Feto-placental Unit: From Development to Function.

The placenta is an intriguing organ that allows us to survive intrauterine life. This essential organ connects both mother and fetus and plays a crucial role in maternal and fetal well-being. This chapter presents an overview of the morphological and functional aspects of human placental development. First, we describe early human placental development and the characterization of the cell types found in the human placenta. Second, the human placenta from the second trimester to the term of gestation is reviewed, focusing on the morphology and specific pathologies that affect the placenta. Finally, we focus on the placenta's primary functions, such as oxygen and nutrient transport, and their importance for placental development.

Tetrahydrobiopterin Role in human umbilical vein endothelial dysfunction in maternal supraphysiological hypercholesterolemia.

Maternal physiological hypercholesterolemia (MPH) allows a proper foetal development; however, maternal supraphysiological hypercholesterolemia (MSPH) associates with foetal endothelial dysfunction and early development of atherosclerosis. MSPH courses with reduced endothelium-dependent dilation of the human umbilical vein due to reduced endothelial nitric oxide synthase activity compared with MPH. Whether MSPH modifies the availability of the nitric oxide synthase cofactor tetrahydrobiopterin is unknown. We investigated whether MSPH-associated lower umbilical vein vascular reactivity results from reduced bioavailability of tetrahydrobiopterin. Total cholesterol <7.2mmol/L was considered as maternal physiological hypercholesterolemia (n=72 women) and ≥7.2mmol/L as MSPH (n=35 women). Umbilical veins rings were used for vascular reactivity assays (wire myography), and primary cultures of human umbilical vein endothelial cells (HUVECs) to measure nitric oxide synthase, GTP cyclohydrolase 1, and dihydrofolate reductase expression and activity, as well as tetrahydrobiopterin content. MSPH reduced the umbilical vein rings relaxation caused by calcitonine gene-related peptide, a phenomenon partially improved by incubation with sepiapterin. HUVECs from MSPH showed lower nitric oxide synthase activity (l-citrulline synthesis from l-arginine) without changes in its protein abundance, as well as reduced tetrahydrobiopterin level compared with MPH, a phenomenon reversed by incubation with sepiapterin. Expression and activity of GTP cyclohydrolase 1 was lower in MSPH, without changes in dihydrofolate reductase expression. MSPH is a pathophysiological condition reducing human umbilical vein reactivity due to lower bioavailability of tetrahydrobiopterin leading to lower NOS activity in the human umbilical vein endothelium.

Maternal insulin therapy does not restore foetoplacental endothelial dysfunction in gestational diabetes mellitus.

Pregnant women diagnosed with gestational diabetes mellitus subjected to diet (GDMd) that do not reach normal glycaemia are passed to insulin therapy (GDMi). GDMd associates with increased human cationic amino acid transporter 1 (hCAT-1)-mediated transport of L-arginine and nitric oxide synthase (NOS) activity in foetoplacental vasculature, a phenomenon reversed by exogenous insulin. Whether insulin therapy results in reversal of the GDMd effect on the foetoplacental vasculature is unknown. We assayed whether insulin therapy normalizes GDMd-associated foetoplacental endothelial dysfunction. Primary cultures of human umbilical vein endothelial cells (HUVECs) from GDMi pregnancies were used to assay L-arginine transport kinetics, NOS activity, p44/42mapk and protein kinase B/Akt activation, and umbilical vein rings reactivity. HUVECs from GDMi or GDMd show increased hCAT-1 expression and maximal transport capacity, NOS activity, and eNOS, and p44/42mapk, but not Akt activator phosphorylation. Dilation in response to insulin or calcitonin-gene related peptide was impaired in umbilical vein rings from GDMi and GDMd pregnancies. Incubation of HUVECs in vitro with insulin (1 nmol/L) restored hCAT-1 and eNOS expression and activity, and eNOS and p44/42mapk activator phosphorylation. Thus, maternal insulin therapy does not seem to reverse GDMd-associated alterations in human foetoplacental vasculature.

Sodium/proton exchanger isoform 1 regulates intracellular pH and cell proliferation in human ovarian cancer.

