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Background: Parental allergic diseases and smoking influence respiratory disease in the offspring but it is not known whether they influence fractional exhaled nitric oxide (FeNO) in the offspring. We investigated whether parental allergic diseases, parental smoking and FeNO levels in parents were associated with FeNO levels in their offspring. Methods: We studied 609 offspring aged 16–47 years from the Respiratory Health in Northern Europe, Spain and Australia generation (RHINESSA) study with parental information from the Respiratory Health in Northern Europe (RHINE) III study and the European Community Respiratory Health Survey (ECRHS) III. Linear regression models were used to assess the association between offspring FeNO and parental FeNO, allergic rhinitis, asthma and smoking, while adjusting for potential confounding factors. Results: Parental allergic rhinitis was significantly associated with higher FeNO in the offspring, both on the paternal and maternal side (percent change: 20.3 % [95%CI 5.0–37.7], p = 0.008, and 13.8 % [0.4–28.9], p = 0.043, respectively). Parental allergic rhinitis with asthma in any parent was also significantly associated with higher offspring FeNO (16.2 % [0.9–33.9], p = 0.037). However, parental asthma alone and smoking were not associated with offspring FeNO. Parental FeNO was not associated with offspring FeNO after full adjustments for offspring and parental factors. Conclusions: Parental allergic rhinitis but not parental asthma was associated with higher levels of FeNO in offspring. These findings suggest that parental allergic rhinitis status should be considered when interpreting FeNO levels in offspring beyond childhood.

Background: Stress hurts problem-solving abilities, while anxiety disorders and depression are associated with unpleasant feelings and impaired daily functioning. Open field test (OFT) is used to assess anxiety-like behavior in animals by observing their exploratory behavior. Pregnant women are vulnerable to stress, which increases the risk of premature birth and low birth weight. Stress during pregnancy can also lead to preeclampsia and behavioural problems in newborns. Selective serotonin reuptake inhibitors (SSRIs), commonly used antidepressants during pregnancy, help manage mental disorders by increasing serotonin levels and regulating the endocrine system. They reduce glucocorticoid levels, thereby alleviating anxiety and stress in pregnant women. Objectives: This research investigates the correlation between the administration of SSRIs to stress-induced expectant mothers, the manifestation of depression-like behaviour, and the expression of glucocorticoid receptors in the offspring's hippocampus. Material and Methods: This study included four mouse groups: control without stress, control with offspring stress, stress model with footshock on dams and o ffspring, and stress with fluvoxamine treatment. Depressive and stress-related behaviors were measured using OFT. Results: OFT was used to assess the behaviour of offspring mice. Significant differences were observed in the number of crossings in the centre area and behaviour. The SSRI treatment showed potential anxiolytic effects, while stress led to reduced behaviour. These findings contribute to understanding anxiety-related responses and the effects of stress and SSRI treatment in animal models. Conclusions: OFT revealed significant differences in anxiety behaviour, specifically in the number of crossing centres, the centre area, and behaviour. SSRI treatment exhibited anxiolytic effects, while stress-decreased behaviour findings enhanced our understanding of anxiety responses and the impact of stress and SSR

Background: The association between intra-uterine exposure to maternal smoking and risk of multiple sclerosis (MS) has been little studied and with conflicting results. Objective: To examine the risk of MS in offspring exposed intra-uterine to maternal smoking. In addition, to re-examine prior observations of an elevated risk of MS among smokers, assuming that self-reported smoking during pregnancy reflects the woman’s general smoking habits. Methods: The study cohort included all Danish women, pregnant in the period 1991–2018, (n = 789,299) and singletons from these pregnancies (n = 879,135). Nationwide information on maternal smoking during pregnancy and MS cases in the study cohort were obtained from the Medical Birth Register and the National Patient Register. Cox regression analysis was used to estimate hazard ratios (HRs) for the association between smoking and MS risk. Results: Women who smoked during pregnancy had a 42% increased risk of developing MS compared with non-smoking women (HR = 1.42 (1.32–1.52), n = 1,296). The risk of MS among singletons of women who smoked during pregnancy was 38% higher than that among singletons born to non-smoking women (HR = 1.38 (1.08–1.76), n = 110). Conclusion: Our observations add further to the evidence implicating smoking in the development of MS and suggest that intra-uterine exposure to tobacco smoke may increase MS risk., Background: The association between intra-uterine exposure to maternal smoking and risk of multiple sclerosis (MS) has been little studied and with conflicting results. Objective: To examine the risk of MS in offspring exposed intra-uterine to maternal smoking. In addition, to re-examine prior observations of an elevated risk of MS among smokers, assuming that self-reported smoking during pregnancy reflects the woman’s general smoking habits. Methods: The study cohort included all Danish women, pregnant in the period 1991–2018, (n = 789,299) and singletons from these pregnancies (n = 879,135). Nationwide information on maternal smoking during pregnancy and MS cases in the study cohort were obtained from the Medical Birth Register and the National Patient Register. Cox regression analysis was used to estimate hazard ratios (HRs) for the association between smoking and MS risk. Results: Women who smoked during pregnancy had a 42% increased risk of developing MS compared with non-smoking women (HR = 1.42 (1.32–1.52), n = 1,296). The risk of MS among singletons of women who smoked during pregnancy was 38% higher than that among singletons born to non-smoking women (HR = 1.38 (1.08–1.76), n = 110). Conclusion: Our observations add further to the evidence implicating smoking in the development of MS and suggest that intra-uterine exposure to tobacco smoke may increase MS risk.

Objective Offspring of parents with schizophrenia spectrum disorders (SSD) have an increased risk of neurodevelopmental disturbances. However, the ability to provide very early interventions to support these children and their families requires profound knowledge regarding characteristic features of both the parents and their offspring. Information on this subject is currently sparse. The aim of the present study is to investigate clinical and sociodemographic variables in offspring in the age range of 0–3 years of mothers diagnosed with SSD. Methods The study is descriptive with a cross-sectional design and includes parent-child dyads consisting of mothers diagnosed with SSD (ICD-10: F20-29) and their offspring aged 0-3 years, who were referred for examination and intervention at the infant and toddler psychiatric units, at the Mental Health Services, Capital Region, Copenhagen University Hospitals in two locations (Bispebjerg and Glostrup). Clinical and sociodemographic data were extracted from the Copenhagen “Infant Psychiatric Database” and processed by descriptive analysis. Results Out of 95 parent–child dyads considered for the study population, 85 were included. 27.8% of the mothers had psychiatric comorbidities, and 18.9% of the fathers had a psychiatric diagnosis at the time of investigation. Of the children, 89.7% were born full term (≥37th week) and most of them had a birth weight of ≥2500 g (81.8%). Of the mothers, 50% had experienced pregnancy complications of varying severity. Birth complications were seen in 62.9% of the dyads. Psychopathology was identified in 50% of the children at age 0–3 years, and 62.2% of the parent–child dyads appeared to have an affected relationship. Conclusion Results show widespread psychopathology in offspring aged 0–3 years of mothers with SSD. Moreover, several psychosocial stressors, clinical parental features, and relational disturbances are identified. These results contribut, Objective: Offspring of parents with schizophrenia spectrum disorders (SSD) have an increased risk of neurodevelopmental disturbances. However, the ability to provide very early interventions to support these children and their families requires profound knowledge regarding characteristic features of both the parents and their offspring. Information on this subject is currently sparse. The aim of the present study is to investigate clinical and sociodemographic variables in offspring in the age range of 0–3 years of mothers diagnosed with SSD. Methods: The study is descriptive with a cross-sectional design and includes parent-child dyads consisting of mothers diagnosed with SSD (ICD-10: F20-29) and their offspring aged 0-3 years, who were referred for examination and intervention at the infant and toddler psychiatric units, at the Mental Health Services, Capital Region, Copenhagen University Hospitals in two locations (Bispebjerg and Glostrup). Clinical and sociodemographic data were extracted from the Copenhagen “Infant Psychiatric Database” and processed by descriptive analysis. Results: Out of 95 parent–child dyads considered for the study population, 85 were included. 27.8% of the mothers had psychiatric comorbidities, and 18.9% of the fathers had a psychiatric diagnosis at the time of investigation. Of the children, 89.7% were born full term (≥37th week) and most of them had a birth weight of ≥2500 g (81.8%). Of the mothers, 50% had experienced pregnancy complications of varying severity. Birth complications were seen in 62.9% of the dyads. Psychopathology was identified in 50% of the children at age 0–3 years, and 62.2% of the parent–child dyads appeared to have an affected relationship. Conclusion: Results show widespread psychopathology in offspring aged 0–3 years of mothers with SSD. Moreover, several psychosocial stressors, clinical parental features, and relational disturbances are identified. These results contribute to a better understanding and iden

