Suicidality and Self-Harm Behavior of Adolescents During the Early Phase of the War in Ukraine.

OBJECTIVE: War profoundly impacts people's lives, causing death, displacement, and psychological trauma, but research investigating suicidality of adolescents in this context has been limited. We compared suicidality or self-harm behavior among adolescents in regions that were, and were not, affected by Russia's initial invasion of Ukraine in 2014. METHOD: This cross-sectional study comprised 2,752 school students aged 11 to 17 years from the war-affected Donetsk region and non-war Kirovograd region. Data collection occurred in 2016 and 2017 using self-report tools to assess suicidality or self-harm behavior; psychopathology including posttraumatic stress disorder (PTSD), depression, and anxiety; and war trauma exposure. RESULTS: Adolescent girls in the war-affected region reported more suicide attempts (9.5% vs 5.1%; adjusted odds ratio [aOR] 1.8, 95% CI 1.2-2.8), suicidal ideation (39.3% vs 19.6%; aOR 2.6, 95% CI 2.01-3.3), or self-harm behavior (19.6% vs 13.1%; aOR 1.6, 95% CI 1.2-2.1), and boys reported more suicidal ideation (17.0% vs 9.8%; aOR 1.7, 95% CI 1.2-2.4). Boys and girls with PTSD, depression, or anxiety showed increased risks for any suicidality or self-harm. A dose-effect relation was observed between war trauma exposure and suicidality or self-harm. The association was strongest for adolescents who had experienced 5 or more different war trauma exposures (aOR 3.2, 95% CI 2.2-4.8). CONCLUSION: War trauma exposure and psychopathology were strongly associated with suicidality or self-harm behavior, with a greater impact in girls than boys. The high prevalence of suicidality found in this study emphasizes the need for intervention on a large scale for adolescents living in war situations.

Vitamin D levels of pregnant immigrant women and developmental disorders of language, learning and coordination in offspring.

BACKGROUND: Prenatal vitamin D deficiency is a common health concern among immigrants. No previous studies have examined the associations between prenatal vitamin D levels and developmental disorders of language, scholastic skills, and coordination in an immigrant sample. METHODS: The sample included 542 immigrant mothers of cases with language, scholastic, coordination or mixed developmental disorders, 443 immigrant mothers of controls without these disorders and 542 Finnish mothers of controls. Maternal vitamin D was measured in serum samples collected during early pregnancy and stored in a national biobank. RESULTS: The mean vitamin D levels during pregnancy were 25.0 (SD 14.4) nmol/L for immigrant mothers of cases, 25.4 (SD 15.5) for immigrant mothers of controls and 42.3 (SD 19.1) for Finnish mothers of controls. Low maternal vitamin D levels during pregnancy were not associated with the selected developmental disorders in offspring when immigrant mothers of cases were compared to immigrant mothers of controls (adjusted OR for continuous log-transformed vitamin D: 1.01, 95% CI 0.75-1.36, p = 0.96). When immigrant mothers of cases were compared to Finnish mothers of controls, the adjusted OR for continuous vitamin D was 18.94 (95% CI 11.47-31.25), p <0.001). The results were similar when vitamin D was examined as a categorical variable or divided into quintiles. CONCLUSIONS: Prenatal vitamin D levels were low, and similar, among immigrant mothers of cases with selected developmental disorders and unaffected controls. This indicates that vitamin D unlikely mediates previously observed associations between maternal immigrant status and the selected developmental disorders in offspring. The proportion of immigrant mothers with severe vitamin D deficiency was very high, which underlines the importance of prenatal counselling and overall public health efforts to improve immigrant health.

Prenatal organochlorine pollutant exposure and risk of schizophrenia in a national birth cohort.

