Health Of Offspring Research Articles

Modifying Levels of Maternal Dietary Folic Acid or Choline to Study the Impact of Deficiencies on Offspring Health Outcomes.

Maternal nutrition during pregnancy and lactation plays an important role in the neurodevelopment of offspring. One-carbon (1C) metabolism, which centers around folic acid and choline, as well as other B vitamins, plays a key role during the closure of the neural tube of the developing fetus. However, the impact of these maternal nutritional deficiencies during pregnancy on offspring health outcomes after birth remains relatively undefined. Furthermore, maternal dietary deficiencies in folic acid or choline may impact other health outcomes in offspring - making this a valuable model. This protocol aims to outline the procedure for inducing a deficiency in 1C metabolism in female mice through dietary modifications. Females are placed on diets at weaning, up to 2 months of age, for 4-6 weeks prior to mating and remain on diet throughout pregnancy and lactation. Offspring from these females can be evaluated for health outcomes. Females can be used multiple times to generate offspring, and tissues from females can be collected to measure for 1C metabolite measurements. This protocol provides an overview of how to induce maternal dietary deficiencies in folic acid or choline to study offspring health outcomes.

MicroRNA and Gut Microbiota Alter Intergenerational Effects of Paternal Exposure to Polyethylene Nanoplastics.

Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health are involved in NP-induced reproductive toxicity remains unclear. In this study, we developed a mouse model where male mice were administered 200 nm polyethylene nanoparticles (PE-NPs) at a concentration of 2 mg/L through daily gavage for 35 days to evaluate the intergenerational effects of PE-NPs in an exclusive male-lineage transmission paradigm. We observed that paternal exposure to PE-NPs significantly affected growth phenotypes and sex hormone levels and induced histological damage in the testicular tissue of both F0 and F1 generations. In addition, consistent changes in sperm count, motility, abnormalities, and gene expression related to endoplasmic reticulum stress, sex hormone synthesis, and spermatogenesis were observed across paternal generations. The upregulation of microRNA (miR)-1983 and the downregulation of miR-122-5p, miR-5100, and miR-6240 were observed in both F0 and F1 mice, which may have been influenced by reproductive signaling pathways, as indicated by the RNA sequencing of testis tissues and quantitative real-time polymerase chain reaction findings. Furthermore, alterations in the gut microbiota and subsequent Spearman correlation analysis revealed that an increased abundance of Desulfovibrio (C21_c20) and Ruminococcus (gnavus) and a decreased abundance of Allobaculum were positively associated with spermatogenic dysfunction. These findings were validated in a fecal microbiota transplantation trial. Our results demonstrate that changes in miRNAs and the gut microbiota caused by paternal exposure to PE-NPs mediated intergenerational effects, providing deeper insights into mechanisms underlying the impact of paternal inheritance.

Exposure to family and domestic violence in the prenatal period is associated with an increased risk of hospitalization for bronchiolitis in children under 2years.

Existing research has acknowledged a correlation between stress in pregnancy and poorer respiratory health in offspring. However, research focusing on stress caused by family and domestic violence in the prenatal period is missing. A retrospective cohort study included children born 1987-2010 who were identified as being exposed to FDV in the prenatal period (n=1477) from two sources: WA Police Information Management System and WA Hospital Morbidity Data Collection (HMDC) and a non-exposed comparison group (n=41 996). Hospitalization for bronchiolitis was identified in HMDC. Cox regression was used to estimate the adjusted and unadjusted hazard ratio and 95% confidence interval for bronchiolitis hospitalizations contact. Children exposed to FDV had a 70% (HR 1.70, 95% CI: 1.49-1.94) increased risk of hospitalization for bronchiolitis than non-exposed counterparts by age two. Children exposed to FDV had a longer average hospital stay for bronchiolitis than non-exposed children (4.0days vs. 3.8days, P<0.001). Prenatal exposure to FDV is associated with bronchiolitis hospitalization in children <2years. Along with other risk factors, clinicians should give consideration to maternal stress factors, including experiencing FDV as a potential contributor to bronchiolitis.