Background and Hypothesis Individuals with schizophrenia or bipolar disorder have attenuated auditory mismatch negativity (MMN) responses, indicating impaired sensory information processing. Computational models of effective connectivity between brain areas underlying MMN responses show reduced connectivity between fronto-temporal areas in individuals with schizophrenia. Here we ask whether children at familial high risk (FHR) of developing a serious mental disorder show similar alterations. Study Design We recruited 67 children at FHR for schizophrenia, 47 children at FHR for bipolar disorder as well as 59 matched population-based controls from the Danish High Risk and Resilience study. The 11–12-year-old participants engaged in a classical auditory MMN paradigm with deviations in frequency, duration, or frequency and duration, while we recorded their EEG. We used dynamic causal modeling (DCM) to infer on the effective connectivity between brain areas underlying MMN. Study Results DCM yielded strong evidence for differences in effective connectivity among groups in connections from right inferior frontal gyrus (IFG) to right superior temporal gyrus (STG), along with differences in intrinsic connectivity within primary auditory cortex (A1). Critically, the 2 high-risk groups differed in intrinsic connectivity in left STG and IFG as well as effective connectivity from right A1 to right STG. Results persisted even when controlling for past or present psychiatric diagnoses. Conclusions We provide novel evidence that connectivity underlying MMN responses in children at FHR for schizophrenia and bipolar disorder is altered at the age of 11–12, echoing findings that have been found in individuals with manifest schizophrenia., BACKGROUND AND HYPOTHESIS: Individuals with schizophrenia or bipolar disorder have attenuated auditory mismatch negativity (MMN) responses, indicating impaired sensory information processing. Computational models of effective connectivity between brain areas underlying MMN responses show reduced connectivity between fronto-temporal areas in individuals with schizophrenia. Here we ask whether children at familial high risk (FHR) of developing a serious mental disorder show similar alterations. STUDY DESIGN: We recruited 67 children at FHR for schizophrenia, 47 children at FHR for bipolar disorder as well as 59 matched population-based controls from the Danish High Risk and Resilience study. The 11-12-year-old participants engaged in a classical auditory MMN paradigm with deviations in frequency, duration, or frequency and duration, while we recorded their EEG. We used dynamic causal modeling (DCM) to infer on the effective connectivity between brain areas underlying MMN. STUDY RESULTS: DCM yielded strong evidence for differences in effective connectivity among groups in connections from right inferior frontal gyrus (IFG) to right superior temporal gyrus (STG), along with differences in intrinsic connectivity within primary auditory cortex (A1). Critically, the 2 high-risk groups differed in intrinsic connectivity in left STG and IFG as well as effective connectivity from right A1 to right STG. Results persisted even when controlling for past or present psychiatric diagnoses. CONCLUSIONS: We provide novel evidence that connectivity underlying MMN responses in children at FHR for schizophrenia and bipolar disorder is altered at the age of 11-12, echoing findings that have been found in individuals with manifest schizophrenia.

Background Knowledge of the association between parental personality disorders and mental disorders in children is limited. To examine the association between parental personality disorders and the risk of mental disorders in offspring. Methods We linked Danish health registers to create a cohort of children born from January 1, 1995, to December 31, 2016. Children were followed until their 18th birthday, diagnosis set, emigration, death, or December 31, 2016. Parental personality disorders according to the International Classification of Diseases (ICD) Eighth or 10th Revision. Poisson regression analyses were used to estimate the incidence risk ratio (IRR) and cumulative incidence of ICD 10th mental disorders in offspring (age 0–17). Results The study cohort included 1,406,965 children. For girls, maternal or paternal personality disorder (MPD/PPD) was associated with mental disorders: MPD girls (IRR, 2.74; 95% CI, 2.59–2.89) and PPD girls (IRR, 2.10; 95% CI, 1.94–2.27). Likewise, the risk was increased for both MPD boys (IRR, 2.44; 95% CI, 2.33–2.56) and PPD boys (IRR, 2.04; 95% CI, 1.91–2.18). For girls and boys combined, exposure to two parents with a personality disorder was associated with the highest risk (IRR, 3.69; 95% CI, 3.15–4.33). At age 18, the cumulative incidence of any mental disorder in children of one or two parents with a personality disorder was 34.1% (95% CI, 33.0–35.1), which was twice the cumulative incidence of mental disorders in nonexposed children (15.2% [95% CI, 15.1–15.3]). Conclusion Children of parents with a personality disorder were at a 2 to 3.5 times higher risk of mental disorders compared with nonexposed offspring. Possible mechanisms of transmission of mental disorders from parent to child involve genetic, environmental, and gene–environment pathways. More research into these mechanisms and research into preventive interventions is warranted., Background: Knowledge of the association between parental personality disorders and mental disorders in children is limited. To examine the association between parental personality disorders and the risk of mental disorders in offspring. Methods: We linked Danish health registers to create a cohort of children born from January 1, 1995, to December 31, 2016. Children were followed until their 18th birthday, diagnosis set, emigration, death, or December 31, 2016. Parental personality disorders according to the International Classification of Diseases (ICD) Eighth or 10th Revision. Poisson regression analyses were used to estimate the incidence risk ratio (IRR) and cumulative incidence of ICD 10th mental disorders in offspring (age 0–17). Results: The study cohort included 1,406,965 children. For girls, maternal or paternal personality disorder (MPD/PPD) was associated with mental disorders: MPD girls (IRR, 2.74; 95% CI, 2.59–2.89) and PPD girls (IRR, 2.10; 95% CI, 1.94–2.27). Likewise, the risk was increased for both MPD boys (IRR, 2.44; 95% CI, 2.33–2.56) and PPD boys (IRR, 2.04; 95% CI, 1.91–2.18). For girls and boys combined, exposure to two parents with a personality disorder was associated with the highest risk (IRR, 3.69; 95% CI, 3.15–4.33). At age 18, the cumulative incidence of any mental disorder in children of one or two parents with a personality disorder was 34.1% (95% CI, 33.0–35.1), which was twice the cumulative incidence of mental disorders in nonexposed children (15.2% [95% CI, 15.1–15.3]). Conclusion: Children of parents with a personality disorder were at a 2 to 3.5 times higher risk of mental disorders compared with nonexposed offspring. Possible mechanisms of transmission of mental disorders from parent to child involve genetic, environmental, and gene–environment pathways. More research into these mechanisms and research into preventive interventions is warranted.

Nowadays there is an increasing concern about exposition during prenatal stage to environmental pollutants such as metals, that make pregnant women a vulnerable group of population. Numerous studies have shown associations between the prenatal exposition to some metals and an impact on cognitive, motor and intellectual development of the child. Metals and metalloid are ubiquitous in the environment and pregnant women are exposed to them though their diet, lifestyle factors or occupational and environmental sources. One hundred of maternal and one hundred of cord blood samples were obtained at delivery from pregnant women after signing of the informed consent to determine simultaneously levels of Al, As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Se and Zn by ICP-MS. Among these metals, essential ones (Cu, Mn, Se and Zn) can have health beneficial effects at low levels, however, in high concentration are potentially toxic. On the other hand, elements such as Al, As, Cd, Hg, Pb are classified as toxic metals, no matter what its concentration was. The aim of this study was to find the potential relationships between these metals and metalloid levels, newborn's parameters, pregnancy details and the epidemiologic information obtained using a questionnaire data from the participant pregnant women from Seville (Spain). A n = 100 of participants have been enrolled, 15.6 % of the women from Virgen del Rocio Hospital were smokers during pregnancy but only 11.1 % from Virgen de Valme had the habit. Dietary habits of all participants from both hospital were quite similar in average rice, fish and canned food consumption. The characteristics of newborns were also quite similar for both hospitals. A positive correlation between maternal and cord blood was found between all metals except for Cr and Cu. The strongest correlation was found for Hg (r = 0.779, p < 0.005). Positive but weaker correlations between maternal blood and lifestyle habits were also established.

