Search Results (86)

Background/Objectives: In phenylketonuria (PKU), high blood phenylalanine (Phe) levels during pregnancy negatively influence foetal organogenesis and growth, leading to maternal PKU syndrome. Pregnancies must be carefully planned in order to maintain blood Phe levels ≤ 360 µmol/L pre-conception and throughout pregnancy. Our aim was to study metabolic control in PKU pregnancies across Europe. Methods: Eleven centres managing PKU participated. Data on blood Phe levels (µmol/L), natural protein intake (g/day), protein substitute intake (g/day) and maternal weight (kg) during pregnancy were collected retrospectively from dietetic records between 2012 and 2018. Results: In total, 84 female patients with PKU, accounting for 102 pregnancies (mean age: 30.4 ± 4.8 years), participated. Of these, 7 had hyperphenylalaninemia (HPA), 26 had mild PKU, 55 had classical PKU and 14 were unclassified. Sapropterin was prescribed in two pregnancies. Only 27% (28/102) of pregnancies successfully achieved consistent blood Phe levels ≤ 360 µmol/L for at least 2 weeks pre-conception. During pregnancy, 88% of blood Phe levels were ≤360 µmol/L, with a mean Phe of 229 ± 65 µmol/L. The mean number of blood Phe samples was 60 (1.5 per week) per pregnancy. In pre-pregnancy, over a mean of 2.9 years, only 35% of blood Phe levels were ≤360 µmol/L and 61% were <600 µmol/L. Post-pregnancy, over a mean of 2.8 years, 43% of Phe levels were <600 µmol/L with mean Phe 462 ± 226 µmol/L and 724 ± 230 µmol/L, respectively. 25% (25/102) had no levels performed post-pregnancy (mean of 2.8 ± 1.6 years) compared to 7% (7/102) pre-pregnancy (mean of 2.9 ± 1.5 years). Mean prescribed Phe intake pre-/during/post-pregnancy was 810 ± 721 vs. 787 ± 552 vs. 1110 ± 722 mg/day. Natural protein intake was 17 ± 15 vs. 17 ± 11 vs. 23 ± 15 g/day. Protein equivalent from protein substitute intake was 57 ± 21 vs. 66 ± 16 vs. 50 ± 23 g/day and total protein remained stable, 73 ± 14 vs. 83 ± 14 vs. 71 ± 19 g/day (1.1 ± 0.3 vs. 1.1 ± 0.4 vs. 1.0 ± 0.4 g/kg/day). Conclusions: Although a high level of metabolic control was maintained during pregnancy, fewer than 30% of pregnancies achieved constant Phe levels ≤ 360 µmol/L prior to conception, with minimal monitoring post-pregnancy. The long-term impact on the offspring remains unknown and requires further investigation. Full article

Consistent behavioural differences among individuals have been documented across many animal taxa, yet their developmental consequences in domestic production systems remain less clear. This gap is especially relevant in managed environments, where food availability and ecological constraints differ markedly from those in the wild. In this study, we assessed behavioural traits in 25 Tibetan sheep (Ovis aries) ewes and examined their associations with early growth in their lambs under semi-captive conditions on the Qinghai–Tibetan Plateau. We quantified docility, exploration, vocal responses, and several physiological measures of responsiveness in the ewes and related these variables to lamb birth weight, early weight gain, and a composite growth index. We found that maternal docility had no significant effect on lamb birth weight, whereas maternal activity, defined as locomotor movement recorded during the open-field phase, was negatively associated with offspring birth weight. One possible interpretation is that ewes showing greater locomotor activity during the open-field phase allocate energy differently during gestation, which could limit foetal growth, although this mechanism was not directly tested in this study. These results suggest that the behavioural effects on offspring development depend strongly on the production context. In this semi-captive system, greater maternal responsiveness was not associated with improved offspring performance, unlike patterns that are often observed in wild populations. This context dependence may be relevant when behavioural traits are considered in Tibetan sheep management or breeding. Full article

