Parental physical disease severity and severe documented physical child abuse: a prospective cohort study.

Successful prevention of physical child abuse is dependent on improvements in risk assessment. The risk of abuse is assumed to increase when family stressors overcome resources. Severe physical disease can increase stress, and parental physical disease has been studied as a risk factor for physical child abuse, but with heterogeneous definitions. This study evaluated the relation between parental physical disease severity and severe documented physical child abuse. Models were based on data on children aged 0-17 years in Denmark between 1997 and 2018, and their parents. Severe documented physical child abuse was modeled as violence against a child registered by either health authorities in treatment or mortality registries, or police authorities in cases confirmed by the courts. Parental physical disease severity was modeled as the sum of Charlson Comorbidity Index scores for the child's parents. The causal connection was examined in two model types: a survival model comparing exposed with non-exposed children, adjusted for covariates at baseline, and a G-model, taking time-varying covariates, including income and parental psychiatric disease into account. Neither model showed an association between parental physical disease severity and severe documented physical child abuse, with RR 0.99 and 95% CI (0.93-1.05) for the survival model and RR 1.08 for the G-model (CI not calculated).  Conclusion: In the model studied, parental physical disease severity was not a risk factor for severe documented physical child abuse. Individual categories of physical disease remain to be examined.  Trial registration: The study was pre-registered on Open Science Framework, https://osf.io/fh2sr . What is Known: • Parental physical disease severity has been studied previously as a risk indicator of physical child abuse, but based on heterogeneous definitions. • Previous studies have not studied parental physical disease severity preceding physical child abuse. What is New: • Parental severe physical disease was not prospectively associated with severe documented physical child abuse in a survival model, a G-model and a number of sensitivity analyses, respectively. • Results should be replicated in samples from populations without universal health care, and using different categories of disease.

Distinct age-related differences among victims in cases of suspected child abuse.

Evidence describing age-related differences among children with suspected physical and sexual child abuse is lacking. We describe findings in severe cases of suspected abuse. Cases with 756 children <15 years old were included during 2001-2013 at the Department of Forensic Medicine, Aarhus University, using forensic evaluation documents, medical records, and court proceedings. Eight percent of children <4 years old died from child abuse, 36% through violence resulting in death, and 64% by manslaughter, whereas 1% > 4 years old died, solely by manslaughter. External injuries were mainly located to head and torso in children <4 years old, changing to the upper and lower extremities in older children. Child sexual abuse was suspected in 52% of cases with living children <4 years old, 83% of children 4-7 years of age, 88% of children 8-11 years of age, and 93% of children >12 years old. Anogenital findings were mainly caused by other medical conditions in children <4 years old, hymenal clefts in the superior half of the hymenal rim were almost exclusively found in children between 8 and 11 years of age, whereas both superficial and complete hymenal clefts in the inferior half of the hymenal rim were found in children >12 years old. The present study describes age-related differences in victims of suspected child abuse. Fatal versus nonfatal child physical abuse and the significance of hymenal findings in child sexual abuse could be studied further.

Emotion regulation in 7-year-old children with familial high risk for schizophrenia or bipolar disorder compared to controls - The Danish High Risk and Resilience Study - VIA 7, a population-based cohort study.

OBJECTIVES: Emotion regulation is a predictor of overall life outcome. Problems of emotion regulation are associated with multiple psychiatric disorders and could be a potential treatment target for improving well-being and functioning. Children at familial high risk of severe mental illness have a markedly increased risk of various psychopathology and constitute a group at significant risk of emotion regulation problems. Investigations of emotion regulation in children at familial high risk of severe mental illness are sparse. METHODS: We applied an instrument for assessing emotion regulation, the Tangram Emotion Coding Manual (TEC-M), to a population-based cohort of 522 7-year-old children born to parents diagnosed with either schizophrenia or bipolar disorder and matched controls. The TEC-M is an ecologically valid, clinician-rated observational test measure of spontaneous emotion regulation. We aimed to compare emotion regulation between risk groups and to investigate associations between emotion regulation and psychopathology and daily life functioning, and between emotion regulation and an acknowledged questionnaire-based dysregulation profile. RESULTS: In this early developmental phase, we found no between group differences in emotion regulation. We found a significant but weak negative association between emotion regulation and both child psychopathology and the presence of a dysregulation profile on the Child Behavior Checklist and a weak positive association between emotion regulation and current level of functioning. CONCLUSIONS: These findings contribute to the understanding of emotion regulation in familial high-risk children and further studies of emotion regulation in children at familial high risk of severe mental illness are warranted.

