Eivind Ystrom

Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study

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.

Breastfeeding cessation and symptoms of anxiety and depression: a longitudinal cohort study

BackgroundNeonatal anxiety and depression and breastfeeding cessation are significant public health problems. There is an association between maternal symptoms of anxiety and depression and early breastfeeding cessation. In earlier studies, the causality of this association was interpreted both ways; symptoms of anxiety and depression prepartum significantly impacts breastfeeding, and breastfeeding cessation significantly impacts symptoms of anxiety and depression.First, we aimed to investigate whether breastfeeding cessation is related to an increase in symptoms of anxiety and depression from pregnancy to six months postpartum. Second, we also investigated whether the proposed symptom increase after breastfeeding cessation was disproportionately high for those women already suffering from high levels of anxiety and depression during pregnancy.MethodsTo answer these objectives, we examined data from 42 225 women in the Norwegian Mother and Child Cohort Study (MoBa). Subjects were recruited in relation to a routine ultra-sound examination, and all pregnant women in Norway were eligible. We used data from the Medical Birth Registry of Norway and questionnaires both pre and post partum. Symptoms of anxiety and depression at six months postpartum were predicted in a linear regression analysis by WHO-categories of breastfeeding, symptoms of anxiety and depression prepartum (standardized score), and interaction terms between breastfeeding categories and prepartum symptoms of anxiety and depression. The results were adjusted for cesarean sections, primiparity, plural births, preterm births, and maternal smoking.ResultsFirst, prepartum levels of anxiety and depression were related to breastfeeding cessation (β 0.24; 95% CI 0.21-0.28), and breastfeeding cessation was predictive of an increase in postpartum anxiety and depression ( β 0.11; 95%CI 0.09-0.14). Second, prepartum anxiety and depression interacted with the relation between breastfeeding cessation and postpartum anxiety and depression ( β 0.04; 95% CI 0.01-0.06). The associations could not be accounted for by the adjusting variables.ConclusionsBreastfeeding cessation is a risk factor for increased anxiety and depression. Women with high levels of anxiety and depression during pregnancy who stop breastfeeding early are at an additional multiplicative risk for postpartum anxiety and depression.

The mutual prospective influence of child and parental post-traumatic stress symptoms in pediatric patients.

BACKGROUND   Previous studies found notable rates of post-traumatic stress symptoms (PTSS) and post-traumatic stress disorder (PTSD) in pediatric patients and their parents and suggest a significant association between child and parent PTSS. However, little is known about mutual influences between child and parental PTSS over time. This study prospectively examined the presence of PTSS and PTSD and the mutual influence of child and parental PTSS in a large sample of pediatric patients with different medical conditions. METHODS   A total of 287 children (aged 6.5-16 years) and their mothers (n = 239) and fathers (n = 221) were assessed at 5-6 weeks and 1 year after an accident or a new diagnosis of cancer or diabetes mellitus type 1 in the child. RESULTS   At the first assessment 11.1% and at the second assessment 10.2% of the children had moderate to severe PTSS. At 5-6 weeks 29.3% of mothers and 18.6% of fathers met criteria for PTSD. At 1 year the rates were 14.6% for mothers and 7.9% for fathers. There were considerable differences of PTSS among different medical diagnostic groups in children and parents. Mothers were more vulnerable than fathers. Structural equation analysis revealed that initially high PTSS in mothers and fathers were longitudinally related to poorer recovery from PTSS in the child. Cross-lagged effects from the child to the parents and from one parent to the other were not significant. CONCLUSIONS   This study highlights the long-term influence of parental PTSS on the childs recovery after trauma and calls for a family systems approach and for early interventions in the treatment of traumatized pediatric patients.

Trajectories of language delay from age 3 to 5: persistence, recovery and late onset

BACKGROUND Knowledge is scarce on what contributes to whether children with early language delay (LD) show persistent, recovering or sometimes late-onset LD without a prior history of early LD in subsequent preschool years. AIMS To explore whether an integrative model of vital risk factors, including poor early communication skills, family history of language-related difficulties and male gender, predicts the development of persistent, recovering or late-onset LD trajectories from 3 to 5 years quantitatively and qualitatively differently. METHODS & PROCEDURES LD was assessed by maternal reports on the Ages and Stages Questionnaire at 3 and 5 years for 10 587 children in The Norwegian Mother and Child Cohort Study. Children were classified across time as having no, late onset, transient or persistent LD. Multinomial logistic regression analyses included the integrative model of vital risk factors and covariates. OUTCOME & RESULTS Across time, 3%, 5% and 6.5% of the children displayed persistent, transient and late-onset LD, respectively. The odds for persistent LD were doubled for boys and children with low language comprehension at 1.5 years; and tripled by late-talking familial risk. These same odds decreased for transient LD, and even further for late-onset LD. Familial risk for writing and reading difficulties especially increased the odds for late-onset and persistent LD, while familial risk of unintelligible speech increased the odds for transient LD. Although girls had on average far better language comprehension than boys, low language comprehension was a stronger risk factor for persistent LD in girls. CONCLUSIONS & IMPLICATIONS Preschool LD trajectories were uniquely predicted from the integrative risk model of poor early communicative skills, family history and male gender. This might benefit identification of different LD trajectories by supporting broader severe vulnerability for persistent LD, milder vulnerability for transient LD, and possibly a specific risk for reading and learning difficulties for children with late-onset LD.

