Paternal use of antidepressants and offspring outcomes in Sweden: nationwide prospective cohort study.
ABSTRACT: To examine the association between paternal antidepressant use at conception and offspring preterm birth, malformations, autism spectrum disorder, and intellectual disability.Observational prospective cohort study with regression methods, and negative control comparison.Sweden nationwide.170?508 children conceived from 29 July 2005 and born in 2006-07, followed up to 2014 at age 8-9 years. This cohort included 3983 children born to fathers receiving antidepressant treatment during the conception period (that is, from four weeks before conception to four weeks after), a control group of 164?492 children not exposed to paternal antidepressant use, and a negative control comparison group of 2033 children born to fathers who did not use antidepressants during the conception period but began antidepressant treatment later during the pregnancy period (that is, from four weeks after conception to childbirth).Offspring preterm birth, malformation diagnosed at birth, diagnosis of autism spectrum disorder, and diagnosis of intellectual disability.Paternal antidepressant use during conception was not associated with preterm birth (adjusted odds ratio 0.91 (95% confidence interval 0.79 to 1.04)) or malformations (1.06 (0.90 to 1.26)) using logistic regression, compared with offspring born to unexposed fathers. No association was seen between antidepressant use during conception and autism (adjusted hazard ratio 1.13 (0.84 to 1.53)) or intellectual disability (0.82 (0.51 to 1.31)) using Cox regression. In children whose fathers initiated antidepressant treatment during pregnancy, results were similar for all outcomes apart from intellectual disability, which had an increased adjusted hazard ratio (1.66 (1.06 to 2.59)). Compared with the 2033 children whose fathers initiated antidepressant treatment during pregnancy, the 3983 children exposed to paternal use of antidepressants at conception had no differences in preterm birth, malformation, and autism, but a reduced risk of intellectual disability (adjusted hazard ratio 0.49 (0.26 to 0.93)).Paternal intake of antidepressants during the period around conception is safe with respect to the risk of the four major adverse outcomes in offspring-preterm birth, malformation, autism, or intellectual disability.
Project description:To investigate the effects of maternal and paternal depression on the risk for preterm birth.National cohort study.Medical Birth Register of Sweden, 2007-2012.A total of 366 499 singleton births with linked information for parents' filled drug prescriptions and hospital care.Prenatal depression was defined as having filled a prescription for an antidepressant drug or having been in outpatient or inpatient hospital care with a diagnosis of depression from 12 months before conception until 24 weeks after conception. An indication of depression after 12 months with no depression was defined as 'new depression', whereas all other cases were defined as 'recurrent depression'.Odds ratios (ORs) for very preterm (22-31 weeks of gestation) and moderately preterm (32-36 weeks of gestation) births were estimated using multinomial logistic regression models.After adjustment for maternal depression and sociodemographic covariates, new paternal prenatal depression was associated with very preterm birth [adjusted OR (aOR) 1.38, 95% confidence interval (95% CI) 1.04-1.83], whereas recurrent paternal depression was not associated with an increased risk of preterm birth. Both new and recurrent maternal prenatal depression were associated with an increased risk of moderately preterm birth (aOR 1.34, 95% CI 1.22-1.46, and aOR 1.42, 95% CI 1.32-1.53, respectively).New paternal and maternal prenatal depression are potential risk factors for preterm birth. Mental health problems in both parents should be addressed for the prevention of preterm birth.Depression in both mothers and fathers is associated with an increased risk of preterm birth.
