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Dolores Malaspina - One of the best experts on this subject based on the ideXlab platform.

  • Paternal Age and mental health of offspring
    Fertility and sterility, 2015
    Co-Authors: Dolores Malaspina, Caitlin Gilman, Thorsten M. Kranz
    Abstract:

    The influence of Paternal Age on the risk for sporadic forms of Mendelian disorders is well known, but a burgeoning recent literature demonstrates, in addition, a Paternal Age effect for complex neuropsychiatric conditions, including schizophrenia, autism, bipolar disorder, and even for learning potential, expressed as intelligence. Mental illness is costly to patients, their family, and the public health system, accounting for the largest portion of disability costs in our economy. The delayed onset of neuropsychiatric conditions and lack of physical manifestations at birth are common frequencies in the population that have obscured the recognition that a portion of the risks for mental conditions is associated with Paternal Age. Identification of these risk pathways may be leverAged for knowledge about mental function and for future screening tests. However, only a small minority of at-risk offspring are likely to have such a psychiatric or learning disorder attributable to Paternal Age, including the children of older fathers.

  • Telomere length, family history, and Paternal Age in schizophrenia
    Molecular genetics & genomic medicine, 2014
    Co-Authors: Dolores Malaspina, Susan Harlap, Raymond R. Goetz, Roberta Dracxler, Julie Walsh-messinger, David L. Keefe, Mary Perrin
    Abstract:

    Leukocyte telomere length (LTL) is longer in association with advanced Paternal Age, but this association has not been examined along with family history (FH) in schizophrenia. LTL was measured by PCR and compared across cases and controls as part of a study to examine the characteristics of Paternal Age related schizophrenia. The 53 schizophrenia cases had similar mean LTL as 20 controls, although cases were significantly older than controls and overwhelmingly smoked cigarettes. Multivariate analyses showed that a FH of schizophrenia was associated with longer LTL in both male and female cases. Later Paternal Age was also related to longer LTL in male cases, but with shorter LTL in female cases. Male cases with older fathers and a FH had the longest LTL. The genetic architecture associated with a familial risk for schizophrenia may include pathways that lengthen LTL. Paternal aging conferred an additional increase in LTL lengthening in male cases, but reduced LTL in female cases. The gender difference in LTL for Paternal aging is consistent with the severe illness features reported for female cases with older fathers and could implicate epigenetic alterations in the Paternal X chromosomal region with advanced Paternal Age in association with the risk for schizophrenia.

  • Later Paternal Age and sex differences in schizophrenia symptoms
    Schizophrenia Research, 2009
    Co-Authors: Paul J. Rosenfield, Raymond R. Goetz, Jill M. Harkavy-friedman, Karine Kleinhaus, Mary Perrin, Mark Opler, Nicole Learned, Arielle D. Stanford, Julie W. Messinger, Dolores Malaspina
    Abstract:

    Objective Advanced Paternal Age is consistently associated with an increased risk for schizophrenia, accounting for up to a quarter of cases in some populations. If Paternal Age-related schizophrenia (PARS) involves a distinct etiopathology, then PARS cases may show specific characteristics, vis-a-vis other schizophrenia cases. This study examined if PARS exhibits the symptom profile and sex differences that are consistently observed for schizophrenia in general, wherein males have an earlier onset Age and more severe negative symptoms than females.

  • Aberrant Epigenetic Regulation Could Explain the Relationship of Paternal Age to Schizophrenia
    Schizophrenia bulletin, 2007
    Co-Authors: Mary Perrin, Alan S. Brown, Dolores Malaspina
    Abstract:

    The causal mechanism underlying the well-established relation between advancing Paternal Age and schizophrenia is hypothesized to involve mutational errors during spermatogenesis that occur with increasing frequency as males Age. Point mutations are well known to increase with advancing Paternal Age while other errors such as altered copy number in repeat DNA and chromosome breakAge have in some cases also been associated with advancing Paternal Age. Dysregulation of epigenetic processes may also be an important mechanism underlying the association between Paternal Age and schizophrenia. Evidence suggests that advancing Age as well as environmental exposures alter epigenetic regulation. Errors in epigenetic processes, such as parental imprinting can have serious effects on the offspring both pre- and postnatally and into adulthood. This article will discuss parental imprinting on the autosomal and X chromosomes and the alterations in epigenetic regulation that may lead to such errors.

