Maternal Vitamin D Deficiency Impairs the Development of ß Cells in Offspring Rats in a Sex-Dependent Manner.

Recent studies have shown that maternal vitamin D deficiency (VDD) causes long-term metabolic changes in offspring. However, little is known about the impact of maternal VDD on offspring endocrine pancreas development and insulin secretion in the adult life of male and female animals. Female rats (Wistar Hannover) were fed either control (1000 IU Vitamin D3/kg), VDD (0 IU Vitamin D3/kg), or a Ca2+-enriched VDD diet (0 IU Vitamin D3/kg + Ca2+ and P/kg) for 6 weeks and during gestation and lactation. At weaning, VDD status was confirmed based on low serum calcidiol levels in dams and pups. Next, male and female offspring were randomly separated and fed a standard diet for up to 90 days. At this age, serum calcidiol levels were restored to normal levels in all groups, but serum insulin levels were decreased in VDD males without affecting glucagon levels, glycemia, or glucose tolerance. Islets isolated from VDD males showed lower insulin secretion in response to different glucose concentrations, but this effect was not observed in VDD females. Furthermore, VDD males, but not females, showed a smaller total pancreatic islet area and lower ß cell mass, an effect that was accompanied by reduced gene expression of Ins1, Ins2, Pdx1, and SLC2A2. The decrease in Pdx1 expression was not related to the methylation profile of the promoter region of this gene. Most of these effects were observed in the male VDD+Ca2+ group, indicating that the effects were not due to alterations in Ca2+ metabolism. These data show that maternal VDD selectively impairs the morphology and function of ß cells in adult male offspring rats and that female offspring are fully protected from these deleterious effects.

Liquefied Petroleum Gas or Biomass Cooking and Severe Infant Pneumonia.

BACKGROUND: Exposure to household air pollution is a risk factor for severe pneumonia. The effect of replacing biomass cookstoves with liquefied petroleum gas (LPG) cookstoves on the incidence of severe infant pneumonia is uncertain. METHODS: We conducted a randomized, controlled trial involving pregnant women 18 to 34 years of age and between 9 to less than 20 weeks' gestation in India, Guatemala, Peru, and Rwanda from May 2018 through September 2021. The women were assigned to cook with unvented LPG stoves and fuel (intervention group) or to continue cooking with biomass fuel (control group). In each trial group, we monitored adherence to the use of the assigned cookstove and measured 24-hour personal exposure to fine particulate matter (particles with an aerodynamic diameter of ≤2.5 µm [PM2.5]) in the women and their offspring. The trial had four primary outcomes; the primary outcome for which data are presented in the current report was severe pneumonia in the first year of life, as identified through facility surveillance or on verbal autopsy. RESULTS: Among 3200 pregnant women who had undergone randomization, 3195 remained eligible and gave birth to 3061 infants (1536 in the intervention group and 1525 in the control group). High uptake of the intervention led to a reduction in personal exposure to PM2.5 among the children, with a median exposure of 24.2 µg per cubic meter (interquartile range, 17.8 to 36.4) in the intervention group and 66.0 µg per cubic meter (interquartile range, 35.2 to 132.0) in the control group. A total of 175 episodes of severe pneumonia were identified during the first year of life, with an incidence of 5.67 cases per 100 child-years (95% confidence interval [CI], 4.55 to 7.07) in the intervention group and 6.06 cases per 100 child-years (95% CI, 4.81 to 7.62) in the control group (incidence rate ratio, 0.96; 98.75% CI, 0.64 to 1.44; P = 0.81). No severe adverse events were reported to be associated with the intervention, as determined by the trial investigators. CONCLUSIONS: The incidence of severe pneumonia among infants did not differ significantly between those whose mothers were assigned to cook with LPG stoves and fuel and those whose mothers were assigned to continue cooking with biomass stoves. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; HAPIN ClinicalTrials.gov number, NCT02944682.).

Impact of low-level prenatal alcohol exposure and maternal stress on autonomic regulation.