Non-genetic prenatal exposures have been associated with schizophrenia risk. However, the role of prenatal exposure to environmental neurotoxicants in offspring schizophrenia risk has been studied in only limited instances. Polychlorinated biphenyls (PCBs) and the pesticide metabolite p,p'-dichlorodiphenyl dichloroethylene (DDE) have been linked to neurodevelopmental outcomes, including impairments implicated in schizophrenia. To determine whether prenatal maternal levels of organochlorine pollutants including PCBs or DDE are associated with schizophrenia in the offspring, an investigation was conducted in the Finnish Prenatal Study of Schizophrenia (FIPS-S), a case-control study nested in a national birth cohort. Cases were born in 1987-1991 and had at least two diagnoses of schizophrenia (ICD-10 F20; ICD-9 295) or schizoaffective disorder (ICD-10 F25; ICD-9 295.7) recorded in the national Care Register for Health Care. Each case was individually matched to a control on sex, date of birth, and residence in Finland on the date of case diagnosis. In 500 case-control pairs, PCB congeners 74, 99, 118, 138, 153, 156, 170, 180, 183, 187, and some widespread organochlorine pesticides or their metabolites including DDE were measured in archived prenatal maternal sera using gas chromatography - high triple quadrupole mass spectrometry. Maternal total PCBs were quantified as the sum of concentrations of the measured congeners. Associations with schizophrenia were examined using conditional logistic regression. Maternal PCB or DDE levels greater than the 75th percentiles of the control distributions showed no evidence of association with offspring schizophrenia (PCBs: adjusted odds ratio (aOR) = 1.13, 95 % CI = 0.85-1.50), p = 0.41; DDE: aOR = 1.08, 95 % CI = 0.80-1.45; p = 0.63). Maternal levels of either pollutant dichotomized at the 90th percentile or considered as a continuous variable also did not show evidence for association with offspring schizophrenia. This study found a lack of evidence that prenatal maternal levels of the organochlorine pollutants DDE and PCBs are associated with offspring risk of schizophrenia.

Maternal Serum Vitamin B12 during Pregnancy and Offspring Autism Spectrum Disorder.

This study examined the association between maternal serum vitamin B12 levels during early pregnancy and offspring autism spectrum disorders (ASD) and subtypes. Based on a Finnish national birth cohort, case offspring (n = 1558) born in 1987-2007 and diagnosed with ASD by 2015 were matched with one control on date of birth, sex and place of birth. Maternal vitamin B12 levels were measured during first and early second trimesters of pregnancy. High maternal vitamin B12 levels (≥81th percentile) was associated with increased risk for offspring childhood autism, adjusted odds ratio, 1.59, 95% confidence interval 1.06-2.41 (p = 0.026). No significant associations were observed between maternal vitamin B12 levels and offspring Asperger's or pervasive developmental disorder/NOS.

Maternal SSRI use during pregnancy and offspring depression or anxiety disorders: A review of the literature and description of a study protocol for a register-based cohort study.

Previous studies examining the relationship between in utero exposure to selective serotonin reuptake inhibitors (SSRI) and long-term offspring depressive or anxiety behaviors are inconclusive. We aimed to critically review the findings of previous studies and describe a new study protocol to investigate the association of prenatal SSRI exposure and offspring depression or anxiety using data from several Finnish national registers. The study includes 1,266,473 mothers and their live-born singleton offspring, born in 1996-2018. The study cohorts include the prenatally SSRI exposed group and three comparison groups: 1) depression exposed/antidepressants unexposed, 2) unexposed to antidepressants or antipsychotics and depression, and 3) discordant siblings. We aim to examine whether depression in prenatally SSRI exposed children is more common or severe than depression in the offspring of mothers with depression but without SSRI exposure. We aim to disambiguate the effects of maternal SSRI from the effects of maternal depression, severity of maternal depression and familial loading history of psychiatric disorders by including data from first-degree relatives of prenatally SSRI exposed and unexposed children. Associations between exposure and outcome are assessed by statistical modeling, accounting for within-family correlation. The study has potential public health significance and in guiding clinicians in considering treatment options for pregnant women.

An Internet-Based Parent Training With Telephone Coaching on Managing Disruptive Behavior in Children at Special Family Counseling Centers During the COVID-19 Pandemic: Feasibility Study.