The role of DNA damage response in human embryonic stem cells exposed to atmospheric oxygen tension: Implications for embryo development and differentiation

Previous retrospective cohort studies have found that, compared with oxygen tension in the uterus and fallopian tubes (2 %-8 %), exposure of pre-implantation embryos to atmospheric oxygen tension (AtmO2, 20 %) during assisted reproductive technology(ART) can affect embryo quality, pregnancy outcomes and offspring health. However, current research on the effects and mechanisms of AtmO2 on the development of embryos and offspring is mainly limited to animal experiments. Human embryonic stem cells (hESCs) play a special and irreplaceable role in the study of early human embryonic development. In this study, we used hESCs as a model to elucidate the possible effects and mechanisms of AtmO2 exposure on human embryonic development. We found that exposure to AtmO2 can reduce cell viability, produce oxidative stress, increase DNA damage, initiate DNA repair, activate autophagy, and increase cell apoptosis. We also noticed that approximately 50 % of hESCs survived, adapted and proliferated through high expression of self-renewal and pluripotency regulatory factors, and affected embryoid body differentiation. These data indicate that hESCs experience oxidative stress, accumulation of DNA damage, and activate DNA damage response under the selective pressure of AtmO2.Some hESCs undergo cell death, whereas other hESCs adapt and proliferate through increased expression of self-renewal genes. The current findings provide in vitro evidence that exposure to AtmO2 during the early preimplantation stage negatively affects hESCs.

Mutual effects of gestational diabetes and schizophrenia: how can one promote the other?: A review.

Although the physical complications of gestational diabetes mellitus (GDM) are well known, emerging evidence suggests a significant link with psychiatric conditions such as schizophrenia (SCZ). This review aimed to explore the extent, nature, and implications of the association between GDM and SCZ, exploring how the 2 conditions may reciprocally influence each other. We conducted a comprehensive literature review and, analyzed clinical and mechanistic evidence supporting the mutual effects of GDM and SCZ. This review examined factors such as neurodevelopment and the impact of antipsychotics. The study found that Maternal GDM increases the risk of SCZ in offspring. Conversely, women with SCZ were more prone to hyperglycemic pregnancies. The research highlights significant regional variations in GDM prevalence, with the highest rate in the Middle East, North Africa, and South-East Asia regions. These regional variations may have an impact on the epidemiology of SCZ. Furthermore, this review identifies the potential biological and environmental mechanisms underlying these associations. There is a bidirectional relationship between GDM and SCZ, with each disorder potentially exacerbating the others. This relationship has significant implications for maternal and offspring health, particularly in regions with high GDM prevalence. These findings underline the need for integrated care approaches for women with SCZ during pregnancy and the importance of monitoring and managing GDM to mitigate the risk of SCZ in the offspring. Notably, this study recognizes the need for further research to fully understand these complex interactions and their implications for healthcare.

Effects of maternal advanced lipoxidation end products diet on the glycolipid metabolism and gut microbiota in offspring mice.

Dietary advanced lipoxidation end products (ALEs), which are abundant in heat-processed foods, could induce lipid metabolism disorders. However, limited studies have examined the relationship between maternal ALEs diet and offspring health. To investigate the transgenerational effects of ALEs, a cross-generation mouse model was developed. The C57BL/6J mice were fed with dietary ALEs during preconception, pregnancy and lactation. Then, the changes of glycolipid metabolism and gut microbiota of the offspring mice were analyzed. Maternal ALEs diet not only affected the metabolic homeostasis of dams, but also induced hepatic glycolipid accumulation, abnormal liver function, and disturbance of metabolism parameters in offspring. Furthermore, maternal ALEs diet significantly upregulated the expression of TLR4, TRIF and TNF-α proteins through the AMPK/mTOR/PPARα signaling pathway, leading to dysfunctional glycolipid metabolism in offspring. In addition, 16S rRNA analysis showed that maternal ALEs diet was capable of altered microbiota composition of offspring, and increased the Firmicutes/Bacteroidetes ratio. This study has for the first time demonstrated the transgenerational effects of maternal ALEs diet on the glycolipid metabolism and gut microbiota in offspring mice, and may help to better understand the adverse effects of dietary ALEs.