Pre-eclampsia and foetal growth restriction (FGR) are major pregnancy complications primarily driven by placental dysfunction, and remain leading causes of maternal and perinatal morbidity. Ultrasound imaging, Doppler studies, and angiogenic biomarkers like placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) constitute the main diagnostic modalities; however, these predominantly reflect established disease rather than early molecular disturbances underlying placentation. The identification of biomarkers directly associated with trophoblast signalling pathways has the potential to improve early risk stratification and enable mechanistic classifications. Kisspeptin signalling via its receptor (KISS1R) regulates trophoblast invasion, extracellular matrix remodelling, ERK1/2 activation, and angiogenic balance, thereby modulating spiral artery transformation. Kisspeptin-10 (KP-10), the minimal bioactive fragment of KISS1, is highly expressed in placental syncytiotrophoblasts and exerts its effects through the G-protein-coupled receptor KISS1R. Core features of early-onset FGR and pre-eclampsia (PE)—including defective placentation, maternal vascular malperfusion, and angiogenic imbalance—have been linked to dysregulation of this pathway. During normal gestation, maternal circulating kisspeptin concentrations rise exponentially. In contrast, pregnancies subsequently complicated by FGR or PE, particularly in the early gestation, are associated with reduced levels. However, the comparability of existing studies and their translational applicability are limited by a substantial methodological heterogeneity, including assay variability, gestational age dependence, and inadequate adjustment for maternal confounders. These limitations hinder robust conclusions regarding the role of kisspeptin in placental pathology. This review critically integrates molecular, pathophysiological, and clinical evidence relating to the role of KP-10 in placental dysfunction. The key question is whether KP-10 represents a mechanistic biomarker of trophoblast signalling dysfunction or merely a secondary marker of reduced placental mass; resolving this distinction is essential. Full article

Preeclampsia is a double-hit vascular disorder centred on the VEGF-HO-1-CSE axis. First, excess placental soluble Flt-1 (sFlt-1) neutralises vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), producing an angiogenic deficit that drives endothelial dysfunction, hypertension, proteinuria and end organ injury. Second, the failure of endogenous vascular brakes, heme oxygenase-1 (HO-1/CO) and cystathionine-γ-lyase (CSE)/hydrogen sulfide (H₂S) removes physiological restraint on anti-angiogenic factor release (sFlt-1; soluble endoglin) and amplifies oxidative–inflammatory stress, lowering the threshold at which VEGF loss precipitates severe disease. We synthesise human, animal and translational data that (i) establish placental sFlt-1 source and release, (ii) demonstrate human mechanistic causality via sFlt-1 removal, (iii) show prospective clinical validation that sFlt-1 rises and free PlGF falls before disease onset, and (iv) identify HO-1 and CSE/H₂S as protective pathways that restrain anti-angiogenic drive. Finally, we summarise preclinical evidence that the orally administered H₂S-donor prodrug MZe786 restores the HO-1/CSE axis, lowers sFlt-1 and soluble endoglin (sEng), and improves maternal haemodynamics and foetal outcomes across complementary pregnancy models, and we outline the role of sFlt-1/PlGF and M-PREG-based triage in clinical decision making. While valuable for short-term triage, current sFlt-1/PlGF-based approaches cannot sub-stratify among positive cases. Framing severe preeclampsia as a double-hit vascular disorder provides a biologically grounded framework that can inform risk stratification strategies like M-PREG^®, a clinical decision support system informed by the double hit framework, and prevention strategies, pairing early risk stratification with mechanism-informed interventions. Full article

Background/Objectives: The first 1000 days of life represent a critical window for growth and neurodevelopment, during which nutrition strongly influences brain development and metabolic programming. In phenylketonuria (PKU), dietary management is essential to prevent neurological impairment and later-life risk of non-communicable diseases (NCDs). This review examines current evidence on PKU from pregnancy through complementary feeding, highlighting the impact of nutritional strategies on neurodevelopmental and metabolic outcomes. Methods: This narrative review, following PRISMA guidelines, used a systematic search of PubMed and Scopus with defined PICO questions. Original research, reviews, and guidelines on PKU nutrition during the first 1000 days were included, emphasizing neurological and metabolic outcomes. Results: Articles addressed prenatal and postnatal factors in PKU. Optimised metabolic control in women with PKU is critical to prevent maternal PKU syndrome, reducing risks of miscarriage, congenital heart defects, microcephaly, and neurocognitive impairment. Pre-conception dietary management, frequent blood Phe monitoring, supplementation with Phe-free protein substitutes (PSs), micronutrients, and emerging pharmacological therapies support maternal and foetal health. Following newborn screening, early dietary treatment in infants with PKU maintains plasma Phe within safe ranges, promoting growth and neurodevelopment. Breastfeeding, combined with Phe-free infant PSs, is feasible, and complementary feeding should be introduced carefully. Frequent monitoring and tailored dietary adjustments, including second-stage PSs, support metabolic control, while data on gut microbiota remain limited. Conclusions: Early multidisciplinary interventions are crucial to optimise metabolic and neurodevelopmental outcomes during this window of opportunity. Further research is needed to address remaining gaps and optimise PKU management across the first 1000 days. Full article