BACKGROUND: There is growing concern about the short- and long-term impacts that the COVID-19 pandemic will have on the mental health and psychosocial well-being of children and families. There are no existing studies about feasibility and outcomes using internet-based parent training programs with telephone coaching for disruptive behavioral problems in childhood during the COVID-19 pandemic in clinical settings. OBJECTIVE: This study explored how the Strongest Families Smart Website (SFSW) parent training program, with telephone coaching, provided support during the COVID-19 pandemic at specialist family counseling centers in Helsinki, Finland, when restrictions made face-to-face counseling impossible. This study followed the success of a randomized controlled trial (RCT) and its implementation study of the SFSW parent training program by primary care child health clinics. The aim was to improve parenting skills, so that parents could tackle disruptive behavior by developing positive parent-child relationships. It started in May 2020, when the COVID-19 pandemic was at its height in Finland. METHODS: In total, 8 family counseling centers in Helsinki identified 50 referrals aged 3-8 years with high levels of parent-reported disruptive behavioral problems. Child psychopathology and functioning and parental skills and well-being were measured at baseline, posttreatment, and 6 months later using a range of tools. The data were extracted from questionnaires completed by the parents. RESULTS: We found that 44 (88%) of the 50 families completed the whole 11-session parent training program. Most of the children (n=48, 96%) had definitive or severe behavioral problems when they were initially screened by the centers, but with those assessed at the 6-month follow-up (n=45, 90%), this dropped to 58% (n=26). There were significant changes from baseline to 6-month follow-up in most of the child psychopathology measures, including the Child Behavior Checklist-Parent Report Form (CBCL) total score (mean change 16.3, SE 3.0, 95% CI 10.2-22.3; P<.001) and externalizing score (mean change 7.0, SE 1.0, 95% CI 4.9-9.0; P<.001). When parenting skills were measured with the Parenting Scale (PS), they showed significant changes from baseline to 6-month follow-up in total scores (mean change 0.5, SE 0.1, 95% CI 0.4-0.7; P<.001). Parents showed significant change in the stress subscore (mean change 3.9, SE 0.8, 95% CI 2.2-5.6; P<.001). Of the parents who filled in the satisfaction questionnaire (n=45, 90%), 42 (93%) reported high satisfaction in the skills and 44 (98%) in the professionalism of the family coaches. CONCLUSIONS: The program proved to be an effective method for improving parenting skills and child psychopathology and functioning. The parents were satisfied with the program, and the dropout rate was exceptionally low. The study shows that the training program could be implemented in specialist clinical settings and during crisis conditions, such as the COVID-19 pandemic.

Associations Between Delivery Modes, Birth Outcomes and Offspring Anxiety Disorders in a Population-Based Birth Cohort of Children and Adolescents.

Objective: Mode of delivery and well-being markers for newborn infants have been associated with later psychiatric problems in children and adolescents. However, only few studies have examined the association between birth outcomes and anxiety disorders and the results have been contradictory. Methods: This study was a Finnish population-based register study, which comprised 22,181 children and adolescents with anxiety disorders and 74,726 controls. Three national registers were used to collect the data on exposures, confounders and outcomes. Mode of delivery, the 1-min Apgar score, umbilical artery pH and neonatal monitoring were studied as exposure variables for anxiety disorders and for specific anxiety disorders. Conditional logistic regression was used to examine these associations. Results: Unplanned and planned cesarean sections increased the odds for anxiety disorders in children and adolescents (adjusted OR 1.08, 95% CI 1.02-1.15 and aOR 1.12, 95% CI 1.05-1.19, respectively). After an additional adjustment for maternal diagnoses, unplanned cesarean sections remained statistically significant (aOR 1.11, 95% CI 1.04-1.18). For specific anxiety disorders, planned cesarean sections and the need for neonatal monitoring increased the odds for specific phobia (aOR 1.21, 95% CI 1.01-1.44 and aOR 1.28, 95% CI 1.07-1.52, respectively). Conclusions: Birth by cesarean section increased the odds for later anxiety disorders in children and adolescents and unplanned cesarean sections showed an independent association. Further studies are needed to examine the mechanisms behind these associations.

Motor Performance in Association with Perceived Loneliness and Social Competence in 11-Year-Old Children Born Very Preterm.