Nowadays there is an increasing concern about exposition during prenatal stage to environmental pollutants such as metals, that make pregnant women a vulnerable group of population. Numerous studies have shown associations between the prenatal exposition to some metals and an impact on cognitive, motor and intellectual development of the child. Metals and metalloid are ubiquitous in the environment and pregnant women are exposed to them though their diet, lifestyle factors or occupational and environmental sources. One hundred of maternal and one hundred of cord blood samples were obtained at delivery from pregnant women after signing of the informed consent to determine simultaneously levels of Al, As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Se and Zn by ICP-MS. Among these metals, essential ones (Cu, Mn, Se and Zn) can have health beneficial effects at low levels, however, in high concentration are potentially toxic. On the other hand, elements such as Al, As, Cd, Hg, Pb are classified as toxic metals, no matter what its concentration was. The aim of this study was to find the potential relationships between these metals and metalloid levels, newborn's parameters, pregnancy details and the epidemiologic information obtained using a questionnaire data from the participant pregnant women from Seville (Spain). A n = 100 of participants have been enrolled, 15.6 % of the women from Virgen del Rocio Hospital were smokers during pregnancy but only 11.1 % from Virgen de Valme had the habit. Dietary habits of all participants from both hospital were quite similar in average rice, fish and canned food consumption. The characteristics of newborns were also quite similar for both hospitals. A positive correlation between maternal and cord blood was found between all metals except for Cr and Cu. The strongest correlation was found for Hg (r = 0.779, p < 0.005). Positive but weaker correlations between maternal blood and lifestyle habits were also established.

Purpose of review. This review summarizes the latest scientific evidence, primarily from systematic reviews/meta-analyses and large cohort studies, on the impact of health issues among women of childbearing age and their effect on their offspring during pregnancy and from birth to adulthood. Recent findings. Women of childbearing age with overweight/obesity, diabetes and hypertension prior to pregnancy are at increased risk for adverse outcomes during pregnancy, such as excessive gestational weight gain, gestational diabetes mellitus and hypertensive disorders of pregnancy. These adverse outcomes could complicate delivery and put their offspring at risk of developing overweight/obesity, diabetes and hypertension (i.e., intergenerational transmission of health issues). Summary. Interventions should target women of childbearing age, especially those who wish to conceive, in order to possibly stop the transmission of women’s health issues to the offspring and favor a healthy pregnancy from the start. This could be one of the best strategies to promote both maternal and child health.

Epigenetic mechanisms are important modulators of neurodevelopmental outcomes in the offspring of animals challenged during pregnancy. Pregnant sows living in a confined environment are challenged with stress and lack of stimulation which may result in the expression of stereotypies (repetitive behaviours without an apparent function). Little attention has been devoted to the postnatal effects of maternal stereotypies in the offspring. We investigated how the environment and stereotypies of pregnant sows affected the neuro-epigenome of their piglets. We focused on the amygdala, frontal cortex, and hippocampus, brain regions related to emotionality, learning, memory, and stress response. Differentially methylated regions (DMRs) were investigated in these brain regions of male piglets born from sows kept in an enriched vs a barren environment. Within the latter group of piglets, we compared the brain methylomes of piglets born from sows expressing stereotypies vs sows not expressing stereotypies. DMRs emerged in each comparison. While the epigenome of the hippocampus and frontal cortex of piglets is mainly affected by the maternal environment, the epigenome of the amygdala is mainly affected by maternal stereotypies. The molecular pathways and mechanisms triggered in the brains of piglets by maternal environment or stereotypies are different, which is reflected on the differential gene function associated to the DMRs found in each piglets' brain region . The present study is the first to investigate the neuro-epigenomic effects of maternal enrichment in pigs' offspring and the first to investigate the neuro-epigenomic effects of maternal stereotypies in the offspring of a mammal.

Coprophagy is a behavior where animals consume feces, and has been observed across a wide range of species, including birds and mammals. The phenomenon is particularly prevalent in juveniles, but the reasons for this remain unclear. One hypothesis is that coprophagy enables offspring to acquire beneficial gut microbes that aid development. However, despite the potential importance of this behavior, studies investigating the effects in juveniles are rare. Here we experimentally test this idea by examining how ingestion of adult feces by ostrich chicks affects their gut microbiota development, growth, feeding behavior, pathogen abundance, and mortality. We conducted extensive longitudinal experiments for 8 weeks, repeated over 2 years. It involved 240 chicks, of which 128 were provided daily access to fresh fecal material from adults and 112 were simultaneously given a control treatment. Repeated measures, behavioral observations, and DNA metabarcoding of the microbial gut community, both prior to and over the course of the experiment, allowed us to evaluate multiple aspects of the behavior. The results show that coprophagy causes (a) marked shifts to the juvenile gut microbiota, including a major increase in diversity and rapid maturation of the microbial composition, (b) higher growth rates (fecal-supplemented chicks became 9.4% heavier at 8 weeks old), (c) changes to overall feeding behavior but no differences in feed intake, (d) lower abundance of a common gut pathogen (Clostridium colinum), and (e) lower mortality associated with gut disease. Together, our results suggest that the behavior of coprophagy in juveniles is highly beneficial and may have evolved to accelerate the development of gut microbiota.

Study questionsThe primary objective of this study is to determine what parental factors or specific ART may influence the risk for adverse cardiometabolic outcomes among children so conceived and their parents. The secondary objective of this study is to prospectively examine the effects of infertility or ART on the intrauterine environment, obstetric and neonatal outcomes.What is known alreadyPregnancies conceived with ART are at an increased risk of being affected by adverse obstetric and neonatal outcomes when compared to spontaneously conceived (SC) pregnancies among fertile women. Small cohort studies have suggested ART-conceived children may have a higher risk of long-term cardiometabolic disturbances as well. Currently, few studies have compared long-term cardiometabolic outcomes among ART-conceived children and non-IVF treated (NIFT) children, to children conceived spontaneously to parents with infertility (subfertile parents).Study design size durationThe Developmental Epidemiological Study of Children born through Reproductive Technologies (DESCRT) is a prospective cohort study that aims to: establish a biobank and epidemiological cohort of children born to subfertile or infertile parents who either conceived spontaneously (without assistance) or used reproductive technologies to conceive (all offspring were from couples assessed and/or treated in the same institute); prospectively examine the effects of infertility or ART on the intrauterine environment, obstetric and neonatal outcomes; and determine what parental factors or ART may influence the cardiometabolic risk of children so conceived. Pregnancies and resultant children will be compared by mode of conception, namely offspring that were conceived without medical assistance or SC or following NIFT, IVF with fresh embryo transfer or frozen embryo transfer (FET), and by fertilization method (conventional versus ICSI). DESCRT has a Child group evaluating long-term outcomes of children as well as a Preg

We present the first description of a diurnal live birth of a wild black howler monkey (Alouatta pigra). The mother formed part of a group of five individuals inhabiting an anthropogenic setting in the tropical lowlands of southeast Mexico. A total of 7 h and 50 min passed from the rupture of the amniotic sac early in the day to the crowning of the infant from the birth canal. The delivery of the infant lasted ~ 3 min. We describe the event while referencing images and time points in a supplementary video recording. We place our findings in the context of the available reports of live births in the Alouatta genus, time of day, birth duration, and group activity budget on the day of the birth. While primates tend to give birth at night to reduce complications from group interactions, the observed birth took place during the day, which may have been possible due to an alteration in group time allocation. Our report provides in-depth details of the events of a birth and important information regarding the natural history of the black howler monkey.

Aims: To compare body composition, visceral adiposity, adipocytokines, and low-grade inflammation markers in prepubertal offspring of mothers who were treated with metformin or insulin for gestational diabetes mellitus (GDM). Methods: 172 offspring of 311 mothers randomized to receive metformin (n = 82) or insulin (n = 90) for GDM were studied at 9 years of age (follow-up rate 55%). Measurements included anthropometrics, adipocytokines, markers of the low-grade inflammation, abdominal magnetic resonance imaging (MRI), magnetic liver spectrometry (MRS), and whole body dual-energy X-ray absorptiometry (DXA). Results: Serum markers of low-grade inflammation, visceral adipose tissue volume, total fat percentage, and liver fat percentage were similar between the study groups. Serum adiponectin concentration was higher in children in the metformin group compared to insulin group (median 10.37 vs 9.50 µg/ml, p = 0.016). This difference between groups was observed in boys only (median 12.13 vs 7.50 µg/ml, p < 0.001). Leptin/adiponectin-ratio was lower in boys in the metformin group than in the insulin group (median 0.30 vs 0.75; p = 0.016). Conclusions: Maternal metformin treatment for GDM had no effects on adiposity, body composition, liver fat, or inflammation markers in prepubertal offspring compared to maternal insulin treatment but was associated with higher adiponectin concentration and lower leptin/adiponectin-ratio in boys.

Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health.

Among the activities essential to the survival and equilibrium of Callipolis, the city described in the Republic, political and military functions occupy a predominant place. To this extent, their exercise is conditional on the possession of a certain number of physical, moral and intellectual qualities, among which is a proportionate mixture of two opposing character traits: gentleness and aggressiveness. To confirm the coexistence of this curious mixture in an individual, Socrates evokes the image of a pedigree dog, in which the coexistence of these two qualities is expressed in its docility towards its masters and its hostility towards strangers. The image of the dog plays a decisive role in the Republic in that it allows Socrates to demonstrate the naturalness of his project and to justify the radical methods for perfecting the genos assigned to political and military functions. The aim of this article is to analyse the theoretical implications of the use of this image as a model of the political order and the way of life of the guardians of the Republic and the way in which this image intervenes in the construction of a conception of physis which, far from being univocal, varies according to the needs of the Socratic argument., Parmi les activités indispensables à la survie et à l’équilibre de Callipolis, la cité décrite dans la République, les fonctions politiques et militaires occupent une place prépondérante. Dans cette mesure, leur exercice est conditionné à la possession d’un certain nombre de qualités physiques, morales et intellectuelles parmi lesquelles un mélange proportionné de deux traits de caractère opposées : la douceur et l’agressivité. Pour confirmer la coexistence de ce curieux mélange chez un individu, Socrate évoque l'image d'un chien de race, chez qui la coexistence de ces deux qualités s’exprime dans sa docilité envers ses maîtres et son hostilité envers les étrangers. L’image du chien joue un roll décisif dans la République en ce qu’elle permet à Socrate de démontrer le caractère naturel de son projet et de justifier la radicalité des méthodes destinées au perfectionnement du génos affecté aux fonctions politiques et militaires. L’objectif de cet article est d’analyser les incidences théoriques de l’emploi de cette image comme modèle de l’ordre politique et du genre de vie des gardiens de la République et la manière dont cette image intervient dans la construction d’une conception de la phusis qui, loin d’être univoque, varie selon les besoins de l’argumentation socratique.

Background The home environment has a major impact on child development. Parental severe mental illness can pose a challenge to the home environment of a child. We aimed to examine the home environment of children of parents with schizophrenia or bipolar disorder and controls longitudinally through at-home assessments. Methods Assessments were conducted within The Danish High Risk and Resilience Study, a nationwide multi-center cohort study of children of parents with schizophrenia or bipolar disorder and population-based controls. The level of at-home stimulation and support was measured at age 7 (N = 508 children) and age 11 (N = 430 children) with the semi-structured HOME Inventory. Results from the 11-year follow-up study were analyzed and compared with 7-year baseline results to examine change across groups. Results At age 11, children of parents with schizophrenia and bipolar disorder had lower levels of stimulation and support than controls (mean (s.d.) = 46.16 (5.56), 46.87 (5.34) and 49.25 (4.37) respectively, p < 0.001). A higher proportion of children with parental schizophrenia or bipolar disorder lived in inadequate home environments at age 11, compared with controls (N (%) = 24 (15.0), 12 (12.2) and 6 (3.5) respectively, p < 0.003). The changes in home environment scores did not differ across groups from age 7 to age 11. Conclusions Assessed longitudinally from the children's age of 7 to 11, children of parents with schizophrenia or bipolar disorder had lower levels of stimulation and support in their homes than controls. Integrated support which can target practical, economic, social and health issues to improve the home environment is indicated.

Parental asthma or allergy have been linked to higher risk of asthma in a child; this occurs to a variable extent in different study populations. Moreover, it is debated whether maternal more so than paternal asthma history is a stronger predisposing factor: while in some countries/populations the maternal effect was clearly seen over paternal, in others the parental effects were equivalent, and in a few studies paternal effect dominated. Here we aimed to determine parental asthma and allergy effect in the Danish GEneral SUburban population Study (GESUS). This cross-sectional study has involved 21,362 adults aged 20+ years in the suburbs of Copenhagen. We used a combination of questionnaire approach, history of prescribed asthma medications and pulmonary function testing to determine odds ratios for maternal and paternal (and combined) asthma and allergy linked to asthma in the test subjects. We found that the input of maternal vs. paternal asthma effect was approximately equal (age and sex-adjusted OR 2.46, 95% CI: 2.15–2.81 for asthmatic mothers vs. 2.97, 2.58–3.42 for asthmatic fathers), except for the “ever asthma” age and sex-adjusted odds ratios where paternal allergy seems to have conferred a marginally greater effect (age and sex-adj. OR 1.96 for maternal allergy vs. 2.44 for paternal allergy, p = 0.03). Stratifying for gestational tobacco smoking did not affect the maternal results. We conclude that in the GESUS study parental asthma or allergy were strongly linked to higher asthma risk in offspring, without a prominent maternal or paternal effect.

During pregnancy, the complex hormonal changes lead to a progressive decrease of insulin sensitivity that can drive the onset of gestational diabetes (GDM) or worsen an already-known condition of insulin resistance like type 2 diabetes, polycystic ovarian syndrome (PCOS), and obesity, with complications for the mother and the fetus. Metformin during pregnancy is proving to be safe in a growing number of studies, although it freely crosses the placenta, leading to a fetal level similar to maternal concentration. The aim of this literature review is to analyze the main available evidence on the use of metformin during, throughout, and beyond pregnancy, including fertilization, lactation, and medium-term effects on offspring. Analyzed studies support the safety and efficacy of metformin during pregnancy. In pregnant women with GDM and type 2 diabetes, metformin improves obstetric and perinatal outcomes. There is no evidence that it prevents GDM in women with pregestational insulin resistance or improves lipid profile and risk of GDM in pregnant women with PCOS or obesity. Metformin could have a role in reducing the risk of preeclampsia in pregnant women with severe obesity, the risk of late miscarriages and preterm delivery in women with PCOS, and the risk of ovarian hyperstimulation syndrome, increasing the clinical pregnancy rate in women with PCOS undergoing in vitro fertilization (IVF/FIVET). Offspring of mothers with GDM exposed to metformin have no significant differences in body composition compared with insulin treatment, while it appears to be protective for metabolic and cardiovascular risk.

Background: Genetically high-risk children carry indicators of brain dysfunctions that adult patients with schizophrenia or bipolar disorder display. The accumulation of risk indicators would have a higher predictive value of a later transition to psychosis or mood disorder than each individual risk indicator. Since more than 50% of adult patients report having been exposed to childhood trauma, we investigated whether exposure to trauma during childhood was associated with the early accumulation of risk indicators in youths at genetic risk. Methods: We first inspected the characteristics of childhood trauma in 200 young offspring (51% male) born to a parent affected by DSM-IV schizophrenia, bipolar disorder, or major depressive disorder. A subsample of 109 offspring (51% male) had measurements on four risk indicators: cognitive impairments, psychotic-like experiences, nonpsychotic nonmood childhood DSM diagnoses, poor global functioning. Trauma was assessed from direct interviews and reviews of lifetime medical and school records of offspring. Results: Trauma was present in 86 of the 200 offspring (43%). The relative risk of accumulating risk indicators in offspring exposed to trauma was 3.33 (95% CI 1.50, 7.36), but more pronounced in males (RR = 4.64, 95% CI 1.71, 12.6) than females (RR = 2.01, 95% CI 0.54, 7.58). Conclusion: Childhood trauma would be related to the accumulation of developmental precursors of major psychiatric disorders and more so in young boys at high genetic risk. Our findings may provide leads for interventions targeting the early mechanisms underlying the established relation between childhood trauma and adult psychiatric disorders.

Introduction: Pregnancy is a transcendent period for the mother and the fetus, characterized by an increase on energy requirements. Mediterranean diet (MD) is considered a healthy eating pattern that can provide the nutritional requirements of pregnancy and protect from the development of obstetric pathologies. Objective: To know the relationship between adherence to the MD and its maternal-fetal benefits. Methodology: A systematic review was conducted by identifying articles in the PubMed and Cochrane databases. The publication date of the studies was between 2010 and 2020, and the inclusion criteria established were that the articles were written in English and Spanish and were accessible in full text. Studies concerning assisted reproduction, gene modulation, conference abstracts, systematic reviews, and pilot studies were excluded. Results: Finally, a total of 14 studies were included in the review. The association between the MD and the reduction of some pathologies of pregnancy, such as gestational diabetes, overweight or obesity, sleep quality, complications of childbirth, urinary tract infections (UTIs), and alterations in fetal growth was demonstrated, as well as perinatal problems, including birth weight, prematurity, gastroschisis, and other childhood problems. Conclusion: The MD is an optimal diet to consume during pregnancy.

