Paternal Alcohol Consumption Research Articles

First Description of a Large Clinical Series of Fetal Alcohol Spectrum Disorders Children and Adolescents in Reunion Island, France.

Despite several diagnostic guidelines, Fetal Alcohol Spectrum Disorders (FASDs) remain underdiagnosed or misdiagnosed, delaying the care of these patients and support for families. This study aims to help professionals caring for these children and their families to suspect this diagnosis earlier and to provide the most appropriate follow-up. A retrospective chart review with monocentric recruitment was performed at the Genetics Unit of the University Hospital of Reunion Island. A total of 147 children and adolescents with FASDs were included. Prenatal alcohol exposure was associated with paternal alcohol consumption in 42.9%, and a high rate of prematurity (33.3%) was observed. Sixty percent of children or adolescents were placed in foster families. Learning difficulties without cognitive deficits were found in 65.8% of cases (50/76). Postural control and fine motor skills disabilities were described, respectively, in 54.7% (35/64) and 72.5% (50/69) of cases. A systematic genetic assessment was carried out, identifying in these FASD patients an associated Copy Number Variation (CNVs) in 22.6% of cases. Children with FASDs combine significant vulnerabilities, associating exposure to alcohol during the preconception and/or the prenatal period, prematurity, complex familial and sociocultural living conditions, and a genetic anomaly in almost a quarter of cases.

Periconceptional maternal and paternal alcohol consumption and embryonic and fetal development: the Rotterdam periconception cohort

Research QuestionWhat is the impact of maternal and paternal alcohol consumption in the periconception period on embryonic and foetal development assessed using three-dimensional ultrasound and VR techniques? DesignThis is a prospective observational study embedded in the Rotterdam Periconception Cohort (Predict study). Participating women received longitudinal 3D transvaginal ultrasound examinations from week 7 up to week 12 of gestation to measure crown-rump length (CRL) and embryonic volume (EV). Mid-pregnancy foetal size parameters and birthweight were retrieved from medical files. Participants filled out a periconception exposure questionnaire and a validated food frequency questionnaire. Linear mixed models were used to analyse the association between parental alcohol consumption, and embryonic and foetal developmental parameters. Results1141 female and 987 male participants were included in our analyses. Maternal moderate alcohol consumption in the periconception period resulted in a smaller head circumference (β=-1.85, SE=0.84, P=0.03), abdominal circumference (β=-2.65, SE=0.93, P=0.004), femur length (β=-0.56, SE=0.22, P=0.01), and estimated foetal weight (β=-9.36, SE=4.35, P=0.03) at 20 weeks of gestation. Paternal alcohol consumption showed significant positive associations, mainly with foetal size parameters (AC: β=0.033, SE=0.01, P=0.008; EFW: β=0.131, SE:0.06, P=0.03). ConclusionsModerate maternal alcohol consumption is negatively associated with foetal growth parameters. Moreover, alcohol is proven a strong teratogen and the consumption before and during pregnancy should be discouraged in both women and men since it affects both several parameters of embryonic and foetal development.

Paternal peri-conceptional physical activity and the risk of congenital heart disease in offspring: A case-control study.

Genetic and environmental factors have been shown to contribute to the development of congenital heart disease (CHD). To date, the focus of scientific articles has primarily centered on genetics and maternal environmental factors, with comparatively less attention given to paternal risk factors. This study aims to investigate the potential association between paternal pre-conceptional physical activity levels (PA), along with paternal peri-conceptional smoking and alcohol consumption, and the risk of CHD in offspring. An observational case-control study was conducted in Lebanon, with 279 participants, aiming to investigate potential risk factors for CHD. We included children with confirmed CHD, born between 2012 and 2022. Controls born in the same timeframe were selected randomly from the general population using online questionnaire forms. Mean age of children included was 6 years old (0-10). The pre-conceptional PA was assessed using the Global Physical Activity Questionnaire validated in Arabic. In addition, paternal smoking, alcohol consumption, and maternal risk factors were collected. The study included 128 CHD cases (45.9%) and their parents, as well as 151 healthy infants (54.1%) and their parents. There were no statistically significant variations in the alcohol consumption noted between the fathers in the case and control groups (p=0.18). The paternal involvement in recreational-related PA during the peri-conception period was associated with a reduced risk of the CHD development in offspring by 46.9% (OR=0.531, 95% CI: 0.301-0.936, p=0.029). Additionally, increasing paternal total sitting time by 1 h above the average, which was approximately 260 min (4h), increased the risk of CHD in offspring by 0.4% (p=0.001). Moreover, paternal smoking exhibited an apparent association with a 56% increased risk of offspring developing CHD, notwithstanding that the confidence intervals included the null (OR=1.56, 95% CI: 0.86-2.8, p=0.136). This observational study is the first to report a potential association between paternal PA, and CHD in offspring. This study aligns with previous reports, advocating for the paternal engagement in PA and the adoption of healthy lifestyle habits, especially during the critical stages of conception. Such practices are strongly recommended to enhance fertility and promote optimal health for offspring. However, due to the subjectivity in reporting PA and lack of molecular proof, additional prospective and molecular studies are required to validate these findings.