Project description:OBJECTIVE:The present study aimed to examine the association between paternal selective serotonin reuptake inhibitor (SSRI) use before conception and the risk of autism spectrum disorder (ASD) in offspring. DESIGN:A population-based cohort study. METHODS:We conducted a cohort study of 669?922 children born from 1998 to 2008, with follow-up throughout 2013. Based on Danish national registers, we linked information on paternal use of SSRIs, ASD diagnosed in children and a range of potential confounders. The children whose fathers used SSRIs during the last 3 months prior to conception were identified as the exposed. Cox regression model was used to estimate the HR for ASD in children. RESULTS:Compared with unexposed children, the exposed had a 1.62-fold higher risk of ASD (95% CI 1.33 to 1.96) and the risk attenuated after adjusting for potential confounders, especially fathers' psychiatric conditions (HR=1.43, 95%?CI 1.18 to 1.74). When extending the exposure window to 1?year before conception, the increased risk persisted in children of fathers using SSRIs only from the last year until the last 3 months prior to conception (HR=1.54, 95%?CI 1.21 to 1.94) but not in children of fathers using SSRIs only during the last 3 months prior to conception (HR=1.17, 95%?CI 0.75 to 1.82). We also performed stratified analyses according to paternal history of affective disorders and observed no increased ASD risk among children whose father had affective disorders. Besides, the sibling analysis showed that the ASD risk did not increase among exposed children compared with their unexposed siblings. CONCLUSIONS:The mildly increased risk of ASD in the offspring associated with paternal SSRI use before conception may be attributable to paternal underlying psychiatric indications related to SSRI use or other unmeasured confounding factors.
Project description:Prenatal antidepressant exposure has been associated with adverse outcomes. Previous studies, however, may not have adequately accounted for confounding.To evaluate alternative hypotheses for associations between first-trimester antidepressant exposure and birth and neurodevelopmental problems.This retrospective cohort study included Swedish offspring born between 1996 and 2012 and followed up through 2013 or censored by death or emigration. Analyses controlling for pregnancy, maternal and paternal covariates, as well as sibling comparisons, timing of exposure comparisons, and paternal comparisons, were used to examine the associations.Maternal self-reported first-trimester antidepressant use and first-trimester antidepressant dispensations.Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 SDs below the mean for gestational age), and first inpatient or outpatient clinical diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder in offspring.Among 1?580?629 offspring (mean gestational age, 279 days; 48.6% female; 1.4% [n?=?22?544] with maternal first-trimester self-reported antidepressant use) born to 943?776 mothers (mean age at childbirth, 30 years), 6.98% of exposed vs 4.78% of unexposed offspring were preterm, 2.54% of exposed vs 2.19% of unexposed were small for gestational age, 5.28% of exposed vs 2.14% of unexposed were diagnosed with autism spectrum disorder by age 15 years, and 12.63% of exposed vs 5.46% of unexposed were diagnosed with attention-deficit/hyperactivity disorder by age 15 years. At the population level, first-trimester exposure was associated with all outcomes compared with unexposed offspring (preterm birth odds ratio [OR], 1.47 [95% CI, 1.40-1.55]; small for gestational age OR, 1.15 [95% CI, 1.06-1.25]; autism spectrum disorder hazard ratio [HR], 2.02 [95% CI, 1.80-2.26]; attention-deficit/hyperactivity disorder HR, 2.21 [95% CI, 2.04-2.39]). However, in models that compared siblings while adjusting for pregnancy, maternal, and paternal traits, first-trimester antidepressant exposure was associated with preterm birth (OR, 1.34 [95% CI, 1.18-1.52]) but not with small for gestational age (OR, 1.01 [95% CI, 0.81-1.25]), autism spectrum disorder (HR, 0.83 [95% CI, 0.62-1.13]), or attention-deficit/hyperactivity disorder (HR, 0.99 [95% CI, 0.79-1.25]). Results from analyses assessing associations with maternal dispensations before pregnancy and with paternal first-trimester dispensations were consistent with findings from the sibling comparisons.Among offspring born in Sweden, after accounting for confounding factors, first-trimester exposure to antidepressants, compared with no exposure, was associated with a small increased risk of preterm birth but no increased risk of small for gestational age, autism spectrum disorder, or attention-deficit/hyperactivity disorder.
Project description:To study the association between parental depression and maternal antidepressant use during pregnancy with autism spectrum disorders in offspring.Population based nested case-control study.Stockholm County, Sweden, 2001-07.4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43,277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16,845 controls with data on maternal antidepressant use nested within a cohort (n=589,114) of young people aged 0-17 years.A diagnosis of autism spectrum disorder, with or without intellectual disability.Parental depression and other characteristics prospectively recorded in administrative registers before the birth of the child. Maternal antidepressant use, recorded at the first antenatal interview, was available for children born from 1995 onwards.A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. All associations were higher in cases of autism without intellectual disability, there being no evidence of an increased risk of autism with intellectual disability. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder.In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. However, assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly towards the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases.
