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High parental age at childbirth has repeatedly been linked to childhood malignancies, while few studies have focused on the offspring's risk of adult cancer. In this population-based case-control study, we identified 32,000 patients with lymphoid neoplasms, diagnosed at ages 0-79 years during the period 1987-2011, and 160,000 matched controls in Sweden. Using prospectively registered data on their first-degree relatives, we evaluated the impact of parental age on the risk of lymphoid neoplasms by subtype. Overall, each 5-year increment in maternal age was associated with a 3% increase in incidence of offspring lymphoid neoplasms (hazard ratio = 1.03, 95% confidence interval: 1.02, 1.04). The association was similar for paternal age and present even among individuals older than 70 years of age at diagnosis. Stratified analyses further revealed that the association was limited to certain subtypes, mostly of indolent nature. Risks of chronic lymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma were 5%-10% higher per 5-year increment in maternal age, but no associations were observed for acute lymphoblastic leukemia, plasma cell neoplasms, or diffuse large B-cell lymphoma. These findings indicated that prenatal genetic or epigenetic changes influence risk of adult lymphoid neoplasms and suggest a difference in this association between aggressive and indolent lymphoma subtypes. [ABSTRACT FROM AUTHOR]

Background: Infant leukaemia (IL) is extremely rare with fewer than 150 cases occurring each year in the United States. Little is known about its causes. However, recent evidence supports a role of de novo mutations in IL aetiology. Parental age has been associated with several adverse outcomes in offspring, including childhood cancers. Given the role of older parental age in de novo mutations in offspring, we carried out an analysis of parental age and IL.Methods: We evaluated the relationship between parental age and IL in a case-control study using registry data from New York, Minnesota, California, Texas, and Washington. Records from 402 cases [219 acute lymphoblastic leukaemia (ALL), 131 acute myeloid leukaemia (AML), and 52 other] and 45 392 controls born during 1981-2004 were analysed. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Estimates were adjusted for infant sex, birth year category, maternal race, state, and mutually adjusted for paternal or maternal age, respectively.Results: Infants with mothers' age ≥40 years had an increased risk of developing AML (OR 4.80, 95% CI 1.80, 12.76). In contrast, paternal age <20 was associated with increased risk of ALL (OR 3.69, 95% CI 1.62, 8.41).Conclusion: This study demonstrates increased risk of infant ALL in relation to young paternal age. Given record linkage, there is little concern with recall or selection bias, although data are lacking on MLL gene status and other potentially important variables. Parent of origin effects, de novo mutations, and/or carcinogenic exposures may be involved in IL aetiology. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that paternal age at birth influences myriad developmental outcomes among children, but few studies have examined the possibility for father's age to influence children's intellectual development among a sample of high-risk families. The authors use data from the Fragile Families and Child Wellbeing Study to examine the association between paternal age at birth among 480 male and 449 female children's verbal IQ scores, as assessed with a version of the Peabody Picture Vocabulary Test at 9 years old. The nonlinear association between paternal age and children's verbal intelligence was also examined. Paternal age at birth appears to have a marginally significant nonlinear relationship with male children's verbal IQ scores, despite controlling for a number of possible confounders associated with both young and advanced paternal age. [ABSTRACT FROM PUBLISHER]

Background: Young maternal age is one of the numerous risk factors for delivery before 37 weeks of gestation, yet the mechanisms are unclear. The purpose of the current study was to investigate the association between teenagers and the risk of preterm birth (PTB) in a large and recent cohort study. Methods: We conducted a population-based retrospective cohort study using 2007-2011 California birth certificate records linked with hospital discharge indices and United States census data for nulliparous 13-20 year olds who gave birth to singletons. Maternal age was examined categorically at 1 year intervals. PTB was defined as delivery at < 37 weeks of gestation with further distinction between < 32 and 32-36 weeks, and between spontaneous and medically indicated deliveries. Adjusted multivariable logistic regression was used to estimate odds ratios (OR) for PTB. Results: The prevalence of PTB was highest among the youngest (13 year olds, 14.5%) and lowest among the oldest (20 year olds, 6.7%). After adjusting for maternal and paternal race/ethnicity, paternal age, initiation of prenatal care, source of payment, pre-pregnancy body-mass-index (BMI), height, smoking, and poverty; young mothers of ages 13, 14, 15, and 16 years had increased odds for spontaneous PTB at < 32 weeks [OR (CI): 3.76 (1.83-7.75), 1.65 (1.10-2.48), 1.55 (1.24-1.93), 1.19 (1.00-1.42), respectively] compared to 20 year olds. All teenagers, excluding 19 year olds, had elevated odds of spontaneous PTB at 32-36 weeks. Conclusions: Nulliparous teenagers were at increased risk for spontaneous PTB, especially those 16 years or younger. Medically indicated PTB was not associated with young age. [ABSTRACT FROM AUTHOR]