The Strengths and Difficulties Questionnaire Is of Clinical Significance Regarding Emotional and Behavioral Problems in 7-Year-Old Children With Familial Risk of Schizophrenia or Bipolar Disorder and Population-Based Controls the Danish High Risk and Resilience Study-VIA 7; A Population-Based Cohort Study.

Background: Children born to parents with severe mental illness are at increased risk of mental and behavioral difficulties during childhood. We aimed to investigate the occurrence of clinically significant behavioral difficulties in 7-year-old children of parents diagnosed with schizophrenia or bipolar disorder as well as in control children by using the Strengths and Difficulties Questionnaire (SDQ). Further, we aimed to determine if the SDQ could function as a screening instrument for clinically relevant behavioral problems of children at high risk of these severe mental illnesses. Methods: By means of the Danish National Registers, we established a cohort of 522 7-year old children stratified by familial high risk for schizophrenia spectrum disorder (N = 202), bipolar disorder (N =120), and controls (N = 200). The child's primary caregiver completed the SDQ parent version and the Child Behavior Checklist (CBCL) while the schoolteacher completed the SDQ teacher version and the CBCL teacher equivalent; the Teachers Report Form (TRF). Finally, global functioning was assessed with the Children's Global Assessment Scale (CGAS). Results: Children with familial high risk of schizophrenia spectrum disorder or bipolar disorder have a significantly increased risk (OR = 3.8 and 2.3) of suffering clinically significant behavioral difficulties at age 7-years according to SDQ parent ratings. The SDQ discriminates with moderate to high sensitivity and high specificity between familial high-risk children with and without a psychiatric diagnosis and has overall compelling discriminatory abilities in line with the more time consuming CBCL/TRF.Conclusions Familial high-risk children have more behavioral difficulties and more frequently at a level indicative of mental illness compared to control children as measured by the SDQ. The SDQ works well as a screening instrument for clinically relevant behavioral problems in high-risk children.

The relationship between online courses and mental health among Chinese children.

BACKGROUND: Previous studies on the association of online courses and mental health were mainly conducted in universities, and no study investigated the relationship between characteristics of online courses and children's mental health in primary and secondary school. This study aimed to explore the association of online courses and children's mental health in primary and secondary school. METHODS: A cross-sectional study was conducted through an online survey among 540 primary and secondary school students and their parents in the eastern, central and western region of China from April to May in 2020. Children's mental health was assessed by the Strengths and Difficulties Questionnaire (SDQ). Borderline mental health problems (SDQ total difficulties score ≥ 16) and mental health problems (SDQ total difficulties score ≥ 20) were defined according to Goodman's standard. Multivariable linear and logistic regression models were used to examine the association between online courses and children's mental health. RESULTS: Compared with those who did not have problems of online courses, children having the difficulty in understanding the content of online courses had a higher SDQ total difficulties score [ß = 1.80, 95% confidence interval (CI): 0.89, 2.71] and a higher risk of borderline mental health problems [odds ratio (OR) = 1.93, 95%CI: 1.07, 3.49], while device or internet connection problems were not significantly associated with children's mental health. Compared with children who had live courses, those having video-recorded courses had a higher SDQ total difficulties score (ß = 0.90, 95%CI: 0.01, 1.80). Children who spent more than 4 h on online courses had a higher SDQ total difficulties score than those of less than or equal to 4 h (ß = 0.95, 95%CI: 0.09, 1.81). CONCLUSION: We found that online courses with inappropriate characteristics were associated with children's mental health. The findings called for the efforts to optimize the online courses and improve children's mental health.

Perceived stress among adolescents as a marker for future mental disorders: A prospective cohort study.

