Roshan Chudal

Preterm Birth and Poor Fetal Growth as Risk Factors of Attention-Deficit/Hyperactivity Disorder

BACKGROUND: Previous studies have shown an association between prematurity and attention-deficit/hyperactivity disorder (ADHD). Results concerning late preterm infants are controversial, and studies examining fetal growth represented by weight for gestational age are scarce. Our objective was to examine the association between gestational age by each week of fetal maturity, weight for gestational age, and ADHD. METHODS: In this population-based study, 10 321 patients with ADHD, diagnosed according to the International Classification of Diseases and 38 355 controls individually matched for gender, date and place of birth, were identified from Finnish nationwide registers. Perinatal data were obtained from the Finnish Medical Birth Register. Conditional logistic regression was used to examine the association between gestational age, weight for gestational age, and ADHD after controlling for confounding factors. RESULTS: The risk of ADHD increased by each declining week of gestation. The associations were robust after adjusting for confounders. An elevated risk also was seen among late preterm and early term infants. As for fetal growth, the odds ratio showed a U-shaped curve with an increased risk seen when the weight for gestational age was 1 SD below and 2 SD above the mean. CONCLUSIONS: Our findings suggest that each gestational week has significance for child’s subsequent neurodevelopment and risk for ADHD. We also showed that poor fetal growth increased the risk of ADHD. This highlights the importance of taking into account both prematurity and poor fetal growth when planning the timing of birth as well as later follow-up and support policies.

Risk of Psychiatric and Neurodevelopmental Disorders Among Siblings of Probands With Autism Spectrum Disorders

IMPORTANCE Previous research has focused on examining the familial clustering of schizophrenia, bipolar disorder, and autism spectrum disorders (ASD). Little is known about the clustering of other psychiatric and neurodevelopmental disorders among siblings of persons with ASD. OBJECTIVE To examine the risk for psychiatric and neurodevelopmental disorders among full siblings of probands with ASD. DESIGN, SETTING, AND PARTICIPANTS The Finnish Prenatal Study of Autism and Autism Spectrum Disorders used a population-based cohort that included children born from January 1, 1987, to December 31, 2005, who received a diagnosis of ASD by December 31, 2007. Each case was individually matched to 4 control participants by sex and date and place of birth. The siblings of the cases and controls were born from January 1, 1977, to December 31, 2005, and received a diagnosis from January 1, 1987, to December 31, 2009. This nested case-control study included 3578 cases with ASD with 6022 full siblings and 11 775 controls with 22 127 siblings from Finnish national registers. Data were analyzed from March 6, 2014, to February 12, 2016. MAIN OUTCOMES AND MEASURES The adjusted risk ratio (RR) for psychiatric and neurodevelopmental disorders among siblings of probands with ASD vs siblings of matched controls. Additional analyses were conducted separately for ASD subgroups, including childhood autism, Asperger syndrome, and pervasive developmental disorders not otherwise specified. Analyses were further stratified by sex and intellectual disability among the probands. RESULTS Among the 3578 cases with ASD (2841 boys [79.4%]) and 11 775 controls (9345 boys [79.4%]), 1319 cases (36.9%) and 2052 controls (17.4%) had at least 1 sibling diagnosed with any psychiatric or neurodevelopmental disorder (adjusted RR, 2.5; 95% CI, 2.3-2.6). The largest associations were observed for childhood-onset disorders (1061 cases [29.7%] vs 1362 controls [11.6%]; adjusted RR, 3.0; 95% CI, 2.8-3.3), including ASD (374 cases [10.5%] vs 125 controls [1.1%]; adjusted RR, 11.8; 95% CI, 9.4-14.7), tic disorders (28 cases [0.8%] vs 24 controls [0.2%]; adjusted RR, 4.3; 95% CI, 2.3-8.2), attention-deficit/hyperactivity disorder (189 cases [5.3%] vs 180 controls [1.5%]; adjusted RR, 3.7; 95% CI, 2.9-4.7), learning and coordination disorders (563 cases [15.7%] vs 697 controls [5.9%]; adjusted RR, 3.2; 95% CI, 2.8-3.6), intellectual disability (104 cases [2.9%] vs 137 controls [1.2%]; adjusted RR, 3.1; 95% CI, 2.3-4.2), conduct and oppositional disorders (180 cases [5.0%] vs 221 controls [1.9%]; adjusted RR, 2.8; 95% CI, 2.2-3.5), and emotional disorders with onset specific to childhood (126 cases [3.5%] vs 157 controls [1.3%]; adjusted RR, 2.6; 95% CI, 1.9-3.4). Autism spectrum disorders were also associated with schizophrenia spectrum disorders, affective disorders, anxiety disorders, and other neurotic and personality disorders among siblings. CONCLUSIONS AND RELEVANCE Psychiatric and neurodevelopmental disorders cluster among siblings of probands with ASD. For etiologic research, these findings provide further evidence that several psychiatric and neurodevelopmental disorders have common risk factors.

