Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers.

BACKGROUND: Autism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis. METHODS: Serum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B9) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation. RESULTS: We found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase: 1.70, 95% CI 1.22-2.37, FDR adjusted P = 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D3 levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring. CONCLUSIONS: Our findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.

Parents of extremely and moderately preterm children reported long-lasting impressions of medical care and the hospital environment.

AIM: Few studies have examined the parents of moderately preterm children. The aim of this study was to investigate the experiences of parents of both extremely and moderately preterm children. METHODS: Qualitative telephone interviews were conducted in 2013-2014 with 13 mothers and 10 fathers of extremely preterm children and with 11 mothers and seven fathers of moderately preterm children. The children were born between 2000 and 2003. Data were analysed with a narrative approach. RESULTS: Parents of extremely preterm children recounted dramatic birth stories that, for most, ended positively. Parents of moderately preterm children presented more neutral birth stories, and most recounted that their children did not receive attention for prematurity from medical staff. Parents from both groups described staff members' treatment in terms of long-lasting impressions, and they were deeply affected by the hospital environment and the other parents and children admitted. Parents whose children died or were disabled recounted dramatic stories and endless fights for support. CONCLUSION: Parents from both groups reported long-lasting impressions of the medical staff and the hospital environment, which they found important to talk about, even a decade after the birth of their child/children.

Parents of preterm children narrate constructive aspects of their experiences.

AIMS AND OBJECTIVES: To explore how parents of preterm infants express the constructive aspects of their experiences. Using the notion of post-traumatic growth as a back-drop, this study supplements the research on parents' difficulties by providing a more nuanced understanding of what it is like to have a preterm child. BACKGROUND: Researchers have reported that parents feel afraid, worried, helpless, powerless, guilty and stressed, as well as that preterm birth can be associated with physical and psychological ill health among parents; however, a few researchers have found indications of post-traumatic growth among parents. DESIGN: This study includes qualitative interviews and relates to COREQ guidelines for reporting qualitative research. METHODS: A total of 13 mothers and 10 fathers of extremely preterm children, as well as 11 mothers and 7 fathers of moderately preterm children, were interviewed. The data analysis was based on thematic analysis. RESULTS: The analysis resulted in six themes that describe various constructive aspects of having a preterm child: acceptance of the fact that events do not always occur as planned; gratitude and reconsideration of the situation; reappraisal of close relationships; reliance on one's own ability to deal with events; thankfulness for what one has; and openness to being exposed to various kinds of people and their experiences. CONCLUSIONS: The parents recounted constructive aspects of their experiences such as an altered understanding of themselves, others and life itself. These themes provide a more nuanced way of understanding how parents can relate to having preterm children. RELEVANCE TO CLINICAL PRACTICE: This knowledge can help professionals to enable parents to activate their social network and to acknowledge their care for each other, as well as to help parents see beyond cultural ideals regarding childbirth and family life and to find their own solutions to everyday life.

Increase of internalized mental health symptoms among adolescents during the last three decades.

BACKGROUND: Previous studies suggest an overall increase of adolescent mental health symptoms globally since the 1980s until today, especially an increase of internalizing symptoms in girls. Due to methodological limitations of these studies, further studies are warranted to obtain a more solid knowledgebase. METHODS: This study was cross-sectional and compared two separate but geographically identical groups of adolescents in a middle-sized industrial municipality in Northern Sweden at two time-points [(i) 1981, n = 1083, (505 girls, 577 boys), response rate 99.7%; (ii) 2014, n = 682, (338 girls, 344 boys), response rate 98.3%]. All students in their last year of compulsory school were included. The same self-report questionnaire, consisting of four sub-scales (functional somatic-, anxiety-, depressive symptoms and conduct problems), was used at both occasions. Data were analyzed with descriptive statistics, two-way ANOVA and general linear model. RESULTS: Symptoms of anxiety and depression and functional somatic symptoms, increased among both boys and girls from 1981 until 2014 (P < 0.001 for all subscales), and the increase of these symptoms was higher in girls. Conduct problems were significantly higher in boys in 1981 and decreased over time so that in 2014 there was no longer a significant difference between boys and girls regarding conduct problems (P = 0.286). CONCLUSION: In this population-based study spanning over 30 years, both girls and boys showed increasing internalizing problems, while conduct problems decreased. To halt this trend, we need a deeper understanding of the impact of the major societal changes that have occurred during the last three decades.

Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years: a randomized controlled trial.

BackgroundLow-birth-weight infants (LBW) are at an increased risk of iron deficiency that has been associated with impaired neurodevelopment. We hypothesized that iron supplementation of LBW infants improves cognitive scores and reduces behavioral problems until school age.MethodsWe randomized 285 marginally LBW (2,000-2,500 g) infants to receive 0, 1, or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age. At 7 years of age, 205 participants were assessed regarding cognition using Wechsler Intelligence Scale for Children (WISC-IV) and behavior using the parental questionnaires Child Behavior Checklist (CBCL) and Five to Fifteen (FTF).ResultsThere were no significant differences between the intervention groups in WISC-IV or FTF. However, the CBCL scores for externalizing problems were significantly different, in favor of supplemented children (P=0.045). When combining the supplemented groups, they had significantly lower scores for externalizing behavior compared with placebo (median (interquartile range): 44 [34;51] vs. 48.5 [41;56] P=0.013), and their risk ratio (95% confidence interval) for a total behavioral score above the cutoff for clinical problems was 0.31 (0.09-1.0), P=0.054.ConclusionLower scores of externalizing behavior in supplemented children support our previous findings at 3 years, and suggest that iron supplementation may have long-lasting effects on behavioral functions.

Behavioral Patterns in Adolescents Born at 23 to 25 Weeks of Gestation.

BACKGROUND: This study examined mental health outcomes in extremely preterm children (EPT) born at 23 to 25 weeks of gestation between 1992 and 1998 at 2 Swedish tertiary care centers that offered regional and active perinatal care to all live-born EPT infants. METHODS: We assessed 132 (98%) of the 134 EPT survivors at 10 to 15 years of age alongside term-born controls. Behavioral and emotional problems were evaluated by using Achenbach's Child Behavior Checklist and Teacher Report Form and Conners' Parent and Teacher scales for attention-deficit/hyperactivity disorder. RESULTS: Parents and teachers reported significantly more problems with internalizing behaviors as well as attention, social, and thought problems in EPT children than in controls, even when those with major neurodevelopmental disabilities (NDDs) were excluded. Multivariate analysis of covariance of the behavioral problems reported by parents and teachers revealed no interactions, but significant main effects emerged for group status (EPT versus control) and sex, with all effect sizes being medium to large and accounting for 8% to 14% of the variance. Compared with the controls, EPT children without NDDs had significantly increased rates of ≥90th percentile for total Conners' attention-deficit/hyperactivity disorder problem scores (parents: 40% vs 15%, odds ratio: 3.7, P < .001) (teachers: 24% vs 9%, odds ratio: 3.3, P = .005). The corresponding rates were higher in the total population. CONCLUSIONS: EPT children with or without NDDs had behavioral problems characterized by a higher risk for anxiety and attention, social, and thought problems. These findings further strengthen the proposition that a preterm behavioral phenotype is recognizable in adolescents born EPT.

Chronic Conditions and Health Care Needs of Adolescents Born at 23 to 25 Weeks' Gestation.

OBJECTIVE: We examined chronic conditions, functional limitations, and special health care needs in extremely preterm children (EPT; 23-25 weeks' gestation) born between 1992 and 1998 at 2 Swedish tertiary care centers that offered regional and active perinatal care to all live-born EPT infants. METHODS: Of 134 surviving EPT children, 132 (98%) were assessed at 10 to 15 years of age alongside 103 term-born controls. Identification of children with functional limitations and special health care needs was based on a questionnaire administered to parents. Categorization of medical diagnoses and developmental disabilities was based on child examinations, medical record reviews, and parent questionnaires. RESULTS: In logistic regression analyses adjusting for social risk factors and sex, the EPT children had significantly more chronic conditions than the term-born controls, including functional limitations (64% vs 6%; odds ratio [OR], 15; 95% confidence interval [CI], 6.1-37.2; P < .001), compensatory dependency needs (60% vs 29%; OR, 3.8; 95% CI, 2.2-6.6; P < .001), and services above those routinely required by children (64% vs 25%; OR, 5.4; 95% CI, 3.0-9.6; P < .001). Specific diagnoses and disabilities for the EPT group versus controls included cerebral palsy (9.1% vs 0%; P < .001), asthma (21.2% vs 6.8%; P = 001), IQ < -2 SD (31.1% vs 4.9%; P < .001), poor motor skills without neurosensory impairment (21.9% vs 1.9%; P < .001), and psychiatric conditions (15.2% vs 1.9%; P < .001). CONCLUSIONS: Adolescents born EPT have considerable long-term health and educational needs. Few had severe impairments that curtailed major activities of daily life.

