizing behavior problems (CI 0.21, 0.41). We found gender differences for all literacy skills in favor of girls. The gender gap in naming and adding numbers was small, but in favor of girls. Increasing age was associated with improved pre-academic skills and school readiness, as well as reduction of attention problems and language difficulties, the latter especially for boys. Conclusions: We conclude that gender differences favoring girls exist prior to school entry for a broad range of pre-academic, behavioral and neurodevelopmental skills relevant to school functioning.

Purpose Current knowledge of the effect of prenatal caffeine exposure on the child’s neurodevelopment is contradictory. The current study aimed to study whether caffeine intake during pregnancy was associated with impaired child neurodevelopment up to 8 years of age. Method A total of 64,189 full term pregnancies from the Norwegian Mother, Father and Child Cohort Study were included. A validated food-frequency questionnaire administered at gestational week 22 was used to obtain information on maternal caffeine intake from different sources. To assess child neurodevelopment (behaviour, temperament, motor development, language difficulties) validated scales were used to identify difficulties within each domain at 6, 18, 36 months as well as 5 and 8 years of age. Adjusted logistic regression models and mixed linear models were used to evaluate neurodevelopmental problems associated with maternal caffeine intake. Results Prenatal caffeine exposure was not associated with a persistently increased risk for behaviour, temperament, motor or language problems in children born at full-term. Results were consistent throughout all follow-ups and for different sources of caffeine intake. There was a minor trend towards an association between consumption of caffeinated soft drinks and high activity level, but this association was not driven by caffeine. Conclusion Low to moderate caffeine consumption during pregnancy was not associated with any persistent adverse effects concerning the child’s neurodevelopment up to 8 years of age. However, a few previous studies indicate an association between high caffeine consumption and negative neurodevelopment outcomes.

Studies have identified concurrent, longitudinal, and bidirectional associations between language difficulties and internalizing problems. This is commonly explained by social exclusion or withdrawal from peers, but underlying mechanisms are not well understood. This study uses sibling data to investigate if the comorbidity between language difficulties and internalizing problems is best explained by familial factors shared by siblings, such as genes or family environment, or nonfamilial factors specific to each child, such as peer environment. Data include 5,568 siblings at 5 years and 3,654 siblings at 8 years participating in the Norwegian Mother, Father and Child Cohort Study (MoBa). We constructed a latent factor model at 5 and 8 years, including a family comorbidity factor capturing correlations between language and internalizing problems that were equally strong between as within siblings. Results showed that the correlation between one sibling’s internalizing problems and the other sibling’s language problems was mostly accounted for by a family comorbidity factor. The best-fitting longitudinal model included stability of the family comorbidity factor and stability of language and internalizing problems within each sibling and no cross-sibling or cross-trait longitudinal associations. This suggests that the association between language and internalizing problems may be best explained by family factors.

Background: Three to seven percent of pre-schoolers have developmental problems or child psychiatric disorders. Randomized controlled trials (RCTs) indicate that interventions in early childhood education and care improve long-term outcomes of children from disadvantaged backgrounds. It is unknown if effects generalize beyond the well-structured context of RCTs and to children who may not have a disadvantaged background but have developmental problems or psychiatric disorders. Methods: We use data from the population-based Norwegian Mother, Father and Child Cohort Study, recruiting pregnant women from 1999 to 2009, with child follow-up from ages 6, 18, and 36 months to ages 5, 7, and 8 years. This sub-study included 2499 children with developmental problems or psychiatric disorders at age five. We investigate the effects of special educational assistance at age five on mother-reported internalizing, externalizing, and communication problems at age eight. We analyse bias due to treatment by indication with directed acyclic graphs, adjust for treatment predictors to reduce bias, and estimate effects in different patient groups and outcome domains with a hierarchical Bayesian model.Results: In the adjusted analysis, pre-schoolers with special educational assistance had on average by 0.1 (0.04-0.16) standardised mean deviation fewer psycho-social difficulties in elementary school. Mean effect sizes varied between groups and outcomes.Conclusion: We estimate positive effects of educational assistance during the transition from preschool to the school years. It should therefore be considered as an intervention for pre-schoolers with developmental or behaviour problems. More research with improved measurements of treatment and outcomes is needed to identify success factors for their implementation.

Background and Purpose Schoolchildren with language difficulties experience more peer victimization compared to their typically developing (TD) peers. Whether these children also bully their peers (bully perpetration) more than TD children is unclear. Furthermore, little is known about peer victimization and bully perpetration among preschool children with language difficulties and how it may be related to different paths of language difficulties. This study aimed to investigate associations between language difficulties, peer victimization, and bully perpetration from preschool to school age as well as the risk of peer victimization and bully perpetration for children with different developmental paths of language difficulties and mild language difficulties compared to TD children. Method The sample was drawn from the Norwegian Mother, Father and Child Cohort Study. Participants with completed questionnaires at 3, 5, and 8 years of age ( n = 22,628) were included. Paths between latent variables of language skills at 3, 5, and 8 years of age, peer victimization at 5 and 8 years of age, and bully perpetration at 8 years of age were examined with structural equation modeling. Logistic regression was used to investigate peer victimization and bully perpetration for predefined paths of language difficulties. Results Poor language skills at 3 and 5 years of age were associated with peer victimization at 5 years of age. Poor language skills at 5 and 8 years of age were associated with peer victimization and bully perpetration at 8 years of age. The association between poor language skills at 5 years of age and bully perpetration at 8 years of age was stronger for girls. Persistent paths of language difficulties at 3, 5, and 8 years of age showed the highest risk of peer victimization and bully perpetration. Conclusions Language difficulties are associated with peer victimization and bully perpetration. The risk of peer victimization and bully perpetration differs according to different developmental paths of language difficulties from preschool to school age.