  • Advancing Paternal Age and Autism
    Archives of general psychiatry, 2006
    Co-Authors: Abraham Reichenberg, Raz Gross, Mark Weiser, Michealine Bresnahan, Jeremy M. Silverman, Susan Harlap, Jonathan Rabinowitz, Cory Shulman, Dolores Malaspina, Gad Lubin
    Abstract:

    Context Maternal and Paternal Ages are associated with neurodevelopmental disorders. Objective To examine the relationship between advancing Paternal Age at birth of offspring and their risk of autism spectrum disorder (ASD). Design Historical population-based cohort study. Setting Identification of ASD cases from the Israeli draft board medical registry. Participants We conducted a study of Jewish persons born in Israel during 6 consecutive years. Virtually all men and about three quarters of women in this cohort underwent draft board assessment at Age 17 years. Paternal Age at birth was obtained for most of the cohort; maternal Age was obtained for a smaller subset. We used the smaller subset (n = 132 271) with data on both Paternal and maternal Age for the primary analysis and the larger subset (n = 318 506) with data on Paternal but not maternal Age for sensitivity analyses. Main Outcome Measures Information on persons coded as having International Classification of Diseases, 10th Revision ASD was obtained from the registry. The registry identified 110 cases of ASD (incidence, 8.3 cases per 10 000 persons), mainly autism, in the smaller subset with complete parental Age data. Results There was a significant monotonic association between advancing Paternal Age and risk of ASD. Offspring of men 40 years or older were 5.75 times (95% confidence interval, 2.65-12.46; P Conclusions Advanced Paternal Age was associated with increased risk of ASD. Possible biological mechanisms include de novo mutations associated with advancing Age or alterations in genetic imprinting.

Patrick Thonneau - One of the best experts on this subject based on the ideXlab platform.

  • Paternal Age 40 years an important risk factor for infertility
    American Journal of Obstetrics and Gynecology, 2003
    Co-Authors: Elise De La Rochebrochard, Patrick Thonneau
    Abstract:

    Abstract Objective The purpose of this study was to examine the risk of infertility that is associated with Paternal Age, because this factor rarely has been investigated, whereas maternal Age of ≥35 years is a well-known risk factor. Study Design This large, retrospective, population-based sample included 6188 European women (from Denmark, Italy, Spain, Germany) Aged 25 to 44 years who were selected randomly from census registers in 1991 through 1993. Results Among couples composed of a woman Aged 35 to 39 years, risks were significantly higher when Paternal Age was ≥40 years than when Paternal Age was Conclusion Like maternal Age of ≥35 years, Paternal Age of ≥40 years should be considered to be a key risk factor for infertility.

  • Paternal Age ≥ 40 years: an important risk factor for infertility
    American Journal of Obstetrics and Gynecology, 2003
    Co-Authors: Elise De La Rochebrochard, Patrick Thonneau
    Abstract:

    OBJECTIVE: The purpose of this study was to examine the risk of infertility that is associated with Paternal Age, because this factor rarely has been investigated, whereas maternal Age of >or=35 years is a well-known risk factor. STUDY DESIGN: This large, retrospective, population-based sample included 6188 European women (from Denmark, Italy, Spain, Germany) Aged 25 to 44 years who were selected randomly from census registers in 1991 through 1993. RESULTS: Among couples composed of a woman Aged 35 to 39 years, risks were significantly higher when Paternal Age was >or=40 years than when Paternal Age was or=35 years, Paternal Age of >or=40 years should be considered to be a key risk factor for infertility.

  • Paternal Age ≥40 years: An important risk factor for infertility
    American journal of obstetrics and gynecology, 2003
    Co-Authors: Elise De La Rochebrochard, Patrick Thonneau
    Abstract:

    Abstract Objective The purpose of this study was to examine the risk of infertility that is associated with Paternal Age, because this factor rarely has been investigated, whereas maternal Age of ≥35 years is a well-known risk factor. Study Design This large, retrospective, population-based sample included 6188 European women (from Denmark, Italy, Spain, Germany) Aged 25 to 44 years who were selected randomly from census registers in 1991 through 1993. Results Among couples composed of a woman Aged 35 to 39 years, risks were significantly higher when Paternal Age was ≥40 years than when Paternal Age was Conclusion Like maternal Age of ≥35 years, Paternal Age of ≥40 years should be considered to be a key risk factor for infertility.