AIM: The mental health problems of adolescents are important in relation to their future health and life course. The aim of this study was to investigate perceived stress in adolescence as a marker for later mental disorders. METHODS: The data consisted of a combination of questionnaire and register data for 11,929 adolescents. Perceived stress was measured using Cohen's Perceived Stress Scale divided into low, moderate and high perceived stress. Mental disorder was identified using the ICD-10 codes for Mental and Behavioural Disorders classified into whether the adolescents were diagnosed or not. Logistic regression was used to examine the prospective association between perceived stress and mental disorders during about 12 months of follow-up, including the adolescents self-rated health, sex and parental education. RESULTS: In total, 247 adolescents (2.1%) were diagnosed with a mental disorder during follow-up. The perceived stress of the adolescents was associated with mental disorders, yielding two-fold higher odds of developing a mental disorder for adolescents reporting moderate perceived stress and six-fold higher odds among adolescents reporting high perceived stress in the adjusted model. CONCLUSIONS: Adolescents with high levels of perceived stress were more likely to develop a mental disorder. Interventions to reduce perceived stress among adolescents could therefore potentially help to identify groups at high risk for later mental disorders.

The association of asthma, atopic dermatitis, and allergic rhinitis with peripartum mental disorders.

BACKGROUND: Atopic diseases are characterized by dysregulated inflammatory response, which may incur the onset of peripartum mental disorders, but the impact remains unknown. This study examined whether and to what extent the history of atopic diseases is associated with newly onset peripartum mental disorders. METHODS: Using population-based registries, we identified all primiparous women who gave birth to live singletons in Denmark during 1978-2016 (n = 937,422). The exposure was hospital contact due to the three major types of atopic diseases-asthma, atopic dermatitis, and allergic rhinitis-before conception. The primary outcome was any hospital contact for mental disorder during pregnancy and 1-year postpartum, which was further classified into affective disorders, neurotic, stress-related and somatoform disorders, and substance abuse. The follow-up started from the date of conception and ended at the date of the first diagnosis of mental disorders, 1-year postpartum, death, emigration, or December 31, 2016, whichever came first. Cox regression was used, adjusted for calendar year, age at childbirth, education, residence, and Charlson comorbidity index. RESULTS: A total of 24,016 (2.6%) women received diagnosis of at least one of the three atopic diseases before conception (asthma, 1.7%; atopic dermatitis, 0.6%; and allergic rhinitis, 0.8%). Exposure to asthma, atopic dermatitis, or allergic rhinitis was associated with a 37% increased overall risk of peripartum mental disorders (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.27-1.49). Higher risks were observed among women with more frequent hospital contacts for atopic disease (HR, 1.80; 95% CI, 1.37-2.35; ≥5 times), and with recent hospital contacts for atopic disease (HR, 1.74; 95% CI, 1.48-2.06; within 2 years before conception). Specific associations were observed between asthma and neurotic, stress-related and somatoform disorders (HR, 1.40; 95% CI, 1.21-1.62), and between atopic dermatitis and substance abuse (HR, 1.62; 95% CI, 1.12-2.34). CONCLUSIONS: History of asthma, atopic dermatitis, and allergic rhinitis before conception was associated with increased risks of peripartum mental disorders. Women who have atopic diseases before pregnancy may benefit from systematic mental health monitoring.

Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: A national population-based cohort study.

