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41 pages, 1640 KiB  
Review
Early Roots of Childhood Obesity: Risk Factors, Mechanisms, and Prevention Strategies
by Giuseppina Rosaria Umano, Simonetta Bellone, Raffaele Buganza, Valeria Calcaterra, Domenico Corica, Luisa De Sanctis, Anna Di Sessa, Maria Felicia Faienza, Nicola Improda, Maria Rosaria Licenziati, Melania Manco, Carla Ungaro, Flavia Urbano, Giuliana Valerio, Malgorzata Wasniewska and Maria Elisabeth Street
Int. J. Mol. Sci. 2025, 26(15), 7388; https://doi.org/10.3390/ijms26157388 - 30 Jul 2025
Viewed by 710
Abstract
Childhood obesity is a growing global health concern, with established links to physical activity, nutrition, and, increasingly, to prenatal and perinatal factors. Emerging evidence highlights the significant role of maternal conditions such as obesity, comorbidities, nutrition, and environmental exposures in predisposing offspring to [...] Read more.
Childhood obesity is a growing global health concern, with established links to physical activity, nutrition, and, increasingly, to prenatal and perinatal factors. Emerging evidence highlights the significant role of maternal conditions such as obesity, comorbidities, nutrition, and environmental exposures in predisposing offspring to long-term metabolic and cardiovascular diseases. The “Developmental Origins of Health and Disease” (DOHaD) paradigm provides a framework for understanding how early life environmental exposures, particularly during the periconceptional, fetal, and neonatal periods, can program future health outcomes through epigenetic mechanisms. Epigenetic modifications alter gene expression without changing the DNA sequence and are increasingly recognized as key mediators in the development of obesity. This narrative review summarizes current findings on the early determinants of childhood obesity, emphasizing the molecular and epigenetic pathways involved. A comprehensive literature search was conducted across multiple databases and international sources, focusing on recent studies from the past decade. Both human and animal research were included to provide a broad perspective. This review aims to consolidate recent insights into early life influences on obesity, underscoring the need for preventive strategies starting as early as the preconception period. Full article
(This article belongs to the Special Issue Genetic and Molecular Mechanisms of Obesity)
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27 pages, 2012 KiB  
Article
Dual Effects of Maternal Diet and Perinatal Organophosphate Flame Retardant Treatment on Offspring Development, Behavior and Metabolism
by Ali Yasrebi, Catherine M. Rojas, Shabree Anthony, Samantha Feltri, Jamilah Evelyn, Kimberly Wiersielis, Samantha Adams, Veronia Basaly, Grace L. Guo, Lauren M. Aleksunes and Troy A. Roepke
Toxics 2025, 13(8), 639; https://doi.org/10.3390/toxics13080639 - 29 Jul 2025
Viewed by 284
Abstract
The maternal–fetal environment is influenced by multiple factors, including nutrition and environmental contaminants, which can impact long-term development. Perinatal exposure to organophosphate flame retardants (OPFRs) disrupts energy homeostasis and causes maladaptive behaviors in mice. Maternal obesity affects development by impairing blood–brain barrier (BBB) [...] Read more.
The maternal–fetal environment is influenced by multiple factors, including nutrition and environmental contaminants, which can impact long-term development. Perinatal exposure to organophosphate flame retardants (OPFRs) disrupts energy homeostasis and causes maladaptive behaviors in mice. Maternal obesity affects development by impairing blood–brain barrier (BBB) formation, influencing brain regions involved in energy regulation and behavior. This study examined the combined effects of maternal obesity and perinatal OPFR treatment on offspring development. Female mice were fed either a low-fat (LFD) or a high-fat diet (HFD) for 8 weeks, mated, and treated with either sesame oil or an OPFR mixture (tris(1,3-dichloro-2-propyl)phosphate, tricresyl phosphate, and triphenyl phosphate, 1 mg/kg each) from gestational day 7 to postnatal day 14. Results showed that both maternal diet and OPFR treatment disrupted blood–brain barrier integrity, energy balance, and reproductive gene expression in the hypothalamus of neonates. The expression of hepatic genes related to lipid and xenobiotic metabolism was also altered. In adulthood, LFD OPFR-treated female offspring exhibited increased avoidance behavior, while HFD OPFR-treated females demonstrated memory impairments. Metabolic assessments revealed decreased energy expenditure and nighttime activity in LFD OPFR-treated females. These findings suggest that maternal diet and OPFR treatment alter hypothalamic and liver gene expression in neonates, potentially leading to long-term metabolic and behavioral changes. Full article
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18 pages, 852 KiB  
Article
Impact of COVID-19 on Pregnancy Outcomes: A Phase-Based Analysis from a Spanish Tertiary Hospital (2020–2023)
by María-Asunción Quijada-Cazorla, María-Virgilia Simó-Rodríguez, Ana-María Palacios-Marqués, María Peláez-García and José-Manuel Ramos-Rincón
J. Clin. Med. 2025, 14(14), 5136; https://doi.org/10.3390/jcm14145136 - 19 Jul 2025
Viewed by 408
Abstract
Background/Objectives: Pregnancy has been considered a risk factor for severe SARS-CoV-2 infection, as well as for adverse maternal and neonatal outcomes. This study aimed to assess the clinical impact of COVID-19 on pregnant women managed at a Spanish tertiary care hospital across different [...] Read more.