Prenatal exposure to air pollution and maternal depression: Combined effects on brain aging and mental health in young adulthood

IntroductionBoth maternal depression problems during pregnancy and prenatal exposure to air pollution have been associated with changes in the brain as well as worse mood and anxiety in the offspring in adulthood. However, it is not clear whether these effects are independent or whether and how they might interact and impact the brain age and mental health of the young adult offspring. MethodsA total of 202 mother–child dyads from a prenatal birth cohort were assessed for maternal depression during pregnancy through self-report questionnaires administered in the early 90s, exposure to air pollutants (Sulfur dioxide [SO2], nitrogen oxides [NOx], and suspended particle matter [SPM]) during each trimester based on maternal address and air quality data, mental health of the young adult offspring (28–30 years of age; 52% men, all of European ancestry) using self-report questionnaires for depression (Beck Depression Inventory), mood dysregulation (Profile of Mood States), anxiety (State-Trait Anxiety Inventory), and psychotic symptoms (Schizotypal Personality Questionnaire), and brain age, estimated from structural magnetic resonance imaging (MRI) and previously published neuroanatomical age prediction model using cortical thickness maps. The brain age gap estimate (BrainAGE) was computed by subtracting structural brain age from chronological age. Trajectories of exposure to air pollution during pregnancy were assessed using Growth Mixture Modeling. The interactions of prenatal depression and prenatal exposure to air pollutants on adult mental health and BrainAGE were assessed using hierarchical linear regression. ResultsWe revealed two distinct trajectories of exposure to air pollution during pregnancy: “early exposure,” characterized by high exposure during the first trimester, followed by a steady decrease, and “late exposure,” characterized by low exposure during the first trimester, followed by a steady increase in the exposure during the subsequent trimesters. Maternal depression during the first half of pregnancy interacted with NOX exposure trajectory, predicting mood dysregulation and schizotypal symptoms in young adults. In addition, maternal depression during the second half of pregnancy interacted with both NOx and SO2 exposure trajectories, respectively, and predicted BrainAGE in young adults. In those with early exposure to NOx, maternal depression during pregnancy was associated with worse mental health and accelerated brain aging in young adulthood. In contrast, in those with early exposure to SO2, maternal depression during pregnancy was associated with slower brain aging in young adulthood. ConclusionsOur findings provide the first evidence of the combined effects of prenatal exposure to air pollution and maternal depression on mental health outcomes and brain age in young adult offspring. Moreover, they point out the importance of the timing and trajectory of the exposure during prenatal development.

Hyperemesis gravidarum and the risk of offspring morbidity: a longitudinal cohort study.

Hyperemesis gravidarum has the potential to affect the long-term health of offspring. We examined whether maternal hyperemesis gravidarum was associated with the risk of hospitalization for childhood morbidity. We conducted a longitudinal cohort study of 1,189,000 children born in Quebec, Canada, between April 2006 and March 2021. The main exposure measure was maternal hyperemesis gravidarum requiring hospitalization in the first or second trimester. The outcome was any pediatric admission between birth and 16years of age, with follow-up ending in March 2022. We used Cox regression models adjusted for maternal and socioeconomic factors to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between maternal hyperemesis gravidarum and childhood hospitalization. Among 1,189,000 children, 6904 (0.6%) were exposed to maternal hyperemesis gravidarum. Hospitalization rates at age 16years were higher for children exposed to hyperemesis gravidarum than unexposed children (47.6 vs 43.9 per 100 children). Relative to no exposure, hyperemesis gravidarum was associated with a 1.21 times greater risk of any hospitalization before 16years (95% CI 1.17-1.26). Hyperemesis gravidarum was associated with hospitalization for neurologic (HR 1.50, 95% CI 1.32-1.71), developmental (HR 1.51, 95% CI 1.29-1.76), digestive (HR 1.40, 95% CI 1.30-1.52), and allergic disorders (HR 1.39, 95% CI 1.24-1.56). When contrasted with preeclampsia, hyperemesis gravidarum was a stronger risk factor for these outcomes. Maternal hyperemesis gravidarum is associated with an increased risk of childhood hospitalization, especially for neurologic, developmental, digestive, and atopic disorders. • Hyperemesis gravidarum is associated with neurodevelopmental disorders in offspring. • However, the effect of hyperemesis gravidarum on other childhood morbidity is unclear. • In this longitudinal cohort study of 1.2 million children, maternal hyperemesis gravidarum was associated with a greater risk of hospitalization before age 16years. • Exposure to hyperemesis gravidarum was associated with developmental, neurologic, atopic, and digestive morbidity in childhood.

