Risk Of Offspring Research Articles

Obesity and gestational diabetes independently and collectively induce specific effects on placental structure, inflammation and endocrine function in a cohort of South African women.

Maternal obesity and gestational diabetes mellitus (GDM) are associated with insulin resistance and health risks for mother and offspring. Obesity is also characterized by low-grade inflammation, which in turn, impacts insulin sensitivity. The placenta secretes inflammatory cytokines and hormones that influence maternal glucose and insulin handling. However, little is known about the effect of maternal obesity, GDM and their interaction, on placental morphology, hormones and inflammatory cytokines. In a South African cohort of non-obese and obese pregnant women with and without GDM, this study examined placental morphology using stereology, placental hormone and cytokine expression using real-time PCR, western blotting and immunohistochemistry, and circulating TNFα and IL-6 concentrations using ELISA. Placental expression of endocrine and growth factor genes was not altered by obesity or GDM. However, LEPTIN gene expression was diminished, syncytiotrophoblast TNFα immunostaining elevated and stromal and fetal vessel IL-6 staining reduced in the placenta of obese women in a manner that was partly influenced by GDM status. Placental TNFα protein abundance and maternal circulating TNFα concentrations were reduced in GDM. Both maternal obesity and, to a lesser extent, GDM were accompanied by specific changes in placental morphometry. Maternal blood pressure and weight gain and infant ponderal index were also modified by obesity and/or GDM. Thus, obesity and GDM have specific impacts on placental morphology and endocrine and inflammatory states that may relate to pregnancy outcomes. These findings may contribute to developing placenta-targeted treatments that improve mother and offspring outcomes, which is particularly relevant given increasing rates of obesity and GDM worldwide. KEY POINTS: Rates of maternal obesity and gestational diabetes (GDM) are increasing worldwide, including in low-middle income countries (LMIC). Despite this, much of the work in the field is conducted in higher-income countries. In a well-characterised cohort of South African women, this study shows that obesity and GDM have specific impacts on placental structure, hormone production and inflammatory profile. Moreover, such placental changes were associated with pregnancy and neonatal outcomes in women who were obese and/or with GDM. The identification of specific changes in the placenta may help in the design of diagnostic and therapeutic approaches to improve pregnancy and neonatal outcomes with particular significant benefit in LMICs.

Association of maternal late-gestation lipid mobilization and their offspring's disease risk during the pre-weaned period and performance through first lactation: A cohort study in a dairy herd.

Excessive maternal lipid mobilization in late gestation may impact the immune function of the newborn. However, the long-term effects remain unknown. The objective was to explore associations between excessive maternal lipid mobilization in the last 2 weeks of gestation with offspring health and performance. A retrospective study was performed including 1,511 calves (heifer = 692, bull = 819) born between 2015 and 2020 in one MI farm. Plasma non-esterified fatty acids (NEFA) was measured from cows 7 to 14 d before calving. Calves were categorized in 2 groups based NEFA concentration: physiological lipid mobilization (PLM = 1,373; NEFA <0.3 mM) and excessive lipid mobilization (ELM = 138; NEFA ≥0.3 mM). Calf records were obtained from the herd's management software. Outcomes of interest were the hazard of pre-weaned digestive and respiratory disease, pre-weaned ADG, age at first breeding and calving, first lactation 305 d mature equivalent milk yield (305ME), and survival until first calving. Statistical models included dam NEFA category adjusted by year and season of birth, parity of the dam, and sex of the calf. Cox proportional analysis was used to determine the hazard of a pre-weaned health event, first breeding, and first calving. Linear regression was used to evaluate ADG and 305ME. The survival until first calving was analyzed with logistic regression. No difference was detected in the hazard of diarrhea (HRPLM vs. ELM = 1.06; 95% CI = 0.82-1.38) and respiratory disease (HRPLM vs. ELM = 1.29; 95% CI = 0.79-2.10) by NEFA category in the pre-weaned period. Also, no difference was detected for the LSM (±SE) of pre-weaned ADG (PLM = 0.77±1.55, ELM = 0.72±2.76 kg/d). In heifers, the hazard for first breeding favored the PLM group (HRPLM vs. ELM = 1.59; 95% CI = 1.18-2.12), with a reduced median age at first breeding (PLM = 400 d, 95% CI = 397-402; ELM = 412 d, 95% CI = 404-421). However, NEFA category was not associated with the hazard of first calving (HRPLM vs. ELM = 0.94; 95% CI = 0.69-1.27), first lactation 305ME (PLM = 16,665±165 kg; ELM = 16,256±532), the odds of presenting at least 1 health event in the first lactation (ORPLM vs. ELM = 0.78; 95% CI = 0.41-1.49), or the odds of leaving the herd before first calving (ORPLM vs. ELM = 1.21; 95% CI = 0.56-2.02). Overall, dam ELM affected the hazard of first breeding but no other indicators of health or long-term performance. However, associations between maternal lipid mobilization and calf outcomes cannot be excluded, as the NEFA cut-off used has not been established as a predictor of offspring health and performance.