Linking birth records and cancer registry data from California, we conducted a population-based study with 23,419 cases and 87,593 matched controls born during 1978-2009 to investigate the relationship of parental age to risk of pediatric cancer. Compared with children born to mothers aged 20-24 years, those born to mothers in older age groups had a 13%-36% higher risk of pediatric cancer; the odds ratio for each 5-year increase in maternal age was 1.06 (95% confidence interval (CI): 1.04, 1.09). For cancer diagnosed in children in age groups 0-14 years and 15-19 years, the odds ratios for each 5-year increase in maternal age were 1.05 (95% CI: 1.02, 1.07) and 1.14 (95% CI: 1.09, 1.19), respectively. Having an older father also conferred an increased risk, with an odds ratio for each 5-year increase of 1.03 (95% CI: 1.02, 1.05) for cancer diagnosed at ages 0-19 years and 1.03 (95% CI: 1.02, 1.05) for cancer diagnosed at ages 0-14 years. While advancing maternal age increased risk of leukemia and central nervous system tumors, older paternal age was not associated with risk of either type. Both maternal and paternal older ages were associated with risk of lymphoma. In this large, population-based record-linkage study, advancing parental age, especially advancing maternal age, was associated with higher pediatric cancer risk, with variations across types of cancer. [ABSTRACT FROM AUTHOR]

Study Question: How has the mean paternal age in the USA changed over the past 4 decades?Summary Answer: The age at which men are fathering children in the USA has been increasing over time, although it varies by race, geographic region and paternal education level.What Is Known Already: While the rise in mean maternal age and its implications for fertility, birth outcomes and public health have been well documented, little is known about paternal characteristics of births within the USA.Study Design, Size, Duration: A retrospective data analysis of paternal age and reporting patterns for 168 867 480 live births within the USA since 1972 was conducted.Participants/materials, Setting, Methods: All live births within the USA collected through the National Vital Statistics System (NVSS) of the Centers for Disease Control and Prevention (CDC) were evaluated. Inverse probability weighting (IPW) was used to reduce bias due to missing paternal records.Main Results and the Role Of Chance: Mean paternal age has increased over the past 44 years from 27.4 to 30.9 years. College education and Northeastern birth states were associated with higher paternal age. Racial/ethnic differences were also identified, whereby Asian fathers were the oldest and Black fathers were the youngest. The parental age difference (paternal age minus maternal age) has decreased over the past 44 years. Births to Black and Native American mothers were most often lacking paternal data, implying low paternal reporting. Paternal reporting was higher for older and more educated women.Limitations, Reasons For Caution: Although we utilized IPW to reduce the impact of paternal reporting bias, our estimates may still be influenced by the missing data in the NVSS.Wider Implications Of the Findings: Paternal age is rising within the USA among all regions, races and education levels. Given the implications for offspring health and demographic patterns, further research on this trend is warranted.Study Funding/competing Interest(s): No funding was received for this study and there are no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Higher paternal age at offspring conception increases de novo genetic mutations. Based on evolutionary genetic theory we predicted older fathers' children, all else equal, would be less likely to survive and reproduce, i.e. have lower fitness. In sibling control studies, we find support for negative paternal age effects on offspring survival and reproductive success across four large populations with an aggregate N > 1.4 million. Three populations were pre-industrial (1670–1850) Western populations and showed negative paternal age effects on infant survival and offspring reproductive success. In twentieth-century Sweden, we found minuscule paternal age effects on survival, but found negative effects on reproductive success. Effects survived tests for key competing explanations, including maternal age and parental loss, but effects varied widely over different plausible model specifications and some competing explanations such as diminishing paternal investment and epigenetic mutations could not be tested. We can use our findings to aid in predicting the effect increasingly older parents in today's society will have on their children's survival and reproductive success. To the extent that we succeeded in isolating a mutation-driven effect of paternal age, our results can be understood to show that de novo mutations reduce offspring fitness across populations and time periods. [ABSTRACT FROM AUTHOR]