Paternal preconception alcohol consumption increased Angiotensin II-mediated vasoconstriction in male offspring cerebral arteries via oxidative stress-AT1R pathway.

Alcohol consumption is popular worldwidely and closely associated with cardiovascular diseases. Influences of paternal preconception alcohol consumption on offspring cerebral arteries are largely unknown. Male rats were randomly given alcohol or water before being mated with alcohol-naive females to produce alcohol- and control-sired offspring. Middle cerebral artery (MCA) was tested with a Danish Myo Technology wire myograph, patch-clamp, IONOPTIX, immunofluorescence and quantitative PCR. Alcohol consumption enhanced angiotensin II (AngII)-mediated constriction in male offspring MCA mainly via AT1R. PD123,319 only augmented AngII-induced constriction in control offspring. AngII and Bay K8644 induced stronger intracellular calcium transient in vascular smooth muscle cells (VSMCs) from MCA of alcohol offspring. L-type voltage-dependent calcium channel (L-Ca2+ ) current at baseline and after AngII-stimulation was higher in VSMCs. Influence of large-conductance calcium-activated potassium channel (BKC a ) was lower. Caffeine induced stronger constriction and intracellular calcium release in alcohol offspring. Superoxide anion was higher in alcohol MCA than control. Tempol and thenoyltrifluoroacetone alleviated AngII-mediated contractions, while inhibition was significantly higher in alcohol group. The mitochondria were swollen in alcohol MCA. Despite lower Kcnma1 and Prkce expression, many genes expressions were higher in alcohol group. Hypoxia induced reactive oxygen species production and increased AT1R expression in control MCA and rat aorta smooth muscle cell line. In conclusion, this study firstly demonstrated paternal preconception alcohol potentiated AngII-mediated vasoconstriction in offspring MCA via ROS-AT1R. Alcohol consumption increased intracellular calcium via L-Ca2+ channel and endoplasmic reticulum and decreased BKCa function. The present study provided new information for male reproductive health and developmental origin of cerebrovascular diseases.

Paternal Alcohol Consumption and Childhood Malnutrition: A Community-based Participatory Case-control Study among Adivasis in Rural South India.

Childhood malnutrition in India remains among the highest in the world. Adult alcohol consumption and severe malnutrition have increased among indigenous people in South India. However, the association between them is poorly understood. We aimed to evaluate this association, which could help design better intervention strategies. This case-control observational study was conducted in the Nilgiri district in South India. Cases included children aged 1-5 years with moderate malnutrition. Controls were defined as children in the same age group with normal weight-for-age. A questionnaire was used to collect data on demographics, socioeconomic status (SES), and parental education. The WHO Alcohol Use Disorders Identification Test (AUDIT) questionnaire was used to estimate parental alcohol use. Health-care workers collected data from within the community. The baseline demographics of the children in the control (n = 250) and case groups (n = 177) were similar. Paternal age and AUDIT scores were not different in the two groups. SES was lower in the malnourished group, while maternal education among cases was significantly lower. Maternal and paternal education were associated with childhood malnutrition (odds ratio [OR]: 0.728 [95% confidence interval (CI): 0.583-0.903] and OR: 0.753 [95% CI: 0.589-0.957], respectively). After adjustment for covariates, paternal alcohol use was associated with a higher risk of malnutrition (OR: 1.56 [95% CI: 1.00-2.47]), which SES partly mediated. Paternal alcohol consumption is associated with childhood malnutrition, partially mediated by lower SES. Furthermore, lower SES appeared to be strongly associated with paternal alcohol consumption.