Parental exposure to famine in early life and child overweight in offspring in Chinese populations

Little is known about the transgenerational effect of nutrition deficiency in early life. This study aimed to evaluate the associations of fetal and childhood exposure to famine of parents with their offspring's risk of overweight during childhood. This analysis included a total of 3734 participants of the China Health and Nutrition Survey aged 1-17 years whose fathers and/or mothers were born in 1955-1966. These children were classified into subgroups according to parental famine exposure status (unexposed and exposed) and timing (fetal-exposed and childhood-exposed). Random effects models were applied to evaluate the associations of parental famine exposure with body mass index (BMI) and overweight of offspring. Fractional polynomial functions were adopted to describe trajectories of BMI against age. Compared with children of unexposed parents, there was a lower risk of overweight among offspring of childhood-exposed fathers [OR (95%CI): 0.80 (0.61, 1.04)] or exposed parents [0.84 (0.68, 1.04)], particularly among male offspring, but not among those with exposed mothers only [0.98 (0.65, 1.47)]. For BMI, children with exposed mothers only had a slightly higher BMI [β(95%CI): 0.17 (-0.15, 0.49)], while those with exposed fathers only had no difference [-0.02 (-0.23, 0.19)] or exposed parents had a slightly lower BMI [-0.17 (-0.33, 0.00)] (p<0.05 for interaction between maternal and paternal exposures). Stratified analysis showed little heterogeneity between male and female offspring, but the association between paternal childhood exposure to famine and lower overweight risk in offspring was more evident in high (vs low) paternal education group (p for interaction< 0.05). The transgenerational associations of early-life exposure to famine with lower risks of child overweight may be via the paternal line and differ by the educational levels of parents. Further studies are warranted to confirm the results and reveal the biological mechanisms underlying.

Gestational palmitic acid suppresses embryonic GATA-binding protein 4 signaling and causes congenital heart disease

Dysregulated maternal fatty acid metabolism increases the risk of congenital heart disease (CHD) in offspring with an unknown mechanism, and the effect of folic acid fortification in preventing CHD is controversial. Using gas chromatography coupled to either a flame ionization detector or mass spectrometer (GC-FID/MS) analysis, we find that the palmitic acid (PA) concentration increases significantly in serum samples of pregnant women bearing children with CHD. Feeding pregnant mice with PA increased CHD risk in offspring and cannot be rescued by folic acid supplementation. We further find that PA promotes methionyl-tRNA synthetase (MARS) expression and protein lysine homocysteinylation (K-Hcy) of GATA4 and results in GATA4 inhibition and abnormal heart development. Targeting K-Hcy modification by either genetic ablation of Mars or using N-acetyl-L-cysteine (NAC) decreases CHD onset in high-PA-diet-fed mice. In summary, our work links maternal malnutrition and MARS/K-Hcy with the onset of CHD and provides a potential strategy in preventing CHD by targeting K-Hcy other than folic acid supplementation.