BACKGROUND: The prevalence of cardiovascular disease (CVD) has been increasing in children, adolescents, and young adults in recent decades. Exposure to adverse intrauterine environment in fetal life may contribute to the elevated risk of early-onset CVD. Many studies have shown that maternal hypertensive disorders of pregnancy (HDP) are associated with increased risks of congenital heart disease, high blood pressure, increased BMI, and systemic vascular dysfunction in offspring. However, empirical evidence on the association between prenatal exposure to maternal HDP and early-onset CVD in childhood and adolescence remains limited. METHODS AND FINDINGS: We conducted a population-based cohort study using Danish national health registers, including 2,491,340 individuals born in Denmark from 1977 to 2018. Follow-up started at birth and ended at the first diagnosis of CVD, emigration, death, or 31 December 2018, whichever came first. Exposure of maternal HDP was categorized as preeclampsia or eclampsia (n = 68,387), gestational hypertension (n = 18,603), and pregestational hypertension (n = 15,062). Outcome was the diagnosis of early-onset CVD from birth to young adulthood (up to 40 years old). We performed Cox proportional hazards regression to evaluate the associations and whether the association differed by maternal history of CVD or diabetes before childbirth. We further assessed the association by timing of onset and severity of preeclampsia. The median follow-up time was 18.37 years, and 51.3% of the participants were males. A total of 4,532 offspring in the exposed group (2.47 per 1,000 person-years) and 94,457 in the unexposed group (2.03 per 1,000 person-years) were diagnosed with CVD. We found that exposure to maternal HDP was associated with an increased risk of early-onset CVD (hazard ratio [HR]: 1.23; 95% CI = 1.19 to 1.26; P < 0.001). The HRs for preeclampsia or eclampsia, gestational hypertension, and pregestational hypertension were 1.22 (95% CI, 1.18 to 1.26; P < 0.001), 1.25 (95% CI, 1.17 to 1.34; P < 0.001), and 1.28 (95% CI, 1.15 to 1.42; P < 0.001), respectively. We also observed increased risks for type-specific CVDs, in particular for hypertensive disease (HR, 2.11; 95% CI, 1.96 to 2.27; P < 0.001) and myocardial infarction (HR, 1.49; 95% CI, 1.12 to 1.98; P = 0.007). Strong associations were found among offspring of mothers with CVD history (HR, 1.67; 95% CI, 1.41 to 1.98; P < 0.001) or comorbid diabetes (HR, 1.56; 95% CI, 1.34 to 1.83; P < 0.001). When considering timing of onset and severity of preeclampsia on offspring CVD, the strongest association was observed for early-onset and severe preeclampsia (HR, 1.48, 95% CI, 1.30 to 1.67; P < 0.001). Study limitations include the lack of information on certain potential confounders (including smoking, physical activity, and alcohol consumption) and limited generalizability in other countries with varying disparities in healthcare. CONCLUSIONS: Offspring born to mothers with HDP, especially mothers with CVD or diabetes history, were at increased risks of overall and certain type-specific early-onset CVDs in their first decades of life. Further research is warranted to better understand the mechanisms underlying the relationship between maternal HDP and early-onset CVD in offspring.

Association of maternal diabetes during pregnancy with high refractive error in offspring: a nationwide population-based cohort study.

AIMS/HYPOTHESIS: We aimed to investigate the associations between maternal diabetes before or during pregnancy and the risk of high refractive error (RE) in offspring until the age of 25 years. METHODS: This nationwide register-based cohort study comprised 2,470,580 individuals born in 1977-2016. The exposure was maternal diabetes during or before pregnancy (type 1 diabetes, type 2 diabetes and gestational diabetes). Cox regression was used to examine the association between maternal diabetes and the risk of high RE in offspring from birth until the age of 25 years, adjusting for multiple potential confounders. RESULTS: During up to 25 years of follow-up, 553 offspring of mothers with diabetes and 19,695 offspring of mothers without diabetes were diagnosed with high RE. Prenatal exposure to maternal diabetes was associated with a 39% increased risk of high RE: HR 1.39 (95% CI 1.28, 1.51), p < 0.001; standardised cumulative incidence in unexposed offspring at 25 years of age 1.18% (95% CI 1.16%, 1.19%); cumulative incidence difference 0.72% (95% CI 0.51%, 0.94%). The elevated risks were observed for hypermetropia (HR 1.37 [95% CI 1.24, 1.51], p < 0.001), myopia (HR 1.34 [95% CI 1.08, 1.66], p = 0.007) and astigmatism (HR 1.58 [95% CI 1.29, 1.92], p < 0.001). The increased risks were more pronounced among offspring of mothers with diabetic complications (HR 2.05 [95% CI 1.60, 2.64], p < 0.001), compared with those of mothers with diabetes but no diabetic complications (HR 1.18 [95% CI 1.02, 1.37], p = 0.030). CONCLUSIONS/INTERPRETATION: Our findings suggest that maternal diabetes during pregnancy is associated with an increased risk of high RE in offspring, in particular among those of mothers with diabetic complications. Early ophthalmological screening should be recommended in offspring of mothers with diabetes diagnosed before or during pregnancy.

Long-term growth in offspring of infertile parents: A 20-year follow-up study.