Unveiling the hidden risk: paternal smoking and alcohol exposure prior to conception as independent factors for allergic rhinitis in children.

Limited knowledge exists regarding the impact of paternal smoking and alcohol exposure on the development of allergic rhinitis in offspring. Our study aimed to investigate the potential association between preconception paternal smoking and alcohol exposure and the likelihood of children allergic rhinitis. A retrospective case-control study of 556 prepubertal children aged 3-12 years was performed. The participants were 278 children with allergic rhinitis and 278 healthy controls matched for age and gender. Self-administered questionnaires were distributed and collected on-site, focusing on various factors related to the children's fathers, mothers, and the children themselves during the first year of life and the past 12 months, from March to October 2022. Multivariate analysis demonstrated that paternal smoking, paternal alcohol consumption prior to conception, paternal allergic diseases, children with a family history of allergies, maternal allergic diseases and pregnancy complications were identified as independent risk factors for allergic rhinitis in their offspring. Moreover, after considering confounding factors, it was observed that paternal smoking exceeding 5 cigarettes per day in the year preceding pregnancy and exceeding 11 years significantly elevated the likelihood of allergic rhinitis in children (OR = 2.009 and 2.479, respectively). Furthermore, the consumption of alcohol by the father at intervals of less than one month in the year prior to pregnancy and a duration of alcohol consumption exceeding 11 years prior to pregnancy are both associated with a significantly increased risk of allergic rhinitis in children (OR = 2.005 and 3.149, respectively). Paternal smoking and alcohol consumption prior to conception contribute to an increased risk of allergic rhinitis in children, with the risk being dependent on the dosage and duration of exposure. Therefore, it is important to not only focus on personal and maternal environmental exposures when considering the occurrence risk of allergic rhinitis in children, but also to consider paternal detrimental exposures prior to conception.

Paternal alcohol consumption as a modulator of FASD in a mouse model

Fetal Alcohol Spectrum Disorders (FASDs) include a wide range of mental and physical developmental disabilities that leave a lasting impact across the lifetime. Prenatal alcohol exposure most significantly effects the developing brain and facial characteristics, yet not all alcohol exposed pregnancies result in altered brain and facial morphology. Recent compelling evidence for periconceptional environmental factors experienced by both parents and their influence on offspring health has highlighted the need for further research into paternal contributions to FASD.In order to redress the stigma that FASDs are exclusively the mother’s fault, we sought to investigate the environmentally induced patterns of inheritance contributed by both the mother and father as well as their interaction in the establishment of FASD outcomes. We hypothesized that FASD-associated developmental defects would become exacerbated in a dual parental model of alcohol consumption. To test this hypothesis, we exposed both male and female adult C57BL/6J mice to either control or alcohol (10% EtOH) preconception treatment groups using the Drinking in the Dark method of voluntary alcohol consumption. A mating paradigm was used in order to generate control, maternal, paternal, and dual parental alcohol-exposed litters. Upon pregnancy diagnosis on gestational day 10, pregnant females were removed from treatment exposures and the litters were either dissected during late gestation or allowed to continue to birth for postnatal investigations. During gestation we found that maternal, paternal, and dual parental alcohol exposures resulted in distinct craniofacial patterning in both sexes and that both craniofacial patterning and neurological development are parental dose dependent. Beyond the gross morphological level, we implemented RNA sequencing and found distinct changes in the cortical transcriptome between sexes and treatment group. Finally, we sought to investigate whether these changes persisted into later life and found that maternal, paternal, and dual parental alcohol exposures produce unique behavioral phenotypes that are age dependent. Specifically, when both parents consume alcohol, behavioral changes (assessed using novel object recognition, a measure of cognition and memory) can be seen earlier in adolescence, while maternal alcohol induced changes become evident later in adolescence. Importantly, dual parental alcohol exposure also led to decreased mobility in later adulthood indicating early onset of disease.In conclusion, these results fill a large gap in our understanding of the penetrance of FASD and describe the wide variation seen in presenting symptoms. Importantly, we identify paternal alcohol consumption as a significant inducer and contributor to FASD phenotypes. Moreover, these results redress the stigma that maternal alcohol is solely to blame for FASD and elucidate the father’s role in FASD outcomes. This work was supported by a Medical Research Grant from the W.M. Keck Foundation and NIH grant R01AA028219 from the NIAAA. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Need for Educational Reform Concerning the Paternal Role in FASD Pathogenesis

