To investigate the impact of gestational exposure to selective serotonin reuptake inhibitors (SSRIs) on offspring neurodevelopment.
This is a cohort study using national register data in Finland ...between the years 1996 and 2010. Pregnant women and their offspring were categorized into 4 groups: SSRI exposed (n = 15,729); exposed to psychiatric disorder, no antidepressants (n = 9,651); exposed to SSRIs only before pregnancy (n = 7,980); and unexposed to antidepressants and psychiatric disorders (n = 31,394). We investigated the cumulative incidence of offspring diagnoses of depression, anxiety, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) for the 4 groups from birth to 14 years, adjusting for confounders.
The cumulative incidence of depression among offspring exposed prenatally to SSRIs was 8.2% (95% CI = 3.1-13.3%) by age 14.9 years, compared with 1.9% (95% CI = 0.9-2.9%) in the psychiatric disorder, no medication group (adjusted hazard ratio HR = 1.78; 95% CI = 1.12-2.82; p = .02) and to 2.8% (95% CI = 1.4-4.3%) in the SSRI discontinued group (HR = 1.84; 95% CI = 1.14-2.97; p = .01). Rates of anxiety, ASD, and ADHD diagnoses were comparable to rates in offspring of mothers with a psychiatric disorder but no medication during pregnancy. Comparing SSRI exposed to unexposed individuals, the HRs were significantly elevated for each outcome.
Prenatal SSRI exposure was associated with increased rates of depression diagnoses in early adolescence but not with ASD or ADHD. Until confirmed, these findings must be balanced against the substantial adverse consequences of untreated maternal depression.
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.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim
To examine the association between several perinatal and obstetric risk factors and reactive attachment disorder in children diagnosed in specialised services.
Methods
In this nested case‐control ...study, 614 cases with reactive attachment disorder and 2423 controls matched with age and sex were identified from Finnish national registers. Conditional logistic regression was used to examine the association between a number of perinatal risk factors and reactive attachment disorder.
Results
In the adjusted analysis, a low birthweight of <2500 g was associated with an increased odds of reactive attachment disorder, with an odds ratio (OR) of 1.96 and 95% confidence interval (CI) of 1.17, 3.30 and a birthweight of 4000‐4499 grams was associated with decreased odds OR 0.49 (95% CI 0.31, 0.75). The odds for being diagnosed with reactive attachment disorder increased with a gestational age of <32 weeks OR 3.72 (95% CI 1.52, 9.10), induced labour OR 1.34 (95% CI 1.03, 1.75) and monitoring in a neonatal intensive care unit (NICU) OR 1.67 (95% CI 1.09, 2.55).
Conclusion
We found associations between low birthweight, preterm birth, NICU admission and reactive attachment disorder. The findings add to the current literature on the understanding of the development of reactive attachment disorder in children.
Maternal inflammation level during pregnancy was related to risk of schizophrenia
in offspring, adding new evidence for the association of infection and immune
activation with the development of the ...disorder.
Objective
The objective of the present study was to investigate an association between
early gestational C-reactive protein, an established inflammatory biomarker,
prospectively assayed in maternal sera, and schizophrenia in a large,
national birth cohort with an extensive serum biobank.
Method
A nested case-control design from the Finnish Prenatal Study of Schizophrenia
cohort was utilized. A total of 777 schizophrenia cases (schizophrenia,
N=630; schizoaffective disorder, N=147) with maternal sera available for
C-reactive protein testing were identified and matched to 777 control
subjects in the analysis. Maternal C-reactive protein levels were assessed
using a latex immunoassay from archived maternal serum specimens.
Results
Increasing maternal C-reactive protein levels, classified as a continuous
variable, were significantly associated with schizophrenia in offspring
(adjusted odds ratio=1.31, 95% confidence interval=1.10–1.56). This finding
remained significant after adjusting for potential confounders, including
maternal and parental history of psychiatric disorders, twin/singleton
birth, urbanicity, province of birth, and maternal socioeconomic status.
Conclusions
This finding provides the most robust evidence to date that maternal
inflammation may play a significant role in schizophrenia, with possible
implications for identifying preventive strategies and pathogenic mechanisms
in schizophrenia and other neurodevelopmental disorders.
An increasing number of studies has shown an association between parental age and psychiatric disorders. However, there are inconsistent results regarding whether age at parenthood is associated with ...attention-deficit/hyperactivity disorder (ADHD). The aim of this study is to examine whether low or advanced parental age is associated with ADHD.
In this nested case-control study, we identified 10,409 individuals with ADHD born in Finland during 1991 to 2005 and diagnosed with ADHD between 1995 and 2011, along with 39,125 controls matched on sex, date, and place of birth, from nationwide population-based registers. Conditional logistic regression was used to examine the association between parental age and ADHD in offspring, adjusting for potential confounding due to parental psychiatric history, maternal socioeconomic status, marital status, maternal smoking during pregnancy, number of previous births, and birth weight for gestational age.
Fathers younger than 20 years had a 1.5-fold (odds ratio OR = 1.55, 95% CI = 1.11-2.18, p = .01) increased risk of having offspring with ADHD as compared to fathers aged 25 to 29 years. Mothers of the same age group had a 1.4-fold (OR = 1.41, 95% CI = 1.15-1.72, p =.0009) increased risk. Advanced maternal age was inversely associated with ADHD (OR = 0.79, 95% CI = 0.64-0.97, p = .02).
ADHD was associated with young fathers or mothers at the time of birth. Health professionals working with young parents should be aware of the increased risk of ADHD in offspring. This will improve early detection; however, for the development of preventive measures and appropriate interventions, more information on the developmental pathways is needed.