INTRODUCTION: Long-term growth has been poorly investigated in boys and girls born to parents receiving fertility treatment. This study aimed to investigate the growth of children born following fertility treatment up to adulthood hypothesizing comparable growth in children born to parents receiving fertility treatment or to subfertile parents conceiving spontaneously to that in children spontaneously conceived by fertile parents. MATERIAL AND METHODS: In this historical long-term follow-up study the study population consisted of 4151 singletons born at term in the Aarhus Birth Cohort between 1990 and 1992. Parental lifestyle and sociodemographic characteristics together with multiple measurements of weight and height were collected up to 20 years of age (6.1% of children contributed with at least one measurement for height or weight at age 20 years). The main outcome was difference in z-score for height (m) and weight (kg) between children conceived spontaneously (reference) and children conceived following fertility treatment, children conceived spontaneously by subfertile parents, or unplanned. Results were adjusted for pre-pregnancy maternal and paternal body mass index, maternal educational level, smoking during pregnancy, maternal age, and parity. RESULTS: Singletons conceived following fertility treatment (n = 164; 4.0%) or by subfertile parents (n = 271; 6.5%) had comparable magnitude of weight estimates to children conceived spontaneously (difference in z-score per year 0.0148 [95% CI 0.0026-0.0270] and 0.0069 [95% CI -0.0028 to 0.0165], respectively). Height estimates were also comparable between groups of children conceived following fertility treatment or by subfertile parents (difference in z-score per year 0.0022 [95% CI -0.0075 to 0.0119]) compared with children conceived spontaneously (difference in z-score per year -0.0026 (95% CI -0.0103 to 0.0052). From the beginning of adolescence, we found lower weight for children born to subfertile parents and to parents receiving fertility treatment compared with spontaneously conceived children. CONCLUSIONS: The main finding was equal long-term growth for children born at term by parents who received fertility treatment or parents waiting more than 12 months to conceive compared with spontaneously conceived children.

Obstetric oxytocin exposure and ADHD and ASD among Danish and Finnish children.

BACKGROUND: Some studies have indicated an increased risk of attention deficit hyperactivity disorder (ADHD) and a small, sex-specific association with autism spectrum disorder (ASD) among children prenatally exposed to obstetric oxytocin. Since oxytocin is widely used in the obstetric ward, these potentially deleterious effects are of concern. Thus, we aimed to examine whether obstetric oxytocin treatment for labour induction or augmentation is associated with ADHD and ASD in offspring born in a two-country design based on data from Denmark and Finland. METHODS: This population-based study used data from national registers in Denmark and Finland. Singletons born in Denmark 2000-10 (n = 577 380) and Finland 1991-2010 (n = 945 543), who survived infancy, were followed until 31 December 2015. ADHD and ASD were defined using diagnostic codes. For ADHD, we also included information on prescribed and redeemed ADHD medication in the definition. Hazards ratios (HRs) with 95% confidence intervals (CI), modelled with age as the underlying time scale, were calculated to estimate the associations. RESULTS: Oxytocin was used in 31% and 46% of the included deliveries in Denmark and Finland, respectively. In crude analyses, prenatal oxytocin was associated with an approximately 20% increased risk of ADHD and ASD, but confounder adjustment attenuated the association. The adjusted HR was 1.03, 95% CI 1.01-1.05, for ADHD and 1.05, 95% CI 1.02-1.08, for ASD. The results were similar in across country and gender. CONCLUSIONS: We found an association between synthetic oxytocin and ADHD or ASD which is unlikely to reflect a causal association and thus should not support the concern of clinical use. Our results help to allay concerns of obstetric use of oxytocin causing ADHD or ASD.

Behavioral Problems at Age 11 Years After Prenatal and Postnatal Exposure to Acetaminophen: Parent-Reported and Self-Reported Outcomes.

Several studies have reported associations between prenatal acetaminophen exposure and behavioral outcomes in young children. We aimed to evaluate the associations of prenatal and postnatal exposures to acetaminophen with behavioral problems in children at age 11 years, using behavioral measures reported by parents and children. We studied 40,934 mother-child pairs from the Danish National Birth Cohort enrolled during 1996-2002. Parent-reported and child-reported Strengths and Difficulties Questionnaire (SDQ) responses were collected during the 11-year follow-up. We estimated risk ratios for behavioral problems including total difficulties as well as internalizing or externalizing behaviors following prenatal (during pregnancy) or postnatal (within the first 18 months after birth) acetaminophen exposure. Parent-reported and child-reported SDQ scores were moderately correlated; higher for externalizing (r = 0.59) than internalizing (r = 0.49) behaviors. Prenatal acetaminophen exposure was associated with 10%-40% higher risks for total difficulties and internalizing and externalizing problems based on parent- or child-reported SDQ, with the association being stronger for greater cumulative weeks of acetaminophen use. Postnatal exposure was associated with 16%-19% higher risks for parent-reported internalizing behaviors, but the associations were weak or null for child-reported scores except for prosocial behavior. Our study corroborates published associations between prenatal exposures to acetaminophen and behavioral problems and extends the literature to early adolescence.