Project description:Importance:Although phthalate exposure during pregnancy has been associated with preterm birth, the association of preconception exposure in either parent with preterm birth constitutes a knowledge gap. Objective:To examine the association of paternal and maternal preconception urinary concentrations of biomarkers of phthalates and phthalate substitutes with singleton preterm birth. Design, Setting, and Participants:This study, conducted at an academic fertility center in Boston, Massachusetts, included a prospective preconception cohort of subfertile couples comprising 419 mothers and 229 fathers and their 420 live-born singleton offspring born between January 1, 2005, and December 31, 2018. Statistical analysis was performed from August 1 to October 31, 2019. Exposures:Urinary concentrations of metabolites of phthalates and phthalate substitutes obtained before conception. Main Outcomes and Measures:Gestational age was abstracted from delivery records and validated using the American College of Obstetricians and Gynecologists guidelines for births after medically assisted reproduction. The risk ratio (RR) of preterm birth (live birth before 37 completed weeks' gestation) was estimated in association with urinary concentrations of 11 individual phthalate metabolites, the molar sum of 4 di-(2-ethylhexyl) phthalate (?DEHP) metabolites, and 2 metabolites of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH, a nonphthalate plasticizer substitute) using modified Poisson regression models adjusted for covariates. Results:The mean (SD) age of the 419 mothers was 34.7 (4.0) years, the mean (SD) age of the 229 fathers was 36.0 (4.5) years, and the mean (SD) gestational age of the 420 singleton children (217 boys) was 39.3 (1.7) weeks, with 34 (8%) born preterm. In adjusted models, maternal preconception ?DEHP concentrations (RR, 1.50; 95% CI, 1.09-2.06; P?=?.01) and cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH, a metabolite of DINCH) concentrations (RR, 1.70; 95% CI, 0.89-3.24; P?=?.11) were associated with an increased risk of preterm birth. After additional adjustment for prenatal ?DEHP or MHiNCH concentrations, the association of maternal preconception exposure to ?DEHP and preterm birth remained robust (RR, 1.69; 95% CI, 1.17-2.44; P?=?.006), while the association of maternal preconception exposure to MHiNCH and preterm birth was attenuated (RR, 1.17; 95% CI, 0.49-2.81; P?=?.72). The remaining urinary metabolites examined in either parent showed no association with preterm birth. Conclusions and Relevance:In this prospective cohort of subfertile couples, maternal preconception exposure to ?DEHP metabolites was associated with an increased risk of preterm birth. The results suggest that female exposure to select phthalate plasticizers during the preconception period may be a potential risk factor for adverse pregnancy outcomes, which may need to be considered in preconception care strategies.
Project description:Objectives To study the association between maternal use of antidepressants during pregnancy and autism spectrum disorder (ASD) in offspring.Design Observational prospective cohort study with regression methods, propensity score matching, sibling controls, and negative control comparison.Setting Stockholm County, Sweden.Participants 254?610 individuals aged 4-17, including 5378 with autism, living in Stockholm County in 2001-11 who were born to mothers who did not take antidepressants and did not have any psychiatric disorder, mothers who took antidepressants during pregnancy, or mothers with psychiatric disorders who did not take antidepressants during pregnancy. Maternal antidepressant use was recorded during first antenatal interview or determined from prescription records.Main outcome measure Offspring diagnosis of autism spectrum disorder, with and without intellectual disability.Results Of the 3342 children exposed to antidepressants during pregnancy, 4.1% (n=136) had a diagnosis of autism compared with a 2.9% prevalence (n=353) in 12?325 children not exposed to antidepressants whose mothers had a history of a psychiatric disorder (adjusted odds ratio 1.45, 95% confidence interval 1.13 to 1.85). Propensity score analysis led to similar results. The results of a sibling control analysis were in the same direction, although with wider confidence intervals. In a negative control comparison, there was no evidence of any increased risk of autism in children whose fathers were prescribed antidepressants during the mothers' pregnancy (1.13, 0.68 to 1.88). In all analyses, the risk increase concerned only autism without intellectual disability.Conclusions The association between antidepressant use during pregnancy and autism, particularly autism without intellectual disability, might not solely be a byproduct of confounding. Study of the potential underlying biological mechanisms could help the understanding of modifiable mechanisms in the aetiology of autism. Importantly, the absolute risk of autism was small, and, hypothetically, if no pregnant women took antidepressants, the number of cases that could potentially be prevented would be small.