Association of self-reported mother–infant relationship with child and adolescent mental health

The quality of the relationship between mother and infant may have profound implications for the development of a child. Early indicators of psychological vulnerability may allow targeting of support for the child's cognitive, emotional and social development. A challenging mother-infant relationship could be one indicator of risk. This study examined variations in psychological well-being and psychopathology among boys and girls according to early maternal perception of the mother-infant relationship. This study is based on 64 663 mother-infant pairs from the Danish National Birth Cohort, for which data on the mother-infant relationship were collected at 6 months postpartum. Behavioural problems were assessed with the Danish version of the Strengths and Difficulties Questionnaire (SDQ) at child ages 7, 11 and 18 years, and we retrieved information on diagnosed childhood and adolescent psychiatric disorders and prescriptions of psychotropic drugs from Danish registries. Children in the challenging mother-infant relationship group had higher odds of behavioural problems at age 7 among both boys and girls. The same pattern of elevated estimates was identified for boys across all SDQ domains and for girls in three of five SDQ domains. All associations were attenuated at age 18, but increased odds of behavioural problems still existed. A challenging early mother-infant relationship increased the offspring's risk of being diagnosed with a psychiatric disorder or being prescribed a psychotropic drug before the age of 18. A challenging self-reported mother-infant relationship was associated with later psychopathological difficulties. Routine clinical enquiry may be useful in identification of future vulnerability.

Exposure to war and conflict: The individual and inherited epigenetic effects on health, with a focus on post-traumatic stress disorder.

War and conflict are global phenomena, identified as stress-inducing triggers for epigenetic modifications. In this state-of-the-science narrative review based on systematic principles, we summarise existing data to explore the outcomes of these exposures especially in veterans and show that they may result in an increased likelihood of developing gastrointestinal, auditory, metabolic and circadian issues, as well as post-traumatic stress disorder (PTSD). We also note that, despite a potential "healthy soldier effect", both veterans and civilians with PTSD exhibit the altered DNA methylation status in hypothalamic-pituitary-adrenal (HPA) axis regulatory genes such as NR3C1. Genes associated with sleep (PAX8; LHX1) are seen to be differentially methylated in veterans. A limited number of studies also revealed hereditary effects of war exposure across groups: decreased cortisol levels and a heightened (sex-linked) mortality risk in offspring. Future large-scale studies further identifying the heritable risks of war, as well as any potential differences between military and civilian populations, would be valuable to inform future healthcare directives.

Maternal Diet Quality During Pregnancy and Offspring Hepatic Fat in Early Childhood: The Healthy Start Study

BackgroundOvernutrition in utero may increase offspring risk of nonalcoholic fatty liver disease (NAFLD), but the specific contribution of maternal diet quality during pregnancy to this association remains understudied in humans. ObjectivesThis study aimed to examine the associations of maternal diet quality during pregnancy with offspring hepatic fat in early childhood (median: 5 y old, range: 4–8 y old). MethodsData were from 278 mother–child pairs in the longitudinal, Colorado-based Healthy Start Study. Multiple 24-h recalls were collected from mothers during pregnancy on a monthly basis (median: 3 recalls, range: 1–8 recalls starting after enrollment), and used to estimate maternal usual nutrient intakes and dietary pattern scores [Healthy Eating Index-2010 (HEI-2010), Dietary Inflammatory Index (DII), and Relative Mediterranean Diet Score (rMED)]. Offspring hepatic fat was measured in early childhood by MRI. Associations of maternal dietary predictors during pregnancy with offspring log-transformed hepatic fat were assessed using linear regression models adjusted for offspring demographics, maternal/perinatal confounders, and maternal total energy intake. ResultsHigher maternal fiber intake and rMED scores during pregnancy were associated with lower offspring hepatic fat in early childhood in fully adjusted models [Back-transformed β (95% CI): 0.82 (0.72, 0.94) per 5 g/1000 kcal fiber; 0.93 (0.88, 0.99) per 1 SD for rMED]. In contrast, higher maternal total sugar and added sugar intakes, and DII scores were associated with higher offspring hepatic fat [Back-transformed β (95% CI): 1.18 (1.05, 1.32) per 5% kcal/d added sugar; 1.08 (0.99, 1.18) per 1 SD for DII]. Analyses of dietary pattern subcomponents also revealed that lower maternal intakes of green vegetables and legumes and higher intake of “empty calories” were associated with higher offspring hepatic fat in early childhood. ConclusionsPoorer maternal diet quality during pregnancy was associated with greater offspring susceptibility to hepatic fat in early childhood. Our findings provide insights into potential perinatal targets for the primordial prevention of pediatric NAFLD.

Associations between sugar-sweetened beverages before and during pregnancy and offspring overweight/obesity in Japanese women: the TMM BirThree Cohort Study.