Fetal alcohol spectrum disorders (FASD) is an umbrella term for a group of neurodevelopmental impairments caused by prenatal alcohol exposure. FASD pathogenesis often implicates the mother, largely focused on maternal alcohol consumption prior to or during pregnancy. As such, most FASD interventions are geared towards the mother. However, an array of risk factors within the family environment, notably paternal alcohol consumption and attitudes toward maternal consumption during pregnancy, can impact FASD development in the offspring. This paper sheds light on the paternal role in FASD pathogenesis that is rarely discussed and promotes the importance of family-centred interventions. FASD is a preventable disorder: prophylactic measures such as increasing the information and educational resources to reach a larger population could greatly reduce the risk and incidence of FASD.

Transgenerational Abnormalities Induced by Paternal Preconceptual Alcohol Drinking: Findings from Humans and Animal Models.

Alcohol consumption during pregnancy and lactation is a widespread preventable cause of neurodevelopmental impairment in newborns. While the harmful effects of gestational alcohol use have been well documented, only recently, the role of paternal preconceptual alcohol consumption (PPAC) prior to copulating has drawn specific epigenetic considerations. Data from human and animal models have demonstrated that PPAC may affect sperm function, eliciting oxidative stress. In newborns, PPAC may induce changes in behavior, cognitive functions, and emotional responses. Furthermore, PPAC may elicit neurobiological disruptions, visuospatial impairments, hyperactivity disorders, motor skill disruptions, hearing loss, endocrine, and immune alterations, reduced physical growth, placental disruptions, and metabolic alterations. Neurobiological studies on PPAC have also disclosed changes in brain function and structure by disrupting the growth factors pathways. In particular, as shown in animal model studies, PPAC alters brain nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF) synthesis and release. This review shows that the crucial topic of lifelong disabilities induced by PPAC and/or gestational alcohol drinking is quite challenging at the individual, societal, and familial levels. Since a nontoxic drinking behavior before pregnancy (for both men and women), during pregnancy, and lactation cannot be established, the only suggestion for couples planning pregnancies is to completely avoid the consumption of alcoholic beverages.

Impact of paternal alcohol consumption on foetus and adolescence.

Madam, Ethanol being a carcinogen as well as a teratogen agent can be injurious to the consumer but also can induce cognitional impairments in the progeny. However, chronic consumption significantly impacts liver and cardiovascular system leading to alcoholic liver or heart diseases. The alcohol consumption per capita of males in Pakistan is known to be significantly higher than that of women (1). Paternal alcohol consumption has harmful and adverse effects on developing fetus (3), leading to behavioral and intellectual problems within the adolescent age group. Despite its delirious effect, alcohol consumption has increased in Pakistan over the years. The total increase in alcohol consumption per capita (15+) age group has a value of 0.084 from the interval 2000-2018 which is quite significant when compared to Bangladesh which shows a drastic drop to a value of 0.056 in its alcohol consumption per capita in the same time interval (3). As of yet, there is no proper awareness regarding the harmful effects of paternal alcohol consumption in this high risk age group. A study in 2015 suggested that paternal ethanol induces physiologic abnormalities in offspring in the absence of maternal ethanol exposure (2). A prior study published in 1984 also concluded that paternal alcohol usage affects cognitive behavior and decreases the performance of their child (age 16+) with regards to his intelligence (4). Cognitive battery test, showed that sons of alcoholic fathers have a delayed first response time compared with non-alcoholic fathers (p<0.01). According to statistical data by The World Bank in 2018, it was recorded that alcohol consumption rate is 0.57 per capita in males aged (15+) in Pakistan (3), This triggers an alarming situation that the next few generations in Pakistan may face severe consequences of foetal disorders leading to cognitive disabilities in children (age 16+). Physicians should ensure to counsel the couple regarding the adverse effects of alcohol on childbirth and its after-effects in the adolescent age. If planning to conceive, the couple should be mindful of reducing the consumption of alcohol. Moreover, the couple should discuss this matter with the physician if they are chronic alcohol consumers so that they are aware of the consequences of alcohol consumption beforehand. Continuous...

Paternal alcohol consumption has intergenerational consequences in male offspring.