Although controversial, increasing paternal age has been shown to negatively affect assisted reproductive technology (ART) outcomes and success rates. Most studies investigating the effect of paternal age on ART outcomes use a donor oocyte model to minimize maternal aneuploidy contribution. This study sought to determine whether increasing paternal age is associated with adverse in vitro fertilization (IVF) outcomes when aneuploidy is minimized using preimplantation genetic screening. There were 573 single thawed euploid embryo transfers from 473 patients undergoing oocyte donor and autologous IVF cycles. Cycles were categorized according to paternal age at oocyte retrieval, and an age adjustment was performed for maternal age in order to evaluate for an isolated paternal age effect. Fertilization rate was found to decrease significantly with increasing paternal age (P = .04). After controlling for oocyte age, there was no significant difference in pregnancy outcomes across all paternal age categories after euploid embryo transfer, including implantation rate (P = .23), clinical pregnancy rate (P = .51), and spontaneous abortion rate (P = .55). Therefore, if a couple is able to produce and transfer a single thawed euploid embryo, no difference in IVF pregnancy outcomes is identified with increasing paternal age. [ABSTRACT FROM AUTHOR]

The association between advanced paternal age (APA) and increased risk of schizophrenia (SZ) is well established. The objectives of the present study were to further determine if SZ participants with APA (APA+), versus those without (APA-), had: (i) different illness characteristics; (ii) different responses to antipsychotic medication; and (iii) different cognitive characteristics. Participants were a non-selected representative multicentric sample of stabilized community-dwelling people diagnosed with SZ included in the FACE-SZ cohort. 389 participants (73% males, mean aged 32.7 years, mean illness duration 10.8 years) formed the study sample, with each comprehensively evaluated, clinically and neuropsychologically, over 2 days. 118 participants (30.3%) were defined as APA+ according to their father's age at birth (≥35 years). APA+ was associated with a wide range of cognitive dysfunctions in univariate analyses. In multivariate analyses, the only significant difference was the age at onset, with a mean 1.6 year earlier in APA+, compared to APA- (20.7 vs. 22.3 years; p=0.02). This difference is independent of sociodemographic characteristics and I.Q. No association with clinical symptomatology and treatment response was found. The present study supports the neomutation hypothesis and confirms APA as a relevant clinical variable to discriminate potential schizophrenia subtypes. Potential underlying pathophysiological mechanisms are discussed. [ABSTRACT FROM AUTHOR]

Objective: Advanced paternal age (APA) at conception has been linked with autism and schizophrenia in offspring, neurodevelopmental disorders that affect social functioning. The current study explored the effects of paternal age on social development in the general population.Method: We used multilevel growth modeling to investigate APA effects on socioemotional development from early childhood until adolescence, as measured by the Strengths and Difficulties Questionnaire (SDQ) in the Twins Early Development Study (TEDS) sample. We also investigated genetic and environmental underpinnings of the paternal age effects on development, using the Additive genetics, Common environment, unique Environment (ACE) and gene-environment (GxE) models.Results: In the general population, both very young and advanced paternal ages were associated with altered trajectory of social development (intercept: p = .01; slope: p = .03). No other behavioral domain was affected by either young or advanced age at fatherhood, suggesting specificity of paternal age effects. Increased importance of genetic factors in social development was recorded in the offspring of older but not very young fathers, suggesting distinct underpinnings of the paternal age effects at these two extremes.Conclusion: Our findings highlight that the APA-related deficits that lead to autism and schizophrenia are likely continuously distributed in the population. [ABSTRACT FROM AUTHOR]

Objective: Increasing evidence implicates advanced paternal age at offspring birth in neuropsychiatric disorders. Advanced maternal age has also been associated with schizophrenia and other neurodevelopmental disorders, whereas younger maternal age has been linked with behavioral disorders. Few studies have considered the specificity of the associations with respect to comorbidity. In addition, most prior studies have been conducted in clinical samples or registries that may reflect more severe forms of psychopathology. The aim of this research is to examine the independent and joint associations of maternal and paternal age with specific subtypes of psychopathology in offspring in a pediatric sample of adolescents with emergent psychiatric syndromes.Method: A total of 8,725 youths (aged 8-21 years) from the Philadelphia Neurodevelopmental Cohort were included in the analyses. Logistic regression models with parental age predicting offspring psychopathology were adjusted for sociodemographic factors and comorbid disorders.Results: We found that younger parental ages were generally associated with increased rates of offspring psychopathology. After controlling for sociodemographic characteristics and comorbidity, both younger maternal and paternal ages were associated with behavior syndromes and psychosis in youth, whereas advanced paternal age was associated with pervasive developmental disorders/autism spectrum disorder (PDD/ASD).Conclusion: These findings suggest that both younger and older parental age at birth are associated with specific forms of psychopathology in offspring. The persistence of the influence of parental age after control for demographic factors and an index of social environment suggests that additional explanations for these findings should be examined in future studies. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that young mothers more often have children with ADHD. We used sibling comparisons to examine the nature of this association and to investigate if this association is explained by early environment or genetic and socioeconomic factors.Methods: A large population-based cohort including all singletons born in Denmark from 1 January 1991 through 31 December 2005 was followed from birth until 30 April 2011. Data were available for 94% ( N  = 943 785) of the population. Offspring ADHD was identified by an ICD-10 diagnosis of Hyperkinetic Disorder (HKD). We used sibling-matched Cox regression to control for genetic and socioeconomic factors.Results: In the population cohort we found that children born by parents aged 20 years or younger had more than twice the risk of being diagnosed with ADHD compared with children with parents between 26 and 30 years of age. When comparing full siblings the associations were attenuated, but we found a trend of increased risk of ADHD with decreasing maternal age, which was not seen for paternal age.Conclusions: Sibling comparisons suggested that the associations between both maternal and paternal age and ADHD are partly explained by common genetic and socioeconomic factors. The trend of increased risk of ADHD with decreasing maternal age, but not with paternal age, may be linked to pregnancy or early-life environmental factors. Even though only a smaller part of the association can be attributed to environmental factors, there is a public health interest to support young parents through their first years of parenthood. [ABSTRACT FROM AUTHOR]