Background/Objectives: Pregnancy has been considered a risk factor for severe SARS-CoV-2 infection, as well as for adverse maternal and neonatal outcomes. This study aimed to assess the clinical impact of COVID-19 on pregnant women managed at a Spanish tertiary care hospital across different phases of the pandemic. Methods: A retrospective observational study was conducted at Dr. Balmis General University Hospital (Alicante, Spain) between March 2020 and May 2023. All pregnant women who received hospital care with confirmed SARS-CoV-2 infection were included. Maternal and neonatal outcomes were analyzed and compared with the 6120 total births recorded during the same period. Results: A total of 249 pregnant women with COVID-19 were included, with 30.8%, 25.0%, and 7.9% hospitalized during each respective pandemic phase. The overall incidence of infection was 41 cases per 1000 births. Hospitalized pregnant women showed significantly higher rates of preterm birth, labor induction (70.4% vs. 47.0%; OR: 2.67; 95% CI: 1.12–6.43), and cesarean delivery (46.9% vs. 24.9%, OR: 2.60; 95% CI: 1.27–5.50). Neonatal outcomes included lower Apgar scores, increased admission to the neonatal unit (25.8% vs. 8.2%, p = 0.007), and a higher rate of neonatal complications (23.3% vs. 7.7%, p = 0.015). Maternal obesity and non-Spanish nationality were associated with more severe maternal disease. Vaccination against SARS-CoV-2 significantly reduced the risk of hospitalization due to the infection (OR: 0.30; 95% CI: 0.13–0.69). Conclusions: Pregnant women admitted with COVID-19 had increased risks of adverse obstetric and neonatal outcomes, underscoring the importance of preventive strategies, such as vaccination. Full article
(This article belongs to the Special Issue New Advances in COVID-19 and Pregnancy)
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17 pages, 334 KiB  
Article
Maternal Obesity Modifies the Impact of Active SARS-CoV-2 Infection on Placental Pathology
by Francisca Carmo, Carla Ramalho, Susana Guimarães and Fátima Martel
Viruses 2025, 17(7), 1013; https://doi.org/10.3390/v17071013 - 18 Jul 2025
Viewed by 346
Abstract
Background: Obesity during pregnancy is associated with an elevated risk of severe COVID-19, including higher rates of maternal complications, intensive care admission, and adverse neonatal outcomes. The impact of combination of SARS-CoV-2 infection and maternal obesity in placental pathology has not been properly [...] Read more.
Background: Obesity during pregnancy is associated with an elevated risk of severe COVID-19, including higher rates of maternal complications, intensive care admission, and adverse neonatal outcomes. The impact of combination of SARS-CoV-2 infection and maternal obesity in placental pathology has not been properly investigated. Aim: To compare the histopathological changes in the placenta induced by active SARS-CoV-2 infection in obese and non-obese patients. Methods: This retrospective cohort study included human placentas from non-obese women and pre-gestationally obese women with active SARS-CoV-2 infection (SARS and OB+SARS, respectively), and placentas from non-obese women and pre-gestationally obese women without SARS-CoV-2 infection (control and OB, collected in the post- and pre-pandemic periods, respectively). Results: A higher (50%) occurrence of ischemic injury and subchorionic fibrin deposits and a 15× higher risk of occurrence of these lesions were found in the OB+SARS group, in relation to control. In contrast, a 10% lower risk of developing chorangiosis in the OB+SARS group than the OB group was observed. Conclusions: An increased risk of lesions related to both maternal and fetal malperfusion and ischemic injury and a lower risk for chorangiosis exist in placentas from obese women affected by SARS-CoV-2 infection. Importantly, these differences were not observed in placentas from non-obese women. Full article
(This article belongs to the Special Issue SARS-CoV-2, COVID-19 Pathologies, Long COVID, and Anti-COVID Vaccines)
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14 pages, 1623 KiB  
Review
Idiopathic Intracranial Hypertension in Neonates, Infants, and Toddlers
by Efstathios Beys-Kamnarokos and Ioannis Mavridis
J. Clin. Med. 2025, 14(14), 5084; https://doi.org/10.3390/jcm14145084 - 17 Jul 2025
Viewed by 387
Abstract
Idiopathic intracranial hypertension (IIH) with (IIHWP) and without papilledema (IIHWOP) is characterized by increased cerebrospinal fluid (CSF) pressure and no evident cause, mostly affecting obese women of childbearing age and possibly leading to vision loss. However, in neonates, infants, and toddlers, these conditions [...] Read more.
