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BMC Medicine Nov 2023Maternal pre-gestational diabetes (PGDM), gestational diabetes mellitus (GDM), and overweight/obesity have been associated with increased risks of offspring...
BACKGROUND
Maternal pre-gestational diabetes (PGDM), gestational diabetes mellitus (GDM), and overweight/obesity have been associated with increased risks of offspring neurodevelopmental conditions (NDCs) including autism, intellectual disability (ID), and attention deficit/hyperactivity disorder (ADHD). Less is known about whether and how obstetric and neonatal complications (e.g., preterm birth, neonatal asphyxia) could mediate these associations.
METHODS
In this Swedish register-based cohort study, we examined complications during pregnancy, delivery, and the neonatal period as potential mediators of the relationships between maternal metabolic conditions and offspring NDCs. We quantified the extent to which these obstetric and neonatal factors could mediate the associations of maternal metabolic conditions with offspring NDCs by applying parametric regression models for single mediation analyses and weighting-based methods for multiple mediation analyses under counterfactual frameworks.
RESULTS
The study sample included 2,352,969 singleton children born to 1,299,692 mothers from 1987-2010 who were followed up until December 31, 2016, of whom 135,832 children (5.8%) were diagnosed with at least one NDC. A substantial portion of the association between maternal PGDM and children's odds of NDCs could be explained by the combined group of obstetric and neonatal complications in the multiple mediation analysis. For instance, these complications explained 44.4% of the relationship between maternal PGDM and offspring ID risk. The proportion of the relationship between maternal overweight/obesity and children's risk of NDCs that could be explained by obstetric and neonatal complications was considerably smaller, ranging from 1.5 to 8.1%. Some complications considered on their own, including pregnancy hypertensive diseases, preterm birth, neonatal asphyxia, and hematological comorbidities, could explain at least 10% of the associations between maternal PGDM and offspring NDCs. Complications during the neonatal period showed a stronger joint mediating effect for the relationship between PGDM and offspring NDCs than those during pregnancy or delivery.
CONCLUSIONS
Obstetric and neonatal complications could explain nearly half of the association between maternal PGDM and offspring risk of NDCs. The mediating effects were more pronounced for complications during the neonatal period and for specific complications such as pregnancy hypertensive diseases, preterm birth, neonatal asphyxia, and hematological comorbidities. Effective preventive strategies for offspring NDCs should holistically address both the primary metabolic issues related to PGDM and the wide array of potential complications, especially those in the neonatal period.
Topics: Pregnancy; Child; Female; Infant, Newborn; Humans; Overweight; Cohort Studies; Premature Birth; Asphyxia; Diabetes, Gestational; Obesity
PubMed: 37936224
DOI: 10.1186/s12916-023-03116-x -
Frontiers in Endocrinology 2023Maternal endocrine homeostasis is vital to a successful pregnancy, regulated by several hormones such as human chorionic gonadotropin, estrogen, leptin, glucocorticoid,... (Review)
Review
Maternal endocrine homeostasis is vital to a successful pregnancy, regulated by several hormones such as human chorionic gonadotropin, estrogen, leptin, glucocorticoid, insulin, prostaglandin, and others. Endocrine stress during pregnancy can modulate nutrient availability from mother to fetus, alter fetoplacental growth and reproductive functions. Endocrine disrupters such as bisphenols (BPs) and phthalates are exposed in our daily life's highest volume. Therefore, they are extensively scrutinized for their effects on metabolism, steroidogenesis, insulin signaling, and inflammation involving obesity, diabetes, and the reproductive system. BPs have their structural similarity to 17-β estradiol and their ability to bind as an agonist or antagonist to estrogen receptors to elicit an adverse response to the function of the endocrine and reproductive system. While adults can negate the adverse effects of these endocrine-disrupting chemicals (EDCs), fetuses do not equip themselves with enzymatic machinery to catabolize their conjugates. Therefore, EDC exposure makes the fetoplacental developmental window vulnerable to programming . On the one hand prenatal BPs and phthalates exposure can impair the structure and function of the ovary and uterus, resulting in placental vascular defects, inappropriate placental expression of angiogenic growth factors due to altered hypothalamic response, expression of nutrient transporters, and epigenetic changes associated with maternal endocrine stress. On the other, their exposure during pregnancy can affect the offspring's metabolic, endocrine and reproductive functions by altering fetoplacental programming. This review highlights the latest development in maternal metabolic and endocrine modulations from exposure to estrogenic mimic chemicals on subcellular and transgenerational changes in placental development and its effects on fetal growth, size, and metabolic & reproductive functions.
