Prenatal developmental origins of behavior and mental health: The influence of maternal stress in pregnancy.

Accumulating research shows that prenatal exposure to maternal stress increases the risk for behavioral and mental health problems later in life. This review systematically analyzes the available human studies to identify harmful stressors, vulnerable periods during pregnancy, specificities in the outcome and biological correlates of the relation between maternal stress and offspring outcome. Effects of maternal stress on offspring neurodevelopment, cognitive development, negative affectivity, difficult temperament and psychiatric disorders are shown in numerous epidemiological and case-control studies. Offspring of both sexes are susceptible to prenatal stress but effects differ. There is not any specific vulnerable period of gestation; prenatal stress effects vary for different gestational ages possibly depending on the developmental stage of specific brain areas and circuits, stress system and immune system. Biological correlates in the prenatally stressed offspring are: aberrations in neurodevelopment, neurocognitive function, cerebral processing, functional and structural brain connectivity involving amygdalae and (pre)frontal cortex, changes in hypothalamo-pituitary-adrenal (HPA)-axis and autonomous nervous system.

Food and nutrient intakes by temperament traits: findings in the Helsinki Birth Cohort Study.

BACKGROUND/OBJECTIVES: Previous studies have shown that the temperament traits are related to risk factors for chronic diseases, which could be partly explained by lifestyle habits. However, little is known whether temperament traits associate with diet. The aim of this study was to examine the cross-sectional associations between temperament traits and the whole diet. SUBJECTS/METHODS: We studied 1668 men and women, aged 56-70, from the Helsinki Birth Cohort Study. Temperament was measured using the Tridimensional Personality Questionnaire. Information on diet was collected by a validated 128-item food frequency questionnaire. The associations of temperament traits; novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (P), with diet were tested by linear regression analysis. RESULTS: After adjustment for potential confounders, greater HA was related to poorer diet quality, including lower consumption of vegetables, fruits, fish and several vitamins. RD was associated with healthier diet quality, including higher consumption of vegetables and intake of vitamin E and lower intake of alcohol. NS was significantly related to higher intake of fish, fat and alcohol and lower consumption of cereals, milk products and carbohydrates. No significant associations between P and intake of foods and nutrients were observed. CONCLUSIONS: Our results suggest that there is an association between temperament traits and diet. Especially greater HA seems to associate with poorer diet quality and greater RD with healthier diet quality.

Psychological, social and role functioning as predictors of psychosis in an adolescent psychiatric sample.

AIM: Recent evidence from psychosis risk studies of preselected samples suggests that early functional impairment may be a vulnerability marker for psychosis. We investigated whether functional impairment predicted later risk of psychotic disorder and psychiatric hospitalizations in adolescents at entry to general psychiatric services. METHODS: A total of 154 adolescents, aged 15 to 18 years, were recruited to the study at entry to general adolescent psychiatric services in Helsinki, Finland. Structured Interview for Prodromal Syndrome and Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorder for DSM-IV, Clinical version interviews were used to assess psychotic-like symptoms, psychosis risk and psychiatric diagnoses. Of the adolescents, 46 met the criteria for clinical high risk status. The level of functioning was assessed with Global Functioning Social, Role and Psychological scales. The adolescents were followed for 3 to 9 (median = 5) years via a hospital discharge register. Cox regression analyses were used to examine whether baseline functioning predicted psychotic disorders and psychiatric hospitalizations when controlling for the effect of psychosis risk symptoms. RESULTS: Impairments in social, role or psychological functioning did not predict psychotic disorders beyond risk symptoms. Impairment in psychological functioning was the only significant predictor of any psychiatric hospitalization after adjusting for positive psychosis risk symptom severity and level of social and role functioning. CONCLUSIONS: Psychosis was predicted by psychotic-like experiences at entry to psychiatric services. No aspect of functioning predicted psychosis in adolescents, which is likely to be explained by the low incidence of psychosis transitions. Severe mental disorders as assessed by psychiatric hospitalizations were predicted by more severe symptomatology as assessed by the psychological functioning scale.

Maternal depressive symptoms during and after pregnancy are associated with attention-deficit/hyperactivity disorder symptoms in their 3- to 6-year-old children.