Idiopathic intracranial hypertension (IIH) with (IIHWP) and without papilledema (IIHWOP) is characterized by increased cerebrospinal fluid (CSF) pressure and no evident cause, mostly affecting obese women of childbearing age and possibly leading to vision loss. However, in neonates, infants, and toddlers, these conditions remain understudied entities. This review investigates clinical features, risk factors, treatments, and outcomes to inform their care. From 2278 publications found in PubMed, 2974 in Scopus, and 1684 in the Web of Science Core Collection, 104 relevant articles were analyzed. Among 300 cases, 48.3% were male and 26.0% female, with 43.0% meeting the modified Dandy criteria. Typical signs and symptoms, besides papilledema (23.0%) or its absence (49.0%), included bulging fontanelle (67.7%), irritability (34.3%), vomiting (33.0%), and fever (18.3%). The most triggering factors were medications (35.3%) and infections (15.0%). The mean CSF opening pressure was 35.1 cm H2O, ranging from 9.5 to 77 cm H2O. Main treatment options were lumbar punctures (72.7%), discontinuation of triggering medications (26.3%), acetazolamide (18.7%), and corticosteroids (7.7%); 3.0% required shunting. Unlike in adults, males were more commonly affected, and papilledema was less frequent. Most cases resolved with conservative treatment. A nosological distinction between IIHWP and IIHWOP seems unlikely. Considering our findings and age-specific CSF pressure limits, new diagnostic criteria are proposed. Full article
(This article belongs to the Section Clinical Pediatrics)
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20 pages, 868 KiB  
Article
Association of Pre- and Gestational Conditions and Barriers to Breastfeeding with Exclusive Breastfeeding Practices
by Reyna Sámano, Gabriela Chico-Barba, Hugo Martínez-Rojano, María Eugenia Mendoza-Flores, María Hernández-Trejo, Carmen Hernández-Chávez, Andrea Luna-Hidalgo, Estefania Aguirre-Minutti, Ricardo Gamboa, María Eugenia Flores-Quijano, Otilia Perichart-Perera and Andrea López-Ocampo
Nutrients 2025, 17(14), 2309; https://doi.org/10.3390/nu17142309 - 13 Jul 2025
Viewed by 471
Abstract
Background: Breastfeeding is essential for preventing non-communicable diseases. However, mothers with chronic illnesses tend to breastfeed less, increasing the likelihood of abandoning breastfeeding, especially if they experience gestational complications. Objective: To analyze the association between factors such as prepregnancy maternal characteristics, gestational complications, [...] Read more.
Background: Breastfeeding is essential for preventing non-communicable diseases. However, mothers with chronic illnesses tend to breastfeed less, increasing the likelihood of abandoning breastfeeding, especially if they experience gestational complications. Objective: To analyze the association between factors such as prepregnancy maternal characteristics, gestational complications, food security, barriers, and facilitators with the practice of exclusive breastfeeding. Methods: Cross-sectional study with 566 women who had prenatal care and gave birth at the National Institute of Perinatology (Mexico City) between 2021 and 2024. Surveys were administered on breastfeeding practices, food insecurity, barriers, and facilitators of exclusive breastfeeding in mothers. In addition, sociodemographic information, medical history (prepregnancy conditions and complications), gestational weight gain, and neonatal outcomes were recorded. Results: Of the 566 women, only 43.6% practiced exclusive breastfeeding, with a median duration of 4 months. Exclusive breastfeeding was more frequent in young, stay-at-home mothers with lower educational attainment and in those with food insecurity, who also tended to delay the introduction of complementary foods until after six months. Prepregnancy risk conditions (OR 1.56, 95% CI 1.06–2.30) and multiparity (OR 1.64, 95% CI 1.08–2.49) increased the risk of non-exclusive breastfeeding. Conversely, food insecurity (OR 0.40, 95% CI 0.20–0.78) and counseling from healthcare personnel (OR 0.09, 95% CI 0.01–0.51) showed a protective effect. The analysis also showed that paid employment (OR 4.68, 95% CI 1.65–13.21), the perception of low milk production (OR 6.45, 95% CI 2.95–14.10), maternal illness/medication (OR 3.91, 95% CI 1.36–11.28), and fatigue (OR 4.67, 95% CI 1.36–11.28) increased the probability of non-exclusive breastfeeding. Conclusions: In Mexico, the promotion of exclusive breastfeeding faces challenges, especially in mothers who begin pregnancy with significant chronic conditions such as diabetes, hypertension, obesity, advanced maternal age, and hypothyroidism, among others. Healthcare personnel should provide personalized advice to each woman from the prenatal stage on strategies to achieve and maintain exclusive breastfeeding. Full article
(This article belongs to the Section Nutrition in Women)
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18 pages, 251 KiB  
Protocol
Glucose Homeostasis, Metabolomics, and Pregnancy Outcomes After Bariatric Surgery (GLORIA): Protocol for a Multicentre Prospective Cohort Study
by Ellen Deleus, Niels Bochanen, Dries Ceulemans, Hanne Debunne, Bénédicte Denys, Roland Devlieger, Ina Geerts, Annouschka Laenen, Lisbeth Jochems, Els Lannoey, Matthias Lannoo, Anne Loccufier, Toon Maes, Joke Marlier, Astrid Morrens, Nele Myngheer, Luna Tierens, Griet Vandenberghe, Annick Van den Bruel, Lien Van den Haute, Bart Van der Schueren, Inge Van Pottelbergh and Katrien Benhalimaadd Show full author list remove Hide full author list
J. Clin. Med. 2025, 14(13), 4782; https://doi.org/10.3390/jcm14134782 - 7 Jul 2025
Viewed by 501
Abstract
Background: Metabolic bariatric surgery is a highly effective and long-lasting treatment for obesity and related chronic conditions. Women of reproductive age represent the largest group undergoing these procedures. Observational studies suggest an increased risk of preterm birth and impaired foetal growth in this [...] Read more.