Elise De La Rochebrochard - One of the best experts on this subject based on the ideXlab platform.

  • Paternal Age 40 years an important risk factor for infertility
    American Journal of Obstetrics and Gynecology, 2003
    Co-Authors: Elise De La Rochebrochard, Patrick Thonneau
    Abstract:

    Abstract Objective The purpose of this study was to examine the risk of infertility that is associated with Paternal Age, because this factor rarely has been investigated, whereas maternal Age of ≥35 years is a well-known risk factor. Study Design This large, retrospective, population-based sample included 6188 European women (from Denmark, Italy, Spain, Germany) Aged 25 to 44 years who were selected randomly from census registers in 1991 through 1993. Results Among couples composed of a woman Aged 35 to 39 years, risks were significantly higher when Paternal Age was ≥40 years than when Paternal Age was Conclusion Like maternal Age of ≥35 years, Paternal Age of ≥40 years should be considered to be a key risk factor for infertility.

  • Paternal Age ≥ 40 years: an important risk factor for infertility
    American Journal of Obstetrics and Gynecology, 2003
    Co-Authors: Elise De La Rochebrochard, Patrick Thonneau
    Abstract:

    OBJECTIVE: The purpose of this study was to examine the risk of infertility that is associated with Paternal Age, because this factor rarely has been investigated, whereas maternal Age of >or=35 years is a well-known risk factor. STUDY DESIGN: This large, retrospective, population-based sample included 6188 European women (from Denmark, Italy, Spain, Germany) Aged 25 to 44 years who were selected randomly from census registers in 1991 through 1993. RESULTS: Among couples composed of a woman Aged 35 to 39 years, risks were significantly higher when Paternal Age was >or=40 years than when Paternal Age was or=35 years, Paternal Age of >or=40 years should be considered to be a key risk factor for infertility.

  • Paternal Age ≥40 years: An important risk factor for infertility
    American journal of obstetrics and gynecology, 2003
    Co-Authors: Elise De La Rochebrochard, Patrick Thonneau
    Abstract:

    Abstract Objective The purpose of this study was to examine the risk of infertility that is associated with Paternal Age, because this factor rarely has been investigated, whereas maternal Age of ≥35 years is a well-known risk factor. Study Design This large, retrospective, population-based sample included 6188 European women (from Denmark, Italy, Spain, Germany) Aged 25 to 44 years who were selected randomly from census registers in 1991 through 1993. Results Among couples composed of a woman Aged 35 to 39 years, risks were significantly higher when Paternal Age was ≥40 years than when Paternal Age was Conclusion Like maternal Age of ≥35 years, Paternal Age of ≥40 years should be considered to be a key risk factor for infertility.

Abraham Reichenberg - One of the best experts on this subject based on the ideXlab platform.

  • Understanding the association between advanced Paternal Age and schizophrenia and bipolar disorder.
    Psychological medicine, 2019
    Co-Authors: Mark Weiser, Abraham Reichenberg, Daphna Fenchel, Or Frenkel, Eyal Fruchter, Shimon Burshtein, Ariel Ben Yehuda, Rinat Yoffe, Tal Bergman-levi, Michael H. Davidson
    Abstract:

    BACKGROUND Previous studies reported an association between advanced Paternal Age at birth and increased risk for schizophrenia and bipolar disorder. While some hypothesize that this association is caused by de-novo mutations in Paternal spermatozoa, others cite factors associated with psycho-social characteristics of fathers who have children at a late Age. This study aims to test these hypotheses. METHODS A historical-prospective, population-based cohort study, performed by linking the Israeli Draft Board Registry and the Israeli National Psychiatric Hospitalization Registry (N = 916 439; 4488 with schizophrenia, 883 with bipolar disorder). Odds ratios (OR) and two-sided 95% confidence intervals (CI) were calculated by logistic regression models, using Paternal Age as predictor and risk for later hospitalizations for schizophrenia or bipolar disorder as outcome measure. Models were first fitted unadjusted, then adjusted for Paternal Age at birth of the first child. RESULTS In the unadjusted model, offspring of fathers Aged 45 and above at birth had increased risk of schizophrenia (OR = 1.71, 95% CI 1.49-1.99) and bipolar disorder (OR = 1.63, 95% CI 1.16-2.24). However, taking into account Paternal Age at birth of first child, advanced Paternal Age was no longer associated with increased risk of schizophrenia (OR = 0.60, 95% CI 0.48-0.79) or bipolar disorder (OR = 1.03, 95% CI 0.56-1.90). CONCLUSIONS Controlling for Paternal Age at birth of the first offspring, advanced Paternal Age does not predict increased risk for schizophrenia or bipolar disorder. These data indicate that the association between advanced Paternal Age and having an offspring with schizophrenia and bipolar disorder is likely due to psychos-social factors, or common genetic variation associated with delayed initial fatherhood.

  • AdvantAgeous developmental outcomes of advancing Paternal Age
    Translational psychiatry, 2017
    Co-Authors: Magdalena Janecka, Fruhling Rijsdijk, Dheeraj Rai, Amirhossein Modabbernia, Abraham Reichenberg
    Abstract:

    Advanced Paternal Age (APA) at conception has been associated with negative outcomes in offspring, raising concerns about increasing Age at fatherhood. Evidence from evolutionary and psychological research, however, suggests possible link between APA and a phenotypic advantAge. We defined such advantAge as educational success, which is positively associated with future socioeconomic status. We hypothesised that high IQ, strong focus on the subject of interest and little concern about ‘fitting in’ will be associated with such success. Although these traits are continuously distributed in the population, they cluster together in so-called ‘geeks’. We used these measures to compute a ‘geek index’ (GI), and showed it to be strongly predictive of future academic attainment, beyond the independent contribution of the individual traits. GI was associated with Paternal Age in male offspring only, and mediated the positive effects of APA on education outcomes, in a similar sexually dimorphic manner. The association between Paternal Age and GI was partly mediated by genetic factors not correlated with Age at fatherhood, suggesting contribution of de novo factors to the ‘geeky’ phenotype. Our study sheds new light on the multifaceted nature of the APA effects and explores the intricate links between APA, autism and talent.

  • Paternal Age Alters Social Development in Offspring
    Journal of the American Academy of Child and Adolescent Psychiatry, 2017
    Co-Authors: Magdalena Janecka, Abraham Reichenberg, Claire M. A. Haworth, Angelica Ronald, Eva Krapohl, Francesca Happé, Jonathan Mill, Leonard C. Schalkwyk, Cathy Fernandes, Fruhling Rijsdijk
    Abstract:

    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 A dditive genetics, C ommon environment, unique E nvironment (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.

  • Advancing Paternal Age and psychiatric disorders
    World psychiatry : official journal of the World Psychiatric Association (WPA), 2015
    Co-Authors: Emma M. Frans, James H. Maccabe, Abraham Reichenberg
    Abstract:

    Age of first and subsequent parenthood has been increasing all over the world. From a public health perspective, it is becoming apparent that this shift might have negative consequences. When considering the potential negative effects of late parenthood, focus has traditionally been on older maternal Age, which has been associated with multiple adverse outcomes in the offspring (1). More recently, however, the offspring of older fathers have been shown to have increased risk for a wide range of adverse health conditions, including psychiatric disorders. These findings received considerable attention because they challenge traditional views on male fertility and reproduction. However, research findings on the links between advancing Paternal Age and psychiatric disorders have not always been replicable, and the mechanism or mechanisms behind the Paternal Age effect remain unclear, adding to the controversies around the findings. In this paper we provide an updated overview of the research on the association between advancing Paternal Age and psychiatric disorders in the offspring and discuss potential biological and social mechanisms.