Background Three to seven percent of pre-schoolers have developmental problems or child psychiatric disorders. Randomized controlled trials (RCTs) indicate that interventions in early childhood education and care (ECEC) improve long-term outcomes of children from disadvantaged backgrounds. It is unknown if such effects generalize beyond the well-structured context of RCTs and to children who may not have a disadvantaged background but have developmental problems or psychiatric disorders. Methods We used data from the population-based Norwegian Mother, Father and Child Cohort Study, recruiting pregnant women from 1999 to 2009, with child follow-up from ages 6, 18, and 36 months to ages 5, 7, and 8 years. This sub-study included 2499 children with developmental problems or psychiatric disorders at age five. We investigated the effects of special educational assistance at age five on mother-reported internalizing, externalizing, and communication problems at age eight. We analysed bias due to treatment by indication with directed acyclic graphs, adjusted for treatment predictors to reduce bias, and estimated effects in different patient groups and outcome domains with a hierarchical Bayesian model. Results In the adjusted analysis, pre-schoolers who received special educational assistance had on average by 0.1 (0.04–0.16) standardised mean deviation fewer psycho-social difficulties in elementary school. Conclusion In a sample of children from mostly higher socioeconomic backgrounds we estimate a positive effects of special educational assistance during the transition from preschool to the school years. It may therefore be considered as an intervention for pre-schoolers with developmental or behaviour problems. More research with improved measurements of treatment and outcomes is needed to solidify the findings and identify success factors for the implementation of special educational assistance in ECEC.

ObjectivesTo estimate the impact of being laid off from work, having to work from home or having been diagnosed with COVID-19 on self-reported satisfaction with life.DesignNationwide population-based cohort study.SettingNorway.ParticipantsWe followed more than 80 000 participants in an ongoing cohort study, the Norwegian Mother, Father and Child Cohort Study (MoBa), during the COVID-19 pandemic. We analysed current life satisfaction in April and again in September/October 2020 for subjects whose work situation and infection status had changed.Main outcome measuresSelf-reported satisfaction with life, using a scale from 0 (worst) to 10 (best). We analysed the scale both continuously and as a binary variable (ResultsTemporary and permanent layoffs, working from a home-based office, and getting a COVID-19 diagnosis were all associated with modestly, but significantly lower concurrent life satisfaction, both in the total on a population level and for subjects experiencing a change in job status between spring and autumn. The associations with change in work situation were stronger for men. For men with permanent job loss, the adjusted odds ratio (OR) for low life satisfaction (ConclusionLayoffs, home office and infection status had clear impact on the quality of life as measured with a global life satisfaction scale. These findings suggest that social differentials in quality of life, are increasing during the pandemic.

ObjectivesTo analyse the population effects on life quality of being laid off from work, having to work from home, or having been diagnosed with COVID-19.DesignNationwide population-based cohort study.SettingNorway.ParticipantsWe followed more than 80,000 participants in an ongoing cohort study, the Norwegian Mother, Father and Child Cohort Study (MoBa) during the COVID-19 pandemic. We analysed current life satisfaction in April and again in September/October 2020 for subjects whose work situation and infection status had changed.Main outcome measuresSelf-reported satisfaction with life, using a scale from 0 (worst) to 10 (best).ResultsTemporary and permanent layoffs, working from a home-based office, and getting a COVID-19 diagnosis were associated with modestly, but significantly lower concurrent life satisfaction, both on a population level and for subjects who changed status. The associations with change in work situation were stronger for men. For men with permanent job loss, the adjusted odds ratio for low life satisfaction (ConclusionLayoffs, home office and infection status had clear impact on the quality of life as measured with a global life satisfaction scale. These findings suggest that social differentials in quality of life, are increasing during the pandemic.FundingThis work was funded by the Norwegian Research Council’s Centres of Excellence Funding Scheme (no. 262700) and by the Norwegian Institute of Public Health (NIPH).SUMMARY BOXESWhat is already known on this topic−Being laid off from work or having to work from a home-based office is usually associated with reduced life quality.−The population effect has not been estimated during the present surge in cases of COVID-19 in Europe.What this study adds−This population-based study shows that life satisfaction in Norway has been stable from the first to the second wave of the pandemic, but that both layoffs and working from home is associated with reduced life satisfaction, especially among men.−The reduced life satisfaction in people working from a home-based office implies that large proportions of the population are affected.

Background: Low educational attainment in parents is associated with child psychopathology. It is not clear whether the associations are due to risk factors that family members share or due to effects of maternal or paternal education on the offspring. We investigate whether associations between maternal and paternal educational attainment and child symptoms of attention deficit/hyperactivity disorder (ADHD), depression, and academic problems are due to shared genetic factors, shared family environmental factors, or effects of the parental phenotype educational attainment itself. Methods: This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa). The sample comprised 34,958 children (17,128 girls) in 28,372 extended‐family units. We used data from related nuclear families linked by siblings in the parent generation. We applied a quasi‐experimental extended children‐of‐twins design that included siblings in both generations and took account of nonrandom mating by including partners. Educational attainment was self‐reported by mothers and fathers. Mothers reported children's symptoms of ADHD, symptoms of depression, and academic problems by questionnaire when the children were 8 years old. Results: Children of lowly educated parents scored higher on all outcomes and had an approximate doubling of the risk of high symptom levels. The association between maternal and paternal educational attainment and child symptoms of ADHD and academic problems persisted after controlling for shared genetic and family environmental factors. Phenotypic transmission to depression was weaker and in the best fitting model fully explained by genetic factors shared by the two generations. Conclusions: Associations between educational attainment of mothers and fathers and child symptoms of ADHD and academic problems could not be ascribed to shared familial risk factors, whereas associations with symptoms of depression could. Parental education or resources and behaviors resulting from low education might be targets of interventions aimed at reducing symptoms of ADHD and academic problems. publishedVersion