The association between high sugar-sweetened beverages (SSB) intake during pregnancy and offspring overweight/obesity has been reported only from Western countries. The objective of this study was to examine the association between SSB intake before and during pregnancy and offspring overweight/obesity among Japanese women. Japanese prospective birth cohort study. We analysed mother-offspring pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017. SSB intake during pregnancy was evaluated using the FFQ and classified into three groups: none (0 g/d), medium (<195 g/d) and high (>195 g/d). Overweight or obesity at 1 year of age in offspring was defined as having a BMI Z-score greater than 2 sd, calculated based on the BMI reference data for Japanese children. Multiple logistic regression analyses were performed to examine the associations between SSB intake before and during pregnancy and offspring overweight/obesity, after adjusting for covariates. Japanese mother-offspring pairs (n 7114). The overweight/obesity rate of the offspring was 8·8 %. Pregnant women with a high intake of SSB in early to mid-pregnancy had a higher risk of overweight/obesity in their offspring compared with those who did not; the OR was 1·52 (95 % CI (1·09, 2·12)). High SSB intake in early to mid-pregnancy was associated with an increased risk of offspring overweight/obesity at 1 year of age.

Maternal age at childbirth and the risk of attention-deficit/hyperactivity disorder and learning disability in offspring.

Studies have shown that young maternal age at childbirth can increase the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring, but a study of the U.S. population has not been reported. Moreover, there is no reported research on young and advanced maternal age at childbirth and whether it can contribute to the risk of learning disability (LD) in offspring. This study evaluated the association between young and advanced maternal age at childbirth and offspring risk of ADHD and LD in the U.S. population. Using data from 8,098 participants included in the National Health and Nutrition Examination Survey (NHANES) conducted in 1999-2004, we analyzed the association between maternal age at childbirth and ADHD and LD risk in offspring. Odds ratios (ORs) and 95% confidence intervals (CIs) for maternal age at childbirth in association with ADHD and LD risk in offspring were estimated using multivariate logistic regression models after adjustment for age, sex, race, body mass index (BMI), poverty income ratio, smoking status during pregnancy, and NHANES cycle. Restricted cubic spline (RCS) models were used to evaluate potential non-linear relationships. Sensitivity analyses were performed to ensure the reliability of the results. Among all participants, the offspring of subjects with a maternal age at childbirth of 18-24 years had an increased risk of ADHD (OR = 1.34, 95% CI: 1.01, 1.79) and LD (OR = 1.36, 95% CI: 1.06, 1.79) or either ADHD or LD (OR = 1.48, 95% CI: 1.20, 1.81). Additionally, compared with subjects with a maternal age at childbirth of 25-29 years, subjects with a maternal age at childbirth of 35-39 years had lower odds of having offspring with ADHD (OR = 0.60, 95% CI: 0.36, 1.00) and higher odds of having offspring with LD (OR = 1.34, 95% CI: 1.01, 1.78). The relationship between maternal age at childbirth and LD risk presented a U-shaped curve. These results provide epidemiological evidence showing that young and advanced maternal age at childbirth are associated with ADHD and LD risk.