Topics: Pregnancy; Female; Humans; Placenta; Endocrine System; Estrogens; Fetal Development; Insulins
PubMed: 37854189
DOI: 10.3389/fendo.2023.1215353 -
Italian Journal of Pediatrics Oct 2023Maternal diabetes might be related to a high risk of allergic disease in offspring. However, it remains unknown if maternal gestational diabetes mellitus (GDM) is also... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Maternal diabetes might be related to a high risk of allergic disease in offspring. However, it remains unknown if maternal gestational diabetes mellitus (GDM) is also associated with a high incidence of childhood asthma in offspring. A systematic review and meta-analysis was performed to investigate the above association.
METHODS
Relevant observational studies were obtained by search of electronic databases including Medline, Embase, Cochrane Library, and Web of Science. A randomized-effects model was selected to pool the data by incorporating the influence of potential heterogeneity. The Newcastle-Ottawa Scale was used for study quality evaluation. Subgroup analyses were performed to evaluate the potential influences of study characteristics on the outcome.
RESULTS
Ten datasets from seven moderate to high quality cohort studies, involving 523,047 mother-child pairs were included in the meta-analysis. Overall, maternal GDM was associated with a higher risk of childhood asthma in offspring (risk ratio [RR]: 1.22, 95% confidence interval [CI]: 1.07 to 1.39, p = 0.003; I = 30%). Subgroup analyses showed that the association was not significantly affected by study design, validation methods for GDM, or diagnostic strategy for asthma (p for subgroup analyses all > 0.05). The association between maternal GDM and asthma in offspring was more remarkable after adjusting maternal body mass index in early pregnancy (RR: 1.50 versus 1.06, p < 0.001), but significantly weakened after adjusting hypertensive disorders during pregnancy (RR: 1.08 versus 1.50, p = 0.001).
CONCLUSIONS
Maternal GDM may be associated with an increased incidence of childhood asthma in offspring.
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Cohort Studies; Asthma
PubMed: 37840137
DOI: 10.1186/s13052-023-01532-6 -
Cureus Dec 2023Gestational diabetes mellitus (GDM) is a complex and significant health concern affecting pregnant individuals and their offspring. This review provides a comprehensive... (Review)
Review
Gestational diabetes mellitus (GDM) is a complex and significant health concern affecting pregnant individuals and their offspring. This review provides a comprehensive examination of GDM, focusing on diagnostic strategies and the associated maternal and offspring complications. We delve into the challenges and controversies surrounding GDM diagnosis, including the variability in diagnostic criteria, diagnostic accuracy and reproducibility issues, ethical considerations, and the influence of ethnicity and genetics. Maternal complications, such as preeclampsia, cesarean sections, long-term health implications, and neonatal complications like macrosomia, hypoglycemia, and respiratory distress syndrome, are explored in detail. Additionally, we investigate the long-term risks of childhood obesity and type 2 diabetes in offspring and potential cognitive and developmental outcomes. This review underscores the critical importance of early detection and effective management of GDM, the need for standardized diagnostic criteria, personalized care plans, and the ongoing pursuit of research to enhance our understanding of this complex condition. GDM remains a dynamic field where ongoing innovation and research promise to improve the health outcomes of pregnant individuals and their children.