Background: Metabolic bariatric surgery is a highly effective and long-lasting treatment for obesity and related chronic conditions. Women of reproductive age represent the largest group undergoing these procedures. Observational studies suggest an increased risk of preterm birth and impaired foetal growth in this population, though the underlying mechanisms remain unclear. A key hypothesis is that altered glucose metabolism, characterised by frequent hypoglycaemia and glycaemic fluctuations, may contribute to these adverse outcomes. While glycaemic variability following metabolic bariatric surgery has been documented, its pattern during pregnancy and impact on pregnancy outcomes are still underexplored. Methods: In this Belgian multicentre prospective cohort study, we will investigate glycaemic patterns during pregnancy in women who have undergone metabolic bariatric surgery. Women aged 18–45 years with a confirmed singleton pregnancy up to 11 weeks and 6 days and a history of Roux-en-Y gastric bypass or sleeve gastrectomy will be eligible for inclusion. Women with pregestational diabetes or those taking medication known to interfere with glucose metabolism will be excluded. All participants will receive blinded continuous glucose monitoring (Dexcom® G6) for a 10-day period at four time points throughout the pregnancy. Foetal body composition and growth will be measured during routine ultrasound; skinfolds will be measured in the neonate. The primary outcome is the association between mean glycemia and glycaemic variability on continuous glucose monitoring and birth weight. The planned sample size is ninety-five women. Linear mixed models for repeated measurements will be used for analysis. Confounders such as smoking, micronutrient deficiency, and surgery-to-conception interval will be added to the model as covariates. In a second exploratory phase, each participant in the surgical group will be matched with a control participant—without a history of metabolic bariatric surgery—based on pre-pregnancy BMI and age. Control participants will undergo the same study procedures, allowing for exploratory comparison of glycaemic patterns and other study outcomes. Discussion: This prospective longitudinal study will be the largest study using continuous glucose monitoring to investigate glucose metabolism during pregnancy after metabolic bariatric surgery and its impact on foetal growth and newborn body composition. Trial registration: ClinicalTrials.gov: NCT05084339. Registration date: 15 October 2021. Full article
(This article belongs to the Section Obstetrics & Gynecology)
15 pages, 1159 KiB  
Article
Maternal and Fetal–Neonatal Complications of Romanian Women with Gestational Diabetes: A Retrospective Comparative Study
by Adriana Gherbon, Mirela Frandes, Corina Dalia Toderescu, Darius Dirpes, Romulus Timar, Marioara Neagu Nicula, Calin Dascau, Razvan Daniluc and Bogdan Timar
Medicina 2025, 61(7), 1190; https://doi.org/10.3390/medicina61071190 - 30 Jun 2025
Viewed by 436
Abstract
Background and Objectives: Gestational diabetes mellitus (GDM) is a complex condition characterized by metabolic disorders of blood glucose that significantly impact the health of both mother and fetus. The objectives of this study were to assess the prevalence and risk factors for maternal [...] Read more.