Alcoholism is a heterogeneous set of disorders caused by ethanol intake. Harmful effects of paternal consumption on the offspring are poorly explored and not fully understood. We analyzed the effect of paternal alcohol consumption on both their own reproductive capacity and that of their male offspring. We used a model of ethanol consumption (15% v/v in drinking water) for 12days in adult CF-1 male mice. DNA integrity and post-translational modifications of histones were assessed in sperm; testicular weight, histology, and DNA fragmentation were analyzed. Treated or untreated male mice were mated with non-treated females to obtain two cell embryos that were cultured for 7days; morphology and embryonic cell death were evaluated. Males of both groups were mated with non-treated females. Adult male offspring was euthanized, and sperm and testicular parameters determined. Paternal ethanol consumption caused histological and epigenetic changes, as well as damage in DNA integrity in the testicular germline and sperm. These alterations gave rise to deleterious effects on embryonic development and to testicular and spermatic changes in the offspring. This study provides critical information on reproductive disturbances brought about by paternal alcohol consumption and the profound impact these could have on the male progeny. The need to explore the effects of paternal alcohol consumption in detail and warn about the importance of controlling alcohol intake for the well-being of future generations should not be underscored.

Preconceptional paternal alcohol consumption and the risk of child behavioral problems: a prospective cohort study

Animal studies demonstrated that paternal alcohol exposure before conception increases the risk of adverse neurodevelopment in offspring, but limited evidence is known in humans. Based on Shanghai-Minhang Birth Cohort Study, we aimed to examine associations between preconceptional paternal alcohol consumption and child behavioral problems. Paternal alcohol consumption during the last 3 months before conception was obtained by maternal report. Children born to fathers who drank alcohol at least once a week were classified as exposed. Child behavioral problems were assessed using the Child Behavior Checklist (CBCL) at age of 2, 4, and 6. Negative binomial regression was used to estimate the rate ratio (RR) of CBCL raw scores in 796 offspring. The risks of rating scores on anxious/depressed were increased by 33% (RR 1.33, 95% CI 1.09, 1.61) and 37% (RR 1.37, 95% CI 1.02, 1.84) among boys in the exposed group at age of 4 and 6, respectively. We also found that risks of somatic complaints were increased by 18% (RR 1.18, 95%CI 1.00, 1.40) and 65% (RR 1.65, 95%CI 1.14, 2.38) among girls in the exposed group at age of 4 and 6. The increased risks of sleep problems (RR 1.25, 95% CI 1.00, 1.55) in girls at age 4, thought problems (RR 1.32, 95% CI 1.01, 1.73) in girls at age 6, rule-breaking behaviors (RR 1.35, 95% CI 1.09, 1.67) in boys at age 6 were also found. The risks of CBCL scores on anxious/depressed and sleep problems in girls at age 4, as well as the risks of somatic complaints and rule-breaking behaviors in boys at age 6 increased with the level of exposure to paternal alcohol consumption. Our findings provided preliminary evidence that preconceptional paternal alcohol consumption may increase risks of child behavioral problems.

P-718 Paternal smoking in the preconception period is associated with an increased risk of spontaneous miscarriage in a dose-dependent manner: a systematic review and meta-analysis

Abstract Study question What is the association between paternal lifestyle ­factors in the preconception period and the risk of spontaneous miscarriage? Summary answer Preconception paternal cigarette smoking is associated with an increased risk of spontaneous miscarriage, while no associations were found with paternal alcohol consumption and obesity. What is known already Although maternal lifestyle risk factors for miscarriage are well-established, studies on potentially contributing paternal factors remain sparse. Recently, a significant association was found between advanced paternal age and spontaneous miscarriage. Biological evidence indicates that smoking, excessive alcohol consumption and obesity may lead to sperm oxidative DNA damage, being a known risk factor for miscarriage. Study design, size, duration Systematic review and meta-analysis. Participants/materials, setting, methods PubMed and Embase databases were searched in August 2020. Paternal factors examined were: cigarette smoking, alcohol consumption and Body Mass Index (BMI). A qualitative risk of bias assessment was performed for all included studies. Meta-analysis was performed if sufficient data was available from studies that controlled for maternal factors. PRISMA guidelines for systematic reviews were followed. Main results and the role of chance The systematic search included 3386 articles of which 11 articles met the inclusion criteria. In a meta-analysis of eight studies, paternal smoking of > 10 cigarettes per day in the preconception period was found to be associated with an increased risk of spontaneous miscarriage, after adjustment for maternal smoking status (1-10 cigarettes per day: 1.01, 95% CI 0.97-1.06; 11-20 cigarettes per day: 1.12, 95% CI 1.08-1.16; >20 cigarettes per day: 1.23, 95% CI 1.17-1.29). Based on five available studies, no clear association was found between paternal alcohol consumption and spontaneous miscarriage. No studies were retrieved that evaluated the association between paternal BMI and spontaneous miscarriage. Limitations, reasons for caution Investigating the relation between paternal lifestyle factors and spontaneous miscarriage is challenging and prone to different forms of bias, especially in retrospective studies. Wider implications of the findings Awareness of the association between heavy paternal smoking in the preconception period and the risk of spontaneous miscarriage should be raised. More well-designed studies are needed to further investigate the effects of other paternal lifestyle factors on the risk of spontaneous miscarriage. Trial registration number not applicable