Executive functions in 7-year-old children of parents with schizophrenia or bipolar disorder compared with controls: The Danish High Risk and Resilience Study-VIA 7, a population-based cohort study.

Cognitive impairments are strongly associated with schizophrenia (SZ) and bipolar disorder (BP) with executive functions (EF) impairments as a likely key feature. Studies of everyday behavior rated EF in young children at familial high risk of SZ (FHR-SZ) are scarce and, to our knowledge, non-existent in young children at familial high risk of BP (FHR-BP). We aimed to compare everyday behavior-rated EF of FHR-SZ, FHR-BP, and control children. A nationwide population-based cohort of 522 7-year-old children with parents diagnosed with either SZ (N = 202) or BP (N = 120) and matched controls (N = 200) were recruited using the Danish national registries. The children's EF were assessed with the Behavior Rating Inventory of Executive Functions questionnaire rated by primary caregivers and teachers. According to primary caregiver assessments, FHR-SZ children displayed widespread EF impairments and had an odds ratio of 3.7 (2.0-6.9) of having clinically significant global EF impairments compared to controls. FHR-BP children were most severely impaired regarding EF related to emotional control and had an odds ratio of 2.5 (1.2-5.1) of clinically significant global EF impairments compared to controls. Teacher assessments were overall comparable to primary caregiver assessments but teachers rated more difficulties in the FHR-SZ group than primary caregivers. Already at age 7, children with a parental history of SZ or BP displayed significant impairments of EF in everyday-life situations. FHR-SZ children displayed widespread significant impairments of EF, whereas FHR-BP children were most severely impaired on emotional control. Clinicians should be aware of potential EF impairments in FHR children.

Differential Parent and Teacher Reports of ADHD Symptoms According to the Child's Country of Origin: A Quantitative Study From Denmark Exploring the Implication for Diagnosis.

Objective: This study aimed to investigate differences in parent- and teacher-reported ADHD symptoms according to the child's country of origin. Method: We conducted a cross-sectional study of 4,207 nonimmigrant (Danish origin) and 233 immigrant (non-Danish origin) children including ratings of phenotypical ADHD symptoms on the Strengths and Difficulties Questionnaires. The association between ADHD symptoms and country of origin, separately for parents and teachers, was analyzed using multiple logistic regression. Results: Teachers reported similar numbers of ADHD symptoms for immigrant and nonimmigrant children (odds ratio [OR] = 0.95, confidence interval [CI] = [0.58, 1.54]), whereas immigrant parents were less likely than nonimmigrant parents to report ADHD symptoms (OR = 0.42, CI = [0.21, 0.84]). Conclusion: Immigrant parents were less likely than nonimmigrant parents to report ADHD symptoms, whereas the teachers reported similar amount of ADHD symptoms in the two groups of children. Our results emphasize the importance of paying attention to teacher reporting of ADHD symptoms when assessing immigrant children.

Five-Minute Apgar Score and the Risk of Mental Disorders During the First Four Decades of Life: A Nationwide Registry-Based Cohort Study in Denmark.