Background: Very preterm birth may affect motor performance and social competence up to adulthood. Our objective was to describe perceived loneliness and social competence in children born very preterm in relation to motor impairment. Methods: 165 children born very preterm (birth weight ≤ 1500 g and/or gestational age < 32 weeks) were assessed at 11 years of age. Cerebral palsy (CP) was diagnosed by 2 years of age. At 11 years of age, motor outcome was assessed using the Movement Assessment Battery for Children­Second edition (Movement ABC-2). Loneliness was evaluated by using the Peer Network and Dyadic Loneliness scale and social competence by using the Multisource Assessment of Children's Social Competence Scale. Results: In total, 6 (4%) children had CP, 18 (11%) had Developmental Coordination Disorder (DCD) (Movement ABC-2 ≤ 5th percentiles), and 141 (85%) had typical motor development. There was no correlation between percentiles for total scores of the Movement ABC-2 and perceived loneliness or social competence when the children with motor impairment (CP or DCD) were excluded. Children with DCD reported less perceived loneliness, but more problems with social competence compared to children with CP. Conclusions: It is important to recognize children born very preterm with DCD to provide interventions and support services to prevent social exclusion.

Effectiveness of an Internet-Based and Telephone-Assisted Training for Parents of 4-Year-Old Children With Disruptive Behavior: Implementation Research.

BACKGROUND: There is a lack of effectiveness studies when digital parent training programs are implemented in real-world practice. The efficacy of the internet-based and telephone-assisted Finnish Strongest Families Smart Website (SFSW) parent training intervention on the disruptive behavior of 4-year-old children was studied in a randomized controlled trial setting in Southwest Finland between 2011 and 2013. After that, the intervention was implemented nationwide in child health clinics from 2015 onwards. OBJECTIVE: The main aim of this study was to compare the treatment characteristics and effectiveness of the SFSW parent training intervention between the families who received the intervention when it was implemented as a normal practice in child health clinics and the families who received the same intervention during the randomized controlled trial. METHODS: The implementation group comprised 600 families who were recruited in the SFSW intervention between January 2015 and May 2017 in real-world implementation. The RCT intervention group comprised 232 families who were recruited between October 2011 and November 2013. The same demographic and child and parent measures were collected from both study groups and were compared using linear mixed-effect models for repeated measurements. The child psychopathology and functioning level were measured using the Child Behavior Checklist (CBCL) version 1.5-5 for preschool children, the Inventory of Callous-Unemotional Traits (ICU), and a modified version of the Barkley Home Situations Questionnaire. Parenting skills were measured using the 31-item Parenting Scale and the shorter 21-item Depression, Anxiety and Stress Scale (DASS-21). The estimated child and parent outcomes were adjusted for CBCL externalizing scores at baseline, maternal education, duration of the behavior problems, and paternal age. The baseline measurements of each outcome were used as covariates. RESULTS: The implementation group was more likely to complete the intervention than the RCT intervention group (514/600, 85.7% vs 176/232, 75.9%, respectively; P<.001). There were no significant differences between the implementation and RCT intervention groups with regard to child measures, including CBCL externalizing score (-0.2, 95% CI -1.3 to 1.6; P=.83), total score (-0.7, 95% CI -3.0 to 4.5; P=.70), internalizing score (-0.3, 95% CI -1.0 to 1.6; P=.64), and ICU total score (-0.4, 95% Cl -1.9 to 1.2; P=.64). No significant difference was detected in the Parenting Scale total score (0.0, 95% Cl -0.1 to 0.1; P=.50), while DASS-21 total score differed nearly significantly (2.5, 95% Cl 0.0-5.1; P=.05), indicating better improvement in the implementation group. CONCLUSIONS: The internet-based and telephone-assisted SFSW parent training intervention was effectively implemented in real-world settings. These findings have implications for addressing the unmet needs of children with disruptive behavior problems. Our initiative could also provide a quick socially distanced solution for the considerable mental health impact of the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT01750996; https://clinicaltrials.gov/ct2/show/NCT01750996. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/1471-2458-13-985.

Maternal serum persistent organic pollutant exposure and offspring diagnosed ADHD in a national birth cohort.