BACKGROUND: Prenatal alcohol exposure (PAE) impacts the neurodevelopment of the fetus, including the infant's ability to self-regulate. Heart rate variability (HRV), that is, the beat-to-beat variability in heart rate, is a non-invasive measurement that can indicate autonomic nervous system (ANS) function/dysfunction. METHODS: The study consisted of a subset of our ENRICH-2 cohort: 80 participants (32 PAE and 48 Controls) who had completed three visits during pregnancy. The participants completed a comprehensive assessment of PAE and other substances throughout pregnancy and assessments for stress, anxiety, and depression in the third trimester. At 24 h of age, infant HRV was assessed in the hospital during the clinically indicated heel lance; 3- to 5-min HRV epochs were obtained during baseline, heel lancing, and recovery episodes. RESULTS: Parameters of HRV differed in infants with PAE compared to Controls during the recovery phase of the heel lance (respiratory sinus arrhythmia (RSA) and high-frequency (HF), p < 0.05). Increased maternal stress was also strongly associated with abnormalities in RSA, HF, and low-frequency / high-frequency (LF/HF, p's < 0.05). CONCLUSIONS: Alterations in ANS regulation associated with PAE and maternal stress may reflect abnormal development of the hypothalamic-pituitary-adrenal axis and have long term implications for infant responsiveness and self-regulation. IMPACT: Previous studies have focused on effects of moderate to heavy prenatal alcohol exposure (PAE) on autonomic dysregulation, but little is known about the effects of lower levels of PAE on infant self-regulation and heart rate variability (HRV). Prenatal stress is another risk factor for autonomic dysregulation. Mild PAE impacts infant self-regulation, which can be assessed using HRV. However, the effect of prenatal stress is stronger than that of mild PAE or other mental health variables on autonomic dysregulation.

Associations of concurrent early-life famine exposure and adulthood obesity with type 2 diabetes mellitus in middle-aged Chinese.

BACKGROUND: Evidence has shown that early-life famine exposure and obesity in adulthood are independently associated with the risk of type 2 diabetes mellitus (T2DM). However, few studies had revealed the combined effect of these risk factors. METHODS: Two sets of groups from the China Health and Retirement Longitudinal Study (CHARLS) were selected. The fetal-exposure group born in 1959-1961 from 2011 wave (N = 958) and nonexposure group born in 1963-1965 from 2015 wave (N = 1540) were selected as Comparison 1. The early childhood-exposure group born in 1955-1957 from 2011 wave (N = 1510) and fetal-exposure group born in 1959-1961 from 2015 wave (N = 943) were Comparison 2. Logistic regressions were applied to examine the associations of different famine exposure periods and obesity patterns with T2DM risk. RESULTS: Compared with nonexposed participants without central overweight/obesity in adulthood, central overweight/obesity in adulthood together with nonexposure (odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.19-3.00) or fetal-exposure (OR: 1.99, 95% CI: 1.23-3.23) was associated with higher risks of T2DM. Compared with the early childhood-exposure group, the fetal-exposed participants showed higher risks of T2DM (OR: 1.30, 95% CI: 1.02-1.66). The coexistence of fetal famine exposure and central overweight/obesity in adulthood was associated with higher risks of T2DM (OR: 1.82, 95% CI: 1.19-2.79). Consistent associations were observed among males and participants from less severely affected areas. CONCLUSIONS: In conclusion, central overweight/obesity in adulthood is associated with the increased risk of T2DM, but the effect of early-life famine exposure is not very clear.

Gastrulation-stage alcohol exposure induces similar rates of craniofacial malformations in male and female C57BL/6J mice.