Background and Objectives: Gestational diabetes mellitus (GDM) is a complex condition characterized by metabolic disorders of blood glucose that significantly impact the health of both mother and fetus. The objectives of this study were to assess the prevalence and risk factors for maternal and fetal–neonatal complications in women with GDM, comparing them to a control group (pregnant women without GDM) and pregnant women with type 1 diabetes mellitus (T1DM) or type 2 diabetes (T2DM). Materials and Methods: A retrospective observational study was conducted with 1418 pregnant women (279 with GDM, 74 with T1DM, 107 with T2DM, and 958 in the control group). The retrospective data included information on demographics, diagnostic test results, the medical history of pregnant women, treatments administered, identified complications, and other relevant variables for the study’s purpose. Results: Significant differences were found regarding maternal and neo-fetal complications between GDM and the control group in terms of abortion, pregnancy-induced hypertension, and increased fetal weight (macrosomia). Women with T1DM and T2DM showed a higher rate of abortion, premature birth, and an APGAR score of <7 at 5 min compared to those with GDM, and for T1DM, there was a higher rate of fetal mortality than in GDM cases. The primary risk factors for maternal complications included age OR = 1.03 (95% CI: 1.01–1.05, p = 0.002), obesity OR = 2.37 (95% CI: 1.42–3.94, p < 0.001), and chronic hypertension OR = 2.51 (95% CI: 1.26–5.01, p = 0.009). Age and obesity were also significant cofactors for maternal complications. Furthermore, the main significant risk factors for fetal–neonatal complications were obesity OR = 2.481 (95% CI:1.49–4.12, p < 0.001) and chronic hypertension OR = 2.813 (95% CI:1.44–5.49, p = 0.002), both independently and as cofactors. Conclusions: We found that obesity and chronic hypertension are risk factors for both maternal and fetal–neonatal complications. It is essential to prevent and adequately treat these two factors among pregnant women to avoid the onset of GDM. Additionally, screening for GDM is necessary to prevent maternal and fetal complications. Our results highlight the importance of specialized medical care and tailored management protocols in mitigating risks and ensuring positive outcomes for both mother and child during and after childbirth. Full article
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21 pages, 1133 KiB  
Article
Effect of a Low Glycemic Index/Slow Digesting (LGI/SD) Carbohydrate Product on Maternal Glycemia and Neonatal Body Composition in Obese Pregnant Women: The NIGOHealth Randomized Clinical Trial
by Mercedes G. Bermúdez, María García-Ricobaraza, José Antonio García-Santos, M. Teresa Segura, Alberto Puertas-Prieto, José Luis Gallo-Vallejo, Carmen Padilla-Vinuesa, Berthold Koletzko, Geraldine E. Baggs, Elena Oliveros, Ricardo Rueda and Cristina Campoy
Nutrients 2025, 17(11), 1942; https://doi.org/10.3390/nu17111942 - 5 Jun 2025
Viewed by 1056
Abstract
Background/Objectives: Obesity during pregnancy is strongly related to increased insulin resistance, and subsequent development of metabolic syndrome-like disorders, such as glucose intolerance, pre-eclampsia, as well as preterm birth, and cesarean delivery. Nutrition can influence the evolution of glycemic response and may help improve [...] Read more.
Background/Objectives: Obesity during pregnancy is strongly related to increased insulin resistance, and subsequent development of metabolic syndrome-like disorders, such as glucose intolerance, pre-eclampsia, as well as preterm birth, and cesarean delivery. Nutrition can influence the evolution of glycemic response and may help improve adverse pregnancy outcomes and long-term complications. The main objective of the Nutritional Intervention during Gestation and Offspring Health (NIGOHealth) randomized clinical trial (ClinicalTrials.gov Identifier: NCT02285764) was to investigate the potential effects of a low glycemic index/slow digesting (LGI/SD) carbohydrate product on maternal glycemia (glucose AUC at 27+0–28+6 weeks; maternal fasting blood glucose (MFBG) at 34+0–36+0 weeks), and neonatal body composition. Methods: Obese pregnant women were randomized: 230 in the intervention group (IG), who consumed two servings of an LGI/SD study product daily from 15 weeks of pregnancy until delivery, and 102 participants in the Standard of Care (SOC) group. Results: When analyzing baseline characteristics, significant differences were found in glucose metabolic parameters with higher values for IG than for the SOC group, compromising the group’s comparability. Despite this, a statistical analysis was conducted (intention-to-treat analysis/evaluable cohort): no differences were detected regarding maternal blood glucose AUC at 27+0–28+6 weeks, nor for MFBG at 34+0–36+0 weeks. Nonetheless, HbA1c (%) at 34+0–36+0 weeks was significantly lower in the IG vs. the SOC group (5.26 ± 0.03, 5.31 ± 0.04, p = 0.007) after adjusting for baseline conditions. Conclusion: This result might suggest a potential effect of the intervention on Evaluable participants. However, it should be taken with caution, due to the limitations of the study. More RCTs should be carried out to explore the effects of LGI/SD products on glycemic response in obese pregnant women. Full article
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18 pages, 513 KiB  
Review
Physiologically Based Pharmacokinetic Modeling of Antibiotics in Children: Perspectives on Model-Informed Precision Dosing
by Ryota Tanaka, Kei Irie and Tomoyuki Mizuno
Antibiotics 2025, 14(6), 541; https://doi.org/10.3390/antibiotics14060541 - 24 May 2025
Viewed by 1365
Abstract
The appropriate use of antibiotics is crucial and involves selecting an optimal dosing regimen based on pharmacokinetic (PK) and pharmacodynamic (PD) indicators. Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool that integrates drugs’ physicochemical properties with anatomical and physiological data to predict [...] Read more.