PubMed: 38264369
DOI: 10.7759/cureus.51016 -
Hormone and Metabolic Research =... Oct 2023Maternal obesity is associated with fetal complications predisposing later to the development of metabolic syndrome during childhood and adult stages. High-fat diet... (Review)
Review
Maternal obesity is associated with fetal complications predisposing later to the development of metabolic syndrome during childhood and adult stages. High-fat diet seems to influence individuals and their subsequent generations in mediating weight gain, insulin resistance, obesity, high cholesterol, diabetes, and cardiovascular disorder. Research evidence strongly suggests that epigenetic alteration is the major contributor to the development of metabolic syndrome through DNA methylation, histone modifications, and microRNA expression. In this review, we have discussed the outcome of recent studies on the adverse and beneficial effects of nutrients and vitamins through epigenetics during pregnancy. We have further discussed about the miRNAs altered during maternal obesity. Identification of new epigenetic modifiers such as mesenchymal stem cells condition media (MSCs-CM)/exosomes for accelerating the reversal of epigenetic abnormalities for the development of new treatments is yet another aspect of the present review.
Topics: Adult; Female; Pregnancy; Humans; Metabolic Syndrome; Obesity, Maternal; Obesity; Metabolic Diseases; Epigenesis, Genetic
PubMed: 37813098
DOI: 10.1055/a-2159-9128 -
Journal of Bone and Mineral Research :... Dec 2023Conditions during gestation, such as maternal smoking, may affect offspring's bone structure. This could increase the offspring's risk of bone fractures during...
Conditions during gestation, such as maternal smoking, may affect offspring's bone structure. This could increase the offspring's risk of bone fractures during childhood. In this study, we aimed to assess the association between prenatal exposure to maternal smoking and childhood bone fracture risk. We used a register-based birth cohort that included all children born in Finland between January 1987 and September 1990. After exclusions, the final study population consisted of 220,699 persons. Using a unique national identification number, we linked the cohort data to the fracture diagnosis in specialty care and covariate data using the Medical Birth Register (MBR), Statistics Finland and Care Register for Health Care (CRHC). The fractures were analyzed in three groups: all fractures, non-high-energy fractures, and high-energy fractures. The analyses were adjusted for sex, parity, child's year of birth, mother's age at childbirth, mother's and father's educational level, and mother's fracture status. We tested the association in three age groups: <1 year, 1-<5 years, and 5-<15 years using Cox and (recurrent fractures) Poisson regression. A total of 18,857 (8.5%) persons had at least one bone fracture diagnosis before the age of 15 years. In the age group 5-<15 years, maternal smoking during pregnancy was associated with higher fracture risk in all of the studied fracture groups: hazard ratio (HR) = 1.12 (95% confidence interval [CI] 1.06-1.17) in all fractures, 1.13 (95% CI 1.07-1.19) in non-high-energy, and 1.15 (95% CI 1.00-1.32) in high-energy fractures. There were no significant associations in other age groups in any of the fracture groups. No statistically significant association between maternal smoking during pregnancy and offspring's risk of recurrent fractures was found. In conclusion, 5- to 15-year-olds whose mothers have smoked during pregnancy have an increased risk of bone fractures treated in specialty care. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Child; Female; Pregnancy; Humans; Adolescent; Infant; Smoking; Fractures, Bone; Finland; Minerals
PubMed: 37823763
DOI: 10.1002/jbmr.4923 -
Metabolites Jul 2023Obesity incidence has been increasing at an alarming rate, especially in women of reproductive age. It is estimated that 50% of pregnancies occur in overweight or obese... (Review)
Review
Obesity incidence has been increasing at an alarming rate, especially in women of reproductive age. It is estimated that 50% of pregnancies occur in overweight or obese women. It has been described that maternal obesity (MO) predisposes the offspring to an increased risk of developing many chronic diseases in an early stage of life, including obesity, type 2 diabetes, and cardiovascular disease (CVD). CVD is the main cause of death worldwide among men and women, and it is manifested in a sex-divergent way. Maternal nutrition and MO during gestation could prompt CVD development in the offspring through adaptations of the offspring's cardiovascular system in the womb, including cardiac epigenetic and persistent metabolic programming of signaling pathways and modulation of mitochondrial metabolic function. Currently, despite diet supplementation, effective therapeutical solutions to prevent the deleterious cardiac offspring function programming by an obesogenic womb are lacking. In this review, we discuss the mechanisms by which an obesogenic intrauterine environment could program the offspring's cardiovascular metabolism in a sex-divergent way, with a special focus on cardiac mitochondrial function, and debate possible strategies to implement during MO pregnancy that could ameliorate, revert, or even prevent deleterious effects of MO on the offspring's cardiovascular system. The impact of maternal physical exercise during an obesogenic pregnancy, nutritional interventions, and supplementation on offspring's cardiac metabolism are discussed, highlighting changes that may be favorable to MO offspring's cardiovascular health, which might result in the attenuation or even prevention of the development of CVD in MO offspring. The objectives of this manuscript are to comprehensively examine the various aspects of MO during pregnancy and explore the underlying mechanisms that contribute to an increased CVD risk in the offspring. We review the current literature on MO and its impact on the offspring's cardiometabolic health. Furthermore, we discuss the potential long-term consequences for the offspring. Understanding the multifaceted effects of MO on the offspring's health is crucial for healthcare providers, researchers, and policymakers to develop effective strategies for prevention and intervention to improve care.