BACKGROUND: Evidence implicates environmental factors in attention-deficit/hyperactivity disorder (ADHD) risk. Prenatal exposures to polychlorinated biphenyls (PCBs) and the pesticide metabolite p,p'-dichlorodiphenyl dichloroethylene (DDE) have been linked to lower cognitive ability, increased impulsivity, and attention related deficits in the offspring. However, information on the relationship of these exposures to the risk of clinically diagnosed ADHD is limited. OBJECTIVES: To determine whether prenatal maternal levels of PCBs or DDE are associated with ADHD diagnosis in the offspring. METHODS: The investigation was conducted in the Finnish Prenatal Study of ADHD (FIPS-ADHD), a case-control study nested in a national birth cohort. Cases were born in 1998 or 1999 and diagnosed with ADHD (ICD-9 314x or ICD-10 F90. x) according to the national Care Register for Health Care. Each case was individually matched to a control on sex, date, and place of birth. PCB congeners (PCB 74, 99, 118, 138, 153, 156, 170, 180, 183, 187) and DDE were quantified from archived prenatal maternal sera from 359 matched case-control pairs using gas chromatography - high triple quadrupole mass spectrometry. Maternal total PCBs were quantified as the sum of concentrations of the measured congeners. Associations with ADHD were examined using conditional logistic regression. RESULTS: Maternal PCB or DDE levels greater than the 75th percentiles of the control distributions showed no evidence of association with offspring ADHD (PCBs: adjusted odds ratio (aOR) = 1.01, 95% CI = 0.63, 1.60), p = 0.98; DDE: aOR = 1.13, 95% CI = 0.71, 1.81; p = 0.60). Maternal levels of either pollutant dichotomized at the 90th percentile or considered as a continuous variable also did not show evidence for association with offspring ADHD diagnosis. DISCUSSION: This study did not find evidence for association of maternal prenatal levels of PCBs or DDE with clinical diagnosis of offspring ADHD; however, this does not rule out the possibility of an impact on subclinical phenotypes.

Single-Session, Internet-Based Cognitive Behavioral Therapy to Improve Parenting Skills to Help Children Cope With Anxiety During the COVID-19 Pandemic: Feasibility Study.

BACKGROUND: The COVID-19 pandemic has had a major impact on families' daily routines and psychosocial well-being, and technology has played a key role in providing socially distanced health care services. OBJECTIVE: The first objective of this paper was to describe the content and delivery of a single-session, internet-based cognitive behavioral therapy (iCBT) intervention, which has been developed to help parents cope with children's anxiety and manage daily situations with their children. The second objective was to report user adherence and satisfaction among the first participants who completed the intervention. METHODS: The Let's Cope Together intervention has been developed by our research group. It combines evidence-based CBT elements, such as psychoeducation and skills to manage anxiety, with parent training programs that strengthen how parents interact with their child and handle daily situations. A pre-post design was used to examine user satisfaction and the skills the parents learned. Participants were recruited using advertisements, media activity, day care centers, and schools and asked about background characteristics, emotional symptoms, and parenting practices before they underwent the iCBT. After they completed the 7 themes, they were asked what new parenting skills they had learned from the iCBT and how satisfied they were with the program. RESULTS: Of the 602 participants who filled in the baseline survey, 196 (32.6%) completed the program's 7 themes, and 189 (31.4%) completed the postintervention survey. Most (138/189, 73.0%) of the participants who completed the postintervention survey were satisfied with the program and had learned skills that eased both their anxiety (141/189, 74.6%) and their children's anxiety (157/189, 83.1%). The majority (157/189, 83.1%) reported that they learned how to organize their daily routines better, and just over one-half (100/189, 53.0%) reported that the program improved how they planned each day with their children. CONCLUSIONS: The single-session iCBT helped parents to face the psychological demands of the COVID-19 pandemic. Future studies should determine how the participation rate and adherence can be optimized in digital, universal interventions. This will help to determine what kinds of programs should be developed, including their content and delivery.

Digital mental health literacy -program for the first-year medical students' wellbeing: a one group quasi-experimental study.