Parental age and the risk of attention-deficit/hyperactivity disorder: a nationwide, population-based cohort study.

OBJECTIVE 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. METHOD 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. RESULTS 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). CONCLUSION 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.

A nationwide register study of the characteristics, incidence and validity of diagnosed Tourette syndrome and other tic disorders

The aim of this study was to describe the characteristics and incidence rates of diagnosed tic disorders in the Finnish Hospital Discharge Register, including changing incidence rates between 1991 and 2010. We also aimed to validate the diagnoses of Tourettes syndrome recorded in the register.

Perinatal factors and the risk of bipolar disorder in Finland.

BACKGROUND Complications during the perinatal period have been associated with neurodevelopmental disorders like schizophrenia and autism. However, similar studies on bipolar disorder (BPD) have been limited and the findings are inconsistent. The aim of this study was to examine the association between perinatal risk factors and BPD. METHODS This nested case-control study, based on the Finnish Prenatal Study of Bipolar Disorders (FIPS-B), identified 724 cases and 1419 matched controls from population based registers. Conditional logistic regression was used to examine the associations between perinatal factors and BPD adjusting for potential confounding due to maternal age, psychiatric history and educational level, place of birth, number of previous births and maternal smoking during pregnancy. RESULTS Children delivered by planned cesarean section had a 2.5-fold increased risk of BPD (95% CI: 1.32-4.78, P<0.01). No association was seen between other examined perinatal risk factors and BPD. LIMITATIONS The limitations of this study include: the restriction in the sample to treated cases of BPD in the population, and usage of hospital based clinical diagnosis for case ascertainment. In addition, in spite of the large sample size, there was low power to detect associations for certain exposures including the lowest birth weight category and pre-term birth. CONCLUSIONS Birth by planned cesarean section was associated with risk of BPD, but most other perinatal risk factors examined in this study were not associated with BPD. Larger studies with greater statistical power to detect less common exposures and studies utilizing prospective biomarker-based exposures are necessary in the future.

Parental age and the risk of bipolar disorders.

Studies on the association between parental age and bipolar disorder (BPD) are scarce and with inconsistent findings. The aim of this study was to examine the association of parental age and age difference between parents with risk of BPD in offspring.

Finnish Prenatal Study of Bipolar Disorders (FIPS-B): Overview, design and description of the sample

Abstract Background: Bipolar disorders (BPD) are chronic mental illnesses, the development of which involves genetic factors and environmental influences. Aims: The aim of this paper is to provide an overall description of the Finnish Prenatal Study of Bipolar Disorders (FIPS-B), including the study design, national registers and linkage of the registers. Methods: FIPS-B is a population-based prenatal epidemiological study of BPD with a nested case–control study design using several national registers. The registers used are: the Finnish Medical Birth Register (FMBR), the Finnish Hospital Discharge Register (FHDR), the Population Central Register and the Finnish Maternity Cohort (FMC), which are linked using the unique personal identity code (PIC). FIPS-B includes all children born from January 1, 1983 to December 31, 1998 and diagnosed with BPD in Finland by December 31, 2008. Results: The total number of cases included in the FIPS-B is 1887. The age at first diagnosis ranged from 4 to 25 years. Half (50.4%) of the cases utilized only outpatient services, 12.7% only inpatient services and the rest (36.9%) utilized both services. Offspring of mothers with the lowest educational level had an increased odds of BPD (OR = 1.46, 95% CI 1.13–1.88). The cumulative incidence of BPD in the population aged 25 years or younger was 11.6/10,000 in 2008. Conclusions:  FIPS-B has all the strengths of a register-based prenatal epidemiological study, along with the availability of maternal biomarkers, enabling it to examine several prenatal, perinatal and familial risk factors for BPD.