PubMed: 37512552
DOI: 10.3390/metabo13070845 -
Frontiers in Neurology 2023This study aimed to explore the influencing factors of adverse outcomes in the offspring of women with epilepsy (WWE) and to analyze the changes brought about by the...
OBJECTIVE
This study aimed to explore the influencing factors of adverse outcomes in the offspring of women with epilepsy (WWE) and to analyze the changes brought about by the epilepsy knowledge popularization campaign in China (EKPCIC).
METHODS
This nested case-control study focused on WWE and their offspring from a female epilepsy cohort in mainland China. From January 2009 to August 2022, WWE was prospectively enrolled in 32 study centers. This study aimed to observe the health outcomes of their offspring within 1 year of age. The main outcome measure assessed the health status of the offspring within their first year of age. We aimed to analyze the effects of seizures, anti-seizure medicines (ASMs), and a lack of folic acid supplementation on adverse outcomes in the offspring of WWE and to explore the changes in perinatal management and adverse outcomes of the offspring after dissemination of the EKPCIC in 2015. Additionally, subgroup analyses were conducted to compare seizure control during pregnancy between the valproate and non-valproate groups.
RESULTS
In total, 781 pregnancies in 695 WWE were included, of which 186 (23.69%) had adverse outcomes. The National Hospital Epilepsy Severity Scale score, number of seizures, status epilepticus, ASM type, and valproate and folic acid doses were associated with a high risk of adverse outcomes. After the EKPCIC, the use of ASMs ( = 0.013) and folic acid ( < 0.001), the seizure-free rate during pregnancy ( = 0.013), and the breastfeeding rate ( < 0.001) increased, whereas the incidence of complications during pregnancy decreased ( = 0.013). However, there was no significant difference in the incidence of adverse outcomes between the analyzed offspring pre-/post-EKPCIC. Additionally, there was no association between the frequency of seizures at different time points during pregnancy and the use of valproate ( = 1.514, = 0.221).
CONCLUSION
Possible factors influencing adverse outcomes in the offspring of WWE include seizures, type and number of ASM usage, and a lack of folic acid supplementation. Although the management of WWE during pregnancy is now more standardized, further efforts are needed to reduce adverse outcomes in offspring.
PubMed: 37638195
DOI: 10.3389/fneur.2023.1195003 -
Frontiers in Public Health 2023The dietary pattern followed during pregnancy, specifically healthy dietary patterns such as the Mediterranean diet, is a key factor in the mother's and the offspring's...
BACKGROUND AND AIMS
The dietary pattern followed during pregnancy, specifically healthy dietary patterns such as the Mediterranean diet, is a key factor in the mother's and the offspring's health. Pregnant women dietary intake is not enough to cover the micronutrient requirements of pregnancy, and higher adherence to the Mediterranean diet may improve dietary quality and nutritional density. The aim of the present study was to describe the dietary nutrient intake and diet quality during pregnancy and to evaluate whether a high adherence to Mediterranean diet was associated with a more adequate intake of micronutrients.