Later Emotional and Behavioral Problems Associated With Sleep Problems in Toddlers: A Longitudinal Study

IMPORTANCE Childhood sleep problems have been linked to a range of adverse health outcomes, but there is limited knowledge as to the temporal association between sleep problems and subsequent emotional and behavioral problems in young children. OBJECTIVE To examine whether sleep problems in toddlers aged 18 months are related to both concurrent and subsequent emotional and behavioral problems in preschool children aged 5 years. DESIGN, SETTING, AND PARTICIPANTS A large population-based longitudinal study was conducted in September 2014 using data from the Norwegian Mother and Child Cohort Study conducted at the Norwegian Institute of Public Health from June 1, 1999, to December 31, 2008. A total of 32 662 children or pregnancies were included. EXPOSURES Sleep was assessed by mother-reported child sleep duration and nocturnal awakenings. MAIN OUTCOMES AND MEASURES Emotional and behavioral problems were measured with items from the Child Behavior Checklist and operationalized according to recommended clinical cutoffs, corresponding to T scores of greater than 65 (93rd percentile). Risk ratios (RRs) were calculated using negative binomial regression, controlling for emotional and behavioral problems at 18 months and other relevant covariates. RESULTS Short sleep duration (≤10 hours) in 556 children (1.7%) and frequent nocturnal awakenings (≥3 times) in 1033 children (3.2%) at 18 months significantly predicted both concurrent and later incidence of emotional and behavioral problems at 5 years. The longitudinal RRs were generally larger for internalizing problems, with adjusted RRs of 1.59 (95% CI, 1.23-2.08) for both short sleep duration and 1.57 (95% CI, 1.28-1.93) for nocturnal awakenings; RRs for externalizing problems were 1.77 (95% CI, 1.37-2.30) and 1.25 (95% CI, 1.00-1.58), respectively. Additional adjustment for emotional and behavioral problems at 18 months slightly reduced the strength of these associations, and all RRs remained significant in the fully adjusted models. CONCLUSIONS AND RELEVANCE Early sleep problems predict later development of emotional and behavioral problems. Intervention studies are needed to examine whether sleep programs targeting early childhood may avert the onset of later adverse outcomes.

Is difficult temperament related to overweight and rapid early weight gain in infants? A prospective cohort study

Objective: Childhood overweight and rapid weight gain during the first months of life have been shown to be major risk factors for the development of later overweight. Studies in children show that there are temperamental risk factors for the development of overweight, but little is known about early infancy. Methods: The present study investigated the relationship of infant difficult temperament, assessed at age 6 months, with overweight status at birth and at 6 months of age and with rapid weight gain during this period. Data collection was conducted as part of the Norwegian Mother and Child Cohort Study at the Norwegian Institute of Public Health (1999–2006). The analyses are based on data retrieved from the Medical Birth Registry of Norway, health charts, and maternal reports during pregnancy and when the child was 6 months of age. After application of eligibility criteria, 29,182 infants could be included in the study. Results: In adjusting for infants’ sex, formula feeding, maternal age, body mass index and diabetic status, and parental duration of education, infant difficult temperament was slightly negatively associated with overweight status at birth but not at age 6 months. In addition, infant difficult temperament was slightly positively associated with rapid weight gain during the first 6 months of life. Conclusions: Despite statistical significance, these associations do not appear to be clinically relevant. Future studies should explore whether the impact of temperament increases with age.

Impact of gender, maternal education, and birth order on the development of language comprehension: a longitudinal study from 18 to 36 months of age.

Objective: To investigate the impact of child gender, maternal education, and birth order on language comprehension (LC) status at 18 and 36 months of age and on the change in LC between these time points. Gender interactions and interactions between maternal education and birth order are also examined. Methods: This study is based on data from the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. Maternal report data on education, birth order, and child language in a sample of 44,921 children were used in linear regression analyses. Results: At 18 and 36 months of age, first-born girls of mothers with high educational attainment had the highest level of LC. Between 18 and 36 months of age, first-born boys of mothers with high educational attainment had the highest increase in LC. Having a highly educated mother contributed more to the increase in LC in boys than in girls. The boys whose mothers had the highest education level had lower scores than the girls whose mothers had the lowest educational level, at both ages. Although significant, the considerable effect of high maternal education was not substantially dependent on birth-order status. Conclusions: Boys develop LC at a faster rate than girls between 18 and 36 months, but girls still remain superior in their level of LC at 36 months of age. Being firstborn or having a highly educated mother does not compensate for this lag.