Cancer cells generate protons (H+) that are extruded to the extracellular medium mainly via the Na+/H+ exchanger 1 (NHE1), which regulates intracellular pH (pHi) and cell proliferation. In primary cultures of human ascites-derived ovarian cancer cells (haOC) we assayed whether NHE1 was required for pHi modulation and cell proliferation. Human ovary expresses NHE1, which is higher in haOC and A2780 (ovarian cancer cells) compared with HOSE cells (normal ovarian cells). Basal pHi and pHi recovery (following a NH4Cl pulse) was higher in haOC and A2780, compared with HOSE cells. Zoniporide (NHE1 inhibitor) caused intracellular acidification and pHi recovery was independent of intracellular buffer capacity, but reduced in NHE1 knockdown A2780 cells. Zoniporide reduced the maximal proliferation capacity, cell number, thymidine incorporation, and ki67 (marker of proliferation) fluorescence in haOC cells. SLC9A1 (for NHE1) amplification associated with lower overall patient survival. In conclusion, NHE1 is expressed in human ovarian cancer where it has a pro-proliferative role. Increased NHE1 expression and activity constitute an unfavourable prognostic factor in these patients.

Nitric oxide and pH modulation in gynaecological cancer.

Nitric oxide plays several roles in cellular physiology, including control of the vascular tone and defence against pathogen infection. Neuronal, inducible and endothelial nitric oxide synthase (NOS) isoforms synthesize nitric oxide. Cells generate acid and base equivalents, whose physiological intracellular concentrations are kept due to membrane transport systems, including Na+ /H+ exchangers and Na+ /HCO3- transporters, thus maintaining a physiological pH at the intracellular (~7.0) and extracellular (~7.4) medium. In several pathologies, including cancer, cells are exposed to an extracellular acidic microenvironment, and the role for these membrane transport mechanisms in this phenomenon is likely. As altered NOS expression and activity is seen in cancer cells and because this gas promotes a glycolytic phenotype leading to extracellular acidosis in gynaecological cancer cells, a pro-inflammatory microenvironment increasing inducible NOS expression in this cell type is feasible. However, whether abnormal control of intracellular and extracellular pH by cancer cells regards with their ability to synthesize or respond to nitric oxide is unknown. We, here, discuss a potential link between pH alterations, pH controlling membrane transport systems and NOS function. We propose a potential association between inducible NOS induction and Na+ /H+ exchanger expression and activity in human ovary cancer. A potentiation between nitric oxide generation and the maintenance of a low extracellular pH (i.e. acidic) is proposed to establish a sequence of events in ovarian cancer cells, thus preserving a pro-proliferative acidic tumour extracellular microenvironment. We suggest that pharmacological therapeutic targeting of Na+ /H+ exchangers and inducible NOS may have benefits in human epithelial ovarian cancer.

Insulin requires normal expression and signaling of insulin receptor A to reverse gestational diabetes-reduced adenosine transport in human umbilical vein endothelium.

Reduced adenosine uptake via human equilibrative nucleoside transporter 1 (hENT1) in human umbilical vein endothelial cells (HUVECs) from gestational diabetes mellitus (GDM) is reversed by insulin by restoring hENT1 expression. Insulin receptors A (IR-A) and B (IR-B) are expressed in HUVECs, and GDM results in higher IR-A mRNA expression vs. cells from normal pregnancies. We studied whether the reversal of GDM effects on transport by insulin depends on restoration of IR-A expression. We specifically measured hENT1 expression [mRNA, protein abundance, SLC29A1 (for hENT1) promoter activity] and activity (adenosine transport kinetics) and the role of IR-A/IR-B expression and signaling [total and phosphorylated 42 and 44 kDa mitogen-activated protein kinases (p44/42(mapk)) and Akt] in IR-A, IR-B, and IR-A/B knockdown HUVECs from normal (n = 33) or GDM (n = 33) pregnancies. GDM increases IR-A/IR-B mRNA expression (1.8-fold) and p44/42(mapk):Akt activity (2.7-fold) ratios. Insulin reversed GDM-reduced hENT1 expression and maximal transport capacity (V(max)/K(m)), and GDM-increased IR-A/IR-B mRNA expression and p44/42(mapk):Akt activity ratios to values in normal pregnancies. Insulin's effect was abolished in IR-A or IR-A/B knockdown cells. Thus, insulin requires normal IR-A expression and p44/42(mapk)/Akt signaling to restore GDM-reduced hENT1 expression and activity in HUVECs. This could be a protective mechanism for the placental macrovascular endothelial dysfunction seen in GDM.