Aims/Introduction This study aimed to investigate the neurodevelopment of infants born to women with gestational diabetes mellitus (GDM). Materials and Methods Data from the National Birth Cohort in the Japan Environment and Children's Study from 2011 to 2014 (n = 81,705) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The Japanese translation of the Ages and Stages Questionnaires, third Edition, was used to assess neurodevelopment in the following domains: communication skills, gross motor skills, fine motor skills, problem-solving ability, and personal and social skills. The survey was carried out every 6 months from the age of 6 months to 4 years (total of eight times). Generalized estimating equations were used to evaluate the association between maternal GDM and neurodevelopmental delay based on odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Neurodevelopmental delays, particularly in problem-solving ability, fine motor skills, and personal and social skills, were significantly higher in infants born to women with GDM than in those born to women without GDM (adjusted OR 1.24, 95% CI 1.12-1.36; adjusted OR 1.15, 95% CI 1.03-1.27; and adjusted OR 1.18, 95% CI 1.04-1.33). Furthermore, stratification showed no significant increase in the adjusted ORs (95% CIs) of girls. Conclusions Neurodevelopment was significantly delayed up to 4 years-of-age among boys born to women with GDM.

Aims: Rates of parental separation have increased dramatically in recent decades. We evaluated the association of individuals’ childhood family structure with their somatic health over 46 years of follow-up. Methods: Data were drawn from the Northern Finland Birth Cohort, an ongoing project in which 12,058 participants born in 1966 have been followed from their 24th gestational week. Based on information supplied at age 14 years, family structure was categorised as ‘single-parent family’ and ‘two-parent family’. The anthropometric information, data from blood samples and medical history were collected from postal questionnaires and clinical examinations routinely performed at the ages of 31 and 46 years. Results: The study population comprised a total of 10,895 individuals; 85% (n=9253) were offspring of two-parent families and 15% (n=1642) of single-parent families. Type 2 diabetes (P=0.032) or prediabetes (P=0.007), psychoactive drug problems (P<0.001) and sexually transmitted diseases (P<0.001) were more common in the single-parent family group than in the participants from two-parent families. In addition, among men back diseases (P=0.002), and among women hypertension (P=0.003) and ovary infection (P=0.024) were more frequent in individuals affected by parental death than in those from two-parent families. Conclusions: Our results indicate the association of childhood family structure with offspring morbidity during 46 years’ follow-up. The lifetime morbidity was observed to be higher among offspring from a single-parent family compared to two-parent family offspring. Public and scientific concern about the consequences of parental separation on the offspring’ health exist, therefore support from healthcare professionals and society is warranted.

Background: To study the associations between maternal smoking during pregnancy and paternal smoking before pregnancy and adult offspring psychiatric disorders. Methods: Prospective general population cohort study in Northern Finland, with people from the Northern Finland Birth Cohort 1986: 7259 subjects (77% of the original sample). Data on parental smoking were collected from parents during pregnancy using questionnaires. Outcomes were offspring’s register-based diagnoses: any psychiatric disorder, any non-organic psychosis, mood disorder, anxiety disorder and substance use disorder (SUD) until the age of 29–30 years. Maternal smoking during pregnancy and paternal smoking before pregnancy were pooled to three-class variables: (i) none; (ii) 1–9 and (iii) ≥10 cigarettes/day. Information regarding both parents’ alcohol use during pregnancy and at offspring age 15–16 years, maternal education level, family structure, parental psychiatric diagnoses and offspring gender, smoking, intoxication frequency and illicit substance use at the age of 15–16 years were investigated as covariates. Results: In the multivariable analyses, maternal smoking during pregnancy did not associate with the studied outcomes after adjusting for offspring smoking and other substance use at offspring age 15–16 years and parental psychiatric disorders. However, paternal smoking ≥10 cigarettes/day before pregnancy [hazard ratio (HR) = 5.5, 95% confidence interval (CI) 2.7–11.2, P < 0.001] and paternal psychiatric disorders (HR = 1.7, 95% CI 1.1–2.8, P = 0.028) associated with offspring SUD after adjustments. Conclusions: Information across the offspring life course is essential in exploring the association between parental smoking and offspring psychiatric disorders. Paternal smoking before pregnancy and paternal psychiatric disorders may act as modifiers in elevating the risk of substance-use-related problems among offspring.

Background: Greater maternal adiposity before or during pregnancy is associated with greater offspring adiposity throughout childhood, but the extent to which this is due to causal intrauterine or periconceptional mechanisms remains unclear. Here, we use Mendelian randomisation (MR) with polygenic risk scores (PRS) to investigate whether associations between maternal pre-/early pregnancy body mass index (BMI) and offspring adiposity from birth to adolescence are causal. Methods: We undertook confounder adjusted multivariable (MV) regression and MR using mother-offspring pairs from two UK cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) and Born in Bradford (BiB). In ALSPAC and BiB, the outcomes were birthweight (BW; N = 9339) and BMI at age 1 and 4 years (N = 8659 to 7575). In ALSPAC only we investigated BMI at 10 and 15 years (N = 4476 to 4112) and dual-energy X-ray absorptiometry (DXA) determined fat mass index (FMI) from age 10–18 years (N = 2659 to 3855). We compared MR results from several PRS, calculated from maternal non-transmitted alleles at between 29 and 80,939 single nucleotide polymorphisms (SNPs). Results: MV and MR consistently showed a positive association between maternal BMI and BW, supporting a moderate causal effect. For adiposity at most older ages, although MV estimates indicated a strong positive association, MR estimates did not support a causal effect. For the PRS with few SNPs, MR estimates were statistically consistent with the null, but had wide confidence intervals so were often also statistically consistent with the MV estimates. In contrast, the largest PRS yielded MR estimates with narrower confidence intervals, providing strong evidence that the true causal effect on adolescent adiposity is smaller than the MV estimates (Pdifference = 0.001 for 15-year BMI). This suggests that the MV estimates are affected by residual confounding, therefore do not provide an accurate indication of the causal effect size. Con

Objective: The elevated prevalence of cardiometabolic disorders is consistently reported in patients with severe mental illness (SMI). We explored the association between parental SMI and offspring cardiometabolic morbidity. Our hypothesis was that offspring of people with SMI have increased morbidity risk. Method: The Northern Finland Birth Cohort 1966 is a study of offspring whose date of birth was expected in 1966. The follow-up lasted until 2015 (49 years). The final study sample included 11,175 children. We used parental SMI as the exposure in the study. The following cardiometabolic disorders were used as outcome measures: diabetes mellitus, hypertension, hyperlipidemia, coronary artery disease, obesity, and cerebrovascular disorders. Results: There were 139 (14.7%; hazard ratios [HR] = 1.63; 95% confidence interval [CI] = 1.36–1.94) children of parents with SMI who developed cardiometabolic disorder during follow-up and 957 (9.4%) in the comparison cohort. Statistically significant HRs were found in males (HR = 1.95; 95% CI =1.56–2.44), but not in females (HR = 1.29; 95% CI = 0.96–1.73). Conclusions: Having a cardiometabolic disorder was associated with male offspring of parents with SMI. Our findings suggest that there is an elevated risk of coronary artery disease, hyperlipidemia, obesity, and hypertension in the male offspring of parents with SMI. Our results suggest that the somatic health of offspring of parents with SMI should also be considered in addition to their mental health in clinical practice.