BACKGROUND: Medical students are prone to mental disorders, such as depression and anxiety, and their psychological burden is mainly related to their highly demanding studies. Interventions are needed to improve medical students' mental health literacy (MHL) and wellbeing. This study assessed the digital Transitions, a MHL program for medical students that covered blended life skills and mindfulness activities. METHODOLOGY: This was a one group, quasi-experimental pretest-posttest study. The study population was 374 first-year students who started attending the medical faculty at the University of Turku, Finland, in 2018-2019. Transitions was provided as an elective course and 220 students chose to attend and 182 agreed to participate in our research. Transitions included two 60-minute lectures, four weeks apart, with online self-learning material in between. The content focused on life and academic skills, stress management, positive mental health, mental health problems and disorders. It included mindfulness audiotapes. Mental health knowledge, stigma and help-seeking questionnaires were used to measure MHL. The Perceived Stress Scale and General Health Questionnaire measured the students' stress and health, respectively. A single group design, with repeated measurements of analysis of variance, was used to analyze the differences in the mean outcome scores for the 158 students who completed all three stages: the pre-test (before the first lecture), the post-test (after the second lecture) and the two-month follow-up evaluation. RESULTS: The students' mean scores for mental health knowledge improved (-1.6, 95% Cl -1.9 to -1.3, P<.001) and their emotional symptoms were alleviated immediately after the program (0.5, 95% Cl 0.0 to 1.1, P=.040). The changes were maintained at the two-month follow up (-1.7, 95% Cl -2.0 to -1.4, P<.001 and 1.0, 95% Cl 0.2 to 1.8, P=.019, respectively). The students' stress levels reduced (P=.022) and their attitudes towards help-seeking improved after the program (P<.001), but these changes were not maintained at the two-month follow up. The stigma of mental illness did not change during the study (P=.13). CONCLUSIONS: The digital Transitions program was easily integrated into the university curriculum and it improved the students' mental health literacy and wellbeing. The program may respond to the increasing global need for universal digital services, especially during the lockdowns due to the COVID-19 pandemic. TRIAL REGISTRATION: The trial was registered at the ISRCTN registry (26 May 2021), registration number 10.1186/ ISRCTN10565335 ).

Prenatal Vitamin D Levels in Maternal Sera and Offspring Specific Learning Disorders.

Recent evidence has suggested potential harmful effects of vitamin D deficiency during pregnancy on offspring brain development, for example, elevated risks for neuropsychiatric disorders. Findings on general cognition and academic achievement are mixed, and no studies have examined the effect of prenatal 25-hydroxyvitamin D (25(OH)D) levels on diagnosed specific learning disorders, which was the aim of this study. We examined a nested case-control sample from the source cohort of all singleton-born children in Finland between 1996 and 1997 (n = 115,730). A total of 1607 cases with specific learning disorders (mean age at diagnosis: 9.9 years) and 1607 matched controls were identified from Finnish nationwide registers. Maternal 25(OH)D levels were analyzed from serum samples collected during the first trimester of pregnancy and stored in a national biobank. Conditional logistic regression was used to test the association between maternal 25(OH)D and offspring specific learning disorders. There were no significant associations between maternal 25(OH)D levels and specific learning disorders when vitamin D was examined as a log-transformed continuous variable (adjusted OR 0.98, 95% CI 0.82-1.18, p = 0.84) or as a categorical variable (25(OH)D < 30 nmol/L: adjusted OR 1.03, 95% CI 0.83-1.28, p = 0.77 compared to levels of >50 nmol/L), nor when it was divided into quintiles (adjusted OR for the lowest quintile 1.00, 95% CI 0.78-1.28, p = 0.99 compared to the highest quintile). This study found no association between low maternal 25(OH)D in early pregnancy and offspring specific learning disorders.

Maternal Vitamin D Levels During Pregnancy and Offspring Autism Spectrum Disorder.