The appropriate use of antibiotics is crucial and involves selecting an optimal dosing regimen based on pharmacokinetic (PK) and pharmacodynamic (PD) indicators. Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool that integrates drugs’ physicochemical properties with anatomical and physiological data to predict PK behavior. In pediatric populations, PBPK modeling accounts for developmental changes in organ function, making it particularly useful for optimizing antibiotic dosing across different age groups, from neonates to adolescents. In recent decades, PBPK modeling has been widely applied to predict antibiotic disposition in pediatric patients for various clinical and research purposes. Model-informed precision dosing (MIPD) is an evolving approach that enhances traditional therapeutic drug monitoring by integrating multiple information sources into a mathematical framework. By incorporating PBPK modeling, MIPD could offer a more optimized antibiotic dosing that accounts for PK/PD parameters at the site of infection, improving therapeutic outcomes while minimizing toxicity. This review summarizes currently published pediatric PBPK modeling studies on antibiotics, covering various objectives such as evaluating drug–drug interactions, PK/PD analyses in targeted tissues, predicting PK in specific populations (e.g., maternal/fetal, renal impairment, obesity), and PK predictions for preterm neonates. Based on these reports, the review discusses the implications of PBPK modeling for MIPD in pediatric antibiotic therapy. Full article
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21 pages, 581 KiB  
Review
The Gut Microbiome as a Key Determinant of the Heritability of Body Mass Index
by Thomas M. Barber, Stefan Kabisch, Andreas F. H. Pfeiffer and Martin O. Weickert
Nutrients 2025, 17(10), 1713; https://doi.org/10.3390/nu17101713 - 18 May 2025
Viewed by 1477
Abstract
The pathogenesis of obesity is complex and incompletely understood, with an underlying interplay between our genetic architecture and obesogenic environment. The public understanding of the development of obesity is shrouded in myths with widespread societal misconceptions. Body Mass Index (BMI) is a highly [...] Read more.
The pathogenesis of obesity is complex and incompletely understood, with an underlying interplay between our genetic architecture and obesogenic environment. The public understanding of the development of obesity is shrouded in myths with widespread societal misconceptions. Body Mass Index (BMI) is a highly heritable trait. However, despite reports from recent genome-wide association studies, only a small proportion of the overall heritability of BMI is known to be lurking within the human genome. Other non-genetic heritable traits may contribute to BMI. The gut microbiome is an excellent candidate, implicating complex interlinks with hypothalamic control of appetite and metabolism via entero-endocrine, autonomic, and neuro-humeral pathways. The neonatal gut microbiome derived from the mother via transgenerational transmission (vaginal delivery and breastfeeding) tends to have a permanence within the gut. Conversely, non-maternally derived gut microbiota manifest mutability that responds to changes in lifestyle and diet. We should all strive to optimize our lifestyles and ensure a diet that is replete with varied and unprocessed plant-based foods to establish and nurture a healthy gut microbiome. Women of reproductive age should optimize their gut microbiome, particularly pre-conception, ante- and postnatally to enable the establishment of a healthy neonatal gut microbiome in their offspring. Finally, we should redouble our efforts to educate the populace on the pathogenesis of obesity, and the role of heritable (but modifiable) factors such as the gut microbiome. Such renewed understanding and insights would help to promote the widespread adoption of healthy lifestyles and diets, and facilitate a transition from our current dispassionate and stigmatized societal approach towards people living with obesity towards one that is epitomized by understanding, support, and compassion. Full article
(This article belongs to the Special Issue Interaction Between Gut Microbiota and Obesity)
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52 pages, 845 KiB  
Systematic Review
The Relationship Between Obesity, Bariatric Surgery, and Infertility: A Systematic Review
by Charalampos Voros, Antonia Varthaliti, Kyriakos Bananis, Despoina Mavrogianni, Diamantis Athanasiou, Antonia Athanasiou, Aikaterini Athanasiou, Anthi-Maria Papahliou, Constantinos G. Zografos, Panagiota Kondili, Menelaos Darlas, Ioannis Papapanagiotou, Maria Anastasia Daskalaki, Marianna Theodora, Panagiotis Antsaklis, Georgios Daskalakis and Dimitrios Loutradis
Life 2025, 15(5), 758; https://doi.org/10.3390/life15050758 - 9 May 2025
Viewed by 1656
Abstract
Background: Obesity is a complicated, chronic condition that has a major impact on reproductive health, leading to infertility, anovulation, and poor pregnancy outcomes. It alters the hypothalamic–pituitary–ovarian (HPO) axis, promotes insulin resistance, and causes persistent low-grade inflammation, all of which result in hormonal [...] Read more.