Insulin requires A1 adenosine receptors expression to reverse gestational diabetes-increased L-arginine transport in human umbilical vein endothelium.

Gestational diabetes mellitus (GDM) associates with increased L-arginine transport and extracellular concentration of adenosine in human umbilical vein endothelial cells (HUVECs). In this study we aim to determine whether insulin reverses GDM-increased L-arginine transport requiring adenosine receptors expression in HUVECs. Primary cultured HUVECs from full-term normal (n = 38) and diet-treated GDM (n = 38) pregnancies were used. Insulin effect was assayed on human cationic amino acid transporter 1 (hCAT1) expression (protein, mRNA, SLC7A1 promoter activity) and activity (initial rates of L-arginine transport) in the absence or presence of adenosine receptors agonists or antagonists. A1 adenosine receptors (A1AR) and A2AAR expression (Western blot, quantitative PCR) was determined. Experiments were done in cells expressing or siRNA-suppressed expression of A1AR or A2AAR. HUVECs from GDM exhibit higher maximal transport capacity (maximal velocity (V max)/apparent Michaelis Menten constant (K m), V max/K m), which is blocked by insulin by reducing the V max to values in cells from normal pregnancies. Insulin also reversed the GDM-associated increase in hCAT-1 protein abundance and mRNA expression, and SLC7A1 promoter activity for the fragment -606 bp from the transcription start point. Insulin effects required A1AR, but not A2AAR expression and activity in this cell type. In the absence of insulin, GDM-increased hCAT-1 expression and activity required A2AAR expression and activity. HUVECs from GDM pregnancies exhibit a differential requirement of A1AR or A2AAR depending on the level of insulin, a phenomenon that represent a condition where adenosine or analogues of this nucleoside could be acting as helpers of insulin biological effects in GDM.

Over-expression of muscle glycogen synthase in human diabetic nephropathy.

Diabetic nephropathy (DN) is a major complication of diabetic patients and the leading cause of end-stage renal disease. Glomerular dysfunction plays a critical role in DN, but deterioration of renal function also correlates with tubular alterations. Human DN is characterized by glycogen accumulation in tubules. Although this pathological feature has long been recognized, little information exists about the triggering mechanism. In this study, we detected over-expression of muscle glycogen synthase (MGS) in diabetic human kidney. This enhanced expression suggests the participation of MGS in renal metabolic changes associated with diabetes. HK2 human renal cell line exhibited an intrinsic ability to synthesize glycogen, which was enhanced after over-expression of protein targeting to glycogen. A correlation between increased glycogen amount and cell death was observed. Based on a previous transcriptome study on human diabetic kidney disease, significant differences in the expression of genes involved in glycogen metabolism were analyzed. We propose that glucose, but not insulin, is the main modulator of MGS activity in HK2 cells, suggesting that blood glucose control is the best approach to modulate renal glycogen-induced damage during long-term diabetes.

Insulin therapy and fetoplacental vascular function in gestational diabetes mellitus.

NEW FINDINGS: What is the topic of this review? This review focuses on the effects of insulin therapy on fetoplacental vasculature in gestational diabetes mellitus and the potentiating effects of adenosine on this therapy. What advances does it highlight? This review highlights recent studies exploring a potential functional link between insulin receptors and their dependence on adenosine receptor activation (insulin-adenosine axis) to restore placental endothelial function in gestational diabetes mellitus. Gestational diabetes mellitus (GDM) is a disease that occurs during pregnancy and is associated with maternal and fetal hyperglycaemia. Women with GDM are treated via diet to control their glycaemia; however, a proportion of these patients do not achieve the recommended values of glycaemia and are subjected to insulin therapy until delivery. Even if a diet-treated GDM pregnancy leads to normal maternal and newborn glucose levels, fetoplacental vascular dysfunction remains evident. Thus, control of glycaemia via diet does not prevent GDM-associated fetoplacental vascular and metabolic alterations. We review the available information regarding insulin therapy in the context of its potential consequences for fetoplacental vascular function in GDM. We propose the possibility that insulin therapy to produce normoglycaemia in the mother and newborn may require additional therapeutic measures to restore the normal metabolic condition of the vascular network in GDM. A role for A1 and A2A adenosine receptors and insulin receptors A and B as well as a potential functional link in the cell signalling associated with the activation of these receptors is proposed. This possibility could be helpful for the planning of strategies, including adenosine receptor-improved insulin therapy, for the treatment of GDM patients, thereby promoting the wellbeing of the growing fetus, newborn and mother.