Maternal depressive symptoms during pregnancy have been associated with child behavioural symptoms of attention-deficit/hyperactivity disorder (ADHD) in early childhood. However, it remains unclear if depressive symptoms throughout pregnancy are more harmful to the child than depressive symptoms only during certain times, and if maternal depressive symptoms after pregnancy add to or mediate any prenatal effects. 1,779 mother-child dyads participated in the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study. Mothers filled in the Center of Epidemiological Studies Depression Scale biweekly from 12+0-13+6 to 38+0-39+6 weeks+days of gestation or delivery, and the Beck Depression Inventory-II and the Conners' Hyperactivity Index at the child's age of 3 to 6 years (mean 3.8 years, standard deviation [SD] 0.5). Maternal depressive symptoms were highly stable throughout pregnancy, and children of mothers with consistently high depressive symptoms showed higher average levels (mean difference = 0.46 SD units, 95% Confidence Interval [CI] 0.36, 0.56, p < 0.001 compared to the low group), and proportion (32.1% vs. 14.7%) and odds (odds ratio = 2.80, 95% CI 2.20, 3.57, p < 0.001) of clinically significant ADHD symptoms. These associations were not explained by the effects of maternal depressive symptoms after pregnancy, which both added to and partially mediated the prenatal effects. Maternal depressive symptoms throughout pregnancy are associated with increased ADHD symptomatology in young children. Maternal depressive symptoms after pregnancy add to, but only partially mediate, the prenatal effects. Preventive interventions suited for the pregnancy period may benefit both maternal and offspring mental health.

Nutrition after preterm birth and adult neurocognitive outcomes.

BACKGROUND: Preterm birth (<37 gestational weeks) poses a risk of poorer neurocognitive functioning. Faster growth after preterm birth predicts better cognitive abilities and can be promoted through adequate nutrition, but it remains unknown whether variations in nutrient intakes translate into long-term benefits for neurodevelopment. METHODS: In 86 participants of the Helsinki Study of Very Low Birth Weight Adults (birthweight <1500g), we examined if higher intakes of energy, macronutrients, and human milk during the first nine weeks after preterm birth predict performance in tests of cognitive ability at 25.1 years of age (SD = 2.1). RESULTS: 10 kcal/kg/day higher total energy intake at 3 to 6 weeks of age was associated with 0.21 SD higher adult IQ (95% Confidence Interval [CI] 0.07-0.35). Higher carbohydrate and fat intake at 3-6 weeks, and higher energy intake from human milk at 3-6 and at 6-9 weeks were also associated with higher adult IQ: these effect sizes ranged from 0.09 SD (95% CI 0.01-0.18) to 0.34 SD (0.14-0.54) higher IQ, per one gram/kg/day more carbohydrate and fat, and per 10 kcal/kg/day more energy from human milk. Adjustment for neonatal complications attenuated the associations: intraventricular hemorrhage, in particular, was associated with both poorer nutrition and poorer IQ. CONCLUSION: In preterm neonates with very low birth weight, higher energy and human milk intake predict better neurocognitive abilities in adulthood. To understand the determinants of these infants' neurocognitive outcome, it seems important to take into account the role of postnatal nutrition, not just as an isolated exposure, but as a potential mediator between neonatal illness and long-term neurodevelopment.

Maternal lipids in pregnancy are associated with increased offspring cortisol reactivity in childhood.

Prenatal programming of hypothalamic-pituitary-adrenal (HPA) axis activity has long term implications for offspring health. Biological mechanisms underlying programming of the offspring HPA axis are poorly understood. We hypothesised that altered maternal metabolism including higher maternal obesity, glucose and lipids are novel programming factors for altered offspring HPA axis activity. Salivary cortisol levels were measured in 54 children aged 3-5 years under experimental conditions (before and after a delay of self-gratification test). Associations of child cortisol responses with maternal obesity in early pregnancy and with fasting glucose, triglycerides, HDL and total cholesterol measured in each pregnancy trimester were tested. Higher levels of maternal triglycerides and total cholesterol throughout pregnancy were associated with increased offspring cortisol reactivity. The associations were independent of maternal obesity and other confounders, suggesting that exposure to maternal lipids could be a biological mechanism of in utero programming of the offspring's HPA axis.

Maternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD.