Nonsurgical periodontal treatment during pregnancy and rates of preterm birth

Periodontitis during pregnancy is associated with an increased risk of preterm birth (<37 weeks of gestation) or low birthweight (<2500 g) offspring. Beyond periodontal disease, the risk of preterm birth varies both by previous history of preterm birth and in association with social determinants prevalent among vulnerable and marginalized populations. This study hypothesized that the timing of periodontal treatment during pregnancy and/or social vulnerability measures modified the response to dental scaling and root planing for the treatment of periodontitis and prevention of preterm birth. This study aimed to determine the association of timing of dental scaling and root planing for gravidae with a diagnosed periodontal disease on the rates of preterm birth or low birthweight offspring among subgroups or strata of gravidae as part of the Maternal Oral Therapy to Reduce Obstetric Risk randomized controlled trial. All participants in the study had clinically diagnosed periodontal disease and differed by the timing of the periodontal treatment (dental scaling and root planing at <24 weeks [per protocol] or after delivery) or by baseline characteristics. Although all participants met the well-accepted clinical criteria for periodontitis, not all participants acknowledged a priori that they had periodontal disease. This was a per-protocol analysis of data from 1455 participants of the Maternal Oral Therapy to Reduce Obstetric Risk trial evaluating dental scaling and root planing on the risk of preterm birth or low birthweight offspring. Adjusted multiple logistic regression to control for confounders was used to estimate associations comparing the timing of periodontal treatment in pregnancy to receiving treatment after pregnancy (referent control) on rates of preterm birth or low birthweight among subgroups of gravidae with known periodontal disease. Study analyses were stratified, and the associations with the following characteristics-body mass index, self-described race and ethnicity, household income, maternal education, recency of immigration, and self-acknowledgment of poor oral health, were explored. Dental scaling and root planing during the second or third trimester of pregnancy were associated with an increased adjusted odds ratio of preterm birth among those at the lower body mass index strata (18.5 to <25.0 kg/m2) (adjusted odds ratio, 2.21; 95% confidence interval, 1.07-4.98), but not among individuals who were overweight (body mass index of 25.0 to <30.0 kg/m2; adjusted odds ratio, 0.68; 95% confidence interval, 0.29-1.59) or obese (body mass index of ≥30 kg/m2; adjusted odds ratio, 1.26; 95% confidence interval, 0.65-2.49). There was no significant difference in pregnancy outcomes related to the other evaluated variables: self-described race and ethnicity, household income, maternal education, immigration status, or self-acknowledgment of poor oral health. In this per-protocol analysis of the Maternal Oral Therapy to Reduce Obstetric Risk trial, dental scaling and root planing had no preventive benefit against adverse obstetrical outcomes and were associated with increased odds of preterm birth among individuals at lower body mass index strata. There was no significant difference in the occurrence of preterm birth or low birthweight after dental scaling and root planing periodontitis treatment concerning other analyzed social determinants of preterm birth.

The Role of Adiponectin during Pregnancy and Gestational Diabetes.

Pregnancy involves a range of metabolic adaptations to supply adequate energy for fetal growth and development. Gestational diabetes (GDM) is defined as hyperglycemia with first onset during pregnancy. GDM is a recognized risk factor for both pregnancy complications and long-term maternal and offspring risk of cardiometabolic disease development. While pregnancy changes maternal metabolism, GDM can be viewed as a maladaptation by maternal systems to pregnancy, which may include mechanisms such as insufficient insulin secretion, dysregulated hepatic glucose output, mitochondrial dysfunction and lipotoxicity. Adiponectin is an adipose-tissue-derived adipokine that circulates in the body and regulates a diverse range of physiologic mechanisms including energy metabolism and insulin sensitivity. In pregnant women, circulating adiponectin levels decrease correspondingly with insulin sensitivity, and adiponectin levels are low in GDM. In this review, we summarize the current state of knowledge about metabolic adaptations to pregnancy and the role of adiponectin in these processes, with a focus on GDM. Recent studies from rodent model systems have clarified that adiponectin deficiency during pregnancy contributes to GDM development. The upregulation of adiponectin alleviates hyperglycemia in pregnant mice, although much remains to be understood for adiponectin to be utilized clinically for GDM.

Characterisation of the Paternal Influence on Intergenerational Offspring Cardiac and Brain Lipid Homeostasis in Mice.

There is growing evidence that poor paternal diet at the time of conception increase the risk of offspring developing a range of non-communicable metabolic diseases, such as obesity, diabetes and cardiovascular disease, in adulthood. We hypothesise that a paternal low protein-high carbohydrate diet perturbs offspring tissue lipid abundance through both sperm and seminal plasma-mediated mechanisms. To test our hypothesis, we fed male C57BL/6 mice either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 8 weeks. We generated offspring through artificial insemination, in combination with vasectomised male mating. Using this approach, we derived offspring from either NPD or LPD sperm but in the presence of NPD or LPD seminal plasma. Using high resolution mass-spectrometry, we found that offspring derived from either LPD sperm or seminal fluid displayed perturbed cardiac and brain lipid abundance from just three weeks of age, typically associated with the altered abundance of tissue triglycerides. We also observed the differential sex-specific patterns of lipids between the control and experimental offspring's hearts and brains. These observations indicate that poor paternal diet at the time of conception affects offspring cardiac and brain lipid profiles in an age-, sex- and generation-specific manner.

Risk of asthma in offspring of asthmatic fathers versus mothers: A population-based study of 21,000 individuals in Denmark

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.

Letter to the Editor: Influence of maternal NAFLD on infant weight-the real precursor to NAFLD in offspring?