Objective: To examine the effect of prenatal maternal anxiety on birthweight and preterm birth, controlling for genetic confounding using a sibling comparison design. Design: This is a population-based prospective cohort study with a comparison of a population level analysis and a sibling analysis. Setting: This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health (https://www.fhi.no/en/studies/moba/ ). Sample: Women and their chiold participating in the MoBa (n= 78,117) and women participating with more than one pregnancy (n=12,480). Methods: Associations between prenatal maternal anxiety (measured across the 17th and 30th weeks) and birth outcomes (birthweight and gestational age) were examined using linear regression with adjustment for family-shared confounding in a sibling comparison design. Main outcomes: Birthweight (in grams) and gestational age (ultrasound measure in days) were obtained from the Medical Birth Registry of Norway. Results: The maternal anxiety score during pregnancy was inversely associated with newborn’s birthweight (Beta = -112,8 95% CI: –142.7, -83.0) and gestational age (Beta=-1.77, 95% CI: -2.42, -1.13) after adjustment for several covariates. The association of the maternal anxiety score with both newborn’s birthweight (Beta=-173.9, 95% CI: -252.3, -95.4) and gestational age (Beta=-1.08, 95% CI: -2.91, -0.75) remained but was largely weakened after further adjusting for the shared-family confounding in the sibling comparison design. Conclusion: The link between maternal prenatal anxiety and birthweight and gestational age remained after adjusting for shared family confounding, yet estimates were weakened after adjusting for environmental covariates.

Purpose Some studies indicate that mild-to-moderate iodine deficiency in pregnant women might negatively affect offspring neurocognitive development, including previous results from the Norwegian Mother and Child Cohort study (MoBa) exploring maternally reported child development at age 3 years. The aim of this follow-up study was to investigate whether maternal iodine intake in pregnancy is associated with language and learning at 8 years of age. Methods The study sample includes 39,471 mother–child pairs participating in MoBa with available information from a validated food frequency questionnaire covering the first half of pregnancy and a questionnaire on child neurocognitive development at 8 years. Multivariable regression was used to explore associations of iodine intake from food and supplements with maternally reported child outcomes. Results Maternal iodine intake from food less than ~ 150 µg/day was associated with poorer child language skills (p-overall = 0.013), reading skills (p-overall = 0.019), and writing skills (p-overall = 0.004) as well as poorer school test result in reading (p < 0.001), and increased likelihood of the child receiving special educational services (p-overall = 0.042) (in noniodine supplement users). Although significant, differences were generally small. Maternal use of iodine supplements in pregnancy was not significantly associated with any of the outcomes. Conclusions Low habitual iodine intake in pregnant women, i.e., lower than the recommended intake for non-pregnant women, was associated with mothers reporting poorer child language, school performance, and increased likelihood of special educational services. We found no indications of benefits or harm of using iodine-containing supplements in pregnancy. Initiating use in pregnancy might be too late. The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and the Ministry of Education and Research, NIH/ NIEHS (contract no N01-ES-75558), NIH/NINDS (Grant no. 1 UO1 NS 047537-01 and Grant no. 2 UO1 NS 047537-06A1). MHA was supported by a 4 years Grant from the Norwegian Research Council (Grant no. 241430) and the Norwegian dairy company TINE SA.

Introduction: Good communication skills are essential for pharmacy students to help patients with their medicines. Students' attitudes towards communication skills learning will influence their willingness to engage in communication training, and their skills when dealing with patients later on in their professional life. Objective: The aim of this study was to explore Nordic pharmacy students' attitudes to communication skills learning, and the associations between those attitudes and various student characteristics. Method and materials: A cross-sectional questionnaire-based study was conducted in 11 Nordic pharmacy schools between April 2015 and January 2016. The overall response rate for the final study population was 77% (367 out of 479 students). Pharmacy students who had fulfilled all mandatory communication training and most of their pharmacy practical experience periods were included. The communication skills attitudes scale was the main outcome. Linear regression models were fitted with the outcome variable and various student characteristics as the predictors, using generalized estimating equations to account for clustering within pharmacy schools. Results: Nordic pharmacy students in general have moderately positive attitudes towards learning communication skills. Positive attitudes towards learning communication skills among pharmacy students were associated with being female (βadjusted 0.42, 95% CI 0.20 to 0.63, p < 0.001), following a newer pharmacy training program (βadjusted 0.81, 95% CI 0.63 to 0.98, p < 0.001), having higher self-rated need for communication skills improvement (βadjusted 0.50, 95% CI 0.30 to 0.71, p

PURPOSE An increasing consumption of opioids in the general population has been reported in several countries also among pregnant women. Limited information is available regarding the effect of prenatal exposure to analgesic opioids on long-term neurocognitive function in children. The primary aim of the study was to determine the association between prenatal exposure to analgesic opioids and language competence and communication skills at 3 years of age. METHODS The Norwegian Mother and Child Cohort Study (MoBa) prospectively included pregnant women during the period from 1999 to 2008. Participants reported medication use at pregnancy weeks 17-18 and 30, and 6 months after birth. Children's language competence and communication skills were reported by mothers on validated scales. RESULTS A total of 45 211 women with 51 679 singleton pregnancies were included. The use of analgesic opioids was reported in 892 pregnancies (1.7%). In adjusted analyses, no association between opioid use and reduced language competence or communication skills was found, OR = 1.04 (95%CI: 0.89-1.22) and OR = 1.10 (95%CI: 0.95-1.27), respectively. Both pain and use of paracetamol were associated with a small reduction in communication skills. No such association was found for language competence. CONCLUSION The use of analgesic opioids in pregnant women does not seem to affect language development or communication skills in children at 3 years of age. Copyright © 2017 John Wiley & Sons, Ltd.