The present study aimed to assess the potential maternal toxicity of Ficus deltoidea var. kunstleri aqueous extract in pregnant rats, along with its impact on maternal hepatic drug metabolism and foetal skeletal development. Pregnant rats were divided into five groups and orally administered varying doses of F. deltoidea aqueous extract (0, 250, 500, 1000, and 2000 mg/kg body weight) from gestation day 6 to 20. Throughout the administration period, clinical observations, body weight, and food and water intake were monitored. On gestation day 21, the pregnant rats were sacrificed, and their vital organs and foetuses were collected for analysis. Gene expression related to hepatic drug metabolism was evaluated using the RT2 Profiler™ PCR array. Foetal external morphology was examined for abnormalities, and skeletal structures were stained with Alizarin Red to assess the effects of F. deltoidea aqueous extract on bone ossification during organogenesis. No maternal toxicity was observed, except for a significant increase in liver weight in the treated groups (p < 0.05). Analysis of 84 genes revealed significant changes in 15, 4, and 11 genes in the 250, 500, and 2000 mg/kg body weight groups, respectively. Notably, Gpx5 and Pkm, both phase II metabolising enzyme genes were downregulated in a dose-dependent manner. Despite some skeletal variations, the extract did not induce foetal external malformations or skeletal abnormalities. The significant increase in maternal liver weight, together with the downregulation of Gpx5 and Pkm, suggests an adaptive hepatic response to the extract rather than an adverse effect. These findings also suggest that F. deltoidea var. kunstleri aqueous extract does not cause embryo toxicity, foetal growth retardation, or developmental malformations, particularly in skeletal formation. The developmental no-observed-adverse-effect level (NOAEL) was determined to be >2000 mg/kg/day via oral administration. Further research is warranted to explore the synergistic interactions of genes involved in hepatic drug metabolism in response to the extract. Full article

Foetal growth restriction (FGR) is commonly caused by placental insufficiency and increases the risk of perinatal morbidity and mortality. The developing brain is vulnerable to FGR, which can result in adverse long-term neurodevelopmental outcomes. Newborn pigs with spontaneous FGR (<10th centile body weight) and normally grown (NG) littermates were reared to postnatal day 10 (P10; n = 8 FGR and n = 9 NG). Neuropathology was assessed in the prefrontal cortex (PFC) and basal ganglia (BG), which play a key role in cognitive and motor functions. FGR piglets show decreased neuronal count (NeuN) and structural integrity (MAP2) associated with increased apoptotic activity (Casp-3 and -9) in the PFC and BG. Hypomyelination was consistently observed in the white matter of the FGR brain. There was increased microglial activation (Iba-1) and GFAP-positive astrocytes in both the grey and white matter of the PFC and BG, along with increased apoptotic activity in the FGR brain. These findings suggest that the FGR piglet brain shows impaired grey and white matter associated with increased apoptosis in the PFC and BG that persists at P10. Increased glial activation and apoptotic astrocytes may impact neuronal survival and potentially contribute to adverse long-term neurodevelopmental outcomes, highlighting the need for targeted therapeutic interventions to promote effective brain repair in infants with FGR. Full article