BACKGROUND: Prenatal alcohol exposure during gastrulation (embryonic day [E] 7 in mice, ~3rd week of human pregnancy) impairs eye, facial, and cortical development, recapitulating birth defects characteristic of Fetal Alcohol Syndrome (FAS). However, it is not known whether the prevalence or severity of craniofacial features associated with FAS is affected by biological sex. METHODS: The current study administered either alcohol (2.9 g/kg, two i.p. doses, 4 hr apart) or vehicle to pregnant C57BL/6J females on E7, prior to gonadal sex differentiation, and assessed fetal morphology at E17. RESULTS: Whereas sex did not affect fetal size in controls, alcohol-exposed females were smaller than both control females and alcohol-treated males. Alcohol exposure increased the incidence of eye defects to a similar degree in males and females. Together, these data suggest that females might be more sensitive to the general developmental effects of alcohol, but not effects specific to the craniofacies. Whole transcriptomic analysis of untreated E7 embryos found 214 differentially expressed genes in females vs. males, including those in pathways related to cilia and mitochondria, histone demethylase activity, and pluripotency. CONCLUSION: Gastrulation-stage alcohol induces craniofacial malformations in male and female mouse fetuses at similar rates and severity, though growth deficits are more prevalent females. These findings support the investigation of biological sex as a contributing factor in prenatal alcohol studies.

Nurturing through Nutrition: Exploring the Role of Antioxidants in Maternal Diet during Pregnancy to Mitigate Developmental Programming of Chronic Diseases.

Chronic diseases represent one of the major causes of death worldwide. It has been suggested that pregnancy-related conditions, such as gestational diabetes mellitus (GDM), maternal obesity (MO), and intra-uterine growth restriction (IUGR) induce an adverse intrauterine environment, increasing the offspring's predisposition to chronic diseases later in life. Research has suggested that mitochondrial function and oxidative stress may play a role in the developmental programming of chronic diseases. Having this in mind, in this review, we include evidence that mitochondrial dysfunction and oxidative stress are mechanisms by which GDM, MO, and IUGR program the offspring to chronic diseases. In this specific context, we explore the promising advantages of maternal antioxidant supplementation using compounds such as resveratrol, curcumin, N-acetylcysteine (NAC), and Mitoquinone (MitoQ) in addressing the metabolic dysfunction and oxidative stress associated with GDM, MO, and IUGR in fetoplacental and offspring metabolic health. This approach holds potential to mitigate developmental programming-related risk of chronic diseases, serving as a probable intervention for disease prevention.

The Association Between Prenatal Infection and Adolescent Behavior: Investigating Multiple Prenatal, Perinatal, and Childhood Second Hits.

OBJECTIVE: Exposure to infections during pregnancy may be a potential risk factor for later psychopathology, but large-scale epidemiological studies investigating associations between prenatal infection and long-term offspring behavioral problems in the general population are scarce. In our study, we aimed to investigate the following: (1) the association between prenatal infection and adolescent behavior, (2) putative underlying pathways (mediation), and (3) "second hits" interacting with prenatal infection to increase the risk of adolescent behavior problems (moderation). METHOD: Our study was embedded in a prospective Dutch pregnancy cohort (Generation R; n = 2,213 mother-child dyads). We constructed a comprehensive prenatal infection score comprising common infections for each trimester of pregnancy. At age 13 to 16 years, we assessed total, internalizing, and externalizing problems, and autistic traits using the Child Behavioral Checklist and the Social Responsiveness Scale, respectively. We investigated maternal lifestyle and nutrition, perinatal factors (placental health and delivery outcomes), and child health (lifestyle, traumatic events, infections) as mediators and moderators. RESULTS: We observed associations of prenatal infection with adolescent total behavioral, internalizing, and externalizing problems. The association between prenatal infection and internalizing problems was moderated by higher levels of maternal psychopathology, alcohol and tobacco use, and a higher number of traumatic childhood events. We found no association between prenatal infection and autistic traits. Yet, children exposed to prenatal infections and maternal substance use, and/or traumatic childhood events, had a higher risk of autistic traits in adolescence. CONCLUSION: Prenatal infection may be a risk factor for later psychiatric problems as well as a disease primer making individuals susceptible to other hits later in life. STUDY PREREGISTRATION INFORMATION: Prenatal maternal infection and adverse neurodevelopment: a structural equation modelling approach to downstream environmental hits; https://osf.io/cp85a; cp85a. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants.