Purpose An increasing consumption of opioids has been reported. The primary aim of the present study was follow-up of neurocognitive development in children exposed to analgesic opioids during pregnancy, using three different validated instruments to assess language and communication development at 5 years. Methods The Norwegian Mother and Child Cohort Study (MoBa) prospectively included pregnant women 1999 to 2008. Participants reported medication use at pregnancy week 17/18 and 30, and 6 months after birth. Children's language competence and communication skills at 5 years were reported by mothers on three different validated scales; The Ages and Stages Questionnaire (ASQ), The Speech and Language Assessment Scale (SLAS) and The Twenty Statements about Language-Related Difficulties list (Language20Q). Results A total of 27 428 women with 33 407 singleton pregnancies were included. Use of analgesic opioids was reported in 584 pregnancies (1.7%). No associations between opioid use and lower language competence or communication skills were found. For ASQ, the OR of being in the lowest category vs the group with maximum mean score was 0.82 (95%CI 0.57, 1.17), for SLAS the OR of scoring worse than typical for age vs better than typical for age was 0.84 (0.61, 1.17) in children exposed to opioids in utero. For Language20Q using the best performance category as reference, the OR of scoring in the lower performance category was 0.57 (0.35, 0.91) with exposure to opioids. Conclusion Use of analgesic opioids in pregnant women does not seem to negatively affect language development or communication skills in children at 5 years.

Our aim in this study was to estimate the strength of associations between prenatal diet quality and child behavioral, language, and motor functions in the Norwegian Mother and Child Cohort Study (1999–2008). We created a prenatal diet quality index (PDQI) based on adherence to Norwegian dietary guidelines. Child outcomes were defined as sum scores on the Child Behavior Checklist, the Ages and Stages Questionnaire, and the Child Development Index at ages 18, 36, and 60 months. Using a longitudinal cohort study design and Bayesian hierarchical modeling, we estimated association strengths using inverse probability weighting to account for selection bias. In total, 27,529 mother-child pairs were eligible for inclusion. A 1–standard-deviation increase in PDQI score was associated with an absolute reduction in outcome sum scores of 0.02–0.21 and a 3%–7% relative decrease, with larger decreases seen for language and motor functions than for behavioral functions. PDQI scores were inversely associated with all child functions, but the estimated strength of each association was low. The results indicate that the observed variations in PDQI scores in an industrialized Western society may not profoundly influence the child functions studied. Estimating the Strength of Associations Between Prenatal Diet Quality and Child Developmental Outcomes: Results From a Large Prospective Pregnancy Cohort Study

Objective The aim is to investigate if young children with developmental and behavioral difficulties (DBDs) have greater risk of peer-victimization compared with typically developing (TD) children. Method The sample was drawn from the Norwegian Mother and Child Cohort Study (MoBa). MoBa has collected population-based data on children's health and development for 114,500 children. We included children that were 5 years of age (n = 41,609). Multivariate logistic regression was used to estimate the effect of different DBDs and of co-occurring DBDs on peer-victimization compared with TD children. Categories of DBDs included autistic traits, emotional difficulties, behavioral difficulties, general learning difficulties, attention difficulties/impulsive behavior, motor development difficulties, language difficulties, and hearing and vision difficulties. Results were adjusted for socioeconomic status and the child's sex. Results Peer-victimization was 2.8% (933) among TD children, and 8.0% (615) among children with DBD. The highest risk of peer-victimization was found among children with autistic traits and children with five or more co-occurring DBDs (adjusted odds ratios [ORs] = 12.76; 95% confidence interval [CI] 8.64-18.84; p ≤ .001) and 17.37 (95% CI 12.15-24.82; p ≤ .001)], respectively. The lowest risk was found among children with hearing and vision difficulties and children with only one DBD [adjusted ORs = 1.98 (95% CI 1.71-2.29; p ≤ .001) and 1.95 (95% CI 1.70-2.22; p ≤ .001)]. Conclusion Children with DBD have a substantially higher risk of peer-victimization compared with TD children. Peer-victimization varies with type of DBD and increases cumulatively by number of DBDs.

Objective: Potential adverse effects of prenatal antidepressant exposure on child development are still debated. The possibility that associations are due to genetic or familial environmental risk factors rather than antidepressant use per se cannot easily be ruled out in conventional studies. Our objective was therefore to evaluate the association between prenatal antidepressant exposure and behavioural problems in a sibling controlled study. Method: This study used data on 20180 siblings identified from the population-based Norwegian Mother and Child Cohort Study recruited between 1999 and 2008. The mothers were asked to report antidepressant use at gestational weeks 17 and 30 and 6 months post-partum. Child Behavioral Checklist syndrome scales were used to assess externalizing and internalizing behavioural problems by questionnaires sent to mothers at 18 and 36 months postpartum. We performed unmatched and matched sibling analyses using both random- and fixed-effects linear models, respectively, to determine potential behavioural effects of antidepressant exposure. Results: Prenatal exposure to antidepressants was associated with increased levels of anxiety symptoms in 3 year old children after adjusting for maternal familial effects and confounding by indication (i.e. maternal depression). Effect of prenatal exposure to antidepressants was specific to anxiety, and not associated with emotional reactivity, somatic complaints, sleep problems, attention problems or aggression. Conclusion: Using a sibling design, we showed that prenatal antidepressant use was specifically associated with increased anxiety symptoms after adjusting for maternal familial factors and confounding by indication.