The attributable fraction is a commonly used measure that quantifies the public health impact of an exposure on an outcome. It was originally defined for binary outcomes, but an extension has recently been proposed for right-censored survival time outcomes; the so-called attributable fraction function. A maximum likelihood estimator of the attributable fraction function has been developed, which requires a model for the outcome. In this paper, we derive a doubly robust estimator of the attributable fraction function. This estimator requires one model for the outcome, and one joint model for the exposure and censoring. The estimator is consistent if either model is correct, not necessarily both. [ABSTRACT FROM AUTHOR]

Background Attention-deficit/hyperactivity disorder ( ADHD) aggregates in families. To date, the strength, pattern, and characteristics of the familial aggregation have not been thoroughly assessed in a population-based family sample. Methods In this cohort study, we identified relative pairs of twins, full and half-siblings, and full and half cousins from 1,656,943 unique individuals born in Sweden between 1985 and 2006. The relatives of index persons were followed from their third birthday to 31 December 2009 for ADHD diagnosis. Birth year adjusted hazard ratio ( HR), that is, the rate of ADHD in relatives of ADHD-affected index persons compared with the rate of ADHD in relatives of unaffected index persons, was estimated in the different types of relatives using Cox proportional hazards model. Results During the follow-up, 31,865 individuals were diagnosed with ADHD (male to female ratio was 3.7). The birth year adjusted HRs were as follows: 70.45 for monozygotic twins; 8.44 for dizygotic twins; 8.27 for full siblings; 2.86 for maternal half-siblings; 2.31 for paternal half-siblings; 2.24 for full cousins; 1.47 for half cousins. Maternal half-siblings had significantly higher HR than in paternal half-siblings. The HR did not seem to be affected by index person's sex. Full siblings of index persons with ADHD diagnosis present at age 18 or older had a higher rate of ADHD ( HR: 11.49) than full siblings of index persons with ADHD diagnosis only before age 18 ( HR: 4.68). Conclusions Familial aggregation of ADHD increases with increasing genetic relatedness. The familial aggregation is driven by not only genetic factors but also a small amount of shared environmental factors. Persistence of ADHD into adulthood indexes stronger familial aggregation of ADHD. [ABSTRACT FROM AUTHOR]

Objectives Despite the benefits of breastfeeding, less than a fifth of American mothers breastfeed for the recommended duration. Paternal support plays a major role in maternal and child health outcomes; however, the influence of paternal pregnancy intention on breastfeeding duration is under investigated. This study examines the relationship between fathers' pregnancy intention and breastfeeding duration. Methods Data from the 2011-2013 National Survey of Family Growth were analyzed using cross-sectional methodology. Women who were pregnant, never received medical help to become pregnant, whose partner was aged 18-49 years, and who responded to questions related to paternal pregnancy intention and breastfeeding were included in the analysis (N = 2089). Multinomial logistic regression, odds ratios and 95 % confidence intervals were calculated. There was a statistically significant interaction between father's age and father's pregnancy intention ( P = 0.0385) and all models were stratified by paternal age. Results Fathers aged 18-24 years with a mistimed pregnancy were 2.3 times more likely to have a child who was never breastfed, (AOR 2.27, 95 % CI 1.39-3.70) and 1.7 times more likely to have a child who was breastfed 6 months or less (AOR 1.69, 95 % CI 1.28-2.23) compared to fathers with an intended pregnancy. No statistically significant association was observed among fathers aged 25-49 years. Conclusion Findings from this study show a relationship between mistimed pregnancies and breastfeeding duration among younger fathers. Healthcare professionals should develop breastfeeding interventions targeting fathers and young families. [ABSTRACT FROM AUTHOR]