Role of insulin and adenosine in the human placenta microvascular and macrovascular endothelial cell dysfunction in gestational diabetes mellitus.

Microvascular and macrovascular endothelial function maintains vascular reactivity. Several diseases alter endothelial function, including hypertension, obesity, and diabetes mellitus. In addition, micro- and macrovascular endothelial dysfunction is documented in GDM with serious consequences for the growing fetus. Increased l-arginine uptake via hCAT-1 and NO synthesis by eNOS is associated with GDM. These alterations are paralleled by activation of purinergic receptors and increased umbilical vein, but not arteries blood adenosine accumulation. GDM associates with NO-reduced adenosine uptake in placental endothelium, suggested to maintain and/or facilitate insulin vasodilation likely increasing hCAT-1 and eNOS expression and activity. It is proposed that increased umbilical vein blood adenosine concentration in GDM reflects a defective metabolic state of human placenta. In addition, insulin recovers GDM-alterations in hCAT-1 and eNOS in human micro- and macrovascular endothelium, and its biological actions depend on preferential activation of insulin receptors A and B restoring a normal-like from a GDM-like phenotype. We summarized existing evidence for a potential role of insulin/adenosine/micro- and macrovascular endothelial dysfunction in GDM. These mechanisms could be crucial for a better management of the mother, fetus and newborn in GDM pregnancies.

Maternal hypercholesterolemia in pregnancy associates with umbilical vein endothelial dysfunction: role of endothelial nitric oxide synthase and arginase II.

OBJECTIVE: Human pregnancy that courses with maternal supraphysiological hypercholesterolemia (MSPH) correlates with atherosclerotic lesions in fetal arteries. It is known that hypercholesterolemia associates with endothelial dysfunction in adults, a phenomenon where nitric oxide (NO) and arginase are involved. However, nothing is reported on potential alterations in the fetoplacental endothelial function in MSPH. The aim of this study was to determine whether MSPH alters fetal vascular reactivity via endothelial arginase/urea and L-arginine transport/NO signaling pathways. APPROACH AND RESULTS: Total cholesterol <280 mg/dL was considered as maternal physiological hypercholesterolemia (n=46 women) and ≥ 280 mg/dL as MSPH (n=28 women). Maternal but not fetal total cholesterol and low-density lipoprotein-cholesterol levels were elevated in MSPH. Umbilical veins were used for vascular reactivity assays (wire myography), and primary cultures of umbilical vein endothelial cells to determine arginase, endothelial NO synthase (eNOS), and human cationic amino acid transporter 1 and human cationic amino acid transporter 2A/B expression and activity. MSPH reduced calcitonine gene-related peptide-umbilical vein relaxation and increased intima/media ratio (histochemistry), as well as reduced eNOS activity (L-citrulline synthesis from L-arginine, eNOS phosphorylation/dephosphorylation), but increased arginase activity and arginase II protein abundance. Arginase inhibition increased eNOS activity and L-arginine transport capacity without altering human cationic amino acid transporter 1 or human cationic amino acid transporter 2A/B protein abundance in maternal physiological hypercholesterolemia and MSPH. CONCLUSIONS: MSPH is a pathophysiological condition altering umbilical vein reactivity because of fetal endothelial dysfunction associated with arginase and eNOS signaling imbalance. We speculate that elevated maternal circulating cholesterol is a factor leading to fetal endothelial dysfunction, which could have serious consequences to the growing fetus.

Temporal Relationship Between Pain and Mental Health Conditions Among Children and Young People-A Population-Based Register Study in Sweden.