Current Understanding of the Roles of Gut-Brain Axis in the Cognitive Deficits Caused by Perinatal Stress Exposure.

The term 'perinatal environment' refers to the period surrounding birth, which plays a crucial role in brain development. It has been suggested that dynamic communication between the neuro-immune system and gut microbiota is essential in maintaining adequate brain function. This interaction depends on the mother's status during pregnancy and/or the newborn environment. Here, we show experimental and clinical evidence that indicates that the perinatal period is a critical window in which stress-induced immune activation and altered microbiota compositions produce lasting behavioral consequences, although a clear causative relationship has not yet been established. In addition, we discuss potential early treatments for preventing the deleterious effect of perinatal stress exposure. In this sense, early environmental enrichment exposure (including exercise) and melatonin use in the perinatal period could be valuable in improving the negative consequences of early adversities. The evidence presented in this review encourages the realization of studies investigating the beneficial role of melatonin administration and environmental enrichment exposure in mitigating cognitive alteration in offspring under perinatal stress exposure. On the other hand, direct evidence of microbiota restoration as the main mechanism behind the beneficial effects of this treatment has not been fully demonstrated and should be explored in future studies.

Association between prenatal antimicrobial use and offspring attention deficit hyperactivity disorder.

BACKGROUND: Gut-brain cross-talk may play an important role in modulating neurodevelopment. Few studies have examined the association between antimicrobials that influence infant gut microbiota assemblage and attention deficit hyperactivity disorder (ADHD). OBJECTIVE: To examine the association between maternal prenatal antimicrobial use and ADHD in offspring at 10 years of age. METHODS: Data are from the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, a racially and socioeconomically diverse birth cohort in metropolitan Detroit, Michigan. Maternal antimicrobial use was extracted from the medical record. ADHD diagnoses were based on parental report at the 10-year study visit. Poisson regression models with robust error variance were used to calculate risk ratios (RR). Cumulative frequency of exposure to antibiotics, and effect modification were also evaluated. RESULTS: Among the 555 children included in the analysis, 108 were diagnosed with ADHD. During pregnancy, 54.1% of mothers used antibiotics while 18.7% used antifungals. Overall, there was no evidence of an association between prenatal antibiotic exposure and ADHD (RR [95% CI] = 0.98 [0.75, 1.29]), but there was an increased risk of ADHD among those with mothers using 3+ courses of antibiotics (RR [95%CI] = 1.58 [1.10, 2.29]). Prenatal exposure to antifungals was associated with a 1.6 times higher risk of ADHD (RR [95% CI] = 1.60 [1.19, 2.15]). In examining effect modification by child sex for antifungal use, there was no evidence of an association among females (RR [95% CI] = 0.97 [0.42, 2.23]), but among males, prenatal antifungal use was associated with 1.82 times higher risk of ADHD (RR [95% CI] = 1.82 [1.29, 2.56]). CONCLUSIONS: Maternal prenatal antifungal use and frequent prenatal antibiotic use are associated with an increased risk of ADHD in offspring at age 10. These findings highlight the importance of the prenatal environment and the need for careful use of antimicrobials.

Maternal depression or anxiety during pregnancy and offspring type 1 diabetes: a population-based family-design cohort study.

INTRODUCTION: To investigate the association between maternal depression/anxiety during pregnancy and offspring type 1 diabetes, to assess the specific importance of exposure during pregnancy by comparing across different exposure periods before and/or after pregnancy, and to explore potential unmeasured familial confounding. RESEARCH DESIGN AND METHODS: This was a population-based cohort including 1 807 809 offspring born in Sweden 2002-2019. From national registers, data were available on diagnosis or medication prescription for depression/anxiety in and around pregnancy, as well as incident cases of type 1 diabetes defined through diagnosis or insulin treatment. Associations were examined using flexible parametric and Cox regression models. Familial confounding was explored using paternal exposure as a negative control and by comparing offspring exposed to maternal depression/anxiety with their unexposed siblings. RESULTS: For exposure during pregnancy, maternal depression/anxiety was associated with an increased risk of offspring type 1 diabetes onset after, but not before, 8 years of age (adjusted HR (aHR) 1.21 (95% CI 1.03 to 1.42]). Exposure occurring only during pregnancy was similarly associated to type 1 diabetes (aHR 1.24 (0.96 to 1.60)), whereas exposure occurring only before pregnancy was not (aHR 0.91 (0.64 to 1.30)). Associations were close to the null for paternal depression/anxiety (aHR 0.95 (0.72 to 1.25)), and point estimates were above 1 in sibling comparisons, although with wide CIs (aHR 1.36 (0.82 to 2.26)). CONCLUSIONS: Maternal depression/anxiety specifically during pregnancy seems to be associated with offspring type 1 diabetes. Paternal negative control and sibling comparisons indicate that the results cannot entirely be explained by familial confounding.