BACKGROUND: Findings from previous studies on maternal 25-hydroxyvitamin D [25(OH)D] levels during pregnancy and autism spectrum disorder (ASD) in offspring are inconsistent. METHODS: The association between maternal 25(OH)D levels during pregnancy and offspring ASD was examined using data from a nationwide population-based register with a nested case-control study design. The ASD cases (n = 1558) were born between 1987 and 2004 and received a diagnosis of ASD by 2015; cases were matched with an equal number of controls. Maternal 25(OH)D levels during pregnancy were measured using quantitative immunoassay from maternal sera collected during the first and early second trimesters and archived in the national biobank of the Finnish Maternity Cohort. Conditional logistic regression examined the association between maternal 25(OH)D levels and offspring ASD. RESULTS: In the adjusted model, there was a significant association between increasing log-transformed maternal 25(OH)D levels and decreasing risk of offspring ASD (adjusted odds ratio [aOR] 0.75, 95% confidence interval [CI] 0.62-0.92, p = .005). Analyses by quintiles of maternal 25(OH)D levels revealed increased odds for ASD in the 2 lowest quintiles, <20 (aOR 1.36, 95% CI 1.03-1.79, p = .02) and 20-39 (aOR 1.31, 95% CI 1.01-1.70, p = .04), compared with the highest quintile. The increased risk of ASD was observed in association with deficient (<30 nmol/L) (aOR 1.44, 95% CI 1.15-1.81, p = .001) and insufficient (30-49.9 nmol/L) maternal 25(OH)D levels (aOR 1.26, 95% CI 1.04-1.52, p = .01) compared with sufficient levels. CONCLUSIONS: This finding has implications for understanding the role of maternal vitamin D during fetal brain development and increased risk of ASD.

A biomarker-based study of prenatal smoking exposure and autism in a Finnish national birth cohort.

Maternal exposure to tobacco smoke during pregnancy is a common and persistent exposure linked to adverse neurodevelopmental outcomes in the offspring. However, previous studies provide mixed evidence regarding the relationship between prenatal smoking and offspring autism. This study used cotinine level, a biomarker for nicotine, to investigate the relationship between prenatal smoking and autism. The authors conducted a population-based case-control study nested in a national cohort of all births in Finland from 1987 to 2005. Cases diagnosed with childhood autism (ICD-10/9 code F84.0/299.0) through 2007 were identified using data from linked national registers. Each case was matched with a control on date of birth (±30 days), sex, and place of birth (N = 962 pairs). Maternal serum cotinine levels were prospectively measured in first- to early second-trimester serum samples archived in a national biobank using a quantitative immunoassay. Data were analyzed using conditional logistic regression. Prenatal maternal levels of serum cotinine were not associated with the odds of autism, whether cotinine was classified continuously, by deciles, or using previously defined categories corresponding to probable maternal smoking status. After adjusting for maternal age, paternal age, previous births, and any history of parental psychiatric disorder, the odds ratio for categorical high versus low cotinine, using a 3-level exposure variable, was 0.98 (95% CI = 0.76, 1.26; p = 0.88). In conclusion, this national birth cohort-based study does not provide evidence for an association between maternal cotinine, a biomarker of maternal smoking, and risk of autism. LAY SUMMARY: This study explored whether prenatal exposure to tobacco smoke in mothers is related to the diagnosis of autism in their children, by measuring the levels of cotinine, a biomarker for tobacco exposure, in stored serum samples drawn from mothers during pregnancy. The levels of cotinine in the mothers of children diagnosed with autism were similar to those in the mothers of control children of similar age and gender distribution.

Dr. Sucksdorff et al. Reply.

We thank Trivedi et al. for their letter1 raising valuable questions regarding a clinical viewpoint on the observed association between maternal vitamin D levels in early pregnancy and offspring risk of attention-deficit/hyperactivity disorder (ADHD) in our study.2 We are happy that our research has raised discussion and are grateful for the opportunity to reply.

Incidence and comorbidities of disruptive behavior disorders diagnosed in Finnish specialist psychiatric services.

PURPOSE: Disruptive behavior disorders (DBD), including oppositional defiant disorder (ODD) and conduct disorder (CD), are some of the most common psychiatric conditions in childhood. Despite this, there has been limited research on DBDs. We examined the incidence, comorbidity and gender differences of DBDs diagnosed by specialist services. METHOD: This was a nationwide register study of 570,815 children and adolescents born in 1996-2005. The 7050 individuals diagnosed with DBD by specialist healthcare services were matched to 26,804 controls. RESULTS: By the age of 15, the cumulative incidence of diagnosed DBDs was 3.5% for boys and 1.4% for girls. The yearly incidence rate increased for girls after 13 years of age, while the incidence for boys was relatively stable between 8 and 15 years of age. When we compared subjects born between 1996-1998 and 1999-2001, we found that by the age of 12, the cumulative incidence per 100 people had increased from 0.56 to 0.68 among girls and from 2.3 to 2.6 among boys. This indicated a minor increase in treated incidence. The parents of children diagnosed with DBDs had lower educational levels than the parents of controls. Children with DBD were also more likely to have been diagnosed with other psychiatric disorders. CONCLUSION: Although DBDs were 3.5 times more common among boys during the whole follow-up period, the yearly incidence during adolescence was fairly similar between boys and girls. DBD existed alongside various psychiatric disorders at a relatively young age and only a minor increase in treated incidence was found during childhood.