P–718 Paternal smoking in the preconception period is associated with an increased risk of spontaneous miscarriage in a dose-dependent manner: a systematic review and meta-analysis

Abstract Study question What is the association between paternal lifestyle factors in the preconception period and the risk of spontaneous miscarriage? Summary answer: Preconception paternal cigarette smoking is associated with an increased risk of spontaneous miscarriage, while no associations were found with paternal alcohol consumption and obesity. What is known already Although maternal lifestyle risk factors for miscarriage are well-established, studies on potentially contributing paternal factors remain sparse. Recently, a significant association was found between advanced paternal age and spontaneous miscarriage. Biological evidence indicates that smoking, excessive alcohol consumption and obesity may lead to sperm oxidative DNA damage, being a known risk factor for miscarriage. Study design, size, duration: Systematic review and meta-analysis. Participants/materials, setting, methods PubMed and Embase databases were searched in August 2020. Paternal factors examined were: cigarette smoking, alcohol consumption and Body Mass Index (BMI). A qualitative risk of bias assessment was performed for all included studies. Meta-analysis was performed if sufficient data was available from studies that controlled for maternal factors. PRISMA guidelines for systematic reviews were followed. Main results and the role of chance The systematic search included 3386 articles of which 11 articles met the inclusion criteria. In a meta-analysis of eight studies, paternal smoking of > 10 cigarettes per day in the preconception period was found to be associated with an increased risk of spontaneous miscarriage, after adjustment for maternal smoking status (1–10 cigarettes per day: 1.01, 95% CI 0.97–1.06; 11–20 cigarettes per day: 1.12, 95% CI 1.08–1.16; >20 cigarettes per day: 1.23, 95% CI 1.17–1.29). Based on five available studies, no clear association was found between paternal alcohol consumption and spontaneous miscarriage. No studies were retrieved that evaluated the association between paternal BMI and spontaneous miscarriage. Limitations, reasons for caution Investigating the relation between paternal lifestyle factors and spontaneous miscarriage is challenging and prone to different forms of bias, especially in retrospective studies. Wider implications of the findings: Awareness of the association between heavy paternal smoking in the preconception period and the risk of spontaneous miscarriage should be raised. More well-designed studies are needed to further investigate the effects of other paternal lifestyle factors on the risk of spontaneous miscarriage. Trial registration number Not applicable

P–177 Seminal transferrin levels are linked to embryo utilization rates: a prospective observational study