Prebirth effects of climate change on children's respiratory health.

PURPOSE OF REVIEW: To date, there is no evidence that humanity will implement appropriate mitigation measures to avoid the catastrophic impact of climate change on the planet and human health. Vulnerable populations such as pregnant women and children will be the most affected. This review highlights epidemiologic data on climate change-related prenatal environmental exposures affecting the fetus and children's respiratory health. RECENT FINDINGS: Research on outcomes of prenatal exposure to climate change-related environmental changes and pediatric pulmonary health is limited. In addition to adverse pregnancy outcomes known to affect lung development, changes in lung function, increased prevalence of wheezing, atopy, and respiratory infections have been associated with prenatal exposure to increased temperatures, air pollution, and maternal stress. The mechanisms behind these changes are ill-defined, although oxidative stress, impaired placental functioning, and epigenetic modifications have been observed. However, the long-term impact of these changes remains unknown. SUMMARY: The detrimental impact of the climate crisis on pediatric respiratory health begins before birth, highlighting the inherent vulnerability of pregnant women and children. Research and advocacy, along with mitigation and adaptation measures, must be implemented to protect pregnant women and children, the most affected but the least responsible for the climate crisis.

Cardiovascular and renal profiles in rat offspring that do not undergo catch-up growth after exposure to maternal protein restriction.

Maternal protein restriction is often associated with structural and functional sequelae in offspring, particularly affecting growth and renal-cardiovascular function. However, there is little understanding as to whether hypertension and kidney disease occur because of a primary nephron deficit or whether controlling postnatal growth can result in normal renal-cardiovascular phenotypes. To investigate this, female Sprague-Dawley rats were fed either a low-protein (LP, 8.4% protein) or normal-protein (NP, 19.4% protein) diet prior to mating and until offspring were weaned at postnatal day (PN) 21. Offspring were then fed a non 'growth' (4.6% fat) which ensured that catch-up growth did not occur. Offspring growth was determined by weight and dual energy X-ray absorptiometry. Nephron number was determined at PN21 using the disector-fractionator method. Kidney function was measured at PN180 and PN360 using clearance methods. Blood pressure was measured at PN360 using radio-telemetry. Body weight was similar at PN1, but by PN21 LP offspring were 39% smaller than controls (Pdiet < 0.001). This difference was due to proportional changes in lean muscle, fat, and bone content. LP offspring remained smaller than NP offspring until PN360. In LP offspring, nephron number was 26% less in males and 17% less in females, than NP controls (Pdiet < 0.0004). Kidney function was similar across dietary groups and sexes at PN180 and PN360. Blood pressure was similar in LP and NP offspring at PN360. These findings suggest that remaining on a slow growth trajectory after exposure to a suboptimal intrauterine environment does not lead to the development of kidney dysfunction and hypertension.

Early childhood exposure to maternal smoking and obesity: A nationwide longitudinal survey in Japan.

