Incidence of depression, prenatal and perinatal risk factors associated with depression and reactive attachment disorder in children: a nationwide register-based study

Prenatal and perinatal risk factors are associated with development of mental disorders in the offspring. Studying these risk factors in a prospective populationbased design helps to understand more on the etiology and development of depression and reactive attachment disorder (RAD). The aim of the thesis was to study the prenatal and perinatal risk factors associated with depression and RAD among children in a nationwide register-based, nested case-control study. The cases for the study included all individuals born singleton in Finland and diagnosed with depression or RAD according to the Care Register for Health Care (CRHC). The study identified 37,682 cases of depression born between January 1987 and December 2007 and diagnosed before December 2012 and 148,795 controls. There were 614 cases for RAD born between January 1996 and December 2012 and diagnosed before December 2012 and 2,423 controls. Conditional logistic regression models were used to examine the associations between risk factors and depression/RAD. The mean age at diagnosis of depression was 16 years (standard deviation (SD): 3.5 years, range: 5-25 years). The incidence of diagnosed depression increased from 1.8% to 2.9% in females and 1.0% to 1.6% in males when compared with those born in 1987–1993 with those born 1994–2000. In the adjusted analyses, a U-shaped distribution of odds ratio was observed for the association between parental age and depression. Preterm birth was associated with increased odds of depression. The mean age at diagnosis of RAD was 7.36 years (SD: 3.0 years, range: 0-16 years). In the multivariate analyses, parental psychopathology was strongly associated with offspring RAD. Other parental risk factors including maternal smoking during pregnancy, single motherhood and advanced paternal age were also associated with offspring RAD. Preterm birth, low birth weight, admission to neonatal intensive care unit and induced labour were associated with increased odds of RAD. These findings highlight variation among pre- and perinatal risk factors between depression and RAD. It also emphasizes the need for early identification of at-risk population and facilitates targeted interventions as early as the antenatal period.Lasten masennuksen ja reaktiivisen kiintymyssuhdehäiriön esiintyvyys ja niihin liittyvät pre- ja perinataaliset riskitekijät: kansallinen rekisteripohjainen tutkimus Lasten mielenterveyshäiriöiden kehittymiseen liittyy pre- ja perinataalisia riskitekijöitä, joiden tutkiminen prospektiivisella väestöpohjaisella mallilla auttaa ymmärtämään häiriöiden syitä ja kehitystä. Väitöskirjatyön tavoite oli tutkia tällaisia lasten masennukseen ja reaktiiviseen kiintymyssuhdehäiriöön liittyviä riskitekijöitä kansallisella rekisteripohjaisella, pesitetyllä tapaus-verrokkitutkimuksella. Tutkimuksessa olivat mukana kaikki yksisikiöisestä raskaudesta Suomessa syntyneet yksilöt, joilta löytyi diagnosoitu masennus tai reaktiivinen kiintymyssuhdehäiriö hoitoilmoitusrekisteristä. Vuosina 1987–2007 syntyneitä, ennen joulukuuta 2012 diagnosoituja masennustapauksia oli yhteensä 37 682 ja verrokkeja 148 795. Vuosina 1996–2012 syntyneitä ja ennen joulukuuta 2012 diagnosoituja reaktiivisen kiintymyssuhdehäiriön tapauksia oli 614 ja verrokkeja 2423. Riskitekijöiden ja häiriöiden välisiä suhteita tutkittiin käyttäen ehdollisia logistisia regressiomalleja. Masennusdiagnoosi saatiin keskimäärin 16 vuoden iässä (keskihajonta (SD): 3,5 vuotta, vaihteluväli: 5–25 vuotta). Diagnosoitujen tapausten esiintyvyys nousi 1,8%–2,9% naispuolisilla ja 1,0%–1,6% miespuolisilla tutkittavilla verrattaessa vuosina 1987–1993 ja 1994–2000 syntyneitä. Vanhempien iän ja lapsen masennusdiagnoosin välillä oli U:n muotoinen yhteys. Ennenaikainen synnytys oli yhteydessä masennuksen kohonneeseen todennäköisyyteen. Reaktiivisen kiintymyssuhdehäiriön diagnoosi saatiin keskimäärin 7,36 vuoden iässä (SD: 3,0 vuotta, vaihteluväli: 0–16 vuotta). Monimuuttuja-analyyseissa vanhempien psykopatologia liittyi vahvasti lapsen reaktiiviseen kiintymyssuhdehäiriöön, samoin kuin esimerkiksi raskaudenaikainen tupakointi, äidin yksinhuoltajuus sekä isän korkea ikä. Myös ennenaikainen synnytys, alhainen syntymäpaino, vastasyntyneen tehohoito ja synnytyksen käynnistäminen lisäsivät diagnoosin todennäköisyyttä. Löydökset näyttävät pre- ja perinataaliriskitekijöiden vaihtelevan masennuksessa ja reaktiivisessa kiintymyssuhdehäiriössä. Ne osoittavat myös riskiryhmien varhaisen tunnistamisen ja helposti saavutettavan kohdennetun hoidon tarpeen

Maternal Vitamin D Levels during Pregnancy and Offspring Psychiatric Outcomes: A Systematic Review