Both pain and mental health conditions are common among young people. They often co-occur, but we wanted to investigate further whether it is pain (abdominal pain, headache, musculoskeletal pain, menstrual pain) that precedes mental health conditions (depression, anxiety, stress, phobia) or whether it is the other way around, mental health conditions that precede pain. Using electronic health records-the Skåne Healthcare Register-we identified and followed young people aged 7 to 18 over a 13-year period and tracked all their registered diagnoses. Using Poisson regression, we analyzed the incidence rate ratio (IRR) of being diagnosed with mental health conditions after an initial diagnosis of pain and vice versa the IRR of being diagnosed with pain after an initial diagnosis of a mental health condition. Among individuals with pain, 12,054 (23%) later received a diagnosis of a mental health condition. The IRR for a mental health condition after pain was 2.86 (95% (confidence interval) CI = 2.78-2.94) compared to not having pain, adjusted for age, sex, and prior health care consultations. Among individuals with mental health conditions, 3,688 (17%) later received a diagnosis of pain. The adjusted IRR was 1.57 (95% CI = 1.52-1.63). Compared to boys, girls had consistently higher estimates, and the same was found for the younger individuals compared to the older ones. Individuals with pain have a 3-fold increased risk of developing mental health conditions, while the risk of developing pain after mental health conditions was lower although still elevated compared to young people seeking care regardless of cause. PERSPECTIVE: Young people with pain have a 3-fold increased risk of developing mental health conditions, while the reverse risk is lower but still elevated compared to young people without these conditions. Health care professionals must recognize the interplay between pain and mental health in young patients when diagnosing and planning treatment.

Features and behaviours for weight loss in the Chilean cohort with obesity from the ACTION study.

In Latin America, obesity rates are among the highest in the world. Currently, people with obesity (PWO) receive suboptimal care due to several challenges and barriers. The international ACTION-IO study aimed to identify perceptions, attitudes and behaviours of PWO and healthcare providers (HCP), and to assess potential barriers to effective obesity care. The aim of this subanalysis of the Chilean cohort was to compare their characteristics, perceptions, attitudes and behaviours according to the percentage of weight loss (lower weight loss [LWL; ≤10%] or higher weight loss [HWL; >10%] of basal weight). The ACTION-IO survey was completed by 1000 Chilean PWO and 200 HCPs. Mean age of PWO was 38 years (range 18-75); 62% were female. The majority had class I obesity. HWL subgroup represented 17.2% of all Chilean subset. Specific characteristics of patients with HWL were identified (higher educational level, lower proportion of class III obesity, preference for consulting obesity specialists, considering conversations with HCP as very helpful). HWL patients reported higher rates of favourable outcomes following HCP advice and a higher probability of attending scheduled follow-up visits. Certain demographic and behavioural variables (educational level, consultation to obesity specialists, adherence to HCP advice, follow-up scheduled visits and becoming aware of the obesity state) may identify PWO with a higher probability of a greater weight loss.

Prolonged opioid use after distal radius fracture.

BACKGROUND: Prolonged opioid use (more than 90 days) after injury puts the patient at risk for adverse effects. We investigated the patterns of opioid prescription after distal radius fracture and the effect of pre- and post-fracture factors on the risk for prolonged use. METHODS: This register-based cohort study uses routinely collected health care data, including purchases of prescription opioids, in the county of Skåne, Sweden. 9369 adult patients with a radius fracture diagnosed 2015-2018 were followed for 1 year after fracture. We calculated proportions of patients with prolonged opioid use, both in total and according to different exposures. Using modified Poisson regression, we calculated adjusted risk ratios for the following exposures: previous opioid use, mental illness, consultation for pain, surgery for distal radius fracture and occupational/physical therapy after fracture. RESULTS: Prolonged opioid use (4-6 months after fracture) was found in 664 (7.1%) of the patients. A previous, but discontinued, regular use of opioids up to 5 years before fracture increased the risk compared to opioid-naïve patients. Both regular and non-regular opioid use the year before fracture increased the risk. The risk was also higher for patients with mental illness, and those who were treated with surgery, we found no significant effect of pain consultation in previous year. Occupational/physical therapy lowered the risk for prolonged use. CONCLUSION: Considering history of mental illness and previous opioid use while promoting rehabilitation can be important to prevent prolonged opioid use after distal radius fracture. SIGNIFICANCE: We show that a common injury such as distal radius fracture can be a gateway to prolonged opioid use, especially among patients with previous history of opioid use or mental illness. Importantly, previous opioid use as far back as 5 years earlier greatly increases the risk of regular use after the reintroduction of opioids. Considering past use is important when planning treatment with opioids. Occupational or physical therapy after injury is associated with lower risk of prolonged use and should be encouraged.