OBJECTIVES: The associations of long-term risks of the full spectrum of mental disorders with clinically reassuring but suboptimal score range 7-9 remain unclear. This study investigated these associations during up to 38 years of follow-up. METHODS: In a nationwide cohort study of 2,213,822 singletons born in Denmark during 1978-2015, we used cox regression to estimate the hazard ratio (HR) of mental disorders with a 95% CI. RESULTS: A total of 3,00,679 (13.6%) individuals were diagnosed with mental disorders. The associations between suboptimal Apgar score 7-9 and mental disorders differed by attained age. In childhood (≤ 18 years), declining Apgar scores were associated with increased risks of overall mental disorders with HRs (95% CI) of 1.13(1.11-1.15), 1.34 (1.27-1.41), and 1.48 (1.31-1.67) for Apgar scores of 7-9, 4-6, and 1-3, respectively, compared with a score of 10. A dose-response association was seen even within the score range from 9 to 7 (HR 1.11 [95% CI: 1.08-1.13], 1.14 [1.10-1.18], and 1.20 [1.14-1.27], respectively). Of note, individuals with scores of 7-9 had increased risks of organic disorders (HR: 1.27, 95% CI: 1.05-1.53), neurotic disorders (HR: 1.07, 95% CI: 1.03-1.11), and a wide range of neurodevelopmental disorders, such as intellectual disability (1.87, 1.76-1.98), childhood autism (1.13, 1.05-1.22) and attention deficit hyperactivity disorder (1.10, 1.06-1.15). In early adulthood (19-39 years), suboptimal Apgar scores 7-9 were not associated with the risks of overall and specific mental disorders. CONCLUSION: Infants born with clinically reassuring but suboptimal 5-min scores 7-9 are at increased risks of a wide spectrum of mental disorders in childhood.

Prenatal exposure to perfluoroalkyl substances and behavioral difficulties in childhood at 7 and 11 years.

BACKGROUND: Perfluoroalkyl substances (PFAS) are suggested to interfere with thyroid hormone during pregnancy and influence fetal neurodevelopment. Epidemiological evidence regarding behavioral difficulties in childhood associated with prenatal PFAS exposure has been inconclusive. OBJECTIVE: We evaluated the association between prenatal PFAS exposure and behavioral difficulties at 7 and 11 years, and investigated the potential mediating role of maternal thyroid hormones. METHODS: Using pooled samples in the Danish National Birth Cohort established between 1996 and 2002, we estimated the associations between concentrations of six types of PFAS in maternal plasma (median, 8 gestational weeks) and child behavioral assessments from the Strength and Difficulties Questionnaire (SDQ), reported by parents at 7 years (n = 2421), and by parents (n = 2070) and children at 11 years (n = 2071). Behavioral difficulties were defined as having a composite SDQ score above the 90th percentile for total difficulties and externalizing or internalizing behaviors. We used logistic regression to estimate the adjusted Odds Ratio (OR) by doubling increase of prenatal PFAS (ng/ml). The possible mediating effect of maternal thyroid function classified based on thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels were evaluated. RESULTS: Prenatal perfluorononanoic acid (PFNA) was consistently associated with total and externalizing behavioral difficulties in all three SDQ measures reported by parents (OR = 1.40, 95% CI: 1.14-1.73 for age 7; OR = 1.27, 95% CI: 1.05-1.53 for age 11) or children (OR = 1.32, 95% CI: 1.11-1.58) while no consistent associations were observed for other types of PFAS. A small magnitude of natural indirect effects via maternal thyroid dysfunction (ORs ranged from 1.01 to 1.03) of several PFAS were observed for parent-reported total and externalizing behaviors at 7 years only. DISCUSSION: Prenatal PFNA exposure was associated with externalizing behavioral difficulties in childhood in repeated SDQ measures at 7 and 11 years. The slight mediating effects of maternal thyroid hormones in early gestation warrant further evaluation.

Maternal spontaneous abortion and the risk of attention-deficit/hyperactivity disorder in offspring: a population-based cohort study.