OBJECTIVES: To estimate the association between maternal use of acetaminophen during pregnancy and of paternal use before pregnancy with attention-deficit/hyperactivity disorder (ADHD) in offspring while adjusting for familial risk for ADHD and indications of acetaminophen use. METHODS: Diagnoses were obtained from the Norwegian Patient Registry for 112 973 offspring from the Norwegian Mother and Child Cohort Study, including 2246 with ADHD. We estimated hazard ratios (HRs) for an ADHD diagnosis by using Cox proportional hazard models. RESULTS: After adjusting for maternal use of acetaminophen before pregnancy, familial risk for ADHD, and indications of acetaminophen use, we observed a modest association between any prenatal maternal use of acetaminophen in 1 (HR = 1.07; 95% confidence interval [CI] 0.96–1.19), 2 (HR = 1.22; 95% CI 1.07–1.38), and 3 trimesters (HR = 1.27; 95% CI 0.99–1.63). The HR for more than 29 days of maternal acetaminophen use was 2.20 (95% CI 1.50–3.24). Use for CONCLUSIONS: Short-term maternal use of acetaminophen during pregnancy was negatively associated with ADHD in offspring. Long-term maternal use of acetaminophen during pregnancy was substantially associated with ADHD even after adjusting for indications of use, familial risk of ADHD, and other potential confounders.

Background During pregnancy, many women experience sleep problems and anxiety that require treatment. The long-term safety for the child of maternal benzodiazepine (BZD) and z-hypnotic use during pregnancy remains controversial. Method We conducted a cohort and a sibling control study using data from the Norwegian Mother and Child Cohort Study. Data on use of BZD and z-hypnotics, internalizing and externalizing outcomes, and covariates were collected from mothers at gestational weeks 17 and 30 and when children were 0.5, 1.5, and 3 years of age. The total sample consisted of 71,996 children (19,297 siblings) at 1.5 years and 55,081 children (13,779 siblings) at 3 years. Short-term use was defined as use in one pregnancy period only. Long-term use was defined as use in two or more pregnancy periods. Linear full cohort random-effect and sibling-matched fixed-effect regression models were used to compare internalizing and externalizing behavior in children prenatally exposed compared to those unexposed in the full cohort of pregnancies accounting for family clusters, as well as within sibling clusters comparing pregnancies with discordant exposures. Propensity score (PS) adjustment included variables on indication for use (sleep problems, symptoms of anxiety and depression) and other potential confounding factors. Results Long-term prenatal exposure to BZD or z-hypnotics was associated with increased internalizing behavior in crude cohort analyses and at age 1.5 years after PS adjustment in sibling-matched fixed-effect models [β 0.60, 95% confidence interval 0.17–0.95]. Analyses on specific drug groups showed that prenatal exposure to BZD-anxiolytics was associated with increased internalizing problems at both 1.5 years [β 0.25, 0.01–0.49] and 3 years [β 0.26, 0.002–0.52] while exposure to z-hypnotics was not associated with any adverse outcomes after adjustment. Conclusion The findings suggest a moderate association between BZD-anxiolytic exposure and child internalizing problems that is not likely due to stable familial confounding factors.

Background: Methyl mercury (MeHg) is a well-known neurotoxin and evidence suggests that also low level exposure may affect prenatal neurodevelopment. Uncertainty exists as to whether the maternal MeHg burden in Norway might affect child neurodevelopment. Objective: To evaluate the association between prenatal mercury exposure, maternal seafood consumption and child language and communication skills at age five. Methods: The study sample comprised 38,581 mother-child pairs in the Norwegian Mother and Child Cohort Study. Maternal mercury blood concentration in gestational week 17 was analysed in a sub-sample of 2239 women. Prenatal mercury exposure from maternal diet was calculated from a validated FFQ answered in mid-pregnancy. Mothers reported children's language and communications skills at age five by a questionnaire including questions from the Ages and Stages Questionnaire (ASQ), the Speech and Language Assessment Scale (SLAS) and the Twenty Statements about Language-Related Difficulties (language 20). We performed linear regression analyses adjusting for maternal characteristics, nutritional status and socioeconomic factors. Results: Median maternal blood mercury concentration was 1.03μg/L, dietary mercury exposure was 0.15μg/kgbw/wk, and seafood intake was 217g/wk. Blood mercury concentrations were not associated with any language and communication scales. Increased dietary mercury exposure was significantly associated with improved SLAS scores when mothers had a seafood intake below 400g/wk in the adjusted analysis. Sibling matched analysis showed a small significant adverse association between those above the 90th percentile dietary mercury exposure and the SLAS scores. Maternal seafood intake during pregnancy was positively associated with the language and communication scales. Conclusion: Low levels of prenatal mercury exposure were positively associated with language and communication skills at five years. However, the matched sibling analyses suggested an adverse association between mercury and child language skills in the highest exposure group. This indicates that prenatal low level mercury exposure still needs our attention. Keywords: Methylmercury, Diet, Maternal blood levels, Language development, Fish and seafood intake, The Norwegian mother and child cohort study

Background: Severe iodine deficiency in pregnancy has major effects on child neurodevelopment, but less is known about the potential consequences of mild-to-moderate deficiency and iodine supplement use. Objective: We explored the associations between maternal iodine intake and child neurodevelopment at 3 y of age and the potential impact of maternal intake of iodine from supplements on the same outcomes. Methods: This population-based prospective observational study included 48,297 mother-child pairs recruited during pregnancy from 2002 to 2008. Maternal iodine intake was calculated based on a validated food-frequency questionnaire answered during midpregnancy that covered mean intake since the beginning of pregnancy. Associations between iodine intake and maternal-reported child language and motor development and behavior problems were explored by multivariable regression analyses. Results: In 33,047 mother-child pairs, excluding iodine supplement users, maternal iodine intake was associated with child language delay (P = 0.024), externalizing and internalizing behavior problems (both P < 0.001), and fine motor skills (P = 0.002) but not gross motor skills or the risk of not walking unaided at 17 mo of age. In 74% of the participants who had an iodine intake 1.5 SD, and 16% (95% CI: 10%, 21%) of the cases of internalizing behavior problems >1.5 SD. In 48,297 mother-child pairs, including iodine supplement users, we found no protective effects of supplemental iodine during pregnancy on neurodevelopment. Conclusions: Maternal iodine intake below the Estimated Average Requirement during pregnancy was associated with symptoms of child language delay, behavior problems, and reduced fine motor skills at 3 y of age. The results showed no evidence of a protective effect of iodine supplementation during pregnancy.