Reboxetine in therapy-resistant enuresis: A randomized placebo-controlled study.

INTRODUCTION: A significant minority of children with enuresis do not respond to either desmopressin or the enuresis alarm. Anticholinergics have not proven as successful as expected. The fourth evidence-based treatment, the tricyclic antidepressant imipramine, is cardiotoxic when overdosed, which has led to diminished use. AIM: The aim was to determine whether there is a role for the noradrenergic antidepressant reboxetine, as monotherapy or combined with desmopressin, in the treatment of enuresis in children who have not responded to standard therapy, and whether there are side effects involved. We also sought prognostic factors in anamnestic data and in the voiding chart. PATIENTS AND METHODS: The study was a randomized placebo-controlled study with a double-blind cross-over design, in which all patients underwent treatment during three 4-week periods, one with reboxetine 4 mg and placebo, one with reboxetine 4 mg and desmopressin, and one with double placebo treatment. The proportion of wet nights out of 14 was compared before treatment and during the last 2 weeks of each treatment period. RESULTS: Eighteen patients were included. The reduction of wet nights was much better with either reboxetine in monotherapy or in combination with desmopressin than during the placebo period (p = 0.002) (Figure). However, only one patient achieved complete dryness, this during monotherapy. There were three intermediate responders to monotherapy and five to combination treatment. With reboxetine in monotherapy, six children experienced negative side effects compared with three with combination therapy, and two with placebo. All of these side effects were mild and reversible. Only one patient chose to cease treatment because of side effects. No prognostic factors were found in either the case history or in voiding chart data. DISCUSSION: The present study, the first placebo-controlled trial, confirms that reboxetine is an evidence-based alternative to cardiotoxic antidepressant treatment in therapy-resistant enuresis. The fact that few patients achieved complete dryness may be due to the low dosage used. In our clinical practice we increase the dose to 8 mg when dryness is not achieved with the lower dose. Our experience is that this leaves more children with full response, but the evidence of this has yet to be shown. CONCLUSION: Reboxetine seems to be an alternative in the treatment of enuretic children who have not responded to standard treatment.

Stress symptoms among adolescents before and after scoliosis surgery: correlations with postoperative pain.

AIMS AND OBJECTIVES: The aim of this study was to describe stress symptoms among adolescents before and after scoliosis surgery and to explore correlations with postoperative pain. BACKGROUND: Scoliosis surgery is a major surgical procedure. Adolescent patients suffer from preoperative stress and severe postoperative pain. Previous studies indicate that there is a risk of traumatisation and psychological complications during the recovery period. DESIGN: A prospective quantitative cohort study with consecutive inclusion of participants. METHODS: A cohort of 37 adolescent patients aged 13-18. To assess the adolescents' experiences before surgery and at six to eight months after surgery, the Trauma Symptom Checklist for Children - Alternative version, Youth Self-Report and Kiddie Schedule for Affective Disorder and Schizophrenia for children 12-18 were used. The Visual Analogue Scale was used for self-report of postoperative pain on day three. RESULTS: Rates of anxiety/depression and internalising behaviour were significantly higher before surgery than six months after. Preoperative anger, social problems and attention problems correlated significantly with postoperative pain on day three. At follow-up, postoperative pain correlated significantly with anxiety, social problems and attention problems. CONCLUSIONS: The results of this study indicate a need for interventions to reduce perioperative stress and postoperative pain to improve the quality of nursing care. RELEVANCE TO CLINICAL PRACTICE: Attention to preoperative stress and implementation of interventions to decrease stress symptoms could ameliorate the perioperative process by reducing levels of postoperative pain, anxiety, social and attention problems in the recovery period.

School experiences may be important determinants of mental health problems in middle childhood - a Swedish longitudinal population-based study.