Maternal prenatal anxiety is an important risk factor for altered child neurodevelopment but there is uncertainty concerning the biological mechanisms involved and sources of individual differences in children's responses. We sought to determine the role of functional genetic variation in COMT, which encodes catechol-O-methyltransferase, in the association between maternal prenatal anxiety and child symptoms of ADHD and working memory. We used the prospectively-designed ALSPAC cohort (n = 6,969) for our primary data analyses followed by replication analyses in the PREDO cohort (n = 425). Maternal prenatal anxiety was based on self-report measures; child symptoms of ADHD were collected from 4-15 years of age; working memory was assessed from in-person testing at age 8 years; and genetic variation in COMT at rs4680 was determined in both mothers and children. The association between maternal prenatal anxiety and child attention/hyperactivity symptoms and working memory was moderated by the child's rs4680 genotype, with stronger effects obtained for the val/val (G:G) genotype relative to val/met (A:G) (all p<0.01) and met/met (A:A) groups (all p<0.05). Similar findings were observed in the PREDO cohort where maternal prenatal anxiety interacted with child rs4680 to predict symptoms of ADHD at 3.5 years of age. The findings, from two cohorts, show a robust gene-environment interaction, which may contribute to inter-individual differences in the effects of maternal prenatal anxiety on developmental outcomes from childhood to mid-adolescence.

Self-Reported Mental Health Problems Among Adults Born Preterm: A Meta-analysis.

CONTEXT: Preterm birth increases the risk for mental disorders in adulthood, yet findings on self-reported or subclinical mental health problems are mixed. OBJECTIVE: To study self-reported mental health problems among adults born preterm at very low birth weight (VLBW; ≤1500 g) compared with term controls in an individual participant data meta-analysis. DATA SOURCES: Adults Born Preterm International Collaboration. STUDY SELECTION: Studies that compared self-reported mental health problems using the Achenbach Young Adult Self Report or Adult Self Report between adults born preterm at VLBW (n = 747) and at term (n = 1512). DATA EXTRACTION: We obtained individual participant data from 6 study cohorts and compared preterm and control groups by mixed random coefficient linear and Tobit regression. RESULTS: Adults born preterm reported more internalizing (pooled ß = .06; 95% confidence interval .01 to .11) and avoidant personality problems (.11; .05 to .17), and less externalizing (-.10; -.15 to -.06), rule breaking (-.10; -.15 to -.05), intrusive behavior (-.14; -.19 to -.09), and antisocial personality problems (-.09; -.14 to -.04) than controls. Group differences did not systematically vary by sex, intrauterine growth pattern, neurosensory impairments, or study cohort. LIMITATIONS: Exclusively self-reported data are not confirmed by alternative data sources. CONCLUSIONS: Self-reports of adults born preterm at VLBW reveal a heightened risk for internalizing problems and socially avoidant personality traits together with a lowered risk for externalizing problem types. Our findings support the view that preterm birth constitutes an early vulnerability factor with long-term consequences on the individual into adulthood.

Prenatal exposure to maternal very severe obesity is associated with impaired neurodevelopment and executive functioning in children.

BackgroundPrenatal maternal obesity has been associated with an increased risk of neurocognitive problems in childhood, but there are fewer studies on executive functioning.MethodsTests and questionnaires to assess neurodevelopment, executive functioning, and the ability to delay gratification were conducted in 113 children (mean (SD)=4.24 (0.63) years of age) born to mothers with very severe obesity (SO, body mass index (BMI)⩾40 kg/m2, n=51) or to lean mothers (BMI⩽25 kg/m2, n=62).ResultsPrenatal maternal SO predicted poorer neurodevelopment (unstandardized regression coefficient (B)=-0.42, 95% confidence interval (CI) (-0.82; -0.02)), worse problem-solving (odd ratio (OR)=0.60, 95% CI (1.13; 0.07)), and fine motor skills (OR=4.91, 95% CI (1.27; 19.04)), poorer executive functioning in areas of attention, inhibitory control, and working memory (standardized B=3.75, 95% CI (1.01; 13.93)) but not in self-gratification delay. The effects were independent of maternal concurrent psychological well-being and child's BMI, but not independent of maternal education.ConclusionFuture studies should investigate whether perinatal management of maternal obesity could prevent adverse outcomes in child neurodevelopment.

Maternal Licorice Consumption During Pregnancy and Pubertal, Cognitive, and Psychiatric Outcomes in Children.