Project description:OBJECTIVE:While ample research exists about mother-child attachment, so far little focus has been on specifics of father-child attachment. Even less research is available on the nature of the father-child relationship for children born preterm. The objective of this study was to determine whether children born preterm (23 to 37 weeks gestation) differ in their attachment to their fathers and mothers from their term peers (> 37 weeks gestation), and whether specific child characteristics, such as gender, twin status, and developmental status, have an influence on the parent-child relationship. METHODS:The sample consisted of 290 children (n = 140 girls, 48.28%), 190 born before term (including 45 twin pairs) between 12 and 36 months of age (M = 19.5, SD = 5.7) and 100 term children of the same age (M = 18.8, SD = 6.1) with their 245 fathers and mothers. Attachment of the children with their mothers and fathers was assessed using the Attachment Q-sort during two home visits. Children's developmental status was measured with the Bayley Scales of Infant and Toddler Development. RESULTS:Within a multigroup analysis of parents with children born preterm and at term more secure attachment was found for both parents in the term sample than in the preterm group. Correlates of attachment specific to fathers of children born preterm accumulated to an explained variance of R2 = .82. For those fathers, less education as well as lower development scores and male gender of the child were associated with lower attachment scores. In the three other parent-child constellations the explained variance did not exceed 20%. Child development proved to be a significant predictor for father-child attachment regardless of the child's birth status. Male gender was associated with lower attachment scores for children born preterm with either parent. CONCLUSION:The findings highlight the importance of including fathers in research and clinical practice and informing them about preterm birth, possible problems, and developmental consequences as well. Health professionals should be advised to create interventions focusing on both parents to enhance the quality of attachment in parent-child dyads in children born preterm.
Project description:BACKGROUND:Migration is a risk factor for adverse neonatal outcomes. The various impacts of maternal origin have been reported previously. The aim of this study was to investigate associations between paternal origin and adverse neonatal outcomes in births to migrant and Norwegian-born women in Norway. METHODS AND FINDINGS:This nationwide population-based study included births to migrant (n = 240,759, mean age 29.6 years [±5.3 SD]) and Norwegian-born women (n = 1,232,327, mean age 29.0 years [±5.1 SD]) giving birth in Norway in 1990-2016. The main exposure was paternal origin (Norwegian-born, foreign-born, or unregistered). Neonatal outcomes were very preterm birth (22+0-31+6 gestational weeks), moderately preterm birth (32+0-36+6 gestational weeks), small for gestational age (SGA), low Apgar score (<7 at 5 minutes), and stillbirth. Associations were investigated in migrant and Norwegian-born women separately using multiple logistic regression and reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs), adjusted for year of birth, parity, maternal and paternal age, marital status, maternal education, and mother's gross income. In births to migrant women, a foreign-born father was associated with increased odds of very preterm birth (1.1% versus 0.9%, aOR 1.20; CI 1.08-1.33, p = 0.001), SGA (13.4% versus 9.5%, aOR 1.48; CI 1.43-1.53, p < 0.001), low Apgar score (1.7% versus 1.5%, aOR 1.14; CI 1.05-1.23, p = 0.001), and stillbirth (0.5% versus 0.3%, aOR 1.26; CI 1.08-1.48, p = 0.004) compared with a Norwegian-born father. In Norwegian-born women, a foreign-born father was associated with increased odds of SGA (9.3% versus 8.1%, aOR 1.13; CI 1.09-1.16, p < 0.001) and decreased odds of moderately preterm birth (4.3% versus 4.4%, aOR 0.95; CI 0.91-0.99, p = 0.015) when compared with a Norwegian-born father. In migrant women, unregistered paternal origin was associated with increased odds of very preterm birth (2.2% versus 0.9%, aOR 2.29; CI 1.97-2.66, p < 0.001), moderately preterm birth (5.6% versus 4.7%, aOR 1.15; CI 1.06-1.25, p = 0.001), SGA (13.0% versus 9.5%, aOR 1.50; CI 1.42-1.58, p < 0.001), low Apgar score (3.4% versus 1.5%, aOR 2.23; CI 1.99-2.50, p < 0.001), and stillbirth (1.5% versus 