Preconceptional paternal caloric restriction of high-fat diet-induced obesity in Wistar rats dysregulates the metabolism of their offspring via AMPK/SIRT1 pathway

BackgroundObesity is a metabolic syndrome where allelic and environmental variations together determine the susceptibility of an individual to the disease. Caloric restriction (CR) is a nutritional dietary strategy recognized to be beneficial as a weight loss regime in obese individuals. Preconceptional parental CR is proven to have detrimental effects on the health and development of their offspring. As yet studies on maternal CR effect on their offspring are well established but paternal CR studies are not progressing. In current study, the impact of different paternal CR regimes in diet-induced obese male Wistar rats (WNIN), on their offspring concerning metabolic syndrome are addressed.MethodsHigh-fat diet-induced obese male Wistar rats were subjected to caloric restriction of 50% (HFCR-I) and 40% (HFCR-II) and then they were mated with normal females. The male parent’s reproductive function was assessed by sperm parameters and their DNMT’s mRNA expression levels were also examined. The offspring’s metabolic function was assessed by physiological, biochemical and molecular parameters.ResultsThe HFCR-I male parents have shown reduced body weights, compromised male fertility and reduced DNA methylation activity. Further, the HFCR-I offspring showed attenuation of the AMPK/SIRT1 pathway, which is associated with the progression of proinflammatory status and oxidative stress. In line, the HFCR-I offspring also developed altered glucose and lipid homeostasis by exhibiting impaired glucose tolerance & insulin sensitivity, dyslipidemia and steatosis. However, these effects were largely mitigated in HFCR-II offspring. Regarding the obesogenic effects, female offspring exhibited greater susceptibility than male offspring, suggesting that females are more prone to the influences of the paternal diet.ConclusionThe findings highlight that HFCR-I resulted in paternal undernutrition, impacting the health of offspring, whereas HFCR-II largely restored the effects of a high-fat diet on their offspring. As a result, moderate caloric restriction has emerged as an effective weight loss strategy with minimal implications on future generations. This underscores the shared responsibility of fathers in contributing to sperm-specific epigenetic imprints that influence the health of adult offspring.

Exploring the Impact of Extra Virgin Olive Oil on Maternal Immune System and Breast Milk Composition in Rats.

Maternal breast milk plays a key role in providing newborns with passive immunity and stimulating the maturation of an infant's immune system, protecting them from many diseases. It is known that diet can influence the immune system of lactating mothers and the composition of their breast milk. The aim of this study was to establish if a supplementation during the gestation and lactation of Lewis rats with extra virgin olive oil (EVOO), due to the high proportion of antioxidant components in its composition, has an impact on the mother's immune system and on the breast milk's immune composition. For this, 10 mL/kg of either EVOO, refined oil (control oil) or water (REF group) were orally administered once a day to rats during gestation and lactation periods. Immunoglobulin (Ig) concentrations and gene expressions of immune molecules were quantified in several compartments of the mothers. The EVOO group showed higher IgA levels in both the breast milk and the mammary glands than the REF group. In addition, the gene expression of IgA in mammary glands was also boosted by EVOO consumption. Overall, EVOO supplementation during gestation and lactation is safe and does not negatively affect the mother's immune system while improving breast milk immune composition by increasing the presence of IgA, which could be critical for an offspring's immune health.

Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs

Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs)1, which influences offspring development and adult phenotypes1–7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.

The risk of infant mortality among the offspring of the workers of radiation hazardous production

Infant mortality is an indicator of healthcare quality and social well-being in a society and could be used as an important parameter in assessing the effects produced by parental occupational exposures on the offspring health. The objective of the study: to analyze the risk of infant mortality in the cohort of the 1st generation offspring of the workers of Mayak Production Association (PA), the first atomic production facility in Russia. Infant mortality and its components were analyzed in a cohort of children (n = 24,780) born in 1949–1973; the main group comprised 14,435 offspring of Mayak PA workers; the comparison group contained 10,345 children of unexposed parents. Incidence and relative risk of early and late neonatal, postneonatal and infant mortality were assessed taking into account the offspring sex, calendar period of birth, nosologies, parental age, categories of accumulated doses of parental preconception occupational exposure. Relative risk was calculated with 95 % confidence interval. A higher incidence of postneonatal and infant mortality as a whole was established among the offspring of unexposed parents. Infectious pathology as a cause of death was registered among the offspring of Mayak PA workers statistically significantly less often than in the comparison group. Infant mortality rate in the main group was lower in parental age categories of 21–25 and 31–35 years as well as among younger fathers. A higher rate of infant mortality in certain categories of accumulated doses of occupational preconception gamma-exposure was caused by the contribution of infectious nosologies. Infant mortality due to malignant neoplasms in the main group requires further epidemiological analysis. A retrospective analysis demonstrated higher rates of infant mortality and of its components among the children of un-exposed parents that could be possibly explained through the “healthy worker effect” and better social well-being of Mayak PA personnel.

Риск младенческой смертности среди потомков работников радиационно-опасного производства

Infant mortality is an indicator of healthcare quality and social well-being in a society and could be used as an important parameter in assessing the effects produced by parental occupational exposures on the offspring health. The objective of the study: to analyze the risk of infant mortality in the cohort of the 1st generation offspring of the workers of Mayak Production Association (PA), the first atomic production facility in Russia. Infant mortality and its components were analyzed in a cohort of children (n = 24,780) born in 1949–1973; the main group comprised 14,435 offspring of Mayak PA workers; the comparison group contained 10,345 children of unexposed parents. Incidence and relative risk of early and late neonatal, postneonatal and infant mortality were assessed taking into account the offspring sex, calendar period of birth, nosologies, parental age, categories of accumulated doses of parental preconception occupational exposure. Relative risk was calculated with 95 % confidence interval. A higher incidence of postneonatal and infant mortality as a whole was established among the offspring of unexposed parents. Infectious pathology as a cause of death was registered among the offspring of Mayak PA workers statistically significantly less often than in the comparison group. Infant mortality rate in the main group was lower in parental age categories of 21–25 and 31–35 years as well as among younger fathers. A higher rate of infant mortality in certain categories of accumulated doses of occupational preconception gamma-exposure was caused by the contribution of infectious nosologies. Infant mortality due to malignant neoplasms in the main group requires further epidemiological analysis. A retrospective analysis demonstrated higher rates of infant mortality and of its components among the children of un-exposed parents that could be possibly explained through the “healthy worker effect” and better social well-being of Mayak PA personnel.

Indicators of Cobalamin Status During Pregnancy, Pregnancy Outcome and Long-Term Effects on Offspring Health.