Objectives:Studies on the association between parental age and bipolardisorder (BPD) are scarce and with inconsistent findings. The aim of thisstudy was to examine the association of parental age and ...age differencebetween parents with risk of BPD in offspring.Methods:This nested case–control study identified 1,861 cases ofindividuals with BPD born in Finland during 1983–1998 and diagnosedby the end of 2008, and 3,643 sex- and date of birth-matched controlsfrom nationwide population-based registers. Conditional logisticregression was used to examine the association adjusting for potentialconfounding due to age of the other parent, parental psychiatric history,educational level, and place of birth.Results:A U-shaped association of unadjusted odds ratios (ORs) forBPD risk was seen in different paternal age categories, with the oddsincreasing at both ends of the age spectrum. In the adjusted analyses,offspring of fathers aged≥50 years had a 2.8-fold increased oddsOR=2.84, 95% confidence interval (CI): 1.32–6.12 of BPD ascompared to those with fathers aged 30–34 years. The odds wereincreased 1.3-fold (OR=1.35, CI: 1.06–1.72) in fathers aged 20–24 years. No significant association was found between maternal ageand BPD in the adjusted analyses. Age difference between parents wasnot associated with BPD.Conclusions:The increased risk of BPD in offspring of the youngest andoldest fathers in the study suggests the involvement of differentbiological and psychosocial factors at the two ends of the paternal agespectrum. These findings may be significant in the context of advancingparental age in recent times.
Abstract Background Evidence from animal and human studies indicates that thyroid hormone deficiency during early gestation alters brain development. As schizophrenia is associated with prenatal ...brain insults and premorbid cognitive deficits, we tested the a priori hypothesis that serologically defined maternal thyroid deficiency during early gestation to mid-gestation is associated with schizophrenia in offspring. Methods The investigation is based on the Finnish Prenatal Study of Schizophrenia, a nested case-control study that included archived maternal sera from virtually all pregnancies since 1983 ( N = >1 million). We identified all offspring in the cohort with a diagnosis of schizophrenia based on the national inpatient and outpatient register and matched them on sex, date of birth, and residence in Finland at time of onset of the case to comparison subjects (1:1) from the cohort. Maternal sera of 1010 case-control pairs were assessed for free thyroxine, and sera of 948 case-control pairs were assessed for thyroid-stimulating hormone. Results Maternal hypothyroxinemia (free thyroxine ≤10th percentile, normal thyroid-stimulating hormone) was associated with an increased odds of schizophrenia (odds ratio = 1.75, 95% confidence interval = 1.22–2.50, p = .002). When adjusted for maternal psychiatric history, province of birth, and maternal smoking during pregnancy, the association remained significant (odds ratio = 1.70, 95% confidence interval = 1.13–2.55, p = .010). Conclusions In a large, national birth cohort, prospectively documented hypothyroxinemia during early gestation to mid-gestation was associated with increased odds of schizophrenia in offspring. This information can inform translational studies of maternal hypothyroxinemia examining molecular and cellular deviations relevant to schizophrenia.
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.
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.
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).
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.
IMPORTANCE: There is a large gap worldwide in the provision of evidence-based early treatment of children with disruptive behavioral problems. OBJECTIVE: To determine whether an Internet-assisted ...intervention using whole-population screening that targets the most symptomatic 4-year-old children is effective at 6 and 12 months after the start of treatment. DESIGN, SETTING, AND PARTICIPANTS: This 2-parallel-group randomized clinical trial was performed from October 1, 2011, through November 30, 2013, at a primary health care clinic in Southwest Finland. Data analysis was performed from August 6, 2015, to December 11, 2015. Of a screened population of 4656 children, 730 met the screening criteria indicating a high level of disruptive behavioral problems. A total of 464 parents of 4-year-old children were randomized into the Strongest Families Smart Website (SFSW) intervention group (n = 232) or an education control (EC) group (n = 232). INTERVENTIONS: The SFSW intervention, an 11-session Internet-assisted parent training program that included weekly telephone coaching. MAIN OUTCOMES AND MEASURES: Child Behavior Checklist version for preschool children (CBCL/1.5-5) externalizing scale (primary outcome), other CBCL/1.5-5 scales and subscores, Parenting Scale, Inventory of Callous-Unemotional Traits, and the 21-item Depression, Anxiety, and Stress Scale. All data were analyzed by intention to treat and per protocol. The assessments were made before randomization and 6 and 12 months after randomization. RESULTS: Of the children randomized, 287 (61.9%) were male and 79 (17.1%) lived in other than a family with 2 biological parents. At 12-month follow-up, improvement in the SFSW intervention group was significantly greater compared with the control group on the following measures: CBCL/1.5-5 externalizing scale (effect size, 0.34; P < .001), internalizing scale (effect size, 0.35; P < .001), and total scores (effect size, 0.37; P < .001); 5 of 7 syndrome scales, including aggression (effect size, 0.36; P < .001), sleep (effect size, 0.24; P = .002), withdrawal (effect size, 0.25; P = .005), anxiety (effect size, 0.26; P = .003), and emotional problems (effect size, 0.31; P = .001); Inventory of Callous-Unemotional Traits callousness scores (effect size, 0.19; P = .03); and self-reported parenting skills (effect size, 0.53; P < .001). CONCLUSIONS AND RELEVANCE: The study reveals the effectiveness and feasibility of an Internet-assisted parent training intervention offered for parents of preschool children with disruptive behavioral problems screened from the whole population. The strategy of population-based screening of children at an early age to offering parent training using digital technology and telephone coaching is a promising public health strategy for providing early intervention for a variety of child mental health problems. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01750996.
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.
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