STUDY QUESTION: Is a maternal history of spontaneous abortion (SA) associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring? SUMMARY ANSWER: Our results suggest an association between maternal history of SA and ADHD in offspring, with the risk increasing with the number of maternal SA and highest in the firstborn children whose mothers had had recurrent SAs after adjusting for a number of potential confounders. WHAT IS KNOWN ALREADY: A history of SA has been associated with more complications in next pregnancies and adverse childbirth outcomes, which are risk factors for ADHD in the offspring. However, no previous study has investigated whether maternal SA increases risk of ADHD in the offspring. STUDY DESIGN, SIZE, DURATION: This population-based study included all live-born children in Denmark from 1 January 1995 to 31 December 2012 (n = 1 062 667). All children were followed from 3 years of age until the day of ADHD diagnosis, death, emigration or 31 December 2016, whichever came first. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 130 206 (12.2%) children born to mothers who had at least one SA. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). MAIN RESULTS AND THE ROLE OF CHANCE: During a median follow-up of 9.4 years (interquartile range, 5.4-14.3), 25 747 children were diagnosed with ADHD. Overall, children of mothers with a history of SA had an increased rate of ADHD (HR, 1.11; 95% CI, 1.07 to 1.15). The HRs increased with the number of maternal SA, 1.09 (95% CI, 1.05 to 1.13) for one SA and 1.22 (95% CI, 1.12 to 1.33) for at least two SAs, respectively. These findings were consistent when we took into consideration a number of factors, such as maternal socioeconomic status, type of SA, birth order, parental history of psychiatric disorders, pregnancy characteristics and adverse birth outcomes. LIMITATIONS, REASONS FOR CAUTION: Misclassification of SA was possible as we used population-based register data to capture maternal history of SA. However, any misclassification of maternal history of SA would be non-differential with regard to the diagnosis of ADHD in offspring, which generally leads to underestimation of the associations. Furthermore, probabilistic sensitivity analysis suggested that only 1% of change in the estimate may have been due to misclassification of SA. WIDER IMPLICATIONS OF THE FINDINGS: SA is quite frequent (varying from 15 to 20%), and a small increase of neurodevelopmental problems in offspring could have major public health implications. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the National Natural Science Foundation of China (No. 81703237, No. 81530086 and No. 81761128035), National Key Research and Development Program (2018YFC1002801, 2016YFC1000505), Shanghai Municipal Commission of Health and Family Planning (No. 2017ZZ02026, No. 2017EKHWYX-02), the Novo Nordisk Foundation (NNF18OC0052029), the Danish Council for Independent Research (DFF-6110-00019), the Nordic Cancer Union (176673, 186200 and R217-A13234-18-S65), Karen Elise Jensens Fond (2016) and Xinhua Hospital of Shanghai Jiao Tong University School of Medicine (2018YJRC03). All authors report no conflict of interest. TRIAL REGISTRATION NUMBER: NA.

Cumulative social disadvantage and risk of attention deficit hyperactivity disorder: Results from a nationwide cohort study.

Socioeconomic factors correlate with mental health and affect individual life chances. However, the influence of specific and cumulative social disadvantages on children's mental health problems has received little attention. Previous studies have primarily used global measures of mental health problems or aggregated indicators of socioeconomic status. We contribute to this research by including multiple indicators of parental social disadvantage to study independent and accumulative effects. The study focuses on the Attention Deficit/Hyperactivity Disorder (ADHD), which is known to affect children's educational and socioeconomic trajectories. ADHD is one of the most common child mental health problems and although heredity has been estimated to 76 percent, research suggests that a large social component remains in the prevalence. We exploit comprehensive high-quality registry data for the entire population of children born 1990-1999 in Denmark (N = 632,725). The ADHD prevalence is 3.68 percent. Estimates from linear probability models show that parental unemployment, relative income poverty, and low educational attainment increase children's risk of ADHD with 2.1 (95% CI 1.8-2.3), 2.3 (95% CI 2.1-2.5), and 3.5 percentage points (95% CI 3.3-3.7), respectively. Children who live with all three disadvantages face an increased risk of 4.9 percentage points.

Cerebral disorders in the first 7 years of life in children born post-term: a cohort study.

BACKGROUND: To estimate the association between post-term delivery and risk of physical disabilities, mental disabilities, and seizures during the first 7 years of life. METHODS: Data from 57,884 singleton infants born alive in week 39-45 by mothers included in the Danish National Birth Cohort (1997 to 2004) were analyzed, of these 51,268 were born at term (39-41 + 6) and 6616 post-term (42 + 0-44 + 6). Information on clinical endpoints was obtained from an interview at 18 months of gestational age, from a 7-year questionnaire, and from the Danish National Patient Register. Logistic regression and Cox regression were used to estimate odds ratios and hazard rate ratios for the outcome obtained from the interview/questionnaire data and from the register-based data, respectively. RESULTS: We found no statistically significant increased risk of physical disabilities, mental disabilities, and epilepsy among children born post-term, though for most outcomes studied a tendency towards more adverse outcomes was seen. When children born late term (week 41) were compared to children born in week 42 or later the same tendency was found. CONCLUSION: Post-term born children had a tendency to an excess risk of neurological disabilities as followed for up to 7 years of age.