To the editor, We read with enthusiasm the publication by Amadou et al.1 demonstrating that within a large French cohort, extremes of birthweight increased the risk for NAFLD in adulthood. On mediation analysis, findings for low birthweight were explained by prematurity. As the authors’ highlight, an important limitation was unavailable maternal data, including maternal weight. Beyond maternal obesity, there remains a knowledge gap regarding the in-utero influence of maternal NAFLD on infant outcomes. NAFLD rates in pregnancy have nearly tripled over the past decade, and NAFLD cirrhosis is also rising in pregnant women.2,3 In pediatric populations, NAFLD can develop even in utero, and by school-age 10% of all children, and 30%–40% of those with obesity have NAFLD.4 Thus, there is an urgent need to identify early and modifiable risk factors in pregnant women with NAFLD and their offspring. Though prior data link maternal obesity to childhood NAFLD, the influence of maternal NAFLD on long-term metabolic outcomes has not been elucidated. In a large US study we evaluated NAFLD in pregnancy and maternal and perinatal outcomes at delivery.2 Importantly, maternal NAFLD increased risk for both large-for-gestational age infants (adjusted OR of 1.8, 95% CI: 1.4–2.5) and preterm birth (adjusted OR: 1.60, 95% CI: 1.3–2.0), independent of maternal metabolic comorbidities. Likewise, in our Canadian study of cirrhosis in pregnancy, maternal NAFLD independently increased arge-for-gestational age risk as compared with other etiologies of cirrhosis (RR: 1.6, 95% CI: 1.3–2.1).3 These data suggest a direct influence of in utero NAFLD exposure as a contributor to prematurity and arge-for-gestational age infants, key risk factors for long-term NAFLD risk in offspring as demonstrated by Amoudou and colleagues. Although the underlying mechanisms have not been elucidated, independent of diabetes and obesity the liver plays a critical role in the regulation of glucose and lipid metabolism. NAFLD-specific effects beyond the liver include peripheral insulin resistance, systemic inflammation, and dysregulated lipid metabolism, which may help to explain our findings of increased arge-for-gestational age risk in infants of mothers with NAFLD. In summary, we applaud the work by Amadou and colleagues and emerging literature evaluating early influencers of NAFLD. An even earlier focus on preconception through postpartum periods may further define contributors to NAFLD in offspring, and support interventions among expectant mothers to help mitigate rising NAFLD rates in young populations.

Associations of parent-adolescent closeness with P3 amplitude, frontal theta, and binge drinking among offspring with high risk for alcohol use disorder.

Parents impact their offspring's brain development, neurocognitive function, risk, and resilience for alcohol use disorder (AUD) via both genetic and socio-environmental factors. Individuals with AUD and their unaffected children manifest low parietal P3 amplitude and low frontal theta (FT) power, reflecting heritable neurocognitive deficits associated with AUD. Likewise, children who experience poor parenting tend to have atypical brain development and greater rates of alcohol problems. Conversely, positive parenting can be protective and critical for normative development of self-regulation, neurocognitive functioning and the neurobiological systems subserving them. Yet, the role of positive parenting in resiliency toward AUD is understudied and its association with neurocognitive functioning and behavioral vulnerability to AUD among high-risk offspring is less known. Using data from the Collaborative Study on the Genetics of Alcoholism prospective cohort (N= 1256, mean age [SD]=19.25 [1.88]), we investigated the associations of closeness with mother and father during adolescence with offspring P3 amplitude, FT power, and binge drinking among high-risk offspring. Self-reported closeness with mother and father between ages 12 and 17 and binge drinking were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism. P3 amplitude and FT power were assessed in response to target stimuli using a Visual Oddball Task. Multivariate multiple regression analyses showed that closeness with father was associated with larger P3 amplitude (p= 0.002) and higher FT power (p= 0.01). Closeness with mother was associated with less binge drinking (p= 0.003). Among male offspring, closeness with father was associated with larger P3 amplitude, but among female offspring, closeness with mother was associated with less binge drinking. These associations remained statistically significant with father's and mothers' AUD symptoms, socioeconomic status, and offspring impulsivity in the model. Among high-risk offspring, closeness with parents during adolescence may promote resilience for developing AUD and related neurocognitive deficits albeit with important sex differences.