Alcohol dependence in men: reliability and heritability.

BACKGROUND The assessment of a Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) life-time history of alcohol dependence (LTH-AD) has been found to be moderately reliable and substantially heritable. However, in studies of the heritability of LTH-AD, measurement error could not be discriminated from the true unique environmental effects. The aims of this study were to: (i) estimate the reliability of LTH-AD in a population based sample, (ii) identify characteristics of LTH-AD predicting a reliable diagnosis, (iii) investigate the heritability of LTH-AD as a function of diagnostic confidence, and (iv) to estimate the genetic and environmental influences on LTH-AD correcting for measurement error. METHODS An unselected sample of 4,203 male twins was interviewed twice approximately 1-year apart assessing DSM-IV LTH-AD over the same period of life. Logistic regression was used to identify clinical features that predict a reliable diagnosis LTH-AD. Genetic and environmental influences on reliable LTH-AD were examined using structural equation models. RESULTS Reliability of the diagnosis of LTH-AD was moderate (κ = 0.54) and was predicted by the number of AD symptoms, treatment seeking, duration of most severe episode, and a great deal of time spent to obtain, use, or recover from alcohol use (DSM-IV AD criterion #5). Using an index of caseness, heritability of LTH-AD increased as a function of diagnostic confidence. Accounting for errors of measurement in a multivariate twin model, the heritability of LTH-AD increased from 55 to 71%. CONCLUSIONS Reliably diagnosed LTH-AD can be predicted by characteristics relevant to the disorder. LTH-AD appears to be a moderately reliable disorder of high heritability.

Early age of alcohol initiation is not the cause of alcohol use disorders in adulthood, but is a major indicator of genetic risk. A population-based twin study

BACKGROUND AND AIMS An early age of alcohol initiation (AAI) is associated with and has been hypothesized to be a cause of alcohol use disorders (AUD) in adulthood. Results from twin studies, however, indicate that AAI is an indicator of risk for AUD. We aimed to test a causal hypothesis versus a risk indicator hypothesis for the relationship between early AAI and AUD. DESIGN A population-based twin study using biometric twin modelling. SETTING Norway. PARTICIPANTS A population-based sample of 1336 Norwegian twins. MEASUREMENTS Life-time DSM-IV AUDs were assessed by structured clinical interview and AAI by questionnaire. FINDINGS The risk indicator model in which the association between AAI and AUD was explained by common vulnerability was the best fitted to the data. The heritability was 37% [95% confidence interval (CI) = 21%, 53%] for AAI and 62% (95% CI = 51%, 73%) for AUD. Genetic risk for AAI accounted for 44% (95% CI = 17%, 71%) of the total genetic risk for AUD and the correlation between genetic factors for AAI and AUD was -0.66 (95%CI -0.87, -0.46). Individual-specific environmental risk for AAI explained only 1% (95% CI = 0%, 3%) of the risk for AUD. Shared environmental factors did not influence AUD, but accounted for 25% (95% CI = 7%, 35%) of the variance in AAI. CONCLUSIONS The association between early age of alcohol initiation and alcohol use disorders in later life does not reflect a causal relationship, but is due almost entirely to common genetic risk factors.

The impact of maternal negative affectivity on dietary patterns of 18‐month‐old children in the Norwegian Mother and Child Cohort Study

Early dietary habits are formative for dietary habits later in life. Maternal personality might be an important factor in unhealthy feeding of children. The current study aims to assess the degree to which the personality trait of negative affectivity in mothers predicts their childs diet at age 18 months. This study is a part of the Norwegian Mother and Child Cohort Study conducted at the Norwegian Institute of Public Health. A total of 27 763 mothers completed 3 repeated assessments of negative affectivity before and after childbirth and of the childs diet when the child was 18 months old. Exploratory factor analysis was used to identify the dietary patterns, and structural equation modeling was used to investigate the relationship with negative affectivity adjusted for socio-demographical variables. Exploratory factor analysis of a foods frequency questionnaire revealed two dietary patterns in the child, labeled unhealthy diet and wholesome diet. The unhealthy diet comprised foods rich in sugar and fat; the wholesome diet comprised foods rich in fibre, vitamins and minerals. Mothers high in negative affectivity were more inclined to feed their child an unhealthy diet. The results were adjusted for maternal age, years of education, relative income, marital status, number of children, having the child in daycare, maternal smoking, maternal body mass index, and child gender. This study shows that a maternal personality trait, negative affectivity, is related to feeding the child an unhealthy diet after controlling for key socio-demographic variables.