Little attention has been given to prenatal cobalamin insufficiency in settings where dietary cobalamin intake is presumed adequate, such as populations with habitual intake of foods from animal sources. However, low cobalamin status in women of fertile age has been reported in Europe, United States, and Canada. In India, where cobalamin deficiency is highly prevalent, it has been associated with an increased risk of miscarriage, intrauterine growth retardation, as well as insulin resistance and lower neurodevelopment scores in the offspring. Low cobalamin status in pregnancy has been associated with similar outcomes as those reported in the Indian studies although the evidence is scant and conflicting. Consideration should be given to maternal cobalamin status in the context of prevention of adverse pregnancy outcomes as well as cobalamin insufficiency both in the mother and the offspring during lactation. Further attention is now justified with the increasing tendency toward plant-based diets. Reference intervals for cobalamin status during each trimester of pregnancy are needed and further investigation of the long-term conse-quences of low cobalamin status during pregnancy for health and development in the offspring is warranted.

Respiratory morbidity among offspring misclassified as growth restricted.

An ultrasound-based diagnosis implies that some fetuses suspected to be growth-restricted (FGR) are discovered at birth to be appropriately grown (appropriate for gestational age [AGA] birth weight, between the 10th and 90th percentile). These fetuses may thus be exposed to unnecessary medical interventions, including early labor induction. In this study, we have evaluated the long-term respiratory health of offspring misclassified as FGR. A population-based cohort analysis was conducted, including deliveries of AGA singletons between 1991 and 2021 at a tertiary referral hospital. Incidence of morbidity due to various respiratory conditions was compared between AGA offspring with prenatal diagnosis of FGR, and those without a false diagnosis of FGR. The Kaplan-Meier approach was used to estimate cumulative morbidity incidence. The stratified Cox proportional-hazards model was used to control for confounders. A total of 324,620 deliveries of AGA newborns were included in the analyses; 3249 of them (1.0%) were misclassified prenatally as FGR. The FGR subgroup delivered at an earlier gestational age (36.7 vs. 39.1 weeks, p < .001) and had more than 25% higher incidence of respiratory-related morbidity during childhood (33.2% vs. 26.5%), specifically related to asthma and obstructive sleep apnea (p < .001 for all). A higher cumulative morbidity rate due to respiratory conditions was observed in the Kaplan-Meier survival curve (log-rank p value < .001). This association between FGR and respiratory morbidity was independent of preterm delivery, maternal age, cesarean delivery, and child's birth year (adjusted hazard ratio = 1.14, 95% confidence interval: 1.07-1.21, p < .001), using a Cox proportional hazards model. AGA newborns misclassified as FGR, are at an increased risk for long-term respiratory morbidity during childhood and adolescence.

Metabolic profiles of children aged 2-5 years born after frozen and fresh embryo transfer: A Chinese cohort study.

Frozen embryo transfer (FET) has become a widely employed assisted reproductive technology technique. There have historically been concerns regarding the long-term metabolic safety of FET technology in offspring due to pregnancy-induced hypertension and large for gestational age, both of which are well-recognized factors for metabolic dysfunction of children. Therefore, we aimed to compare the metabolic profiles of children born after frozen versus fresh embryo transfer at 2 to 5 years of age. This was a prospective cohort study. Using data from the "Assisted Reproductive Technology borned KIDs (ARTKID)," a birth cohort of offspring born from assisted reproductive technology at the Institute of Women, Children and Reproductive Health, Shandong University, China. We included 4,246 singletons born after FET (n = 2,181) and fresh embryo transfer (n = 2,065) enrolled between 2008 and 2019 and assessed the glucose and lipid variables until the age of 2 to 5 years. During a mean follow-up of 3.6 years, no significant differences were observed in fasting blood glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance Index, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol levels between offspring conceived by fresh and frozen embryo transfer in the crude model and adjusted model (adjusted for parental age, parental body mass index, parental education level, paternal smoking, parity, offspring age and sex). These results remained consistent across subgroup analyses considering offspring age, the stage of embryo transfer, and the mode of fertilization. Results from sensitivity analysis on children matched for age within the cohort remains the same. The main limitation of our study is the young age of the offspring. In this study, the impact of FET on glucose and lipid profiles during early childhood was comparable to fresh embryo transfer. Long-term studies are needed to evaluate the metabolic health of offspring born after FET.