Earlier puberty, especially in girls, is associated with physical and mental disorders. Prenatal glucocorticoid exposure influences the timing of puberty in animal models, but the human relevance of those findings is unknown. We studied whether voluntary consumption of licorice, which contains glycyrrhizin (a potent inhibitor of placental 11ß-hydroxysteroid dehydrogenase type 2, the "barrier" to maternal glucocorticoids), by pregnant women was associated with pubertal maturation (height, weight, body mass index for age, difference between current and expected adult height, Tanner staging, score on the Pubertal Development Scale), neuroendocrine function (diurnal salivary cortisol, dexamethasone suppression), cognition (neuropsychological tests), and psychiatric problems (as measured by the Child Behavior Checklist) in their offspring. The children were born in 1998 in Helsinki, Finland, and examined during 2009-2011 (mean age = 12.5 (standard deviation (SD), 0.4) years; n = 378). Girls exposed to high maternal glycyrrhizin consumption (≥500 mg/week) were taller (mean difference (MD) = 0.4 SD, 95% confidence interval (CI): 0.1, 0.8), were heavier (MD = 0.6 SD, 95% CI: 0.2, 1.9), and had higher body mass index for age (MD = 0.6 SD, 95% CI: 0.2, 0.9). They were also 0.5 standard deviations (95% CI: 0.2, 0.8) closer to adult height and reported more advanced pubertal development (P < 0.04). Girls and boys exposed to high maternal glycyrrhizin consumption scored 7 (95% CI: 3.1, 11.2) points lower on tests of intelligence quotient, had poorer memory (P < 0.04), and had 3.3-fold (95% CI: 1.4, 7.7) higher odds of attention deficit/hyperactivity disorder problems compared with children whose mothers consumed little to no glycyrrhizin (≤249 mg/week). No differences in cortisol levels were found. Licorice consumption during pregnancy may be associated with harm for the developing offspring.

Growth after late-preterm birth and adult cognitive, academic, and mental health outcomes.

BACKGROUND: Late-preterm birth (at 340/7-366/7 wk gestation) increases the risk of early growth faltering, poorer neurocognitive functioning, and lower socio-economic attainment. Among early-preterm individuals, faster early growth benefits neurodevelopment, but it remains unknown whether these benefits extend to late-preterm individuals. METHODS: In 108 late-preterm individuals, we examined if weight, head, or length growth between birth, 5 and 20 months' corrected age, and 56 mo, predicted grade point average and special education in comprehensive school, or neurocognitive abilities and psychiatric diagnoses/symptoms at 24-26 y of age. RESULTS: For every 1 SD faster weight and head growth from birth to 5 mo, and head growth from 5 to 20 mo, participants had 0.19-0.41 SD units higher IQ, executive functioning score, and grade point average (95% confidence intervals (CI) 0.002-0.59 SD), and lower odds of special education (odds ratio (OR) = 0.49-0.59, 95% CIs 0.28-0.97), after adjusting for sex, gestational age, follow-up age, and parental education. Faster head growth from 20 to 56 mo was associated with less internalizing problems; otherwise we found no consistent associations with mental health outcomes. CONCLUSION: Faster growth during the critical early period after late-preterm birth is associated with better adult neurocognitive functioning, but not consistently with mental health outcomes.

Maternal Depressive Symptoms During and After Pregnancy and Psychiatric Problems in Children.

OBJECTIVE: Maternal depressive symptoms during pregnancy are associated with increased risk of psychiatric problems in children. A more precise understanding of the timing of the symptoms during pregnancy and their independence of other prenatal and postnatal factors in predicting child psychopathology risk is needed. We examined whether maternal depressive symptoms during pregnancy predict child psychiatric problems, whether these associations are trimester- or gestational-week-specific and/or independent of pregnancy disorders, and whether maternal depressive symptoms after pregnancy mediate or add to the prenatal effects. METHOD: The study sample comprised 2,296 women and their children born in Finland between 2006-2010, participating in the prospective pregnancy cohort study Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) and followed up from 1.9 to 5.9 years of age. The women completed the Center for Epidemiologic Studies Depression Scale biweekly between gestational weeks+days 12+0/13+6 and 38+0/39+6 or delivery. In the follow-up, they completed the Beck Depression Inventory-II and Child Behavior Checklist 1½-5. RESULTS: Maternal depressive symptoms during pregnancy predicted significantly higher internalizing (0.28 SD unit per SD unit increase [95% CI = 0.24-0.32]), externalizing (0.26 [0.23-0.30]), and total problems (0.31 [0.27-0.35]) in children. These associations were nonspecific to gestational week and hence pregnancy trimester, independent of pregnancy disorders, and independent of, although partially mediated by, maternal depressive symptoms after pregnancy. Psychiatric problems were greatest in children whose mothers reported clinically significant depressive symptoms across pregnancy trimesters and during and after pregnancy. CONCLUSION: Maternal depressive symptoms during pregnancy predict increased psychiatric problems in young children. Preventive interventions from early pregnancy onward may benefit offspring mental health.