Advanced paternal age has been associated with a variety of rare conditions and diseases of great public health impact. An increased number of de novo point mutations in sperm with increasing age have been suggested as a mechanism, which would likely also affect fetal viability. We examined the association between paternal age and stillbirth rate in a large nationwide cohort. We identified all pregnancies in Denmark from 1994 to 2010 carried to a gestational age of at least 22 completed weeks (n = 944,031) as registered in national registers and linked to individual register data about the parents. The hazard ratio of stillbirth according to paternal age was estimated, adjusted for maternal age in 1-year categories, year of outcome, and additionally parental educational levels. The relative rate of stillbirth (n = 4946) according to paternal age was found to be J-shaped with the highest hazard ratio for fathers aged more than 40 years when paternal age was modelled using restricted cubic splines. When modelled categorically, the adjusted hazard ratios of stillbirth were as follows: <25, 1.16 (95% confidence interval, CI 1.01-1.34); 25-29, 1.03 (95% CI 0.95-1.11); 35-39, 1.16 (95% CI 1.07-1.26); 40-44, 1.41 (95% CI 1.26-1.59); 45-49, 1.20 (95% CI 0.97-1.49); 50+, 1.58 (95% CI 1.18-2.11), compared with fathers aged 30-34 years. These estimates attenuated slightly when further adjusted for parental education. Our study showed that paternal age was associated with the relative rate of stillbirth in a J-shaped manner with the highest hazard ratios among fathers aged more than 40 years. [ABSTRACT FROM AUTHOR]

Telomeres are repeating DNA at chromosome ends. Telomere length (TL) declines with age in most human tissues, and shorter TL is thought to accelerate senescence. In contrast, older men have sperm with longer TL; correspondingly, older paternal age at conception (PAC) predicts longer TL in offspring. This PAC-effect could be a unique form of transgenerational genetic plasticity that modifies somatic maintenance in response to cues of recent ancestral experience. The PAC-effect has not been examined in any non-human mammals. Objectives Here, we examine the PAC-effect in chimpanzees ( Pan troglodytes). The PAC-effect on TL is thought to be driven by continual production of sperm-the same process that drives increased de novo mutations with PAC. As chimpanzees have both greater sperm production and greater sperm mutation rates with PAC than humans, we predict that the PAC-effect on TL will be more pronounced in chimpanzees. Additionally we examine whether PAC predicts TL of grandchildren. Materials and methods TL were measured using qPCR from DNA from blood samples from 40 captive chimpanzees and 144 humans. Results Analyses showed increasing TL with PAC in chimpanzees ( p = .009) with a slope six times that in humans ( p = .026). No associations between TL and grandpaternal ages were found in humans or chimpanzees-although statistical power was low. Discussion These results suggest that sperm production rates across species may be a determinant of the PAC-effect on offspring TL. This raises the possibility that sperm production rates within species may influence the TL passed on to offspring. [ABSTRACT FROM AUTHOR]

BackgroundAdvanced paternal age at childbirth is associated with psychiatric disorders in offspring, including schizophrenia, bipolar disorder and autism. However, few studies have investigated paternal age's relationship with eating disorders in offspring. In a large, population-based cohort, we examined the association between paternal age and offspring eating disorders, and whether that association remains after adjustment for potential confounders (e.g. parental education level) that may be related to late/early selection into fatherhood and to eating disorder incidence.MethodData for 2 276 809 individuals born in Sweden 1979–2001 were extracted from Swedish population and healthcare registers. The authors used Cox proportional hazards models to examine the effect of paternal age on the first incidence of healthcare-recorded anorexia nervosa (AN) and all eating disorders (AED) occurring 1987–2009. Models were adjusted for sex, birth order, maternal age at childbirth, and maternal and paternal covariates including country of birth, highest education level, and lifetime psychiatric and criminal history.ResultsEven after adjustment for covariates including maternal age, advanced paternal age was associated with increased risk, and younger paternal age with decreased risk, of AN and AED. For example, the fully adjusted hazard ratio for the 45+ years (v. the 25–29 years) paternal age category was 1.32 [95% confidence interval (CI) 1.14–1.53] for AN and 1.26 (95% CI 1.13–1.40) for AED.ConclusionsIn this large, population-based cohort, paternal age at childbirth was positively associated with eating disorders in offspring, even after adjustment for potential confounders. Future research should further explore potential explanations for the association, including de novo mutations in the paternal germline. [ABSTRACT FROM AUTHOR]