Exploring health professionals' knowledge, practices and attitudes regarding gestational diabetes: A cross-sectional Irish national survey.

Gestational diabetes confers short- and long-term risk of mother and offspring health complications. Healthcare professionals such as endocrinologists, diabetes nurses, dietitians, midwives and general practitioners provide gestational diabetes care. We sought to explore healthcare professionals' perspectives on gestational diabetes care during pregnancy and postpartum. Healthcare professionals in the Republic of Ireland, whose role included gestational diabetes care were invited to complete an online 20-item survey between June and September 2022. Social media, professional organisations and personal networks were used for recruitment. Questions included guideline use, postpartum diabetes screening and advice practices. Analyses were performed using SPSS statistical software and free text was coded using NVivo. Seventeen healthcare professions across primary and secondary care settings participated (n = 127). No differences were noted between groups (medical, nursing/midwifery, allied health/other); therefore, findings were reported as a single group. Healthcare professionals reported using multiple different guidelines to support gestational diabetes management (n = 14). The most cited were 'Health Service Executive guidelines' (24.5%), 'local guidelines' (13.2%) and National Institute for Clinical Excellence guidelines (11.3%); 12.3% cited uncertainty, and 27.5% reported not to follow any named guidelines. For postpartum follow-up, 39% felt clear guidelines were available to support practice, 37% felt appropriate systems were in place and 29% reported effective communication between primary and secondary care services. Qualitative findings emphasised a desire for improved communication between systems, participants and providers, clear interdisciplinary guidelines, and adequate resourcing for gestational diabetes management and postpartum diabetes prevention, including comprehensive support and follow-up. System-level challenges and ineffective communication across settings are barriers to optimum postpartum care. Nationally agreed guidelines for best practice gestational diabetes management including postpartum diabetes prevention are needed.

Effects of vitamin D in pregnancy on maternal and offspring health-related outcomes: An umbrella review of systematic review and meta-analyses

BackgroundVitamin D deficiency has been linked with several adverse maternal and fetal outcomes.ObjectiveTo summarize systematic reviews and meta-analyses evaluating the effects of vitamin D deficiency and of vitamin D supplementation in pregnancy on maternal and offspring health-related outcomes.MethodsPrior to conducting this umbrella review, we registered the protocol in PROSPERO (CRD42022368003). We conducted searches in PubMed, Embase, and Cochrane Library for systematic reviews and meta-analyses on vitamin D in pregnancy, from database inception to October 2, 2023. All outcomes related to vitamin D in pregnancy obtained from the systematic reviews and meta-analyses were extracted. Data Extraction: Two reviewers independently chose studies and collected information on health outcomes. The quality of the included articles’ methodology was assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews–2).ResultsWe identified 16 eligible systematic reviews and meta-analyses, which included 250,569 women. Our results demonstrated that vitamin D deficiency in pregnancy is associated with increased risk of preterm birth, small-for gestational age/low birth weight infants, recurrent miscarriage, bacterial vaginosis and gestational diabetes mellitus. Vitamin D supplementation in pregnancy increases birth weight, and reduces the risk of maternal pre-eclampsia, miscarriage, and vitamin D deficiency, fetal or neonatal mortality, as well as attention-deficit hyperactivity disorder, and autism spectrum disorder in childhood. In women with gestational diabetes mellitus, vitamin D supplementation in pregnancy can reduce the risk of maternal hyperbilirubinemia, polyhydramnios, macrosomia, fetal distress, and neonatal hospitalization.ConclusionDue to the association with adverse maternal and offspring health outcomes, we recommend the vitamin D status in pregnancy should be monitored, particularly in women at high risk of vitamin D deficiency. It is suggested that pregnant women take a dose of >400 IU/day of vitamin D supplementation during pregnancy to prevent certain adverse outcomes.

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring.

Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSDs), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.

Maternal age is related to offspring DNA methylation: A meta-analysis of results from the PACE consortium.

Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10-8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.