Involuntary exposure to tobacco smoke is suspected to be one of the risks factors that are associated with obesity in children. The purpose of this study was to examine the relationship between early childhood exposure to tobacco smoke and the risk of obesity and overweight in Japan. This study utilized a nationwide, population-based longitudinal survey. The participants were restricted to 32 081 children who had available information on maternal smoking history as well as childhood height and weight. We conducted a binomial log-linear regression analysis with children of non-smoking mothers as the reference group. The children with mothers who were smokers had a higher risk of developing obesity or being overweight compared to the children with mothers who were nonsmokers. The risk ratios were 1.20 (95% confidence interval [CI]: 1.09-1.32) for overweight and 1.17 (95% CI: 0.95-1.44) for obesity. Early exposure to maternal smoking increases the risk of being overweight and having obesity during childhood. The increased risk is more pronounced among children with mothers, smoked heavily, or parents, who were smokers.

Maternal exposure to di(2-ethylhexyl) phthalate (DEHP) causes multigenerational adverse effects on the uterus of F1 and F2 offspring rats.

Phthalates are one of the ubiquitous chemicals found in day-to-day products like food packaging, children's toys, and other consumer commodities. There is rising concern that repeated exposure to phthalates during pregnancy and lactation could have long-term effects on maternal and fetal health. We hypothesize that exposure to DEHP during the developmental windows might affect the expression of molecules that regulate uterine function and that this effect would be passed on to further generations. Rat dams were treated with olive oil (vehicle) or DEHP (100 mg/kg b.wt./day) orally from gestational day 9 (GD 9) to the end of lactation (PND 21). F0 maternal DEHP exposure resulted in multigenerational (F1 and F2) reproductive toxicity, as evidenced by an extended estrous cycle, decreased mating, fertility, and fecundity indices. Serum progesterone and estradiol levels were decreased and their cognate receptors (PR and ERα) in the uterus were decreased in the DEHP-exposed offspring rats. Further analysis of the expression of estrogen and progesterone regulatory genes such as Hox a11, VEGF A, Ihh, LIFR, EP4, PTCH, NR2F2, BMP2, and Wnt4 were reduced in the uteri of adult F1 and F2 generation rats born from DEHP-exposed F0 dams. Decreased expression of these crucial proteins due to DEHP exposure may lead to defects in epithelial proliferation and secretion, uterine receptivity, and decidualization in the uteri of successive generations. This study showed that maternal DEHP exposure impairs the expression of molecules that regulate uterine function and this multigenerational effect is transmitted via maternal lineage.

The effects of long-term prenatal exposure to 900, 1800, and 2100 MHz electromagnetic field radiation on myocardial tissue of rats.

It is well-known that wireless communication technologies facilitate human life. However, the harmful effects of electromagnetic field (EMF) radiation on the human body should not be ignored. In the present study, we evaluated the effects of long-term, prenatal exposure to EMF radiation on the myocardium of rats at varying durations. Overall, 18 pregnant Sprague-Dawley rats were assigned into six groups (n = 3 in each group). In all groups other than the control group, three pregnant rats were exposed to EMF radiation (900, 1800 and 2100 MHz) for 6, 12 and 24 h over 20 days. After delivery, the newborn male pups were identified and six newborn male pups from each group were randomly selected. Then, histopathological and biochemical analysis of myocardial samples were performed. When 24-h/day prenatal exposures to 900, 1800, 2100 MHz EMF radiation were evaluated, myocardial damage was greater in the 2100 MHz EMF-24h group than the other groups. In addition, when malondialdehyde (MDA) and glutathione (GSH) levels associated with reactive oxidative species (ROS) were evaluated, the MDA level was higher in the 2100 MHz EMF-24h group compared with the other groups. The GSH level was also lower in the 2100 MHz EMF-24h group. When the 6, 12 and 24 h/day prenatal exposures to 1800 MHz EMF radiation were evaluated, myocardial damage was greater in 1800 MHz EMF-24h group than the remaining groups (p < 0.0001). Also, MDA level was greater in the 1800 MHz EMF-24h group compared with the other groups while the GSH level was lower in this group. It was shown that myocardial tissue was affected more by long-term exposure to EMF radiation at high frequencies. The data raise concerns that the harmful effects of non-ionizing radiation exposure on cardiac tissue will increase with 5G technology.