Aims: To compare anthropometrics, and lipid and glucose metabolism in the 9-year-old offspring of mothers treated with metformin or insulin for gestational diabetes mellitus (GDM). Materials and methods: This was a Finnish two-centre, 9-year follow-up study of two open-label, randomized controlled trials comparing the effects observed in the offspring of mothers who received metformin and insulin treatment for GDM. Measurements included anthropometrics, blood pressure, lipoproteins, and oral glucose tolerance tests. This study was registered with ClinicalTrials.gov, number NCT02417090. Results: At the age of 9 years 172 children (55% of the original study cohort, 82 from the metformin and 90 from the insulin group) participated in the study. No differences were found between the 9-year-old offspring groups in anthropometric variables, including body mass index and waist-to-height ratio. The offspring in the metformin group had higher high-density lipoprotein (HDL) cholesterol concentrations (1.72 vs. 1.54 mmol/L; P = 0.039) but lower low-density lipoprotein cholesterol (2.39 vs. 2.58 mmol/L; P = 0.046) and apolipoprotein B concentrations (0.63 vs. 0.67 g/L; P = 0.043) than the offspring in the insulin group. The difference in HDL cholesterol concentration was found to be significant only in boys (P = 0.003). The 2-hour glucose value in the oral glucose tolerance test was 0.6-mmol/L lower in boys from the metformin group than in those from the insulin group (P = 0.015). Conclusions: Metformin treatment for GDM is associated with similar offspring growth and glucose metabolism but a more favourable lipid profile at the age of 9 years as compared to insulin treatment.

Maternal diabetes and/or obesity in pregnancy are undoubtedly associated with later disease-risk in the offspring. The placenta, interposed between the mother and the foetus, is a potential mediator of this risk through epigenetic mechanisms, including DNA methylation. In recent years, multiple studies have identified differentially methylated CpG sites in the placental tissue DNA in pregnancies complicated by diabetes and obesity. We reviewed all published original research relevant to this topic and analysed our findings with the focus of identifying overlaps, contradictions, and gaps. Most studies focused on the association of gestational diabetes and/or hyperglycaemia in pregnancy and DNA methylation in placental tissue at term. We identified overlaps in results related to specific candidate genes, but also observed a large research gap of pregnancies affected by type 1 diabetes. Other unanswered questions relate to analysis of specific placental cell types and the timing of DNA methylation change in response to diabetes and obesity during pregnancy. Maternal metabolism is altered already in the first trimester involving structural and functional changes in the placenta, but studies into its effects on placental DNA methylation during this period are lacking and urgently needed. Foetal sex is also an important determinant of pregnancy outcome, but only few studies have taken this into account. Collectively, we provide a reference work for researchers working in this large and evolving field. Based on the results of the literature review, we formulate suggestions for future focus of placental DNA methylation studies in pregnancies complicated by diabetes and obesity.

Introducción: la patología tiroidea constituye una de las disfunciones más frecuentes en España y una de las principales alteraciones endocrinas durante el periodo gestacional. Entre ellas, destaca el hipotiroidismo, cuyo tratamiento se basa en retomar la producción normal de la glándula a través de la toma de levotiroxina. Durante el embarazo, existe un aumento de necesidades y una importante transferencia hormonal a nivel placentario, clave para el desarrollo cerebral fetal. Justificación: el número de mujeres tratadas de hipotiroidismo aumenta al inicio de la maternidad. Conocida la susceptibilidad de la síntesis tiroidea en estas patologías, es importante el conocimiento de un oligoelemento en la producción de estas hormonas; el yodo. Aunque su consumo experimentó una mejoría, podría ser deficitario. Objetivos: se pretende conocer la veracidad de la relación entre hipotiroidismo materno y el desenvolvimiento de trastornos en el neurodesarollo fetal, así como el papel del yodo y la utilidad clínica del tratamiento con levotiroxina en la prevención de estas disfunciones cognitivas. Metodología: se inicia una revisión bibliográfica de la evidencia publicada por 22 artículos en los últimos 8 años. Resultados: en relación con los objetivos planteados, se manifiesta cierta controversia entre la bibliografía seleccionada. Discusión y conclusión: existe asociación entre la disfunción hipotiroidea materna con el desesenvolvimiento de trastornos en el neurodesarrollo infantil, fundamentados por cambios cerebrales evidenciables, desconociendo si esto se debe a niveles anormales de tiroxina libre, o bien a una variable ajena, pero relacionada con ambos factores. Se justifica la suplementación con yodo en una situación de deficiencia severa debido a su efecto a nivel cognitivo, pero se mantiene incierta su eficacia en casos de yododeficiencia leve y moderada. En cuanto al tratamiento con levotiroxina, se concluye una mejoría de la función tiroidea, aunque no a nivel cognitiv, Introdución: a patoloxía tiroidea constitúe unha das disfuncións máis frecuentes en España e unha das principais alteracións endocrinas durante o período xestacional. Entre elas, destaca o hipotiroidismo, cuxo tratamento se basea en retomar a produción normal da gl´nadula mediante a toma de levotiroxina. Durante o embarazo, existe un aumento de necesidades e unha importante transferencia hormonal a nivel placentario, clave para o desenvolvemento cerebral fetal. Xustificación: o número de mulleres tratadas de hipotiroidismo aumenta ao inicio da maternidade. Coñecida a susceptibilidade da síntese tiroidea nestas patoloxías, é importante o coñecemento dun oligoelemento na produción destas hormonas; o iodo. Aínda que o seu consumo experimentou unha mellora, podería ser deficitario. Obxectivos: preténdese coñecer a veracidade da relación entre a disfunción hipotiroidea materna e a aparición de trastornos no neurodesenvolvemento fetal, así como o papel do iodo na prevención destas patoloxías e a utilidade clínica do tratamento con levotiroxina no impacto destas disfuncións cognitivas. Metodoloxía: iníciase unha revisión bibliográfica da evidencia publicada por 22 artigos nos últimos 8 anos. Resultados: en relación cos obxectivos plantexados, maniféstase certa controversia entre a bibliografía seleccionada. Discusión e conclusión: existe asociación entre a disfunción hipotiroidea materna coa aparición de trastornos no neurodesenvolvemento infantil, fundamentados por cambios cerebrais evidenciables, descoñecendo se isto se debe a niveis anormais de tiroxina libre, ou ben a unha variable allea, pero relacionada con ámbolos dous factores. Xustifícase a suplementación con iodo nunha situación de deficiencia severa debido ao seu efecto a nivel cognitivo, pero mantense incerta a súa eficacia nun escenario de iododeficiencia leve e moderada. En canto ao tratamento con levotiroxina, conclúese unha mellora da función tiroidea, aínda que non a nivel cognitivo, derivada da normalizac, Introduction: thyroid pathology is one of the most frequent dysfunctions in Spain and one of the main endocrine disorders during the gestational period. Among them, hypothyroidism stands out, whose treatment is based on resuming the normal production of the gland through the taking of levothyroxine. During pregnancy, there is an increase in needs and a significant hormonal transfer at the placental level, key to fetal brain development. Justification: the number of women treated for hypothyroidism increases at the beginning of maternity. Known the susceptibility of thyroid synthesis in these pathologies, it is important to know a trace element in the production of these hormones; iodine. Although its consumption experienced an improvement, it could be deficient. Objectives: to know the veracity of the relationship between maternal hypothyroid dysfunction and the onset of disorders in fetal neurodevelopment, as well as the role of iodine in the prevention of these pathologies and the clinical utility of levothyroxine treatment in the impact of these cognitive dysfunctions. Methodology: a bibliographic review of the evidence published by 22 articles in the last 8 years is initiated. Results: in relation to the objectives set, there is some controversy among the selected bibliography. Discussion and conclusion: the association between maternal hypothyroid dysfunction and the onset of disorders in childhood neurodevelopment, based on evident brain changes, is confirmed, unknowing whether this explanation is due to abnormal levels of free thyroxine , or a foreign variable, but related to both factors. Iodine supplementation is justified in a situation of severe deficiency due to its effect at the cognitive level, but its effectiveness remains uncertain in a mild and moderate iodine deficiency scenario. Regarding the treatment with levothyroxine, an improvement in thyroid function is concluded, although not at the cognitive level, derived from the normalization of the lev

Background: Infrequent deviants in a rapid sequence of sounds elicit a negative cortical potential over the frontocentral midline (mismatch negativity, MMN) followed by a positive deflection (P3a). Both cortical potentials are consistently attenuated in patients with schizophrenia (SZ), and, to a lesser degree, in patients with bipolar disorder (BP). Objective: Since it is unclear when MMN and P3a deficits arise relative to the emergence of symptoms, we examined whether MMN and P3a alterations are already detectable in children with familial high risk. Methods: Using 128-channel electroencephalography, we recorded auditory MMN and P3a evoked by a deviation in sound duration, frequency, or both in 51 children with familial high-risk for SZ (FHR-SZ), 41 children with familial high-risk for BP (FHR-BP), and 39 population-based children (PBC) at a mean age of 12.10. Results: MMN amplitude evoked by a duration deviant was larger in children with FHR-BP compared to PBC and FHR-SZ. P3a amplitude in response to a duration ∗ frequency deviant was larger in children with FHR-BP compared to children with FHR-SZ, but not compared to PBC. MMN- and P3a-peak latency did not differ between groups. Conclusions: At an age of around 12 years, children with FHR-BP display enhanced neural sensitivity to change detection of duration deviants, while FHR-SZ showed a normal response pattern. Longitudinal recordings in high-risk children during adolescence are required to elucidate the temporal trajectories of MMN and P3a responses and how they relate to the emergence of first clinical symptoms in SZ and BP.