Objective To investigate the risk of communication impairments at age 18 and 36 months in children born early term (gestational weeks 37-38) and late preterm (gestational weeks 34-36). Study design A total of 39 423 children and their mothers participated in the Norwegian Mother and Child Cohort Study. The sample included 7109 children (18%) born early term and 1673 (4.2%) born late preterm. Information on gestational age and prenatal and postnatal risk factors was obtained from the Medical Birth Registry of Norway. Information on communication impairments was assessed using standardized questionnaires filled out by the mothers. Stepwise logistic regression analysis was applied to explore the associations between early term/late preterm birth and communication impairments at age 18 and 36 months. Results Compared with children born at term, children born early term and late preterm had an increased risk of communication impairments at age 18 and 36 months. In early term, the aOR was 1.27 (95% CI, 1.12-1.44) at 18 months for communication impairments and 1.22 (95% CI, 1.07-1.39) at 36 months for expressive language impairments. In late preterm, the aOR was 1.74 (95% CI, 1.41-2.14) at 18 months and 1.37 (95% CI, 1.09-1.73) at 36 months. Conclusion Not only children born late preterm, but also those born early term, are at increased risk for communication impairments. Given the large number of children potentially affected, this may result in significant health care costs.

Background Paracetamol is used extensively during pregnancy, but studies regarding the potential neurodevelopmental sequelae of foetal paracetamol exposure are lacking. Method Between 1999 and 2008 all pregnant Norwegian women were eligible for recruitment into the prospective Norwegian Mother and Child Cohort Study. The mothers were asked to report on their use of paracetamol at gestational weeks 17 and 30 and at 6 months postpartum. We used data on 48 631 children whose mothers returned the 3-year follow-up questionnaire by May 2011. Within this sample were 2919 same-sex sibling pairs who were used to adjust for familial and genetic factors. We modelled psychomotor development (communication, fine and gross motor development), externalizing and internalizing behaviour problems, and temperament (emotionality, activity, sociability and shyness) based on prenatal paracetamol exposure using generalized linear regression, adjusting for a number of factors, including febrile illness, infections and co-medication use during pregnancy. Results The sibling-control analysis revealed that children exposed to prenatal paracetamol for more than 28 days had poorer gross motor development [β 0.24, 95% confidence interval (CI) 0.12–0.51], communication (β 0.20, 95% CI 0.01–0.39), externalizing behaviour (β 0.28, 95% CI 0.15–0.42), internalizing behaviour (β 0.14, 95% CI 0.01–0.28), and higher activity levels (β 0.24, 95% CI 0.11–0.38). Children exposed prenatally to short-term use of paracetamol (1–27 days) also had poorer gross motor outcomes (β 0.10, 95% CI 0.02–0.19), but the effects were smaller than with long-term use. Ibuprofen exposure was not associated with neurodevelopmental outcomes. Conclusion Children exposed to long-term use of paracetamol during pregnancy had substantially adverse developmental outcomes at 3 years of age.

An increasing consumption of opioids in the general population has been reported in several countries also among pregnant women. Limited information is available regarding the effect of prenatal exposure to analgesic opioids on long-term neurocognitive function in children. The primary aim of the study was to determine the association between prenatal exposure to analgesic opioids and language competence and communication skills at 3 years of age.The Norwegian Mother and Child Cohort Study (MoBa) prospectively included pregnant women during the period from 1999 to 2008. Participants reported medication use at pregnancy weeks 17-18 and 30, and 6 months after birth. Children's language competence and communication skills were reported by mothers on validated scales.A total of 45 211 women with 51 679 singleton pregnancies were included. The use of analgesic opioids was reported in 892 pregnancies (1.7%). In adjusted analyses, no association between opioid use and reduced language competence or communication skills was found, OR = 1.04 (95%CI: 0.89-1.22) and OR = 1.10 (95%CI: 0.95-1.27), respectively. Both pain and use of paracetamol were associated with a small reduction in communication skills. No such association was found for language competence.The use of analgesic opioids in pregnant women does not seem to affect language development or communication skills in children at 3 years of age. Copyright © 2017 John WileySons, Ltd.

Background Up to 10% of women are exposed to selective serotonin reuptake inhibitors (SSRIs) during pregnancy. Information on their effect on birthweight and gestational age remains conflicting. The aim of this sibling-controlled prospective cohort study is to address shared geneticand family-level confounding to investigate the effects of prenatal SSRI exposure and maternal depression on birthweight and gestational age. Methods We used the Norwegian Mother and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN). Our study population consisted of 27 756 siblings; 194 were prenatally exposed to SSRIs and 27 500 were unexposed to any antidepressant medication. Random and fixed effects analysis with propensity score adjustment was used to evaluate the effectson birthweight and gestational age. Results SSRI exposure during two or more trimesters was associated with a decrease in birthweight of 205 g [95% confidence interval (CI) -372 to - 38] and a decrease in gestational length of 4.9 days (95% CI - 9.1 to - 1.4). Neither maternal SSRI use in one trimester, lifetime history of major depression nor depressive symptoms during pregnancy were associated with these pregnancy outcomes (for non-pharmacologically treated depression in two periods in pregnancy, +5 g (95% CI - 56 to + 67) and +4.9 days (95% CI - 4.7 to + 14.7), respectively). Conclusions Prenatal exposure to SSRIs during two or more trimesters may decrease birthweight and gestational length. Our results indicate that neither maternal depression nor shared genetics and family environment fully explain this association.