Abstract Study question What is the impact of seminal transferrin level on intracytoplasmic sperm injection (ICSI) cycle outcomes? Summary answer Seminal transferrin levels were positively correlated with embryo utilization rates. What is known already Transferrin, a glycoprotein involved in iron transport throughout the body, is produced by various organs such as liver, central nervous system, and testicules. Particularly, Sertoli cells synthesize transferrin to regulate their phagocytotic activity and to ensure iron transportation to germ cells across the blood-testis barrier. In this context, studies have demonstrated the importance of transferrin and iron in spermatogenesis by detecting low levels of seminal transferrin in oligozoospermic men. However, the effects of low seminal transferrin levels on the functionality of spermatozoa and on their ability to maintain embryo development were neither fully investigated nor well understood. Study design, size, duration A prospective study was conducted at Al Hadi IVF center, Lebanon, from July 2019 until May 2020. It included 60 infertile couples who have undergone ICSI cycles. Couples were categorized into two groups based on basic semen parameters assessed according to the World Health Organization recommendations 2010: normozoospermia group (n = 30 couples) and non-normozoospermia group (n = 30 couples). In this study, non-normozoospermia was defined as the presence of at least one abnormality in basic semen parameters. Participants/materials, setting, methods In this prospective study, the inclusion criteria were: couples where women had 38 years old or less at the time of ICSI, using fresh gametes, and using ejaculated semen. Moreover, women with premature ovarian failure, obese women, and ICSI cycles with embryo biopsy were excluded. Seminal levels of transferrin and iron were measured using Cobas 400 plus (Roche Diagnostics). Fertilization rates, embryo utilization rates, and live birth rates were calculated. Main results and the role of chance There were no statistically significant differences in the characteristics of the study population (maternal age, paternal age, maternal body mass index (BMI), paternal BMI, maternal and paternal tobacco intake, maternal and paternal alcohol consumption, number of collected oocytes and number of embryos transferred) (p > 0.05) between normozoospermia and non-normozoospermia groups. A statistically significant difference was detected in seminal transferrin levels (mg/dl) (2(0–23) vs. 1(0–6), p < 0.02) between the two groups. Interestingly, these transferrin levels were positively correlated with sperm concentration (R = 0.29; p = 0.03). In parallel, no statistically significant difference was observed between groups concerning seminal iron levels (µg/dl) (51(21.1–100.8) vs. 48.6 (11–85.7); p = 0.33). Furthermore, there was no statistically significant difference in the fertilization rates (%) between the two groups (74.2 vs. 74.8; p = 0.95). Of particular interest, a statistically significant positive correlation was detected between seminal transferrin levels and embryo utilization rates (R = 0.33; p = 0.013). In contrast, the live birth rates (%) were not different between groups (54.54 vs. 58.3; p = 0.77) and were not correlated with seminal transferrin levels (R=–0.3; p = 0.16). Limitations, reasons for caution A prospective study with a larger sample size is required to confirm the effects of seminal transferrin levels on assisted reproductive technology outcomes. Wider implications of the findings: Deciphering the molecular mechanism by which transferrin level may influence spermatozoa quality and subsequently embryo development will be of paramount importance. Moreover, understanding the reasons behind the altered seminal transferrin level and testing several strategies to restore it, may enhance spermatozoa quality and increase pregnancy chances. Trial registration number Not applicable

Paternal smoking is associated with an increased risk of pregnancy loss in a dose-dependent manner: a systematic review and meta-analysis

<h3>Objective</h3> To study the association between paternal lifestyle factors in the preconception period and the risk of pregnancy loss. <h3>Evidence Review</h3> The Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines for systematic reviews and meta-analysis were followed. PubMed and Embase databases were searched up to August 2020. Original articles in English language addressing the relation between paternal exposure status in the preconception period and pregnancy loss were included. The paternal lifestyle factors examined were smoking, alcohol consumption, and body mass index. Studies that only examined exposure status during pregnancy (and not in the preconception period) and those that solely focused on pregnancy outcome after artificial reproductive technology were excluded. The qualitative risk of bias assessments was performed. Meta-analysis using a random-effects model was performed if sufficient data were available, with the risk of pregnancy loss as the primary outcome. <h3>Results</h3> The systematic search included 3,386 articles, of which 11 met the inclusion criteria. In a meta-analysis of 8 studies, paternal smoking of >10 cigarettes per day in the preconception period was found to be associated with an increased risk of pregnancy loss, after adjustment for maternal smoking status (1–10 cigarettes per day, 1.01; 95% confidence interval [CI], 0.97–1.06; 11–19 cigarettes per day, 1.12; 95% CI, 1.08–1.16; ≥20 cigarettes per day, 1.23; 95% CI, 1.17–1.29). No clear association was found between paternal alcohol consumption and pregnancy loss, based on 5 available studies. No studies were identified evaluating the association between paternal body mass index and spontaneous pregnancy loss. <h3>Conclusion</h3> Awareness of the association between paternal smoking in the preconception period and the risk of pregnancy loss should be raised. More well-designed studies are needed to further investigate the effects of other paternal lifestyle factors on the risk of pregnancy loss.