Maternal Vitamin D Levels and the Risk of Offspring Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Recent evidence has highlighted the importance of vitamin D in the development of the central nervous system. Some studies have shown an association between maternal vitamin D deficiency during pregnancy and offspring attention-deficit/hyperactivity disorder (ADHD) symptoms based on parent or teacher ratings. There are no previous studies on early pregnancy 25-hydroxyvitamin D [25(OH)D] levels and the risk of diagnosed offspring ADHD. Our aim was to examine maternal 25(OH)D levels in early pregnancy and offspring ADHD. METHOD: In this nationwide population-based case-control study, 1,067 ADHD cases (born between 1998 and 1999 and diagnosed according to the International Classification of Diseases) and 1,067 matched controls were identified from Finnish registers. Maternal 25(OH)D levels were measured using quantitative immunoassay from maternal sera, collected during the first trimester and archived in the national biobank. Conditional logistic regression was used to examine the association between maternal 25(OH)D and offspring ADHD. RESULTS: There was a significant association between decreasing log-transformed maternal 25(OH)D levels and offspring ADHD both in the unadjusted analyses (odds ratio 1.65; 95% CI 1.33-2.05; p < .001) and in the analyses adjusting for maternal socioeconomic status and age (odds ratio 1.45; 95% CI 1.15-1.81; p = .002). Analyses by quintiles of maternal 25(OH)D levels in the lowest versus highest quintile revealed an adjusted odds ratio for offspring ADHD of 1.53 (95% CI 1.11-2.12; p = .010). CONCLUSION: This study demonstrated an association between low maternal 25(OH)D during pregnancy and an elevated risk for offspring ADHD. If replicated in independent samples, this finding may have significant public health implications.

Preterm Birth Is Associated With Depression From Childhood to Early Adulthood.

OBJECTIVE: There have been inconsistent findings on the associations among prematurity, poor fetal growth, and depression. We examined the associations among gestational age, poor fetal growth, and depression in individuals aged 5 to 25 years. METHOD: We identified 37,682 case subjects based on International Classification of Diseases, Ninth Revision code 2961 and International Classification of Diseases, Tenth Revision codes F32.0-F32.9 and F33.0-F33.9 from the Care Register for Health Care, and 148,795 matched controls from the Finnish Central Population Register. Conditional logistic regression examined the associations between gestational age by each gestational week, poor fetal growth, and depression. The associations were adjusted for parental age and psychopathology, paternal immigrant status, maternal substance abuse, depression, number of previous births, marital status, socio-economic status, smoking during pregnancy, and the infant's birthplace. RESULTS: In the adjusted models, increased risk of depression was found in children born ≤25 weeks (adjusted odds ratio [aOR] 1.89, 95% CI 1.08-3.31), at 26 weeks (aOR 2.62, 95% CI 1.49-4.61), at 27 weeks (aOR 1.93, 95% CI 1.05-3.53), and ≥42 weeks (aOR 1.11, 95% CI 1.05-1.19). In girls, extremely preterm birth was associated with depression diagnosed at 5 to 12 years (aOR 2.70, 95% CI 1.83-3.98) and 13 to 18 years (aOR 2.97, 95% CI 1.84-4.78). In boys, postterm birth (≥42 weeks) was associated with depression diagnosed at 19 to 25 years (aOR 1.28, 95% CI 1.07-1.54). Poor fetal growth was associated with an increased risk of depression in full-term infants (aOR 1.06, 95% CI 1.03-1.10) and postterm infants (aOR 1.24, 95% CI 1.08-1.43). CONCLUSION: Preterm birth before 28 weeks of gestation appeared to play a role in the development of childhood depression. Smaller effects were also seen in postterm births, especially in boys.