Background: Obesity is a complicated, chronic condition that has a major impact on reproductive health, leading to infertility, anovulation, and poor pregnancy outcomes. It alters the hypothalamic–pituitary–ovarian (HPO) axis, promotes insulin resistance, and causes persistent low-grade inflammation, all of which result in hormonal abnormalities that compromise normal ovarian function. Because standard weight loss procedures frequently fail to provide significant and long-term reproductive benefits, bariatric surgery is becoming increasingly popular as a therapeutic option for obese women trying to conceive. However, continuous research is being conducted to determine the degree of its advantages and potential hazards to fertility and pregnancy outcomes. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and entered into the PROSPERO database. Comprehensive searches in the PubMed, Scopus, and Web of Science databases turned up relevant studies. Studies that examined the effects of bariatric surgery on female fertility, ovulatory function, pregnancy rates, and neonatal outcomes were considered. Methodological quality and risk of bias were evaluated using the Newcastle–Ottawa Scale (NOS) for observational studies and the Cochrane Risk of Bias Tool for randomized controlled trials. Results: This review comprised 34 studies. More than 75% of the studies analyzed showed improvements in ovulatory function, monthly regularity, or spontaneous pregnancy after bariatric surgery. Post-surgical pregnancies are related to a lower incidence of gestational diabetes, hypertension, and macrosomia. However, several studies raised concerns about nutritional inadequacies and the possibility of small-for-gestational-age newborns, particularly following Roux-en-Y gastric bypass. Studies suggest delaying conception for 12 to 18 months after surgery to reduce nutritional hazards and improve pregnancy outcomes. Variability in study design, follow-up duration, and surgical methods reduces the generalizability of findings, emphasizing the importance of uniform research protocols. Conclusions: Bariatric surgery is a highly effective treatment for increasing fertility and pregnancy outcomes in obese women, particularly those with PCOS. However, rigorous preconception planning, postoperative nutritional monitoring, and multidisciplinary follow-up are required to reduce the related hazards. Future research should concentrate on long-term reproductive outcomes, standardizing fertility assessment criteria, and improving clinical guidelines for managing post-bariatric pregnancies. These findings support the incorporation of bariatric surgery into fertility treatment regimens for obese women, and they may shape future revisions to clinical guidelines on reproductive care following weight loss surgery. Full article
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34 pages, 1862 KiB  
Systematic Review
The Influences of Oral Probiotics on the Immunometabolic Response During Pregnancy and Lactation: A Systematic Review
by Valentin Nicolae Varlas, Laurențiu-Camil Bohîlțea and Nicolae Suciu
Nutrients 2025, 17(9), 1535; https://doi.org/10.3390/nu17091535 - 30 Apr 2025
Viewed by 1178
Abstract
Background/Objectives: In recent years, due to the emergence of antimicrobial resistance, probiotics have been increasingly used during pregnancy and lactation with real maternal–fetal benefits. Probiotic intervention, especially multi-strain probiotics, due to their anti-inflammatory, metabolic, and immunomodulatory actions, can be performed prophylactically and therapeutically [...] Read more.
Background/Objectives: In recent years, due to the emergence of antimicrobial resistance, probiotics have been increasingly used during pregnancy and lactation with real maternal–fetal benefits. Probiotic intervention, especially multi-strain probiotics, due to their anti-inflammatory, metabolic, and immunomodulatory actions, can be performed prophylactically and therapeutically with promising results regarding maternal, fetal, and neonatal health. The administration of probiotics can modulate the maternal microbiome, regulate microflora imbalance in various conditions (overweight/obesity, gestational diabetes mellitus (GDM), preeclampsia, allergic diseases), and influence several reactions such as modulating the non-specific cellular immune system, metabolic processes, and inhibition of pathogens. This study aimed to analyze, based on available data, how the administration of probiotic supplements to women during pregnancy can modify immunometabolic responses to microbial dysbiosis to limit weight gain and the risk of obesity, to improve glucose homeostasis and reduce the risk of GDM, to prevent preeclampsia and its effects on maternal–fetal outcomes, and to reduce rates of atopic eczema and allergic diseases in infants. Methods: We performed a systematic search in MEDLINE/PubMed to identify studies that have investigated the effects of probiotic intervention on the immunometabolic response in pregnancy and lactation, especially in women with diabetes, overweight/obesity, preeclampsia, and allergic conditions. Results: Fifty-six RCT studies, totaling 15,044 women, matched the inclusion criteria, of which eight were for interventions on the immune response, twenty on allergic conditions, seven on obesity and excess weight gain in pregnancy, and twenty-one on GDM. Conclusions: Due to the heterogeneous structure and the size of the samples, the methodologies, formulations, moment of initiation, and study durations, future research is needed to establish their effectiveness and safety in pregnancy and lactation regarding maternal-fetal health and outcomes in childhood and adult life. Full article
(This article belongs to the Special Issue Nutrition Strategy for Maternal and Infant Wellbeing)
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15 pages, 404 KiB  
Article
Adipokines as Potential Biomarkers in Pregnancy: A Naturalistic Study of Adipokines in Pregnant Women and Newborns
by Cristina Mihaela Ormindean, Răzvan Ciortea, Andrei Mihai Măluțan, Carmen Elena Bucuri, Doru Mihai Diculescu, Cristian Ioan Iuhas, Ciprian Gheorghe Porumb, Vlad Ormindean, Maria Patricia Roman, Ionel Daniel Nati, Viorela Suciu, Alexandru Emil Hăprean and Dan Mihu
Biomolecules 2025, 15(5), 607; https://doi.org/10.3390/biom15050607 - 22 Apr 2025
Viewed by 507
Abstract
Maternal obesity is an escalating public health concern that adversely affects pregnancy outcomes. Adipokines play a key role in regulating metabolism and fetal development, but their dynamic changes during pregnancy remain inadequately understood. Objective: This study investigates maternal and fetal adipokine variations throughout [...] Read more.