Altered Developmental Programming in a Dual Model of Maternal and Paternal Alcohol Consumption

According to the CDC, Fetal Alcohol Spectrum Disorders (FASDs) are a group of conditions that can occur in a person whose mother drank alcohol during pregnancy. This definition places the fault for FASD-associated mental and physical defects exclusively on the mother. However, emerging research can now link preconception paternal environmental exposures and lifestyle choices with several disease states within the offspring. Despite the efforts to recognize paternal epigenetic contributions, research examining congenital disabilities is limited and remains exclusively focused on maternal exposures. We hypothesized that FASD-associated developmental defects would become exacerbated in a dual parental model of alcohol consumption. To investigate the contributions of dual parental ethanol (EtOH) exposure on offspring development, we exposed C57BL/6J adult [postnatal day (PND) 90] males and females to either control or alcohol (10% EtOH) treatments using the Drinking in the Dark (DID) method. After a preconception treatment period of 6 weeks for males and ten days for females, we mated exposed mice. Pregnancies were confirmed by weight gain at gestational day (GD) 10. Pregnant females ceased alcohol treatments at gestational day ten, and we terminated pregnancies at either GD 16.5 or 18.5. We examined morphometric measures of fetal development and 2D images of the placenta and craniofacial features. From these studies, we find that each exposure source (maternal, paternal, or dual parental) exhibits its unique growth and craniofacial phenotype. This finding draws attention to the need for a thorough investigation of both parents' exposure history when determining the child's overall health status. It also emphasizes that the presence of a defect does not mean that the blame lies solely with the mother. Instead, it might be the combinatorial effect of both parents' life exposures before conception.

DETERMINANTS OF LITHUANIAN PATERNAL AND SPOUSAL TIME ALLOCATION WITH CHILDREN

This article analyzes paternal time allocation with children in Lithuania and explores paternal and spousal cross effects in time investment. Effects of paternal health status, alcohol consumption and health insurance status on paternal-child time allocation are also examined. The research finds a modest after-tax family income effect for paternal time, but not when examining paternal-spousal cross effects for child time investment. Regarding paternal-spousal cross effects, while both are very highly significant statistically, this research finds almost twice the complementarity for the Lithuanian paternal hour with children for spousal time with children than for a spousal hour for paternal time with children. The paper identifies several possible factors in the Lithuanian context contributing to a complementary effect and away from a substitutionary effect. Spousal age and educational effects – the former negative, the latter positive – are found for spousal time allocation with children but not found significant paternally. To our knowledge this is the first study to examine paternal time allocation in Lithuania for children including health status, alcohol consumption, insurance status and paternal/spousal cross effects for time allocation with children. Compared to our previous research, it also supports caution against assuming that parental cross effects on time allocation in a Lithuanian social context mirror such in the U.S.

Association of Preconception Paternal Alcohol Consumption With Increased Fetal Birth Defect Risk

This cohort study investigates the association of paternal drinking before pregnancy with risk of fetal birth defect.

Factors Associated with Congenital Heart Diseases among Children in Uganda: A Case-Control Study at Mulago National Referral Hospital (Uganda Heart Institute)

Congenital Heart Diseases (CHD) are among the leading causes of morbidity and mortality associated with congenital malformations among children. Not knowing the risk profile of CHD among children in Uganda impedes development of effective prevention interventions. In this hospital based unmatched case-control study we examined risk factors for all types of CHD among 179 pair of case and control children aged 0-10 years old at Mulago National Referral Hospital. Odds ratios and their corresponding 95% confidence intervals were calculated using multivariate logistic regression. Low birth weight (adjusted OR: 3.15, 95% CI 1.48 - 6.69), high birth order ≥5^th birth order (adjusted OR: 3.69 (1.10 – 12.54), maternal febrile illness during pregnancy, maternal and paternal alcohol consumption, and paternal socio-economic status were associated with CHD. Family history of CHD, maternal education level, maternal chronic illness, and paternal education level were not associated with CHD. The results suggest: low birth weight, high birth order, and maternal febrile illness during pregnancy, parental alcohol use and paternal socio-economic status as dominant risk factors for CHD among children. Rigorous implementation of public health policies and strategies targeting prevention of febrile illness during pregnancy, maternal malnutrition, parental alcohol consumption, delivery of high number of children per woman, might be important in reducing the burden of CHD among children in Uganda.