Variation in the Early Life and Adult Intestinal Microbiome of Intra-Uterine Growth Restricted Rat Offspring Exposed to a High Fat and Fructose Diet.

Intra-Uterine Growth Restriction (IUGR) is a risk factor for many adult-onset chronic diseases, such as diabetes and obesity. These diseases are associated with intestinal microbiome perturbations (dysbiosis). The establishment of an intestinal microbiome begins in utero and continues postnatally (PN). Hypercaloric diet-induced dysbiosis is a major driver of childhood obesity. We hypothesized that different postnatal diets superimposed on IUGR will alter the postnatal intestinal microbiome. We compared four experimental rat groups: (1) Ad lib fed regular chow diet pre- and postnatally (CON), (2-3) IUGR induced by maternal caloric restriction prenatally followed postnatally (PN) by either (2) the control diet (IUGR-RC) or (3) High-Fat-high-fructose (IUGR-HFhf) diet, and lastly (4) HFhf ad lib pre- and postnatally (HFhf). Fecal samples were collected from dams and male and female rat offspring at postnatal day 2, 21, and adult day 180 for 16S rRNA gene sequencing. Maternal diet induced IUGR led to dysbiosis of the intestinal microbiome at PN21. Postnatal HFhf diet significantly reduced microbial diversity and worsened dysbiosis reflected by an increased Gammaproteobacteria/Clostridia ratio. Dysbiosis arising from a mismatch between IUGR and a postnatal HFhf diet may contribute to increased risk of the IUGR offspring for subsequent detrimental health problems.

Meta Analysis: Effects of Polycystic Ovarian Syndrome and Maternal Diabetes on the Risk of Autism in Children

Background: Autism is a condition of developmental abnormalities in social, communication and behavior aspects. Polycystic ovary syndrome and maternal diabetes during pregnancy contribute more than 50% to the risk of ASD offspring. This study aims to analyze and estimate the influence of polycystic ovarian syndrome and maternal diabetes on autism in children. Subjects and Method: The meta-analysis was carried out according to the PRISMA flow chart and the PICO model. Q: Child, I: Mother with PCOS and maternal diabetes, C: T Mother without PCOS and maternal diabetes, O: Autism. Search for articles in this study through databases that include Google Scholar, Pubmed, ScienceDirect and Sage Journal. With keywords including: Polycystic Ovarian Syndrome” AND “Maternal Diabetes” OR “Gestational Diabetes Mellitus” AND “Autism” OR “Autism Spectrum Disorder” AND “Cohort”. A full paper article with an observational cohort study, the research subject was a child, the size of the relationship used was the adjusted odds ratio, the research outcome was autism. Analysis was performed with Revman 5.3. Results: There were 13 articles with cohort designs originating from America, Denmark, England, Sweden, Israel, China with a total of 4,641,483 research samples. A meta-analysis of 13 cohort studies concluded that children of pregnant women with PCOS had a 1.36 times greater risk of developing autism than those without PCOS, and the effect was statistically significant (aOR= 1.36; 95% CI= 1.24 to 1.49; p&lt;0.001). In addition, pregnant women with maternal diabetes have a 1.24 times higher risk of having a child with autism than those without maternal diabetes, and this effect is statistically significant (aOR= 1.24; 95% CI= 1.08 to 1.43; p=0.002). Conclusion: Pregnant women who have PCOS and maternal diabetes increase the risk of autism in children. Keywords: polycystic ovarian syndrome, maternal diabetes, autism.

Artificial Intelligence in Reproductive Medicine – An Ethical Perspective

Artificial intelligence is steadily being integrated into all areas of medicine. In reproductive medicine, artificial intelligence methods can be utilized to improve the selection and prediction of sperm cells, oocytes, and embryos and to generate better predictive models for in vitro fertilization. The use of artificial intelligence in this field is justified by the suffering of persons or couples who wish to have children but are unable to conceive. However, research into the use of artificial intelligence in reproductive medicine is still in the early experimental stage and furthermore raises complex normative questions. There are ethical research challenges because evidence of the efficacy of certain pertinent systems is often lacking and because of the increased difficulty of ensuring informed consent on the part of the affected persons. Other ethically relevant issues include the potential risks for offspring and the difficulty of providing sufficient information. The opportunity to fulfill the desire to have children affects the welfare of patients and their reproductive autonomy. Ultimately, ensuring more accurate predictions and allowing physicians to devote more time to their patients will have a positive effect. Nevertheless, clinicians must be able to process patient data conscientiously. When using artificial intelligence, numerous actors are involved in making the diagnosis and deciding on the appropriate therapy, raising questions about who is ultimately responsible when mistakes occur. Questions of fairness arise with regard to resource allocation and cost reimbursement. Thus, before implementing artificial intelligence in clinical practice, it is necessary to critically examine the quantity and quality of the data used and to address issues of transparency. In the medium and long term, it would be necessary to confront the undesirable impact and social dynamics that may accompany the use of artificial intelligence in reproductive medicine.