Prenatal exposure to vitamin D may play a significant role in human brain development and function. Previous epidemiological studies investigating the associations between maternal vitamin D status and offspring developmental and psychiatric outcomes in humans have been inconclusive. We aimed to systematically assess the results of previously published studies that examined the associations between maternal vitamin D levels, measured as circulating 25(OH)D levels in pregnancy or at birth, and offspring neuropsychiatric and psychiatric outcomes. Systematic searches were conducted using MEDLINE, Embase, PsychINFO and Web of Science for studies published by 10 August 2022. We included human observational studies that examined associations between prenatal or perinatal vitamin D levels and offspring neuropsychiatric and psychiatric outcomes and were published in English in peer-reviewed journals. Of the 3729 studies identified, 66 studies were screened for full texts and 29 studies published between 2003 and 2022 were included in the final review. There was a small amount of evidence for the association between prenatal vitamin D deficiency and autism spectrum disorder. When studies with larger sample sizes and stricter definitions of vitamin D deficiency were considered, positive associations were also found for attention-deficit/hyperactivity disorder and schizophrenia. Future studies with larger sample sizes, longer follow-up periods and prenatal vitamin D assessed at multiple time points are needed

Parental age and risk of depression: A nationwide, population-based case-control study

Background: The global prevalence of depression has increased in recent decades and so has the average age of parenthood. Younger and older parental age have been associated with several mental disorders in their offspring, but the associations for depression have been inconsistent.Methods: This study comprised 37,682 singleton births in Finland from 1987- 2007. The subjects were living in Finland at the end of 2012 and had a depressive disorder recorded in the Care Register for Health Care. We also randomly identified 148,795 controls from the Population Register. When missing obsevations excluded the sample was Ncases=18,708 and Ncontrols=77,243. The results were adjusted for the parents' psychiatric history, depression history, marital status and place of birth, the mothers' maternal socioeconomic status, smoking during pregnancy and previous births and the children's birth weight.Results: We found a U-shaped association between offspring depression and the age of both parents. The highest odds of depression occurred when the fathers were aged 50 plus years (adjusted Odds Ratio (ORa) 1.51, 95% CI 1.23-1.86) and the mothers were under 20 (ORa 1.44, 95% CI 1.29-1.60) compared to the reference category of parents aged 25-29 years.Limitations: The study was limited to depression diagnosed by specialised health care services and had a relatively short follow-up period. Some data were missing and that could lead to risk estimation biases.Conclusion: Diagnosed depression was higher among the offspring of younger and older parents. The results suggest that the age of the parent is etiologically associated with offspring depression.Keywords: Maternal age; Offspring depression; Parental age; Paternal age.</div

Time trends in the incidence of diagnosed depression among people aged 5-25 years living in Finland 1995-2012

Background: Knowledge of time trends for depression is important for disease prevention and healthcare planning. Only a few studies have addressed these questions regarding the incidence and cumulative incidence of diagnosed depression from childhood to early adulthood and findings have been inconclusive. Aim: The aim of this national register-based Finnish study was to report the time trends of the age-specific and gender-specific incidence and cumulative incidence of diagnosed depression. Methods: The study sample included all 1,245,502 singletons born in Finland between 1 January 1987 and 31 December 2007 and still living in Finland at the end of 2012. The participants were divided into three cohorts by birth year: 1987-1993, 1994-2000 and 2001-2007. Depression diagnoses (ICD-9: 2961; ICD-10: F32, F33) given in 1995-2012 were available and identified from the Care Register for Health Care. Results: Ten percent of the females and five percent of the males were diagnosed with depression in specialized services by age 25 years. The cumulative incidence of depression by age 15 years rose from 1.8% (95% CI 1.8-1.9) to 2.9% (95% CI 2.8-3.0) in females and from 1.0% (95% CI 1.1-1.2) to 1.6% (95% CI 1.6-1.7) in males when the cohorts born 1987-1993 and 1994-2000 were compared. Conclusions: A larger proportion of young people in Finland are diagnosed with depression in specialized services than before. This can be due to better identification, more positive attitudes to mental health problems and increased availability of the services.Peer reviewe

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 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

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 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

Preterm birth, poor foetal growth and anxiety disorders in a Finnish nationwide register sample

Aim: We examined the associations between preterm birth, poor foetal growth and anxiety disorders among children and adolescents. Additionally, we examined the im-pact of common comorbidities and specific anxiety disorders separately.Methods: Three  Finnish  registers  provided  data  on  a  nationwide  birth  cohort  of  22,181 cases with anxiety disorders and 74,726 controls. Conditional logistic regres-sion was used to examine the associations.Results: Extremely very preterm birth and moderate- late preterm birth were associ-ated with increased adjusted odds ratios (aOR) for anxiety disorders (aOR 1.39, 95% CI  1.11–1.75  and  aOR  1.13,  95%  CI  1.03–1.23,  respectively).  Weight  for  gestational  age of less than −2SD (aOR 1.29, 95% CI 1.17–1.42) and −2SD to −1SD (aOR 1.08, 95% CI 1.03–1.14) were associated with increased odds ratios for anxiety disorders. When comorbidities were considered, the associations became statistically insignificant for pure anxiety disorders, but remained significant in the groups with comorbid depres-sive or neurodevelopmental disorders.Conclusion: Preterm birth and poor foetal growth increased the odds for anxiety dis-orders. However, the associations seem to be explained by the conditions of comorbid depressive  and  neurodevelopmental  disorders.  Comorbidities  should  be  considered  when examining and treating child and adolescent anxiety disorders.</p

Perinatal risk factors and reactive attachment disorder: a nationwide population‐based study

AimTo examine the association between several perinatal and obstetric risk factors and reactive attachment disorder in children diagnosed in specialized services.MethodsIn this nested case control study, 614 cases with reactive attachment disorder and 2,423 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.ResultsIn the adjusted analysis, a low birthweight of ConclusionWe 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.</p

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.</p