Objectives: Emotion regulation is a predictor of overall life outcome. Problems of emotion regulation are associated with multiple psychiatric disorders and could be a potential treatment target for improving well-being and functioning. Children at familial high risk of severe mental illness have a markedly increased risk of various psychopathology and constitute a group at significant risk of emotion regulation problems. Investigations of emotion regulation in children at familial high risk of severe mental illness are sparse. Methods: We applied an instrument for assessing emotion regulation, the Tangram Emotion Coding Manual (TEC-M), to a population-based cohort of 522 7-year-old children born to parents diagnosed with either schizophrenia or bipolar disorder and matched controls. The TEC-M is an ecologically valid, clinician-rated observational test measure of spontaneous emotion regulation. We aimed to compare emotion regulation between risk groups and to investigate associations between emotion regulation and psychopathology and daily life functioning, and between emotion regulation and an acknowledged questionnaire-based dysregulation profile. Results: In this early developmental phase, we found no between group differences in emotion regulation. We found a significant but weak negative association between emotion regulation and both child psychopathology and the presence of a dysregulation profile on the Child Behavior Checklist and a weak positive association between emotion regulation and current level of functioning. Conclusions: These findings contribute to the understanding of emotion regulation in familial high-risk children and further studies of emotion regulation in children at familial high risk of severe mental illness are warranted.

Maternal stress during pregnancy is associated with differential DNA methylation in offspring and disrupted cortisol secretion. This study aimed to determine methylation signatures of cortisol levels in children, and whether associations differ based on maternal post-traumatic stress disorder (PTSD). Blood epigenome-wide methylation and fasting cortisol levels were measured in 118 offspring of mothers recruited from the Kosovo Rehabilitation Centre for Torture Victims. Mothers underwent clinically administered assessment for PTSD using Diagnostic and Statistical Manual of Mental Disorders. Correlations between offspring methylation and cortisol levels were examined using epigenome-wide analysis, adjusting for covariates. Subsequent analysis focussed on a priori selected genes involved in the hypothalamic–pituitary–adrenal (HPA) axis stress signalling. Methylation at four sites were correlated with cortisol levels (cg15321696, r = −0.33, cg18105800, r = +0.33, cg00986889, r = −0.25, and cg15920527, r = −0.27). In adjusted multivariable regression, when stratifying based on prenatal PTSD status, significant associations were only found for children born to mothers with prenatal PTSD (p < 0.001). Several sites within HPA axis genes were also associated with cortisol levels in the maternal PTSD group specifically. There is evidence that methylation is associated with cortisol levels, particularly in offspring born to mothers with prenatal PTSD. However, larger studies need to be carried out to independently validate these findings.

Background Genetically informed studies have provided mixed findings as to what extent parental substance misuse is associated with offspring substance misuse and antisocial behavior due to shared environmental and genetic factors. Methods We linked data from nationwide registries for a cohort of 2 476 198 offspring born in Sweden 1958-1995 and their parents. Substance misuse was defined as International Classification of Diseases diagnoses of alcohol/drug use disorders or alcohol/drug-related criminal convictions. Quantitative genetic offspring-of-siblings analyses in offspring of monozygotic and dizygotic twin, full-sibling, and half-sibling parents were conducted. Results Both maternal and paternal substance misuse were robustly associated with offspring substance misuse [maternal adjusted hazard ratio (aHR) = 1.83 (95% confidence interval (CI) 1.80-1.87); paternal aHR = 1.96 (1.94-1.98)] and criminal convictions [maternal aHR = 1.56 (1.54-1.58); paternal aHR = 1.66 (1.64-1.67)]. Additive genetic effects explained 42% (95% CI 25-56%) and 46% (36-55%) of the variance in maternal and paternal substance misuse, respectively, and between 36 and 44% of the variance in substance misuse and criminality in offspring. The associations between parental substance misuse and offspring outcomes were mostly due to additive genetic effects, which explained 54-85% of the parent-offspring covariance. However, both nuclear and extended family environmental factors also contributed to the associations, especially with offspring substance misuse. Conclusions Our findings from a large offspring-of-siblings study indicate that shared genetic influences mostly explain the associations between parental substance misuse and both offspring substance misuse and criminality, but we also found evidence for the contribution of environmental factors shared by members of nuclear and extended families.

Social impairments are suggested as vulnerability markers for schizophrenia and bipolar disorder. Therefore, we investigated the development of social responsiveness and theory of mind (ToM) in children at familial high-risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP). This study is part of The Danish High Risk and Resilience Study, a longitudinal cohort study of children at FHR-SZ or FHR-BP and population-based controls (PBC). Social responsiveness was measured with the Social Responsiveness Scale (SRS-2), completed by teachers and primary caregivers. ToM was measured using The Animated Triangles Task (ATT). Both SRS-2 and ATT were applied at age 7 and 11. A total of 520 children participated (FHR-SZ, n = 201; FHR-BP, n = 119; PBC, n = 200). Results showed no significant time by group interactions. At follow-up, children at FHR-SZ exhibited impaired social responsiveness compared with PBC regardless of the informant. At both timepoints, a higher proportion of children at FHR-SZ were rated at a clinically significant level, implying inference in everyday social interactions. Compared with PBC, primary caregivers reported impairments in social responsiveness in children at FHR-BP at follow-up. The three groups did not differ in ToM at follow-up. Social responsiveness and ToM do not develop differently in children at FHR-SZ, FHR-BP and PBC from age 7 to 11, but impairments in social responsiveness remain stable and may constitute a vulnerability marker particularly in children at FHR-SZ, but also FHR-BP. ToM abilities seem to improve and remain intact, but ToM development and ToM task properties should be taken into consideration.

CCS often wish to have biological children yet harbour concerns about fertility impairment, pregnancy risks and the general health risks of prospective offspring. To clarify these concerns, health outcomes in survivor offspring born following ART (n = 74, 4.5%) or after spontaneous conception (n = 1585) were assessed in our European offspring study by descriptive and bivariate analysis. Outcomes were compared to a sibling offspring cohort (n = 387) in a 4:1 matched-pair analysis (n = 1681). (i) Survivors were more likely to employ ART than their siblings (4.5% vs. 3.7%, p = 0.501). Successful pregnancies were achieved after a median of one cycle with, most commonly, intracytoplasmic sperm injection (ICSI) using non-cryopreserved oocytes/sperm. (ii) Multiple-sibling births (p < 0.001, 29.7% vs. 2.5%), low birth weight (p < 0.001; OR = 3.035, 95%-CI = 1.615–5.706), and preterm birth (p < 0.001; OR = 2.499, 95%-CI = 1.401–4.459) occurred significantly more often in survivor offspring following ART utilisation than in spontaneously conceived children. ART did not increase the prevalence of childhood cancer, congenital malformations or heart defects. (iii) These outcomes had similar prevalences in the sibling population. In our explorative study, we could not detect an influence on health outcomes when known confounders, such as multiple births, were taken into account., + ID der Publikation: unilu_59897 + Sprache: Englisch + Letzte Aktualisierung: 2022-09-26 16:30:11