AIM: Little is known about the association between school experiences and mental health in young schoolchildren. This study explored the cross-sectional and prospective associations between children's school experiences and mental health in middle childhood. METHODS: We gathered comprehensive population-based data on the school experiences and mental health of 592 schoolchildren attending grades three and six in Sweden (ages approximately nine and 12 years). The KIDSCREEN questionnaire was used to measure school experiences in both age groups while the Child Behavior Checklist and the Strengths and Difficulties Questionnaire measured mental health in grades three and six, respectively. RESULTS: Children with problematic school experiences in grade three had an approximately two times higher odds for concurrent total, internalised, externalised, attention-hyperactivity and social problems. They also had a 1.5-2.5 higher odds for these mental health problems three years later. Likewise, there was an association between problematic school experiences in grade three and lower levels of prosocial behaviour three years later. These associations were shown in both boys and girls, but were particularly pronounced in girls. CONCLUSION: This study indicated that school experiences in young schoolchildren may be important determinants of concurrent and later mental health problems.

Addressing challenges of validity and internal consistency of mental health measures in a 27- year longitudinal cohort study - the Northern Swedish Cohort study.

BACKGROUND: There are inherent methodological challenges in the measurement of mental health problems in longitudinal research. There is constant development in definitions, taxonomies and demands concerning the properties of mental health measurements. The aim of this paper was to construct composite measures of mental health problems (according to today's standard) from single questionnaire items devised in the early 1980s, and to evaluate their internal consistency and factorial invariance across the life course using the Northern Swedish Cohort. METHODS: All pupils in the last year of compulsory school in Luleå in 1981 (n = 1083) form a prospective cohort study where the participants have been followed with questionnaires from the age of 16 (in 1981) until the age of 43 (in 2008). We created and tested the following composite measures from self-reports at each follow-up: depressive symptoms, anxiety symptoms, functional somatic symptoms, modified GHQ and positive health. Validity and internal consistency were tested by confirmatory factor analysis, including tests of factorial invariance over time. RESULTS: As an overall assessment, the results showed that the composite measures (based on more than 30-year-old single item questions) are likely to have acceptable factorial invariance as well as internal consistency over time. CONCLUSIONS: Testing the properties of the mental health measures used in older studies according to the standards of today is of great importance in longitudinal research. Our study demonstrates that composite measures of mental health problems can be constructed from single items which are more than 30 years old and that these measures seem to have the same factorial structure and internal consistency across a significant part of the life course. Thus, it can be possible to overcome some specific inherent methodological challenges in using historical data in longitudinal research.

Mental problems and their socio-demographic determinants in young schoolchildren in Sweden, a country with high gender and income equality.

AIMS: Mental problems and their potential socio-demographic determinants were investigated in young schoolchildren in Sweden, a high-income country in the top of income- and gender-equality rankings. METHODS: Cross-sectional study of 1465 schoolchildren in grades 3 and 6. Mental health was measured by the Child Behavior Checklist and the Youth Self Report (Total problems and 14 specific problem areas). Potential socio-demographic determinants were sex, parental education and occupation, family structure, and immigrant status. RESULTS: Mental problems were present in 14% of the sixth graders and in 7% of the third graders. In grade 3, the mean total problem score was lower in girls than in boys, but the prevalence of problems at a subclinical/clinical level did not differ by sex. Furthermore, in nine to 13 of the 14 specific problem areas, problems were equally distributed by sex, parental education, parental occupation, immigrant status, and family structure. In grade 6, both the total mean score and the overall odds of subclinical/clinical problems were similar in girls and boys. Likewise, in all the specific problem areas, problems were evenly distributed by parental education and occupation, and only independently associated with immigrant status and family structure in one problem area. In five specific problem areas, boys had higher odds of problems than girls. CONCLUSIONS: This study shows that also in a relatively wealthy and equal country such as Sweden, mental problems are a significant child public health issue. The association between socio-demographic background and mental problems seems to be rather weak, but differ dependent on the type of mental problem in focus.

Mental health in adolescence as determinant of alcohol consumption trajectories in the Northern Swedish Cohort.

OBJECTIVES: The study aimed to analyze whether poor mental health in adolescence predicts heavy alcohol consumption over the long term. METHODS: Alcohol consumption in the population cohort (n = 1010) was surveyed at the ages of 16, 18, 21, 30 and 42. Utilizing latent class growth analysis, six consumption trajectories ranging from 'Late Onset Low' to 'Early Onset High' were defined and analyzed with respect to internalization (depressiveness and anxiousness) and externalization (truancy and vandalism) at age 16. RESULTS: Poor mental health predicted the Early Onset High trajectory (risk ratios in relation to the compliant trajectory 3.59 for anxiousness, 2.85 for depressiveness, 5.69 for truancy and 7.75 for externalized vandalism). Moreover, significant associations were found for the Early Onset Moderate and Early Onset Low trajectories. CONCLUSIONS: This is the first study to show an association between internalized mental health problems in adolescence and lifelong heavy drinking. The study also confirmed a strong association between externalized behavior and heavy drinking, indicating a need of preventive measures in this group. Nevertheless, the analyses demonstrated that most teenagers with mental health problems continue along a reasonable drinking trajectory.