Prenatal smoking exposure and neuropsychiatric comorbidity of ADHD: a finnish nationwide population-based cohort study

BackgroundPrenatal smoking exposure has been associated with attention-deficit/hyperactivity disorder (ADHD). ADHD is commonly associated with a wide spectrum of psychiatric comorbidity. The association between smoking and neuropsychiatric comorbidity of ADHD has remained understudied. The aim of this study is to examine the association between prenatal exposure to maternal smoking and offspring ADHD, and test whether the smoking-ADHD associations are stronger when ADHD is accompanied by other lifetime neuropsychiatric comorbidities.MethodsThe study is based on a nested case-control design and includes all Finnish singletons born between 1991 and 2005 and diagnosed with ADHD by 2011 (n = 10,132), matched with four controls (n = 38,811) on date of birth, sex and residence in Finland.ResultsThe risk for ADHD with or without comorbidity was significantly increased among offspring exposed to maternal smoking on adjusting for potential confounders (OR = 1.75, CI 95 % = 1.65–1.86). Compared to the only ADHD cases, subjects with comorbid conduct disorder or oppositional defiant disorder had a significantly stronger association with smoking exposure (OR = 1.80, CI 95 % = 1.55–2.11).ConclusionsPrenatal smoking represents an important risk factor for the ADHD comorbid with CD/ODD. Further research on the association between prenatal smoking exposure and neuropsychiatric comorbidity of ADHD is needed considering the increased risk among these subjects of an overall poor health outcome as compared to only ADHD. In particular, studies utilizing biomarkers or including subjects with neuropsychiatric conditions with and without comorbid ADHD are needed.

Obstetric and Neonatal Adversities, Parity, and Tourette Syndrome: A Nationwide Registry.

OBJECTIVE To determine the relationships between parity, obstetric adversities, neonatal factors, and Tourette syndrome in a large nationwide cohort. STUDY DESIGN This nationwide, register-based, nested case-control study identified all children diagnosed with Tourette syndrome born between 1991 and 2010 from the Finnish Hospital Discharge Register (n = 767). Each case was matched to 4 controls. Information on parity, obstetric, and neonatal factors was obtained from the Finnish Medical Birth Register. Conditional logistic regression was used to determine the relationship between parity, obstetric, and neonatal factors, and Tourette syndrome. RESULTS Nulliparity was associated with increased odds for Tourette syndrome (OR 1.7, 95% CI 1.4-2.2), and 3 or more previous births was associated with decreased odds for Tourette syndrome (OR 0.5, 95% CI 0.3-0.9) compared with parity 1-2. Birth weight 4000-4499 g was associated with decreased odds for Tourette syndrome (OR 0.7, 95% CI 0.5-0.9). Low birth weight, gestational age, weight for gestational age, Apgar score at 1 minute, induced labor, birth type or presentation, neonatal treatment, or maternal blood pressure were not associated with Tourette syndrome. CONCLUSIONS Increasing parity and high birth weight are associated with decreased odds for Tourette syndrome.

Is maternal smoking during pregnancy associated with bipolar disorder in offspring

BACKGROUND Prenatal smoking exposure affects fetal growth and development and is associated with increased risk of various neurodevelopmental disorders. Only one previous study has examined the association between maternal smoking during pregnancy and the risk of bipolar disorder (BPD). METHODS In this nested case control study derived from all singleton live births in Finland between January 1st 1987 and December 31st 1998, we identified 724 children diagnosed and/or treated with BPD until 2008 and 1419 matched controls from four nationwide registers. Conditional logistic regression was used to examine the association between maternal smoking during pregnancy and BPD adjusting for potential confounding due to parental psychiatric history, maternal age and education level. RESULTS 18.5% of offspring were exposed to maternal smoking during pregnancy. In the unadjusted analysis, smoking during pregnancy was associated with a 1.41-fold (95% CI 1.12-1.79, P=0.004) increased risk of BPD. In the final model adjusting for potential covariates, the risk was 1.14-fold (95% CI 0.88-1.49, P=0.323). LIMITATIONS The limitations of this study include: hospital based clinical diagnosis for case ascertainment, inclusion of early onset BPD cases, and lack of information on alcohol or other substance abuse during pregnancy. CONCLUSION This study demonstrated that, in this sample, an increased risk of BPD among offspring of mothers who smoked during pregnancy is most likely due to confounding by familial background factors. Future studies including information on serological measures of smoking exposure in pregnancy e.g. cotinine are warranted to further clarify this association.