Maternal high-fat diet consumption during pregnancy and lactation predisposes offspring to renal and metabolic injury later in life: comparative study of diets with different lipid contents.

Accumulating evidence suggests that maternal overnutrition can result in a higher development risk of obesity and renal disease in the offspring's adulthood. The present study tested different lipid levels in the maternal diet during pregnancy and lactation and its repercussions on the offspring of Wistar rats. Offspring of 1, 7, 30 and 90-d-old were divided into the following groups: Control (CNT) - offspring of dams that consumed a standard chow diet (3.5% of lipids); Experimental 1 (EXP1) - offspring of dams exposed to a high-fat diet (HFD) (28% of lipids); and Experimental 2 (EXP2) - offspring of dams exposed to a HFD (40% of lipids). Regarding maternal data, there was a decrease in the amount of diet ingested by EXP2. Daily caloric intake was higher in EXP1, while protein and carbohydrate intakes were lower in EXP2. While lipid intake was higher in the experimental groups, EXP1 consumed more lipids than EXP2, despite the body weight gain being higher in EXP2. Adult offspring from EXP1 presented higher blood glucose. Regarding morphometric analysis, in both experimental groups, there was an increase in the glomerular tuft and renal corpuscle areas, but an increase in the capsular space area only in EXP1. There was a decrease in the glomerular filtration rate (GFR) in EXP1, in contrast to an increase in GFR of EXP2, along with an increase in urinary protein excretion. In conclusion, the maternal HFDs caused significant kidney damage in offspring, but had different repercussions on the type and magnitude of recorded change.

Maternal pea fiber supplementation to a high calorie diet in obese pregnancies protects male offspring from metabolic dysfunction in adulthood.

We investigated the influence of maternal yellow-pea fiber supplementation in obese pregnancies on offspring metabolic health in adulthood. Sixty newly-weaned female Sprague-Dawley rats were randomized to either a low-calorie control diet (CON) or high calorie obesogenic diet (HC) for 6-weeks. Obese animals were then fed either the HC diet alone or the HC diet supplemented with yellow-pea fiber (HC + FBR) for an additional 4-weeks prior to breeding and throughout gestation and lactation. On postnatal day (PND) 21, 1 male and 1 female offspring from each dam were weaned onto the CON diet until adulthood (PND 120) for metabolic phenotyping. Adult male, but not female, HC offspring demonstrated increased body weight and feed intake vs CON offspring, however no protection was offered by maternal FBR supplementation. HC male and female adult offspring demonstrated increased serum glucose and insulin resistance (HOMA-IR) compared with CON offspring. Maternal FBR supplementation improved glycemic control in male, but not female offspring. Compared with CON offspring, male offspring from HC dams demonstrated marked dyslipidemia (higher serum cholesterol, increased number of TG-rich lipoproteins, and smaller LDL particles) which was largely normalized in offspring from HC + FBR mothers. Male offspring born to obese mothers (HC) had higher hepatic TG, which tended to be lowered (p = 0.07) by maternal FBR supplementation.Supplementation of a maternal high calorie diet with yellow-pea fiber in prepregnancy and throughout gestation and lactation protects male offspring from metabolic dysfunction in the absence of any change in body weight status in adulthood.

Elevated level of testosterone in amniotic fluid during prenatal stress and its association with development of Attention-Deficit/Hyperactivity Disorder (ADHD) like symptoms in toddlers.