METHODS
This was a cross-sectional study with 1,356 pregnant women selected during the routine second trimester ultrasound scan (19-23 weeks' gestation). Energy and nutrient intake were calculated using a validated 151-item semi-quantitative food frequency questionnaire and nutrient density was estimated dividing the absolute nutrient intake by total energy intake. Adherence to the Mediterranean diet was evaluated with a 17-item Mediterranean diet adherence score. The criterion used for risk of inadequate nutrient intake has been set below two thirds (2/3) of the dietary reference intakes. The differences were assessed by multivariate linear regression models adjusted for confounders.
RESULTS
A significant proportion of pregnant women had an inadequate intake of macro and micronutrient that was lower in those with high adherence to the Mediterranean diet (≥12 points, = 122, 19%), including calcium (the Mediterranean diet high adherence 2.5% vs. low adherence 26.7%, < 0.001), magnesium (0% vs. 7.6%, = 0.001), iron (24.5% vs. 74.1%, < 0.001), and vitamin B9 (0% vs. 29.8%, < 0.001), vitamin C (0% vs. 1.9%, = 0.033), and vitamin D (61.5% vs. 92.8%, < 0.001) intake. High adherence to Mediterranean diet was associated with higher intake of protein, monounsaturated fatty acids, fiber, vitamins (B1, B9, C, D), calcium, magnesium, iron, zinc, phosphor, potassium, essential fatty acids, and α-linolenic acid, and with a lower intake of α-linoleic acid and trans fatty acids as compared to low adherence to Mediterranean diet.
CONCLUSION
High adherence to Mediterranean diet was associated with higher diet quality and lower proportion of inadequate micro and macronutrient intake. The Mediterranean diet promotion, particularly among pregnant women, may be a useful and public health strategy to avoid overweight and nutrient deficiencies.
Topics: Pregnancy; Female; Humans; Diet, Mediterranean; Calcium; Cross-Sectional Studies; Magnesium; Pregnant Women; Nutrients; Vitamins; Micronutrients
PubMed: 37645706
DOI: 10.3389/fpubh.2023.1144942 -
Cureus Aug 2023Metformin (MTF) is a commonly prescribed medication for women with polycystic ovarian syndrome (PCOS), but its impact on pregnancy outcomes in women with PCOS remains... (Review)
Review
Metformin (MTF) is a commonly prescribed medication for women with polycystic ovarian syndrome (PCOS), but its impact on pregnancy outcomes in women with PCOS remains controversial. This systematic review aims to evaluate the effects of MTF intervention on pregnancy outcomes in women with PCOS and the impact of MTF on offspring. A comprehensive search is conducted in PubMed, Google Scholar, and ScienceDirect databases from 2019 up to May 16, 2023. Only review articles and meta-analyses are included, focusing on women with PCOS who received MTF during pregnancy or as part of infertility treatment. The primary outcomes of interest are clinical pregnancy rate (CPR), miscarriage rate, preterm birth rate, and live birth rate. Secondary outcomes are the safety profile of MTF. Data extraction and quality assessment are performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the assessment using the multiple systematic reviews (AMSTAR) 2 tool, respectively. The initial search produced 1877 studies. Thirteen studies were included in the review. While the use of MTF during pregnancy in women with PCOS may have some benefits in reducing certain pregnancy complications such as pregnancy-induced hypertension (PIH), gestational diabetes mellitus (GDM), preeclampsia, preterm delivery, reducing the risk of ovarian hyperstimulation syndrome (OHSS) in women with PCOS undergoing in vitro fertilization (IVF); however, there is no significant difference in clinical pregnancy and live birth rates overall, but subgroup analysis suggests potential benefits for women with a higher body mass index (BMI). MTF is associated with a larger fetal head circumference and potential long-term effects on offspring's BMI and obesity. Further research is needed to better understand the optimal dosing of MTF, long-term effects, and effects in specific subgroups. The heterogeneity of the included studies limited the ability to analyze the data effectively, leading to challenges in drawing definitive conclusions.
PubMed: 37753037
DOI: 10.7759/cureus.44166