  • Transcriptomic changes in the frontal cortex associated with Paternal Age
    Molecular autism, 2014
    Co-Authors: Rebecca G. Smith, Abraham Reichenberg, Leonard C. Schalkwyk, Cathy Fernandes, Joseph D. Buxbaum, Rachel L. Kember, Jonathan Mill
    Abstract:

    Background: Advanced Paternal Age is robustly associated with several human neuropsychiatric disorders, particularly autism. The precise mechanism(s) mediating the Paternal Age effect are not known, but they are thought to involve the accumulation of de novo (epi)genomic alterations. In this study we investigate differences in the frontal cortex transcriptome in a mouse model of advanced Paternal Age. Findings: Transcriptomic profiling was undertaken for medial prefrontal cortex tissue dissected from the male offspring of young fathers (2 month old, 4 sires, n= 16 offspring) and old fathers (10 month old, 6 sires, n =1 6 offspring) in a mouse model of advancing Paternal Age. We found a number of differentially expressed genes in the offspring of older fathers, many previously implicated in the aetiology of autism. Pathway analysis highlighted significant enrichment for changes in functional networks involved in inflammation and inflammatory disease, which are also implicated in autism. Conclusions: We observed widespread alterations to the transcriptome associated with advanced Paternal Age with an enrichment of genes associated with inflammation, an interesting observation given previous evidence linking the immune system to several neuropsychiatric disorders including autism.

Jorn Olsen - One of the best experts on this subject based on the ideXlab platform.

  • Paternal Age and Offspring Congenital Heart Defects: A National Cohort Study
    PloS one, 2015
    Co-Authors: Wei Yuan, Guo Ying Huang, Jorn Olsen
    Abstract:

    Paternal Age has been associated with offspring congenital heart defects (CHDs), which might be caused by increased mutations in the germ cell line because of cumulated cell replications. Empirical evidences, however, remain inconclusive. Furthermore, it is unknown whether all subtypes of CHDs are affected by Paternal Age. We aimed to explore the relationship between Paternal Age and the risk of offspring CHDs and its five common subtypes using national register data in Denmark. A total of 1 893 899 singletons born in Denmark from 1977 to 2008 were included in this national-based cohort study. Cox’s proportion hazards model with robust sandwich estimate option was used to estimate the hazards ratio (95% confidence interval) for the associations between Paternal Age and all CHDs, as well as subtypes of CHDs (patent ductus arteriosus (PDA), ventricular septal defect (VSD), atrial septal defect (ASD), tetralogy of fallot (TOF) and coarctation of the aorta (CoA)). We did not observe an overall association between Paternal Age and offspring CHDs. However, compared to the Paternal Age of 25–29 years, Paternal Age of older than 45 years was associated with a 69% increased risk of PDA (HR45+ = 1.69, 95%CI:1.17–2.43). We observed similar results when subanalyses were restricted to children born to mothers of 27–30 years old. After taking into consideration of maternal Age, our data suggested that advanced Paternal Age was associated with an increased prevalence of one subtype of offspring congenital heart defects (CHDs), namely patent ductus arteriosus (PDA).

  • Paternal Age and mortality in children
    European Journal of Epidemiology, 2008
    Co-Authors: Jin Liang Zhu, Kreesten Meldgaard Madsen, Mogens Vestergaard, Jorn Olsen
    Abstract:

    Background Since Paternal Age correlates with some diseases that have a high case-fatality, a Paternal Age effect on offspring’s survival is expected but unsettled. We examined the association between Paternal Age and mortality in children in a large population-based cohort taking maternal Age and socioeconomic factors into account. Methods From the Danish Fertility Database (1980–1996), we identified 102,879 couples and their firstborn singleton children. Information on childhood death ( N  = 831) was obtained by linking the cohort to the nationwide register on cause of death (1980–1998). Results We observed a U-shaped association between Paternal Age and the overall mortality rate in children up to 18 years of Age. Adjustment for maternal Age and other confounders reduced the mortality rate ratio (MRR) for children of younger fathers but not for children of older fathers. Compared with children of fathers Aged between 25 and 29 years, the adjusted MRR was 1.77 (95% confidence interval 1.28–2.45) for children of fathers Aged between 45 and 49 years and 1.59 (1.03–2.46) for children of fathers Aged 50 years or more. The cause-specific MRRs were highest for congenital malformations [2.35 (1.42–3.88)] and injury or poisoning [3.43 (1.49–7.92)] for children of fathers Aged 45 years or more. Conclusion Our data revealed a higher mortality in offspring of fathers Aged 45 years or more that lasted into adulthood. This adds to the cumulating evidence on adverse effects of advanced Paternal Age in procreation.