As men age, medical and surgical diseases involving the genitourinary tract become more common. The conditions themselves, if not their treatments, can negatively impact the fertility potential of an affected man. Many older men maintain the desire to father children, so it is critical to understand the disturbed anatomy and physiology involved to properly counsel that individual. Should this or that treatment regimen be employed? Should sperm banking be undertaken before institution of a permanently ablative/suppressive therapy? What are the long-term consequences of one therapy over another vis-à-vis sperm production, sperm quality, and/or sperm transport? In this context, some of the more common genitourinary afflictions of the older male and the treatment options that are available will be discussed. [ABSTRACT FROM AUTHOR]

As paternal age increases in the developed world, more attention has been given to the effects of age on male reproductive and sexual function. Although the biologic potential for reproductive continues for most of a man's life, changes in sperm production do occur. In addition, erectile function changes with age, caused by the same factors that lead to other vascular disease. [ABSTRACT FROM AUTHOR]

Paternal aging is associated with increased risk of genetic disease transmission to the offspring. The changes associated with aging arise predominantly through formation of single nucleotide variation through DNA replication errors, as well as possibly chronic exposure to environmental toxins and reactive oxygen species exposure. Several age-related reproductive factors are also contributory, including the systemic hormonal milieu, accumulation of environmental toxin exposure, aging germ cells, and accumulation of de novo genetic and genomic abnormalities in germ cells. In this article we review the age-related genetic and genomic changes that occur in the male germ line. [ABSTRACT FROM AUTHOR]

Increasing percentages of children are being born to older fathers. This has resulted in concerns about the potential adverse effects of advanced paternal age. To help clinicians counsel couples, a systemic review was performed to attempt to address questions that these couples may ask: Should routine sperm testing be performed in older males? Should preimplantation genetic diagnosis (PGD) be performed? How do providers counsel patients about risk? Should young males freeze sperm if they plan to delay paternity? Using the terms "advanced paternal age", "semen testing", "preimplantation genetic diagnosis/screening", and "cryopreservation", a comprehensive search was performed in PubMed and the Cochrane Library, and numerous international societal guidelines were reviewed. In total, 42 articles or guidelines were reviewed. There were no limits placed on the timing of the articles. Thirty articles were found to be relevant and beneficial to answering the above questions. Each question was answered separately by the supporting literature. While primary research exists to support the role of semen testing, PGD/preimplantation genetic screening, and sperm banking in males who may be affected by advancing age, comprehensive studies on the possible clinical benefit of these interventions have yet to be performed. As a result, societal guidelines have yet to incorporate distinct best-practice guidelines on advanced paternal age. [ABSTRACT FROM AUTHOR]

In this article we review the epidemiologic evidence for adverse health effects in offspring of fathers of advanced age. First the evidence regarding fetal survival is addressed, and afterward we review the evidence regarding morbidity in children with older fathers. The adverse conditions most consistently associated with increased paternal age are stillbirths, musculo-skeletal syndromes, cleft palate, acute lymphoblastic leukemia and retinoblastoma, and neurodevelopmental disorders in the autism spectrum and schizophrenia. Finally, we consider the public health impact of the increasing paternal age. We conclude that the adverse health effects in children that might be caused by the present increase in paternal age are severe but quantitatively of minor importance. However, identification of morbidities that are more frequent in offspring of older fathers, after having taken any maternal age effects and other confounding into account, may lead to a better understanding of the pathogenesis behind such conditions. [ABSTRACT FROM AUTHOR]

The effect of paternal age on offspring attractiveness has recently been investigated. Negative effects are predicted as paternal age is a strong proxy for the numbers of common de novo mutations found in the genomes of offspring. As an indicator of underlying genetic quality or fitness, offspring attractiveness should decrease as paternal age increases, evidencing the fitness-reducing effects of these mutations. Thus far results are mixed, with one study finding the predicted effect, and a second smaller study finding the opposite. Here the effect is investigated using two large and representative datasets (Add Health and NCDS), both of which contain data on physical attractiveness and paternal age. The effect is present in both datasets, even after controlling for maternal age at subject's birth, age of offspring, sex, race, parental and offspring (in the case of Add Health) socio-economic characteristics, parental age at first marriage (in the case of Add Health) and birth order. The apparent robustness of the effect to different operationalizations of attractiveness suggests high generalizability, however the results must be interpreted with caution, as controls for parental levels of attractiveness were indirect only in the present study. [ABSTRACT FROM AUTHOR]