Maternal obesity is an escalating public health concern that adversely affects pregnancy outcomes. Adipokines play a key role in regulating metabolism and fetal development, but their dynamic changes during pregnancy remain inadequately understood. Objective: This study investigates maternal and fetal adipokine variations throughout pregnancy and their associations with maternal body mass index (BMI), abdominal wall thickness, and neonatal outcomes. Methods: A prospective case-control study was conducted involving 74 pregnant women categorized by BMI. Maternal blood samples were collected at mid-pregnancy and delivery, and additional analysis of umbilical-cord blood was performed. Clinical parameters such as BMI, abdominal wall thickness, and fetal growth metrics were also recorded. Results: Adiponectin levels were significantly lower in obese pregnancies, whereas leptin and visfatin levels increased with higher maternal BMI. Umbilical-cord blood leptin levels correlated positively with maternal BMI and neonatal birth weight, while ghrelin levels were reduced in neonates born to obese mothers. Significant adipokine fluctuations were observed between mid-pregnancy and delivery. Conclusions: Maternal obesity is associated with distinct alterations in adipokine profiles. These findings highlight the potential of maternal adipokines, given their links to maternal adiposity, as predictive biomarkers for adverse pregnancy outcomes and long-term metabolic risks in offspring. Further interventional research is warranted to evaluate targeted strategies aimed at improving perinatal metabolic health. Full article
8 pages, 253 KiB  
Article
The Impact of Early Epidural Analgesia on the Course of Labor and Delivery
by Atene Simanauskaite, Gabriele Kavaliauskaite, Justina Kacerauskiene and Vilda Vilimiene
Medicina 2025, 61(4), 750; https://doi.org/10.3390/medicina61040750 - 18 Apr 2025
Viewed by 1394
Abstract
Background and Objectives: This study aimed to assess the impact of early epidural analgesia (EA) on the progression of labor and delivery outcomes among nulliparous women. Materials and Methods: A retrospective analysis was conducted utilizing data from the Birth Registry of [...] Read more.
Background and Objectives: This study aimed to assess the impact of early epidural analgesia (EA) on the progression of labor and delivery outcomes among nulliparous women. Materials and Methods: A retrospective analysis was conducted utilizing data from the Birth Registry of the Department of Obstetrics and Gynecology at LUHS. The dataset encompassed women who underwent childbirth between 1 January 2021 and 31 December 2021 and who received EA for labor pain management. A total of 89 women with low-risk deliveries and EA were included in the study. The cohort was divided into two groups: Group I—parturients who underwent early EA with cervical dilatation ≤3 cm—and Group II—parturients who underwent EA with cervical dilatation >3 cm but <7 cm. The results were processed using IBM SPSS. Results: Group I consisted of 25 (28.1%) women and Group II consisted of 64 (71.9%). The prevalence of obesity was higher in Group II (p = 0.021). Bishop score was statistically elevated in Group II (p = 0.018). Upon hospital admission, Group II exhibited greater cervical dilation (p = 0.001). The rate of cervical dilation was higher in Group II at 1.54 cm/h (p = 0.033). Episiotomy was more frequently performed in Group II (p = 0.014). The average durations of the first stage of labor (p = 0.045), the second stage of labor (p = 0.033), and the overall labor (p = 0.023) were prolonged in Group I. Conclusions: The cervical dilation up to 10 cm occurs at a swifter pace when EA is administered following cervical dilation exceeding 3 cm. Notable associations were observed between EA and the incidence of episiotomy as well as the duration of labor stages. Early EA exhibited no impact on neonatal outcomes. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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