  • Paternal Age and Apgar scores of newborn infants.
    Epidemiology (Cambridge Mass.), 2006
    Co-Authors: Yuelian Sun, Jin Liang Zhu, Kreesten Meldgaard Madsen, Mogens Vestergaard, Jorn Olsen
    Abstract:

    Background: New evidence suggests that advanced Paternal Age is a reproductive hazard, but we do not know whether Paternal Age affects the physical conditions of newborn infants as measured by the Apgar score. Methods: We conducted a register-based cohort study of 70,347 couples and their first singleton infants by using data from the Danish Fertility Database (1980–1996). Information on Apgar score was obtained by linking the children to the National Birth Register. Results: The odds ratio for having a baby with a 1-minute Apgar score of 1–3 was 1.64 (95% confidence interval = 1.08–2.48) for fathers 45 to 49 years of Age and 1.49 (0.76–2.94) for fathers 50+ years compared with fathers 20 to 29 years (P for trend = 0.011). The risk of having a 5-minute Apgar score less than 7 increased among fathers 45+ years old (P for trend = 0.178). Conclusions: Our data suggest a modest effect of advanced Paternal Age on the Apgar score.

  • Paternal Age and congenital malformations
    Human reproduction (Oxford England), 2005
    Co-Authors: Jin Liang Zhu, Kreesten Meldgaard Madsen, Mogens Vestergaard, Olga Basso, Anne Vingaard Olesen, Jorn Olsen
    Abstract:

    BACKGROUND: Spontaneous mutations in germ cells increase with male Age, but an association between Paternal Age and congenital malformations is not well established. We conducted a population-based cohort study to estimate this association. METHODS: A study population of couples and their firstborn children were identified in the Danish Fertility Database between 1980 and 1996 (n = 71937). Diagnoses of congenital malformations in children were obtained by linkAge to the nationwide hospital register (1980–1999). RESULTS: Overall, there were no differences in the prevalence of malformations as a function of Paternal Age. However, the prevalence of malformations of extremities and syndromes of multiple systems, as well as Down’s syndrome, increased with increasing Paternal Age. For example, in comparison with fathers Age 20–29 years, adjusted hazard ratio of syndromes of multiple systems was 1.15 [95% confidence interval (CI) 0.81–1.65] for Age 35–39 years, 1.33 (95% CI 0.79–2.25) for Age 40–44 years, 1.73 (95% CI 0.82–3.65) for Age 45–49 years, and 3.20 (95% CI 1.37–7.48) for Age 50 years (test for trend P = 0.01). CONCLUSIONS: Our data suggest that advanced Paternal Age may be associated with an excess occurrence of some specific malformations. The association could be caused by mutations of th e gametes in men induced by biological or environmental factors.

  • Paternal Age and preterm birth
    Epidemiology, 2005
    Co-Authors: Jin Liang Zhu, Kreesten Meldgaard Madsen, Mogens Vestergaard, Olga Basso, Jorn Olsen
    Abstract:

    Background: There is growing evidence that advanced Paternal Age can be a reproductive hazard. Methods: We studied couples and their first children using nationwide registers in Denmark between 1980 and 1996. We restricted the analysis to mother's Age 20-29 years. We estimated odds ratios (ORs) of preterm (<37 weeks gestation) and very preterm birth (<32 weeks) as a function of Paternal Age using logistic regression to adjust for potential confounding variables. Results: The risk of preterm birth increased with Paternal Age, almost entirely resulting from an association for very preterm birth. Compared with fathers Age 20-24 years, ORs for very preterm birth were 1.3 (Age 25-29), 1.4 (Age 35-39), 1.7 (Age 40-44), 1.6 (Age 45-49), and 2.1 (Age 50+) (test for trend: P = 0.01). Conclusions: Risk of very preterm birth increases among older fathers, perhaps as a result of a Paternal placental effect.