AIM OF THE STUDY: To investigate the "prenatal testosterone hypothesis", according to which, high level of testosterone associated with the development of ADHD like symptoms in younger children, and to investigate whether maternal stress during pregnancy in-creases the risk of developing ADHD like symptoms in early childhood. DESIGN: This was a prospective study with three measurement periods: the first one during pregnancy (12 to 25 weeks of gestation); the second period involved the assessment of infants of this pregnancy at the age of 6 months and the third one the assessment of the same infants at the age of 18 months. The research plan is approved by "David Tvildiani Medical University" Research Ethics Committee. The study does not contain serious predictable risks as the expected benefit overweighs them. MATERIAL AND METHODS: The study group is presented by 40 pregnant women and 40 infants of these pregnancies. Pregnant women were asked about their perceived stress levels, critical life events of the past year and pregnancy-specific stress levels using standardized questionnaires. Child's temperament and behavioral regulation were assessed using the questionnaires. Amniotic fluid was collected undergoing amniocentesis. Total testosterone in amniotic fluid was measured by radioimmunoassay. RESULTS: Although statistically significant relationship was identified between hyperactivity, also impulsiveness symptoms and pre-natal stress, no statistically significant relationship was identified between testosterone level and hyperactivity, also impulsivity symptoms, as well as between testosterone level and prenatal stress level. CONCLUSIONS: The performed study did not support the "hypothesis about prenatal testosterone", because there was a significant negative correlation between the frequency of hyperactivity symptoms and testosterone level.

Maternal Fructose Intake, Programmed Mitochondrial Function and Predisposition to Adult Disease.

Fructose consumption is now recognised as a major risk factor in the development of metabolic diseases, such as hyperlipidaemia, diabetes, non-alcoholic fatty liver disease and obesity. In addition to environmental, social, and genetic factors, an unfavourable intrauterine environment is now also recognised as an important factor in the progression of, or susceptibility to, metabolic disease during adulthood. Developmental trajectory in the short term, in response to nutrient restriction or excessive nutrient availability, may promote adaptation that serves to maintain organ functionality necessary for immediate survival and foetal development. Consequently, this may lead to decreased function of organ systems when presented with an unfavourable neonatal, adolescent and/or adult nutritional environment. These early events may exacerbate susceptibility to later-life disease since sub-optimal maternal nutrition increases the risk of non-communicable diseases (NCDs) in future generations. Earlier dietary interventions, implemented in pregnant mothers or those considering pregnancy, may have added benefit. Although, the mechanisms by which maternal diets high in fructose and the vertical transmission of maternal metabolic phenotype may lead to the predisposition to adult disease are poorly understood. In this review, we will discuss the potential contribution of excessive fructose intake during pregnancy and how this may lead to developmental reprogramming of mitochondrial function and predisposition to metabolic disease in offspring.

How Do the Different Types of Maternal Diabetes during Pregnancy Influence Offspring Outcomes?

Background/Aim of the study: Exposure to maternal diabetes is considered one of the most common in utero insults that can result in an increased risk of complications later in life with a permanent effect on offspring health. In this study, we aim to assess the level of risk associated with each type of maternal diabetes on obesity, glucose intolerance, cardiovascular diseases (CVD), and neurodevelopmental disorders in offspring. Methods: We conducted a systematic review of the literature utilizing PubMed for studies published between January 2007 and March 2022. Our search included human cohorts and case control studies following offspring exposed at least to two different types of maternal diabetes clearly identified during pregnancy. Collected outcomes included prevalence, incidence, odds ratio, hazard ratio and risk ratio. Results: Among 3579 published studies, 19 cohorts were eligible for inclusion in our review. The risks for overweight, obesity, type 2 diabetes (T2D), glucose intolerance, metabolic syndrome, and CVD were increased for all types of maternal diabetes during pregnancy. The risk of overweight or obesity in infancy and in young adults was similar between gestational diabetes mellitus (GDM) and type 1 diabetes (T1D). The risk for T2D or abnormal glucose tolerance was double for offspring from GDM mothers compared to offspring from T1D mothers. In contrast, the risk for T1D in offspring at any age until young adulthood was increased when mothers had T1D compared to GDM and T2D. The risk for CVD was similar for all types of maternal diabetes, but more significant results were seen in the occurrence of heart failure and hypertension among offspring from T2D mothers. The risk of autism spectrum disorders and attention deficit/hyperactivity disorders was mainly increased after in utero exposure to preexisting T1D, followed by T2D. Conclusions: Offspring of diabetic mothers are at increased risk for multiple adverse outcomes with the highest risk detected among offspring from T2D mothers. Future work warrants large multiethnic prospective cohort studies that aim to identify the risks associated with each type of maternal diabetes separately.