The human endometrium is unique in that it has a high potential for regeneration after menstruation without scarring. Although growth factors are thought to be responsible for scar formation, it has recently been shown for foetal skin that CD26-negative fibroblasts are essential. Thus, we investigated whether CD26 might be involved in scar formation. Primary human endometrial stromal cells (HPESCs) were stimulated with interleukin-1 alpha (IL1α) to induce CD26 protein expression, and secretion of the scar-associated proteins collagen 1 alpha 1 (COL1A1) and TGF-β3 was measured using ELISAs. The contribution of CD26 to wound closure was analysed using a wound healing assay. The CD26 inhibitor diprotin A (DPA) was used to attenuate CD26 activity. Immunohistochemistry of human uterine samples showed negligible stromal staining of CD26, but CD26 was abundant in the endometrial glands. Treatment of CD26-negative HPESCs with IL1α induced CD26 protein expression, strongly stimulated wound healing in vitro, and increased secretion of COL1A1, but decreased TGF-β3 secretion. DPA effectively attenuated all IL1α-induced effects. We suggest that the stromal non-expression of the scar-associated protein CD26 might contribute to non-scarring during endometrial wound healing. Full article

Various signalling molecules and pathways critical for wool production and quality regulate wool secondary follicle (SF) development. Circular RNAs (circRNAs) regulate SF morphogenesis through a competing endogenous RNA (ceRNA) mechanism; these novel cyclic non-coding RNAs are not known to regulate the development of SFs in the foetal period of fine-wool sheep. Here, we analysed circRNA expression profiles in the foetal skin of Gansu Alpine fine-wool sheep at 10 developmental stages (E87, E90, E93, E96, E99, E102, E105, E108, E111, and E138) using RNA sequencing. Among the differentially expressed circRNAs (DE circRNAs), 173 were significantly enriched in signalling pathways related to hair follicle (HF) development, such as Wnt/β-catenin, transforming growth factor-β/Smad, Notch, and mitogen-activated protein kinase. Six HF-development-related circRNAs were expressed at different stages and potentially regulated SF development through the ceRNA network. In total, 16 DE circRNAs and their targets, 44 miRNAs, and 65 mRNAs were screened, and 88 ceRNA regulatory network pathways related to SF development were constructed. These key DE circRNAs could be candidate genes for further exploration of the molecular HF development mechanism, providing an important theoretical basis for unravelling the regulatory network of SF development in fine-wool sheep and genetic wool trait improvement. Full article

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

Background: Nowadays, there is an increasing desire among women suffering from pelvic organ prolapse (POP) to choose a uterus-sparing surgical treatment in order to preserve their fertility. The objective of this study was to conduct a systematic review of the literature to assess how pregnancy and delivery affect the recurrence of POP in women who had previously undergone laparoscopic hysteropexy as well as to improve and individualise the future counselling of patients of reproductive age desiring uterine-preserving treatment for POP. Methods: A comprehensive literature review was conducted using the MEDLINE (PubMed), Web of Science, and Scopus databases for articles published until January 2025, without previous historical limits. The research strategy adopted included different combinations of the following terms: hysteropexy, pregnancy, laparoscopy, and prolapse. Results: A total of ten case reports and three case series met the inclusion criteria for the review, comprising 26 patients. All authors used laparoscopic sacral hysteropexy (LSHP) for the treatment of POP. All patients underwent caesarean delivery at a mean gestational age of 38 weeks. Over a mean follow-up period of 9 months, only 4% of patients developed a recurrent uterine prolapse. A total of 8% of the patients developed de novo anterior compartment prolapse, 8% developed a recurrence of anterior compartment prolapse, and 4% developed posterior compartment prolapse. Conclusions: LSHP seems to be a safe option for women of reproductive age with incomplete family planning, as it does not seem to negatively impact foetal growth. Pregnancy does not appear to affect the long-term efficacy of hysteropexy in maintaining apical support. Given the limited data on the safety and efficacy of uterine-sparing surgery for POP followed by a subsequent pregnancy, further evidence is of great importance towards evaluating safety, efficacy, and providing better counselling for women. Full article