An mHealth Intervention to Reduce Gestational Obesity (mami-educ): Protocol for a Randomized Controlled Trial.

BACKGROUND: The World Federation of Obesity warns that the main health problem of the next decade will be childhood obesity. It is known that factors such as gestational obesity produce profound effects on fetal programming and are strong predictors of overweight and obesity in children. Therefore, establishing healthy eating behaviors during pregnancy is the key to the primary prevention of the intergenerational transmission of obesity. Mobile health (mHealth) programs are potentially more effective than face-to-face interventions, especially during a public health emergency such as the COVID-19 outbreak. OBJECTIVE: This study aims to evaluate the effectiveness of an mHealth intervention to reduce excessive weight gain in pregnant women who attend family health care centers. METHODS: The design of the intervention corresponds to a classic randomized clinical trial. The participants are pregnant women in the first trimester of pregnancy who live in urban and semiurban areas. Before starting the intervention, a survey will be applied to identify the barriers and facilitators perceived by pregnant women to adopt healthy eating behaviors. The dietary intake will be estimated in the same way. The intervention will last for 12 weeks and consists of sending messages through a multimedia messaging service with food education, addressing the 3 domains of learning (cognitive, affective, and psychomotor). Descriptive statistics will be used to analyze the demographic, socioeconomic, and obstetric characteristics of the respondents. The analysis strategy follows the intention-to-treat principle. Logistic regression analysis will be used to compare the intervention with routine care on maternal pregnancy outcome and perinatal outcome. RESULTS: The recruitment of study participants began in May 2022 and will end in May 2023. Results include the effectiveness of the intervention in reducing the incidence of excessive gestational weight gain. We also will examine the maternal-fetal outcome as well as the barriers and facilitators that influence the weight gain of pregnant women. CONCLUSIONS: Data from this effectiveness trial will determine whether mami-educ successfully reduces rates of excessive weight gain during pregnancy. If successful, the findings of this study will generate knowledge to design and implement personalized prevention strategies for gestational obesity that can be included in routine primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05114174; https://clinicaltrials.gov/ct2/show/NCT05114174. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44456.

Impact of Remote Monitoring Technologies for Assisting Patients With Gestational Diabetes Mellitus: A Systematic Review.

Introduction: In Chile, 1 in 8 pregnant women of middle socioeconomic level has gestational diabetes mellitus (GDM), and in general, 5-10% of women with GDM develop type 2 diabetes after giving birth. Recently, various technological tools have emerged to assist patients with GDM to meet glycemic goals and facilitate constant glucose monitoring, making these tasks more straightforward and comfortable. Objective: To evaluate the impact of remote monitoring technologies in assisting patients with GDM to achieve glycemic goals, and know the respective advantages and disadvantages when it comes to reducing risk during pregnancy, both for the mother and her child. Methods: A total of 188 articles were obtained with the keywords "gestational diabetes mellitus," "GDM," "gestational diabetes," added to the evaluation levels associated with "glucose level," "glycemia," "glycemic index," "blood sugar," and the technological proposal to evaluate with "glucometerm" "mobile application," "mobile applications," "technological tools," "telemedicine," "technovigilance," "wearable" published during the period 2016-2021, excluding postpartum studies, from three scientific databases: PUBMED, Scopus and Web of Science. These were managed in the Mendeley platform and classified using the PRISMA method. Results: A total of 28 articles were selected after elimination according to inclusion and exclusion criteria. The main measurement was glycemia and 4 medical devices were found (glucometer: conventional, with an infrared port, with Bluetooth, Smart type and continuous glucose monitor), which together with digital technology allow specific functions through 2 identified digital platforms (mobile applications and online systems). In four articles, the postprandial glucose was lower in the Tele-GDM groups than in the control group. Benefits such as improved glycemic control, increased satisfaction and acceptability, maternal confidence, decreased gestational weight gain, knowledge of GDM, and other relevant aspects were observed. There were also positive comments regarding the optimization of the medical team's time. Conclusion: The present review offers the opportunity to know about the respective advantages and disadvantages of remote monitoring technologies when it comes to reducing risk during pregnancy. GDM centered technology may help to evaluate outcomes and tailor personalized solutions to contribute to women's health. More studies are needed to know the impact on a healthcare system.