Background: Younger or older parental age has been linked with a range of adverse offspring endpoints. We investigated associations between parental age and nine adverse offspring outcomes in three correlated domains: (i) Premature death: suicide, unnatural death, natural death; (ii) Psychiatric morbidity: any mental illness, suicide attempt, substance misuse; (iii) Criminality: violent offending, imprisonment, driving whilst intoxicated.Methods: Persons born in Denmark 1966-1996 were followed from their 15th until 40th birthday or December 2011 (N=1,793,681). Incidence rate ratios were estimated.Results: Offspring of teenage mothers had the greatest risks for all nine adverse outcomes, especially for imprisonment, violent offending, substance misuse, and attempted suicide. Teenage fatherhood was also associated with elevated risks for offspring adverse psychiatric and criminality outcomes, but not premature mortality (at ages 15-39 years). For the psychiatric and criminality outcomes there was a U-shape trend linked with paternal age, but risks for premature mortality tended to increase with rising paternal age. On the contrary, maternal age 30 years and over was not linked with raised risks for any of the outcomes examined.Limitations: Parental links are based on legal and not biological relationships.Conclusions: The substantially elevated risks linked with teenage motherhood for a variety of poor offspring outcomes is a concern for clinicians and policymakers. The associations observed across such a wide array of adverse outcomes also suggest that multiple causal mechanisms may be implicated. [ABSTRACT FROM AUTHOR]

This Committee Opinion provides practitioners with suggestions for optimizing the likelihood of achieving pregnancy in couples/individuals attempting conception who have no evidence of infertility. This document replaces the document of the same name previously published in 2013, Fertil Steril 2013;100(3):631-7. [ABSTRACT FROM AUTHOR]

The association between parental age at conception and children's traits has often been studied as it may reflect germline de novo mutation accumulation and is expected to be monotonic negative. However, for IQ, the relationship has often been found to be inverted U-shaped, possibly because of confounding by parental characteristics that correlate with child-bearing age. Here, I leverage polygenic scores (PGS) as an indirect measure of parental intelligence and examine how the effect changes as the explanatory power increase to heritability. Heritability can be estimated by calculating the phenotype variance explained by the genetic effect when the paternal-maternal ratio of the projected age effects after controlling the genetic effect matches the male-female ratio of mutation rate. After controlling for PGS and demographic factors, I estimate a −2.0 (95 % CI, −0.3 to −3.7) IQ points change in intelligence per decade rise in paternal age. After further adjustment for birth order, it declined to −0.6 (−2.6 to 1.6). Even if only the latter estimate is attributable to mutation accumulation, the result would imply a substantial contribution of de novo mutations in the variance of intelligence. However, the association might not equal the effect of de novo mutations and further studies are needed. • The association between parental age and IQ was used to study mutation accumulation. • The association is confounded by factors including parental intelligence. • The study used polygenic scores to control for parental intelligence. • The study presents a new way of estimating heritability. [ABSTRACT FROM AUTHOR]

The genes are involved in brain connectivity, immune response, and inflammation, according to a statement. Medical News in Brief Almost 200 genes are expressed differently in the brains of people with autism compared with controls, according to results from a study of 59 pediatric and adult brain donors published in I PNAS i . [Extracted from the article]

The aim of the study is to examine associations between paternal age at childbirth and offspring cardiovascular risk factors in adolescence. This is a cross-sectional study. Data from the 2007–2016 Korea National Health and Nutrition Examination Survey was used. A total of 4,096 adolescents were included in the final analysis, and their information on blood pressure, fasting glucose level, and lipid profile was collected. Multiple linear regression models were applied to evaluate the effect of paternal age on cardiovascular risk factors with adjustment for potential confounders. The median age of participants was 13 years, and 53.2% were male. Maternal and paternal ages were closely correlated with each other, and older parents had older offspring. Paternal age was positively associated with levels of total cholesterol (p = 0.033) and triglycerides (p = 0.042) after adjusting for confounders. This nationwide study shows that advanced paternal age is associated with a less favorable lipid profile in a dose-dependent manner. - Little is known about the relationship between paternal age and offspring health. - Adolescents with older fathers have a less favorable lipid profile. - Further prospective studies are needed to confirm or refute our findings. [ABSTRACT FROM AUTHOR]