Health-related quality of life in adolescents with chronic physical illness in northern Russia: a cross-sectional study.

BACKGROUND: Health related quality of life (HRQoL) is an important subjectively evaluated outcome of adolescents physical, mental, and social functioning. It gives us the possibility to assess the disease impact on life of adolescents, and to sort out target groups of adolescents for future psychological interventions. The objective of this cross-sectional survey was to study HRQoL in 173 adolescents with chronic physical illness (CPI - diabetes, asthma, and epilepsy), and to find HRQoL predictors in each disease group. METHODS: Disease-specific questionnaires were completed by each adolescent recruited from the local outpatient clinic; mothers answered the questions on socioeconomic status (SES); and the patients' clinicians evaluated the severity of the disease. RESULTS: A high proportion of adolescents in each disease specific sample reported moderate to high levels of HRQoL. Gender was the most prominent predictor of HRQoL in all three studied groups, while disease severity predicted HRQoL in the diabetic group and to some extent in the asthma group. CONCLUSIONS: Our results provide evidence that adolescents with diabetes, asthma, and epilepsy in northern Russia maintain relatively moderate to high levels of HRQoL. The domains affecting HRQoL were related to both disease-specific (severity) and non-disease factors (gender and SES). Our study suggests that future psychosocial interventions should focus on aspects of CPI impacting adolescents in gendered ways, furthermore taking into account disease specific factors.

Self-esteem in adolescents with chronic physical illness vs. controls in Northern Russia.

OBJECTIVE: This work aims to study self-esteem in adolescents with diabetes, asthma and epilepsy; compare the results with those of the representative sample of healthy adolescents; and evaluate the predictive value of certain demographic, family-related, and disease-related factors on self-esteem. METHODS: A total of 148 chronically ill adolescents and 301 matched healthy counterparts completed the Rosenberg Self Esteem Scale and the "I think I am" questionnaire. Adolescents' parents answered socio-economic status questions. Disease severity was evaluated by doctors of the outpatient clinic. RESULTS: Comparison analysis of the three disease groups revealed highest self-esteem perception in adolescents with diabetes, and lowest in adolescents with epilepsy. Unexpectedly, adolescents with diabetes scored higher than their healthy counterparts. There were no significant differences between the reports of adolescents with asthma and controls. In the epilepsy group, self-esteem was predicted mostly by disease severity and socio-economic status in diabetes and asthma groups, as well as by age and gender. CONCLUSION: The maintenance of positive self-esteem in adolescents with diabetes and asthma is a very reassuring finding. The other results of our study provide support for recognizing adolescents with epilepsy as a vulnerable group in the society. A multidisciplinary professional approach targeted on adolescents with epilepsy is needed, with focus on factors connected with maturation and gender issues.

Behaviours related to executive functions and learning skills at 11 years of age after extremely preterm birth: a Swedish national prospective follow-up study.

AIM: We investigated a national cohort of children born extremely immature (<26 weeks gestation, EI) regarding the nature, frequency and severity of the behavioural problems related to the executive functions (EF) and concerning learning skills, from the perspectives of parents and teachers. METHODS: At 11 years of age 86 of 89 survivors of this cohort were studied and compared with an equal number of controls. Behaviours related to EF, and learning skills were assessed by a validated instrument, namely the Five to Fifteen questionnaire sent by mail to parents and teachers. RESULTS: Compared with controls, parents of EI children reported significantly more problems in behaviours related to EF in all areas assessed (Attention, Hyperactivity/Impulsivity, Hypoactivity, Planning/Organizing, and Working Memory). Teachers' ratings showed a similar pattern. EI children also displayed deficient skills in the 4 standard measures of learning skills. Multivariate analysis revealed that prematurity, gender and behavioural composite score was associated with learning skills. Only a relatively small proportion of EI children (10-30%) exhibited clinically significant impairments. CONCLUSION: Despite a favourable outcome in many school-age children born at the threshold of viability, these are at increased risk of developing behavioural problems related to EF.