Background Previous studies showed that children exposed to paracetamol during fetal life might have an increased risk of neurodevelopmental problems. Since paracetamol is one of the most commonly used medications during pregnancy, even small increases in the risk of neurodevelopmental problems may have considerable implications for public health. Methods Using data from the Norwegian Mother and Child Cohort Study, we applied propensity score (PS) matching to examine associations between prenatal paracetamol exposure and neurodevelopmental problems among children at 18 months of age. Paracetamol use was classified into short-term (< 28 days) and long-term (≥ 28 days) of exposure. Results Of the 51 200 pregnancies included in our study, 40.5% of mothers ( n = 20 749) used paracetamol at least once during pregnancy. In the PS-matched analyses, long-term paracetamol exposure during pregnancy was associated with communication problems [odds ratio (OR): 1.38, 95% confidence interval (CI) 0.98-1.95) and delayed motor milestone attainment (OR: 1.35, 95% CI 1.07-1.70). We did not observe increased risks after short-term exposure. Sensitivity analyses for several indications showed similar effects as the PS-matched analyses, suggesting no confounding by indication. Conclusion Long-term exposure to paracetamol in utero was associated with modestly increased risks of motor milestone delay and impaired communication skills among children at 18 months. Caution is warranted when considering long-term use of paracetamol during pregnancy; however, women with severe pain conditions should not be deprived of appropriate pharmacotherapy.

OBJECTIVE To investigate whether children with varying severity of congenital heart defects (CHDs) have a higher risk of internalizing or externalizing emotional problems at 36 months of age. In addition, to analyze whether a history of emotional problems at 6 or 18 months of age increases the risk of emotional problems at 36 months in children with CHDs. METHODS Prospective data from the Norwegian Mother and Child Cohort Study, conducted by the Norwegian Institute of Public Health, was linked with a nationwide CHD registry, and 175 children with CHDs were identified in a cohort of 44,104 children aged 36 months. Maternal reports on child characteristics were assessed by questionnaires at child age 6, 18, and 36 months. RESULTS Children with CHDs did not have elevated scores on internalizing or externalizing problems at 36 months of age compared with controls. Not even the children with CHDs with a history of emotional problems at age 6 or 18 months showed an increased risk. CONCLUSIONS The absence of risk of emotional problems at 36 months of age in children with CHDs could be a consequence of the completion of the most extensive medical treatment.

Aim: To examine the association of the severity of congenital heart defects (CHDs) with internalizing problems in 18-month-olds and to explore the extent to which the internalizing problems are influenced by maternal distress and emotional reactivity in the child at age 6 months. Methods: We linked prospective data from the Norwegian Mother and Child Cohort Study, conducted by the Norwegian Institute of Public Health, with a nationwide CHD registry and identified 198 18-month-olds with CHDs in a cohort of 47 692 toddlers. Maternal reports on the children’s emotional reactivity at age 6 months, the children’s internalizing problems (anxiety, sleep problems, emotional reactivity) at age 18 months and maternal distress were assessed by questionnaires. Results: We found an association at age 18 months between the severity of the CHD and anxiety but not sleep problems or emotional reactivity. Children with severe but not with mild or moderate CHDs were twice as likely to experience the symptoms of anxiety compared with controls. These symptoms are not merely sequelae of earlier psychological reactions or concurrent maternal distress. Conclusion: Should these findings be replicated, future studies ought to investigate the mechanisms leading to elevated anxiety in toddlers with CHDs. In addition, clinical interventions should address the child’s anxiety as well as the interaction between the parents and the child.

Background With the advances in congenital cardiac surgery and medical management,mortality rates for congenital heart defects (CHD) have declined remarkably.As the number of CHD survivors have increased there is a growing focus on developmental morbidity.The objective of the current study is to compare symptoms of communication and social impairment in 18-month-old children with different severity of CHD with those of controls. Method We linked prospective data from the Norwegian Mother and Child Cohort Study, conducted by the Norwegian Institute of Public Health,with a nationwide medical CHD registry and identified 198 18-month-olds with CHD in a cohort of 47 692.Three groups of CHD were distinguished:mild/moderate (n = 122),severe (n = 54) and CHD with comorbidity (n = 22).Mothers reported on the child’s communication and social skills by completing items from the Ages and Stages Questionnaire as part of the Norwegian Mother and Child Cohort Study. Results Children aged 18 months old with CHD differed significantly from controls in levels of symptoms of communication impairment (P ! 0.0001) and social impairment (P ! 0.0001).The largest differences were found in children with CHD and comorbidity.Children with severe CHD also showed higher levels of both symptoms of communication and social impairment.Children with mild/moderate CHD showed a small difference only in symptoms of communication impairment. Conclusion Children with severe CHD and CHD with comorbidity show more symptoms of communication and social impairment compared with a large cohort at the age of 18 months.It is important to broaden the scope of inquiry to involve communication and social developmental domains.

OBJECTIVE: To examine the occurrence of developmental impairments in 3-year-old children with varying severity of congenital heart defects (CHD) and to identify predictors associated with developmental impairment in children with severe CHD. METHODS: Prospective data collected at birth, 6, 18, and 36 months from the Norwegian Mother and Child Cohort Study (MoBa), conducted by the Norwegian Institute of Public Health, were linked with a nationwide medical CHD registry, and 175 three year olds with CHD in a cohort of 44,044 children were identified. Children with mild/moderate (n = 115) and severe (n = 60) CHD were compared with children without CHD (43,929) on motor, communication, and social impairments as reported by mothers in Norwegian Mother and Child Cohort Study questionnaires. Predictors of developmental impairment were analyzed for the group with severe CHD. RESULTS: Children with severe CHD had >3 times higher odds of communication and gross motor impairments compared with controls, and had 2 times higher odds of any developmental impairment compared with controls. Children with mild and moderate CHD had >2 times higher odds of gross motor impairment but did not otherwise differ from controls. Predictors of impairment identified were previous developmental impairments and smaller head circumference at birth. CONCLUSION: Children with severe CHD have increased odds of developmental impairments at age 3 years. Early developmental impairments are associated with later developmental impairments, suggesting lasting impairments and not merely temporary delay. Patient-specific conditions at birth should be considered and motor and communication support provided to potentially improve outcomes in children with CHD.