Background: Prepregnancy overweight and excessive gestational weight gain (GWG) increase the risk of complications and offspring obesity.Objectives: We aimed to investigate the effect of a high-protein low-glycemic index (HPLGI) diet on GWG, birth weight, and risk of gestational complications in pregnant women with obesity.Design: A total of 279 women with pre-pregnancy overweight or obesity (BMI 28-45 kg/m2), between 18 and 45 y old, and in their late first trimester with singleton pregnancies, were randomly assigned to 1 of 2 ad libitum diets: a high -protein low-glycemic index diet (HPLGI: 25%-28% of energy from protein and glycemic index ≤ 55) and a moderate-protein moderate-glycemic index diet (MPMGI: 15%-18% of energy from protein and glycemic index ∼60). Diets were consumed from gestational week 15 and throughout pregnancy. Participants received dietary guidance by a clinical dietician 9 times to facilitate adherence.Results: Out of 141 and 138 women randomly assigned to the HPLGI and MPMGI diets, 105 and 104 completed the intervention, respectively (75%). In the available case analyses, GWG was 6.8 ± 1.3 kg among women assigned the HPLGI diet and this was significantly lower, by -1.7 kg (95% CI: -2.8, -0.5; P = 0.004) than the GWG of 8.5 ± 1.3 kg among women assigned the MPMGI diet. There were no significant differences between diets on major neonatal outcomes (birthweight and other anthropometric measures). The incidence of composite pregnancy complications was lower in the HPLGI compared with the MPMGI diet (35.4% compared with. 53.7%, respectively; P = 0.009), including cesarean delivery (15.4% compared with 28.8%, respectively; P = 0.03). There were no reported maternal, fetal, or neonatal deaths. Incidence of miscarriages (1%-2%) did not differ between groups.Conclusion: A moderate increase in dietary protein in conjunction with a reduction in glycemic inde

BACKGROUND: Genetically informed studies have provided mixed findings as to what extent parental substance misuse is associated with offspring substance misuse and antisocial behavior due to shared environmental and genetic factors. METHODS: We linked data from nationwide registries for a cohort of 2 476 198 offspring born in Sweden 1958-1995 and their parents. Substance misuse was defined as International Classification of Diseases diagnoses of alcohol/drug use disorders or alcohol/drug-related criminal convictions. Quantitative genetic offspring-of-siblings analyses in offspring of monozygotic and dizygotic twin, full-sibling, and half-sibling parents were conducted. RESULTS: Both maternal and paternal substance misuse were robustly associated with offspring substance misuse [maternal adjusted hazard ratio (aHR) = 1.83 (95% confidence interval (CI) 1.80-1.87); paternal aHR = 1.96 (1.94-1.98)] and criminal convictions [maternal aHR = 1.56 (1.54-1.58); paternal aHR = 1.66 (1.64-1.67)]. Additive genetic effects explained 42% (95% CI 25-56%) and 46% (36-55%) of the variance in maternal and paternal substance misuse, respectively, and between 36 and 44% of the variance in substance misuse and criminality in offspring. The associations between parental substance misuse and offspring outcomes were mostly due to additive genetic effects, which explained 54-85% of the parent-offspring covariance. However, both nuclear and extended family environmental factors also contributed to the associations, especially with offspring substance misuse. CONCLUSIONS: Our findings from a large offspring-of-siblings study indicate that shared genetic influences mostly explain the associations between parental substance misuse and both offspring substance misuse and criminality, but we also found evidence for the contribution of environmental factors shared by members of nuclear and extended families.

High-flavonoid cocoa consumption has been associated with beneficial properties. However, there are scarce data concerning the effects of maternal cocoa intake on dams and in their progeny. Here, we evaluated in rats whether maternal supplementation with a high-flavan-3-ol cocoa extract (CCX) during lactation (200 mg.kg−1.day−1) produced beneficial effects on dams and in their normoweight (STD-CCX group) and cafeteria-fed obese (CAF-CCX group) adult male offspring. Maternal intake of CCX significantly increased the circulating levels of adiponectin and decreased the mammary gland lipid content of dams. These effects were accompanied by increased energy expenditure and circulating free fatty acids, as well as by a higher expression of lipogenic and adiponectin-related genes in their mammary glands, which could be related to a compensatory mechanism to ensure enough lipid supply to the pups. CCX consumption programmed both offspring groups towards increased plasma total adiponectin levels, and decreased liver weight and lean/fat ratio. Furthermore, CAF-CCX progeny showed an improvement of the inflammatory profile, evidenced by the significant decrease of the monocyte chemoattractant protein-1 (MCP-1) circulating levels and the mRNA levels of the gene encoding the major histocompatibility complex, class II invariant chain (Cd74), a marker of M1 macrophage phenotype, in the epididymal white adipose tissue. Although further studies are needed, these findings can pave the way for using CCX as a nutraceutical supplement during lactation.

Nutritional status during gestation can influence mother and offspring metabolism. Undernutrition in pregnancy affects women in both western and developing countries, and it is associated with a high prevalence of chronic diseases in later life. The present work was conducted in the rabbit model, as a longitudinal study, to examine the effect of food restriction during early and mid-gestation, and re-feeding ad libitum until the end of pregnancy on metabolic status and body reserves of mother and, its association with development and metabolism of fetuses and female offspring to the juvenile stage. Little changes in live body weight (LBW), compensatory feed intake, similar body reserves, and metabolism were observed in dams. Placenta biometry and efficiency were slightly affected, but fetal BW and phenotype were not modified. However, hyperinsulinemia, insulin resistance, and hypertriglyceridemia were demonstrated in pre-term fetuses. In the juvenile period, these changes were not evidenced, and a similar pattern of growth and serum metabolic parameters in offspring of food-restricted mothers were found, except in serum aminotransferases levels, which increased. These were associated with higher liver fibrosis. Maternal food restriction in the early and mid-pregnancy followed by re-feeding in our rabbit model established a compensatory energy status in dams and alleviated potential long-term consequences in growth and metabolism in the offspring, even if fetal metabolism was altered., Ministerio de Ciencia, Innovación y Universidades (MCIU), UCM funding for RESEARCH GROUPS, Depto. de Producción Animal, Sección Deptal. de Fisiología (Veterinaria), Fac. de Veterinaria, TRUE, pub

As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18-71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms.

[ES] Las técnicas de la biotecnología de la reproducción son utilizadas hoy en día tanto en animales como en humanos con distintos fines; en animales se aplican principalmente para aumentar la productividad y el rendimiento en la industria, mientras que en los humanos permiten obtener descendencia a personas infértiles. A pesar de que su uso ha incrementado rápidamente desde que se inventaron, su impacto en la descendencia sigue siendo poco conocido. En el pasado, la forma de validar estos procedimientos era mediante la obtención de nacidos vivos; sin embargo, recientemente ha surgido la preocupación de si podrían tener un impacto a pesar de obtenerse individuos vivos. Actualmente se conoce que las técnicas reproductivas (que suelen consistir en colocar gametos y embriones en entornos distintos al natural) coinciden con el momento en el que se produce la reprogramación epigenética del genoma tanto en los gametos como en los embriones y, por tanto, pueden inducir algunos cambios en ellos que podrían persistir después del nacimiento. Por tanto, que el objetivo de este trabajo es analizar si realmente existe un impacto en la progenie animal y humana causado por estas técnicas. Para ello, se realizó una revisión sistemática del estado del arte relacionado con este tema; se seleccionaron diferentes palabras para realizar 3 búsquedas en 2 bases de datos: Scopus y Web of Science. Y, tras algunos pasos de selección para reducir la cantidad de resultados a un número razonable, se obtuvieron 37 publicaciones para ser estudiadas. Según el análisis de estas publicaciones, parece que las técnicas de reproducción no son inocuas sino que pueden inducir algunos cambios en el genotipo y fenotipo de la progenie, tanto animal como humana en comparación con los concebidos de forma natural, y también pueden tener un impacto a largo plazo en los adultos. Sin embargo, todavía se desconoce el mecanismo por el cual se producen estas alteraciones., [EN] Reproductive biotechnologies are widely used nowadays in both animals and humans for different purposes; in animals they are applied mainly to increase productivity and yield in the farm industry while in humans they enable the obtaining of offspring from infertile people. In spite of their rapidly increasing use since they were first invented, their impact on the obtained offspring is still poorly understood. In the past, the way of validating these procedures was by obtaining live offspring; however, concern has been risen recently regarding whether they could have an impact despite getting living individuals. It has been now demonstrated that reproductive technologies (that usually consist on placing gametes and embryos in environments other than natural) coincide with the time at which the genome-wide epigenetic reprograming takes place in both gametes and embryos and therefore can induce some changes on them that may persist after birth. Hence, the aim of this project is to analyze whether there is actually an impact on animal and human progeny caused by this techniques. To do so, a systematic review of the state-of-art related to this topic was performed; different words were selected to carry out 3 searches in 2 databases: Scopus and Web of Science. And, after some refining steps to reduce the amount of results to a reasonable number, 37 publications were obtained to be studied. By the analysis of this publications, it looks like the reproductive technologies are not harmless; they can induce some changes in both animal and human progeny’s genotype and phenotype compared to those conceived naturally and may have a long-time impact on adults too. However, the mechanism through which this outcomes are incurred is still unknown.