Maternal bariatric surgery: a sibling-matched analysis comparing health of offspring born before and after surgery

Due to the global escalation in the prevalence of obesity, bariatric surgeries have become a popular solution in many western countries. The aim of the current study was to compare offspring health and obesity of women before and after undergoing bariatric surgeries. A retrospective population based study was performed, including all singleton deliveries which occurred at a tertiary medical center between the years 1991-2021. Among women who had bariatric surgeries, health of the offspring born before and after the surgery were compared. The offspring were followed-up until the age of 18 years, and their hospitalization records were summarized. The incidence of hospitalization with either endocrine, cardiac, respiratory, neurologic or infectious diagnoses were compared between the groups, as well as offspring obesity. Multivariable Cox proportional models were used to match between siblings and to address confounding variables, including maternal age, gestational age at delivery, fertility treatment, smoking and pregnancy hypertensive disorders. The study population included 380,258 deliveries, 3,074 were of women who underwent bariatric surgeries (1,586 were before and 1,488 after the surgery). Offspring born after maternal bariatric surgeries were at a comparable risk for most morbidities (Table), besides endocrine related morbidities (3.2% vs. 5.2%, OR=1.68; 1.17-2.41) and obesity (2.5% vs. 4.1%, OR=1.61; 1.08-2.41). The risk for these morbidities was higher among offspring of mothers after versus before the surgery, although adjustment for maternal age and other confounding variables (Graph). While bariatric surgeries are considered an effective treatment for obesity, it seems to have less effect on offspring of women who underwent such surgeries. Other persistent factors are most likely associated with the offspring risk for morbidities, especially endocrine morbidities and obesity, which remain although the mother underwent bariatric surgeries.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Hyperemesis gravidarum: does it increase offspring risk for inflammatory bowel disease and failure to thrive?

Hyperemesis gravidarum (HG) affects about 3% of pregnancies and may lead to nutritional deficits and distress. Since maternal malnutrition and stress have been shown to affect fetal intestine and immune system development, we aimed to study the association between HG and the risk for offspring inflammatory bowel disease (IBD) and failure to thrive (FTT).Study Design: A retrospective cohort study was performed comparing incidence of offspring IBD and FTT between mothers with and without HG diagnosis. All singleton deliveries of mothers from the largest HMO in the country between the years 1991-2021 were included. Their offspring were followed until the age of 18 years, and the studied outcomes were based on hospitalization records of the pediatric databases of a large single tertiary center. Multivariable Cox survival models were used to adjust for confounding characteristics.Results: The study population included 232476 pregnancies, of them 3225 (1.4%) were complicated with HG. Mothers with HG were more likely to be smokers, and to deliver preterm and by cesarean delivery (CD). The incidence of FTT was higher among offspring born to mothers with HG (3.4% versus 2.5%, OR=1.36; 1.12-1.65, p=0.002), as well as IBD (13.3% versus 8.1%, OR= 1.74; 1.57-1.93, p< 0.001; Figure, Kaplan-Meier log rank, p< 0.001 for both). In the multivariable Cox model, offspring born following pregnancies complicated with HG were more likely to suffer from IBD (adjusted HR=1.81; 1.64-2.00, p< 0.001), and FTT (adjusted HR=1.49; 1.23-1.80, p< 0.001) while adjusting for gestational age, maternal age, CD and ethnicity.Conclusion: Offspring of pregnancies complicated with HG are at increased risk for FTT and IBD, suggesting this early life exposure may have long-term effects on the offspring, possibly due to maternal stress and malnutrition during critical period of fetal development.View Large Image Figure ViewerDownload Hi-res image Download (PPT)