This issue's of Views and Reviews considers the origins of lifetime health established around the time of conception in some prevalent conditions related to infertility. Reviews will look at the effects of advanced paternal and maternal age, the influence of the severe sperm factor, and the impact of some endocrinopathies commonly seen in infertile couples, especially women, like polycystic ovary syndrome, under- and overweight, diabetes, and thyroid disorders. The aim of this Views and Reviews section is to summarize current evidence on the consequences of these conditions on postnatal health to encourage research in this field and the need to develop strategies and preventative measures to reduce or prevent unfavorable outcomes in future generations. [ABSTRACT FROM AUTHOR]

Background: A long line of research has illustrated that fathers play an important role in the development of their children. Few studies, however, have examined the impact of paternal involvement at the earliest stages of life on developmental diagnoses in childhood.Aims: The present study extends this line of research by exploring the possibility that paternal involvement prenatally, postnatally, and at the time of birth may influence offspring risk for various diagnoses in childhood.Study Design: A quasi-experimental, propensity score matching design was used to create treatment and control groups to assess the relationship between paternal involvement at each stage of development and developmental diagnoses.Subjects: Approximately 6000 children, and a subsample of fathers, who participated in the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B).Outcome Measures: Activity, attention and learning, speech or language, and other diagnoses in early childhood, and overall number of diagnoses at 4years of age.Results: We find no consistent evidence that low paternal involvement prenatally or postnatally increases the risk of various developmental diagnoses by age 4. However, children whose fathers were absent at the time of their birth were at significantly greater risk of incurring various developmental diagnoses, as well as a significantly greater number of developmental diagnoses.Conclusions: The findings expand our understanding of exactly how early paternal influence begins and the specific dimensions of early father behaviors that are related to the risk of various developmental diagnoses. Ultimately, these results have important implications concerning father involvement during the earliest stages of the life course. [ABSTRACT FROM AUTHOR]

The increased paternal age at conception (PAC) has been associated with autism spectrum disorder (ASD), schizophrenia and other neurodevelopmental disorders, thus raising questions that imply, potential health concerns in the offspring. As opposed to female oogonia, the male germ cells undergo hundreds of cell divisions during the fertile years. Thus, the advanced paternal age is associated with increase of point mutations in the male spermatogonia DNA, implying that this could be the major driving mechanism behind the paternal age effect observed in the offspring. In addition to replication errors, DNA replication fidelity and inefficient DNA repair machinery in the spermatogonia also contribute to the mutagenic load. Our study population consisted of 38 nonagenarians, participants in the Vitality 90+ Study, born in the year 1920 (women n = 25, men n = 13), for whom the parental birth dates were available. The gene expression profile of the study subjects was determined with HumanHT-12 v4 Expression BeadChip from peripheral blood mononuclear cells. We used Spearman's rank correlation to look for the associations of gene expression with paternal age at conception. Associated transcripts were further analyzed with GOrilla and IPA to determine enriched cellular processes and pathways. PAC was associated with the expression levels of 648 transcripts in nonagenarian subjects. These transcripts belonged to the process of mitochondrial translational termination and the canonical pathway of Mitochondrial dysfunction, more specifically of Oxidative phosphorylation. The observed systematic down-regulation of several mitochondrial respiratory chain components implies compromised function in oxidative phosphorylation and thus in the production of chemical energy. [ABSTRACT FROM AUTHOR]

Advanced paternal age is associated with increased complications in pregnancy and genetic diseases in offspring. Oxidative stress is a major contributor to the damage accumulated in sperm during aging. Complex networks of antioxidants regulate reactive oxygen species (ROS) in the testis. While mounting evident shows that redox dysfunction compromises the quality of developing male germ cells, the mechanisms by which aging causes this remain unclear. Furthermore, therapies to successfully alleviate aging-associated loss in germ cell quality are limited. The antioxidant catalase (CAT) has been used in aging-associated pathologies to alleviate oxidative stress. We used mice overexpressing CAT (MCAT) to determine whether CAT overexpression alleviates the redox dysfunction observed with aging. We found that MCAT mice did not exhibit the age-dependent loss of spermatozoa, nor did they show aging associated loss in testicular germ and Sertoli cells seen in wild type (WT). Low overall ROS and reduced peroxynitrite levels were detected in spermatocytes from aged MCAT mice, following exposure to the pro-oxidant tert-butyl hydroperoxide. Germ cells from young MCATs showed elevated levels of DNA-damage repair markers, γ-H2AX and 53BP1, but this response was lost with aging. Finally, we found oxidative stress induced 8-oxodG lesions to increase in sperm with aging; these lesions were significantly reduced in aged MCAT and these mice showed no decrease in the age-dependent number of pups per litter. Thus we conclude that aged MCAT mice generate sperm at the same rate as young mice; these sperm are protected from oxidative stress associated damage. [ABSTRACT FROM AUTHOR]