Interprofessional teamwork in Swedish pediatric cardiology: a national exploratory study.

This paper aims to describe the nature of pediatric cardiology teams (PCTs) based in Sweden through the use of a mixed methods approach. Questionnaires examining issues about the organization/ways of working, functions/tasks and attitudes were answered by 30 PCTs. Focus group interviews were conducted with six PCTs, selected purposefully by size and location, and information on experiences and attitudes on interprofessional teamwork was explored in depth. Results from the quantitative indicated that in 17 of the teams, where the nurse acted as the central coordinator, there was a positive attitude to the value of teamwork. In the interviews, different problems and needs of improvements were mentioned regarding structure, leadership, presence of physicians in the team as well as the team's mandate. All of the participants, however, agreed that interprofessional teams were required to manage the complexity of the children's care. In conclusion, this study suggests that PCTs need further support to develop structure, leadership and coordination of resources to function in a more effective manner. National plans or recommendations that mandate the organization and working methods of PCTs would be helpful for the ongoing development of PCTs in Sweden.

Platelet serotonin transporter and 5-HT2A receptor binding in adolescents with eating disorders.

The pathogenetic involvement of the serotonergic system in eating disorders is an established finding. Conclusions from platelet studies are based on results from investigations of subjects with a mean age of 20 years or more. The aim was to investigate whether previous findings in adults are valid also for adolescents who are examined within a relatively short interval after the onset of the eating disorder. [(3)H]paroxetine binding to the platelet serotonin transporter and [(3)H]lysergic acid diethylamide ([(3)H]LSD) binding to the 5-HT2A receptor was studied in 15 female adolescents with eating disorders (11 with anorexia nervosa and 4 with clearly anorectic eating behaviour not fulfilling the criteria for anorexia nervosa) and 32 controls. The patients revealed a higher density of serotonin transporters and a lower density of 5-HT2A receptors compared with healthy controls of the same age (775 ± 165 vs. 614 ± 111 fmol/mg protein (p = 0.003) for [(3)H]paroxetine binding and 215 ± 59 vs. 314 ± 151 fmol/mg protein (p = 0.005) for [(3)H]LSD binding). The findings of increased density of platelet serotonin transporters and reduced density of 5-HT2A receptors differ from previous results in older patients. The lower patient age and the short duration of disease in the present study, possibly in conjunction with variations in stress-related psychological and biological factors, may have caused these differences. Although the present findings contradict prevailing evidence, they add further information concerning the nature of serotonergic involvement in eating disorders and indicate that demographic and course-related factors might influence the regulation of the serotonin system in these disorders.

Effects of iron supplementation of LBW infants on cognition and behavior at 3 years.

OBJECTIVE: Low birth weight (LBW) infants are at increased risk of cognitive and behavioral problems and at risk for iron deficiency, which is associated with impaired neurodevelopment. We hypothesized that iron supplementation of LBW infants would improve cognitive scores and reduce behavioral problems. METHODS: In a randomized controlled trial, 285 marginally LBW (2000-2500 g) infants received 0, 1, or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age. At 3.5 years of age, these infants and 95 normal birth weight controls were assessed with a psychometric test (Wechsler Preschool and Primary Scale of Intelligence) and a questionnaire of behavioral problems (Child Behavior Checklist; CBCL). RESULTS: There were no significant differences in IQ between the LBW groups or LBW infants versus controls. Mean (SD) full-scale IQ was 105.2 (14.5), 104.2 (14.7), and 104.5 (12.7) in the placebo, 1 mg, and 2 mg groups, respectively (P = .924). However, for behavioral problems, there was a significant effect of intervention. The prevalence of children with CBCL scores above the US subclinical cutoff was 12.7%, 2.9%, and 2.7% in the placebo, 1-mg, and 2-mg groups, respectively (P = .027), compared with 3.2% in controls. Relative risk (95% confidence interval) for CBCL score above cutoff in placebo-treated children versus supplemented was 4.5 (1.4-14.2). CONCLUSIONS: Early iron supplementation of marginally LBW infants does not affect cognitive functions at 3.5 years of age but significantly reduces the prevalence of behavioral problems. The study suggests a causal relation between infant iron deficiency and later behavioral problems.