Glycaemia dynamics in gestational diabetes mellitus.

Pregnant women may develop gestational diabetes mellitus (GDM), a disease of pregnancy characterised by maternal and fetal hyperglycaemia with hazardous consequences to the mother, the fetus, and the newborn. Maternal hyperglycaemia in GDM results in fetoplacental endothelial dysfunction. GDM-harmful effects result from chronic and short periods of hyperglycaemia. Thus, it is determinant to keep glycaemia within physiological ranges avoiding short but repetitive periods of hyper or hypoglycaemia. The variation of glycaemia over time is defined as 'glycaemia dynamics'. The latter concept regards with a variety of mechanisms and environmental conditions leading to blood glucose handling. In this review we summarized the different metrics for glycaemia dynamics derived from quantitative, plane distribution, amplitude, score values, variability estimation, and time series analysis. The potential application of the derived metrics from self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) in the potential alterations of pregnancy outcome in GDM are discussed.

Exposome and foetoplacental vascular dysfunction in gestational diabetes mellitus.

A balanced communication between the mother, placenta and foetus is crucial to reach a successful pregnancy. Several windows of exposure to environmental toxins are present during pregnancy. When the women metabolic status is affected by a disease or environmental toxin, the foetus is impacted and may result in altered development and growth. Gestational diabetes mellitus (GDM) is a disease of pregnancy characterised by abnormal glucose metabolism affecting the mother and foetus. This disease of pregnancy associates with postnatal consequences for the child and the mother. The whole endogenous and exogenous environmental factors is defined as the exposome. Endogenous insults conform to the endo-exposome, and disruptors contained in the immediate environment are the ecto-exposome. Some components of the endo-exposome, such as Selenium, vitamins D and B12, adenosine, and a high-fat diet, and ecto-exposome, such as the heavy metals Arsenic, Mercury, Lead and Copper, and per- and polyfluoroakyl substances, result in adverse pregnancies, including an elevated risk of GDM or gestational diabesity. The impact of the exposome on the human placenta's vascular physiology and function in GDM and gestational diabesity is reviewed.

Using Machine Learning to Predict Complications in Pregnancy: A Systematic Review.

Introduction: Artificial intelligence is widely used in medical field, and machine learning has been increasingly used in health care, prediction, and diagnosis and as a method of determining priority. Machine learning methods have been features of several tools in the fields of obstetrics and childcare. This present review aims to summarize the machine learning techniques to predict perinatal complications. Objective: To identify the applicability and performance of machine learning methods used to identify pregnancy complications. Methods: A total of 98 articles were obtained with the keywords "machine learning," "deep learning," "artificial intelligence," and accordingly as they related to perinatal complications ("complications in pregnancy," "pregnancy complications") from three scientific databases: PubMed, Scopus, and Web of Science. These were managed on the Mendeley platform and classified using the PRISMA method. Results: A total of 31 articles were selected after elimination according to inclusion and exclusion criteria. The features used to predict perinatal complications were primarily electronic medical records (48%), medical images (29%), and biological markers (19%), while 4% were based on other types of features, such as sensors and fetal heart rate. The main perinatal complications considered in the application of machine learning thus far are pre-eclampsia and prematurity. In the 31 studies, a total of sixteen complications were predicted. The main precision metric used is the AUC. The machine learning methods with the best results were the prediction of prematurity from medical images using the support vector machine technique, with an accuracy of 95.7%, and the prediction of neonatal mortality with the XGBoost technique, with 99.7% accuracy. Conclusion: It is important to continue promoting this area of research and promote solutions with multicenter clinical applicability through machine learning to reduce perinatal complications. This systematic review contributes significantly to the specialized literature on artificial intelligence and women's health.