To examine the association of the severity of congenital heart defects (CHDs) with internalizing problems in 18-month-olds and to explore the extent to which the internalizing problems are influenced by maternal distress and emotional reactivity in the child at age 6 months.We linked prospective data from the Norwegian Mother and Child Cohort Study, conducted by the Norwegian Institute of Public Health, with a nationwide CHD registry and identified 198 18-month-olds with CHDs in a cohort of 47 692 toddlers. Maternal reports on the children's emotional reactivity at age 6 months, the children's internalizing problems (anxiety, sleep problems, emotional reactivity) at age 18 months and maternal distress were assessed by questionnaires.We found an association at age 18 months between the severity of the CHD and anxiety but not sleep problems or emotional reactivity. Children with severe but not with mild or moderate CHDs were twice as likely to experience the symptoms of anxiety compared with controls. These symptoms are not merely sequelae of earlier psychological reactions or concurrent maternal distress.Should these findings be replicated, future studies ought to investigate the mechanisms leading to elevated anxiety in toddlers with CHDs. In addition, clinical interventions should address the child's anxiety as well as the interaction between the parents and the child.

Objective To assess whether the development of children with varying severity of congenital heart defect (CHD) differs from that of children without CHD at age 6 months. Study design A total of 236 children with CHD were compared with 61 032 children from the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. Diagnostic and treatment information was retrieved from a nationwide CHD registry. Four groups of CHD were distinguished: mild (n = 92), moderate (n = 50), severe (n = 70), and CHD with comorbidity (n = 24). At child age 6 months, the children's mothers reported on motor and social development by using the Mother and Child Questionnaire. Results After adjusting for confounders (ie, birth weight), severe CHD increased the odds of gross motor impairment (odds ratio [OR], 3.78; 95% CI, 1.97-7.25) and fine motor impairment (OR, 2.04; 95% CI, 0.96-4.33). CHD with co-morbidity (eg, intestinal malformations) increased the odds of gross motor impairment (OR, 3.00; 95% CI, 0.95-9.51), fine motor impairment (OR, 5.47; 95% CI, 2.03-14.74), and social impairment (OR, 3.43; 95% CI, 1.40-8.41). Conclusion Increased odds of motor impairment are present already in infancy in severe CHD and CHD with comorbidity. CHD with comorbidity increases the odds of social impairment.

Key Points Question Is prenatal exposure to thyroid hormone replacement therapy associated with children’s language, speech, and communication skills at 8 years of age? Findings In this nationwide population-based cohort linkage study of 53 862 mother-child pairs in Norway, prenatal thyroid hormone replacement therapy exposure was not associated with diagnoses and symptoms of child language and speech impairment, compared with the group not exposed to thyroid hormone replacement therapy or the group that received thyroid hormone replacement therapy after delivery. Meaning These findings indicate that the children of mothers treated with thyroid hormone replacement therapy for hypothyroidism were not associated with symptoms of or increased risk of language impairment., Importance Hypothyroidism during pregnancy is associated with neurodevelopmental delays in the offspring. However, it remains unknown whether prenatal thyroid hormone replacement therapy (THRT) has benefits regarding children’s language and communication skills. Objective To quantify associations between prenatal THRT exposure and risk of language impairment diagnosis and parent-reported symptoms of language and communication skill deficits in offspring at 8 years of age. Design, Setting, and Participants The Norwegian Mother, Father and Child Cohort Study (MoBa), a nationwide population-based cohort study, recruited pregnant women from throughout Norway between June 1999 and December 2008. MoBa was linked to several nationwide registries: the Norwegian Medical Birth Registry, Norwegian Prescription Database, and Norwegian Patient Registry. For this study, the analyzed cohort was restricted to singleton pregnancies resulting in a live-born infant, enrolled in the MoBa between 2005 and 2008. Statistical analysis was performed from January 2 to May 7, 2019. Exposures In both study samples, mother-child pairs were categorized into 3 mutually exclusive groups: THRT exposure during pregnancy, based on dispensed prescription records; unexposed to THRT during pregnancy (population comparison); and mothers initiating THRT after delivery (THRT after delivery), comprising incident postpartum THRT users. Main Outcomes and Measures Two defined study samples were analyzed with different outcome measures. In the Norwegian Patient Registry sample, outcome was defined by a diagnosis of language and speech impairment. In the MoBa sample, children were followed up until age 8 years via parental self-completed questionnaires. Hazard ratios were calculated for language impairment diagnosis, estimated by Cox proportional hazards regression. Standardized mean score (β) was calculated for parent-reported symptoms of language and communication deficits, estimated using generalized linear models. Results The Norwegian Patient Registry sample included 53 862 mother-child pairs (mean [SD] age, 30.4 [4.6] years; offspring, 26 145 girls and 27 717 boys; 1204 pairs exposed to THRT [2.2%]) and the MoBa sample included 23 686 mother-child pairs (mean [SD] age, 30.8 [4.4] years; offspring, 11 536 girls and 12 150 boys; 532 pairs exposed to THRT [2.2%]). Language and speech impairment diagnosis was not significantly associated with prenatal THRT exposure compared with the unexposed group (adjusted hazard ratio, 0.75; 95% CI, 0.38-1.43) or the THRT after delivery group (adjusted hazard ratio, 0.63; 95% CI, 0.26-1.53). Language outcomes also did not significantly differ between these groups. Conclusions and Relevance There was no significant difference in child outcomes between children exposed to THRT in the prenatal period compared with children in the population comparison group. These results support current guidelines recommending hypothyroidism treatment during pregnancy. Future research should further examine the use of THRT after delivery or a proper disease comparison group., This population-based cohort study examines associations between prenatal thyroid hormone replacement therapy exposure and risk of language impairment and parent-reported symptoms of language and communication skill deficits in offspring at 8 years of age.