Body image and eating behavior in young adults born preterm.

OBJECTIVE: Previous studies have suggested that people born preterm have increased rates of eating disorders (ED). However, a recent study suggested lower levels of ED-related symptoms in the extreme group of adults born preterm with very low birth weight (<1,500 g). We examined symptoms related to EDs in adults born early (<34 weeks of gestational age) or late (34 to <37 weeks of gestational age) preterm. METHODS: We studied young adults (mean age 24.1 years) from two birth cohorts: ESTER (Northern Finland 1985-1989) and AYLS (Uusimaa, Finland, 1985-1986). Of the participants, 185 were born early preterm, 348 late preterm, and 637 were term-born controls (N = 1,170). They completed three subscales of the Eating Disorder Inventory (EDI)-2, including Drive for Thinness (DT), Body Dissatisfaction (BD), and Bulimia (B). Group differences were examined by linear regression. RESULTS: Young women born early preterm scored 4.1 points (95% CI -8.0, -0.2, P =.04) lower in summed EDI subscale scores than women born at term, when adjusted for age and cohort. This difference was observed also in DT and BD but not for B subscales. The differences persisted after adjustments for current, pre- and neonatal characteristics. We did not observe differences in EDI scores among men or women born late preterm when compared to controls. DISCUSSION: Women born early preterm have significantly fewer symptoms related to EDs in early adulthood when compared to their peers born at term, which may protect from developing an ED. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:572-580).

Maternal Prenatal Positive Affect, Depressive and Anxiety Symptoms and Birth Outcomes: The PREDO Study.

BACKGROUND: We investigated whether maternal prenatal emotions are associated with gestational length and birth weight in the large PREDO Study with multiple measurement points of emotions during gestation. METHODS: Altogether 3376 pregnant women self-assessed their positive affect (PA, Positive and Negative Affect Schedule) and depressive (Center for Epidemiologic Studies Depression Scale, CES-D) and anxiety (Spielberger State Anxiety Scale, STAI) symptoms up to 14 times during gestation. Birth characteristics were derived from the National Birth Register and from medical records. RESULTS: One standard deviation (SD) unit higher PA during the third pregnancy trimester was associated with a 0.05 SD unit longer gestational length, whereas one SD unit higher CES-D and STAI scores during the third trimester were associated with 0.04-0.05 SD unit shorter gestational lengths (P-values ≤ 0.02), corresponding to only 0.1-0.2% of the variation in gestational length. Higher PA during the third trimester was associated with a significantly decreased risk for preterm (< 37 weeks) delivery (for each SD unit higher positive affect, odds ratio was 0.8-fold (P = 0.02). Mothers with preterm delivery showed a decline in PA and an increase in CES-D and STAI during eight weeks prior to delivery. Post-term birth (≥ 42 weeks), birth weight and fetal growth were not associated with maternal prenatal emotions. CONCLUSIONS: This study with 14 measurements of maternal emotions during pregnancy show modest effects of prenatal emotions during the third pregnancy trimester, particularly in the weeks close to delivery, on gestational length. From the clinical perspective, the effects were negligible. No associations were detected between prenatal emotions and birth weight.

Poor sleep and neurocognitive function in early adolescence.