Gestational diabetes mellitus (GDM) is a complication that affects 20% of pregnancies worldwide. It is associated with adverse short- and long-term cardiometabolic outcomes for both mother and infant. Effective management of GDM involves lifestyle modifications, including medical nutrition therapy (MNT) and physical activity (PA), with the addition of insulin or metformin if glycaemic control remains inadequate. However, substantial gaps persist in the determination of optimal medical nutrition therapy (MNT) for women with GDM. Challenges in MNT include individual variation in glucose tolerance and changing maternal physiology and dietary requirements during pregnancy. Achieving optimal glycaemic control depends on careful macronutrient balance, particularly the distribution and quality of carbohydrate intake and sufficient protein and fat intake. Additionally, micronutrient deficiencies, such as inadequate vitamin D, calcium, and essential minerals, may exacerbate oxidative stress, inflammation, and glycaemic dysregulation, further impacting foetal growth and development. Cultural beliefs and dietary practices among pregnant women can also hinder adherence to recommended nutritional guidelines. Conditions like hyperemesis gravidarum (HG) affect ~1% to 2% of pregnant women can result in unintended energy and nutrient deficits. This special issue explores the current evidence and major barriers to optimising dietary therapy for women with GDM. It also identifies future research priorities to advance clinical practice, improve maternal and foetal outcomes, and address gaps in personalised nutrition interventions. Full article

Complex biological processes that enable optimal foetal growth throughout pregnancy are linked to notable haemodynamic and metabolic changes in the mother’s body. An inability to adapt to these changes can affect cardiovascular health. During pregnancy, women may experience mood swings, anxiety, and emotional ambivalence. These symptoms can lead to stress and harm the mental well-being of expectant mothers. It is crucial to know the aspects that can influence the development of cardiovascular problems among pregnant women. Effective management requires identifying risk factors. Applying the PRISMA ScR guidelines, we conducted a scoping review to explore and summarise the evidence regarding the impact of stress and anxiety on cardiovascular health in pregnant women. The following enquiries were looked into as research topics: What effects do anxiety and stress have on a pregnant woman’s cardiovascular health? How is it quantifiable? It is essential to comprehend the physiological changes that the body undergoes throughout pregnancy in order to inform and assist both patients and medical professionals. This makes it possible for them to identify any pathological disorders or risk factors that could worsen the health of expectant mothers. Psychological and cardiovascular risk factor screening, either before or during pregnancy, may be able to uncover circumstances that require specific medical and psychological therapies in order to lower maternal morbidity and death from cardiovascular disease. Our findings underscore the need for systematic psychological and cardiovascular screening during prenatal care to mitigate adverse outcomes and improve maternal–foetal health. Full article

Appropriate placental structure and function assure foetal development, delivery of nutrients, and removal of waste. Collagens, as structural proteins, are crucial for the maintenance of placental growth and function. The aim of this study was to describe the profile of collagen 1 and 4 in the placental tissues of cows and to correlate it to previously described activities of collagenases and adhesive proteins. Placental samples were collected from pregnant cows in the slaughterhouse (2nd, 4th, and 6th month; n = 12) and during parturition after caesarean section. Samples taken during caesarean section were retrospectively divided into retained (R; n = 6) and not retained foetal membranes (NR; n = 6). Determinations were performed of maternal and foetal parts separately after tissue homogenisation. Supernatants were used for the determination of COL1 and COL4 concentrations by ELISA and WB analysis. Significant differences were detected between pregnancy months and parturient samples in COL1 concentrations and between retained and released foetal membranes. The concentrations of COL4 were higher in the foetal as compared to the maternal part of the placenta. Significant differences were detected between retained and released foetal membranes, and, similarly to Col1, values were lower in retained than released foetal membranes. WB analysis showed the presence of examined collagen molecules and their molecular weights. The analysis of collagen profile together with the enzymes of their degradation and other adhesive proteins (glycodelin, decorin, and thrombospondins) in bovine placenta either during pregnancy and parturition showed a close relationship. Either attachment or detachment of the maternal and foetal parts of the bovine placenta requires actions in concert between all these adhesive proteins under the influence of pregnancy hormones. Full article

Background: This study describes a novel biomaterial consisting of a mixture of biphasic bioceramic obtained from waste generated by the sugar industry (Carbocal) and a medical-grade epoxy resin adhesive called LOCTITE^® M31 CLTM. The objective was to demonstrate the possibility of coating non-bioactive and non-biodegradable metallic surfaces on implantable elements. Methods: After preparation, the mixture was applied to the surfaces of hip prostheses composed of two distinct materials: polyetherimide and grade 5 titanium. In both cases, adhesion tests produced favourable results. Additionally, cell cultures were conducted using human foetal osteoblastic cell lines (hFOB 1.19). Results: It was observed that the mixture did not affect the proliferation of bone cells. Conclusions: This composite material was found to promote the growth of bone cells, suggesting its potential for fostering bone tissue development. Full article