0.3%, aOR 4.87; CI 3.98-5.96, p < 0.001) compared with a Norwegian-born father. In Norwegian-born women, unregistered paternal origin was associated with increased odds of very preterm birth (4.6% versus 1.0%, aOR 4.39; CI 4.05-4.76, p < 0.001), moderately preterm birth (7.8% versus 4.4%, aOR 1.62; CI 1.53-1.71, p < 0.001), SGA (11.4% versus 8.1%, aOR 1.30; CI 1.24-1.36, p < 0.001), low Apgar score (4.6% versus 1.3%, aOR 3.51; CI 3.26-3.78, p < 0.001), and stillbirth (3.2% versus 0.4%, aOR 9.00; CI 8.15-9.93, p < 0.001) compared with births with a Norwegian-born father. The main limitations of this study were the restricted access to paternal demographics and inability to account for all lifestyle factors. CONCLUSION:We found that a foreign-born father was associated with adverse neonatal outcomes among births to migrant women, but to a lesser degree among births to nonmigrant women, when compared with a Norwegian-born father. Unregistered paternal origin was associated with higher odds of adverse neonatal outcomes in births to both migrant and nonmigrant women when compared with Norwegian-born fathers. Increased attention to paternal origin may help identify women in maternity care at risk for adverse neonatal outcomes.
Project description:BACKGROUND:The etiology of childhood cancer is largely unknown, though some research suggests an infectious origin of hematopoietic, central nervous system (CNS) and bone cancers. METHODS:We examined parental occupational social contact as a proxy for exposure to infectious agents and risk of childhood cancer. This population-based case-control study utilized a linkage of four Danish data-registries, and included 3581 cases (<17 years, diagnosed 1973-2012) and 358,100 age-matched controls. We examined the risks of leukemia, lymphoma, CNS and bone cancer related to high occupational social contact from (1) conception to birth and (2) birth to diagnosis. RESULTS:Acute lymphoblastic leukemia (ALL) and bone cancer were inversely associated with high maternal social contact from conception to birth (OR: 0.86, 95% CI: 0.67-1.10) and birth to diagnosis (OR: 0.54, 95% CI: 0.34-0.86). Children of fathers with high social contact from birth to diagnosis had an increased risk of bone cancers, particularly in rural areas (OR: 1.65, 95% CI: 1.03-2.63). Parental social contact was associated with increased risk of astrocytoma, with strongest associations found in first-born children (maternal: OR: 1.54, 95% CI: 1.02-2.32; paternal: OR: 1.82, 95% CI: 1.05-3.17). CONCLUSION:Our results support the notion of a role of infections for some cancer types.
Project description:With improved medical outcome in preterm infants, the psychosocial situation of their families is receiving increasing attention. For parents, the birth of a preterm infant is generally regarded as a stressful experience, and therefore many interventions are based on reducing parental stress. Nevertheless, it remains unclear whether parents of children born preterm experience more stress than parents of term-born children, which would justify these interventions. This meta-analysis provides a comprehensive account of parental stress in parents of preterm infants, from birth of the infant through to their adolescence. Mean levels of stress in specific domains of family functioning were investigated, and stress levels in parents of preterm and term infants, and fathers and mothers of preterm infants, were compared. Furthermore, we investigated moderators of parental stress.A random-effects meta-analysis was conducted including 38 studies describing 3025 parents of preterm (<37 wk) and low birth weight (<2500 g) infants. Parental stress was measured with two parent-reported questionnaires, the Parenting Stress Index and the Parental Stressor Scale: Neonatal Intensive Care Unit. The results indicate that parents of preterm-born children experience only slightly more stress than parents of term-born children, with small effect sizes. Furthermore, mothers have slightly more stress than fathers, but these effect sizes are also small. Parents report more stress for infants with lower gestational ages and lower birth weights. There is a strong effect for infant birth year, with decreasing parental stress from the 1980s onward, probably due to increased quality of care for preterm infants.Based on our findings we argue that prematurity can best be regarded as one of the possible complications of birth, and not as a source of stress in itself.