BACKGROUND: Evidence regarding the associations between sleep duration and quality, and neurocognitive function in adolescents remains scanty. This study examined the associations in early adolescence between: sleep duration; efficiency; fragmentation; wake-after-sleep-onset (WASO); catch-up sleep; intelligence; memory; and executive function, including attention. METHODS: This study included 354 girls and boys with a mean age 12.3 years (SD = 0.5) from a birth cohort born in 1998. Sleep was measured with accelerometers for an average of eight nights. Cognitive function was evaluated with subtests from the Wechsler Intelligence Scale for Children-III (WISC-III), the Developmental Neuropsychological Assessment 2 (NEPSY-2), the Wisconsin Card Sorting Task (WCST), Conners' Continuous Performance Task (CPT), and the Trail Making Test (TMT). RESULTS: In girls, a higher WASO and fragmentation index were associated with poorer executive functioning (higher number of perseverative errors in the WCST), and longer catch-up sleep was associated with longer reaction times and better performance in one verbal intelligence test (Similarities subtest of the WISC-III). In boys, shorter sleep duration, lower efficiency, higher WASO, higher sleep fragmentation and shorter catch-up sleep were associated with lower executive functioning (more commission errors, shorter reaction times, and had lower D Prime scores in CPT). CONCLUSIONS: In adolescent girls, poorer sleep quality was only weakly associated with poorer executive functioning, while in boys, poorer sleep quantity and quality were associated with an inattentive pattern of executive functioning. The amount of catch-up sleep during weekends showed mixed patterns in relation to neurocognitive function.

Infant Growth after Preterm Birth and Mental Health in Young Adulthood.

OBJECTIVES: Faster growth after preterm birth benefits long-term cognitive functioning. Whether these benefits extend to mental health remains largely unknown. We examined if faster growth in infancy is associated with better self-reported mental health in young adults born preterm at very low birth weight (VLBW) (< 1500 g). STUDY DESIGN: As young adults, participants of the Helsinki Study of Very Low Birth Weight Adults self-reported symptoms of depression and attention deficit/hyperactivity disorder (ADHD) (n = 157) and other psychiatric problems (n = 104). As main predictors of mental health outcomes in linear regression models, we used infant weight, length, and head circumference at birth, term, and 12 months of corrected age, and growth between these time points. Growth data were collected from records and measures at term and at 12 months of corrected age were interpolated. Additionally, we examined the moderating effects of intrauterine growth restriction. RESULTS: Size at birth, term, or 12 months of corrected age, or growth between these time points were not associated with mental health outcomes (p-values >0.05). Intrauterine growth restriction did not systematically moderate any associations. CONCLUSIONS: Despite the high variability in early growth of VLBW infants, the previously described association between slow growth in infancy and poorer cognitive functioning in later life is not reflected in symptoms of depression, ADHD, and other psychiatric problems. This suggests that the development of cognitive and psychiatric problems may have dissimilar critical periods in VLBW infants.

Maternal Grand Multiparity and the Risk of Severe Mental Disorders in Adult Offspring.

BACKGROUND: Previous studies have shown that maternal grand multiparity may predict an increased risk of mental disorders in young adult offspring, but whether such effects persist throughout adulthood remains unknown. The current study examined if maternal grand multiparity predicts the risks of severe mental disorders, suicides, suicide attempts and dementias throughout adult life. METHODS: Our study sample comprised 13243 Helsinki Birth Cohort Study 1934-1944 participants (6905 men and 6338 women). According to hospital birth records, 341 offspring were born to grand multiparous mothers. From Finnish national hospital discharge and causes of death registers, we identified 1682 participants diagnosed with mental disorders during 1969-2010. RESULTS: Maternal grand multiparity predicted significantly increased risks of mood disorders (Hazard Ratio = 1.64, p = 0.03), non-psychotic mood disorders (Hazard Ratio = 2.02, p = 0.002), and suicide attempts (Hazard Ratio = 3.94, p = 0.01) in adult offspring. Furthermore, women born to grand multiparous mothers had significantly increased risks of any severe mental disorder (Hazard Ratio = 1.79, p = 0.01), non-psychotic substance use disorders (Hazard Ratio = 2.77, p = 0.02) schizophrenia, schizotypal and delusional disorders (Hazard Ratio = 2.40, p = 0.02), mood disorders (Hazard Ratio = 2.40, p = 0.002), non-psychotic mood disorders (Hazard Ratio = 2.91, p<0.001), and suicide attempts (Hazard Ratio = 5.05, p = 0.01) in adulthood. The effects of maternal grand multiparity on offspring psychopathology risk were independent of maternal age and body mass index at childbirth, and of year of birth, sex, childhood socioeconomic position, and birth weight of the offspring. In contrast, no significant effects were found among men. CONCLUSIONS: Women born to grand multiparous mothers are at an increased risk of severe mental disorders and suicide attempts across adulthood. Our findings may inform the development of preventive interventions for mental disorders.