Development of the Hiesho (sensitivity of hands or feet to cold) Care Practice Scale for pregnant women.

AIM: Evidence-based indicators are needed to increase the frequency of practicing care for hiesho, which can be a risk factor during childbirth. Such practice will lead to hiesho prevention. This study aimed to develop a Hiesho Care Practice Scale (HCPS) for pregnant women and examine its reliability and validity. METHODS: To develop a HCPS and examine its reliability and validity, we conducted a questionnaire-based survey among nurses who provide hiesho care for pregnant women in Japan. RESULTS: The analysis included 100 participants (recovery rate: 96%). Exploratory factor analysis produced four factors and 20 items. The model's fit indices obtained from the confirmatory factor analysis include goodness of fit of .80, adjusted goodness of fit of .75, comparative fit index of .88, and root mean squared error of approximation of .08. The correlation coefficients for the patient coaching skill evaluation scale for criterion-related validity test ranged from .23 to .51 (p < .01). Cronbach's α was .88, and intraclass correlation coefficient (ICC) was .81. CONCLUSIONS: The HCPS developed in this study consisted of four factors and 20 items, and its reliability and validity were verified. This scale enables the subjective and objective evaluation of hiesho care practice in the nursing profession. It may contribute to standardizing and developing improvement measures for hiesho care among pregnant women by nurses and midwives.

Reproductive and developmental safety evaluation of Thymelaea hirsuta (L.) leaves aqueous extract in Wistar albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The popularity of herbal medicine is expanding globally due to the common belief that herbal products are natural and nontoxic. Thymelaea hirsuta leaves are traditionally used for the treatment of recurrent abortion in humans and animals. However, a lack of safety evaluation of the plant, particularly in pregnant women, raises serious concerns regarding its potential embryotoxic effects. AIM OF THE STUDY: Therefore, the present study investigated the safety of Thymelaea hirsuta leaves aqueous extract (THLE) during pregnancy and lactation following maternal rat treatment. MATERIALS AND METHODS: THLE phytochemical compounds were identified using high-performance liquid chromatography (HPLC). THLE was orally administered to pregnant rats and lactating dams at dosages of 0, 250, 500, and 1000 mg/kg/day. At the end of the study, dam s' and pups' body weights, serum biochemical and hematological indices, and histopathological changes were investigated. For the fetal observation and histopathological changes were also evaluated. RESULTS: Our findings revealed that THLE is rich in different phenolic and flavonoid compounds. However, biochemical and hormonal parameters such as ALT, AST, and prolactin were significantly increased in dams treated with a higher dosage of THLE when compared to the control dams (P ≤ 0.05). Additionally, external, visceral and skeletal examinations of fetuses revealed a marked increase of malformation rates in treated fetuses. CONCLUSIONS: The results revealed that higher oral dosing of THLE during pregnancy could affect embryonic development in rats, while lower doses are safe and can be used during pregnancy and lactation to attain its beneficial effects.

Exposición a temperaturas extremas y su efecto en la gestación en un departamento de Colombia / Exposure to extreme temperatures and its effect on pregnancy in a department of Colombia

Introducción: Diversas investigaciones han establecido la relación entre temperatura y duración del embarazo, la exposición a temperaturas altas durante el embarazo plantea interrogantes en especial el papel que esta juega frente a los partos prematuros y partos de bajo peso, es indispensable determinar si las temperaturas altas o bajas tienen un comportamiento protector o de riesgo sobre el feto durante la gestación en regiones tropicales. Objetivo: describir la relación entre la exposición a temperaturas altas y bajas durante el embarazo y su efecto en la edad gestacional y peso al momento del parto en los recién nacidos del departamento del Guaviare-Colombia. Metodología: Estudio tipo observacional, analítico, retrospectivo de corte transversal que busco determinar la relación entre exposición a temperaturas altas y bajas durante el embarazo y su efecto en la edad gestacional y peso al momento del parto en los recién nacidos, el universo estuvo conformado por 10.137 nacidos vivos, de los cuales 9.932 cumplieron los criterios de inclusión. Se determinó Odds Ratio para estimar la asociación entre las variables. Resultados: Dentro de la semana de retraso 3 el estar expuesto a temperaturas máximas percentil 90 es un factor protector para la ganancia ponderal de peso OR < 1, la exposición a temperaturas mínimas percentil 10 se asoció como factor protector para el parto prematuro en la semana de retraso 1 y 2 OR < 1.Conclusión: A pesar del beneficio de las altas y bajas temperaturas durante el embarazo en la ganancia ponderal de peso y disminución del parto prematuro, es recomendable prevenir la exposición a temperaturas extremas durante el periodo de gestación[AU]

Introduction: Various investigations have established the relationship between temperature and duration of pregnancy. Exposure to high temperatures during pregnancy raises questions, especially the role it plays in premature births and low-weight births. It is essential to determine whether high temperatures or low have a protective or risky behavior on the fetus during pregnancy in tropical regions.Objective: to describe the relationship between exposure to high and low temperatures during pregnancy and its effect on gestational age and weight at the time of delivery in newborns in the department of Guaviare-Colombia.Methodology:Observational, analytical, retrospective cross-sectional study that sought to determine the relationship between exposure to high and low temperatures during pregnancy and its effect on gestational age and weight at the time of delivery in newborns. The universe was made up of 10,137 births. alive, of which 9,932 met the inclusion criteria. Odds Ratio was determined to estimate the association between the variables.Results:Within the 3rd week of delay, being exposed to maximum temperatures at the 90th percentile is a protective factor for weight gain OR < 1, exposure to minimum temperatures at the 10th percentile was associated as a protective factor for premature birth in the week. of delay 1 and 2 OR < 1. Conclusion: Despite the benefit of high and low temperatures during pregnancy in weight gain and reduction in premature birth, it is advisable to prevent exposure to extreme temperatures during the gestation period[AU]

Introdução: Várias investigações estabeleceram a relação entre temperatura e duração da gravidez. A exposição a altas temperaturas durante a gravidez levanta questões, especialmente o papel que desempenha nos partos prematuros e nos nascimentos de baixo peso. É essencial determinar se as temperaturas altas ou baixas têm um comportamento protetor ou de risco para o feto durante a gravidez em regiões tropicais. Objetivo:descrever a relação entre a exposição a altas e baixas temperaturas durante a gravidez e seu efeito na idade gestacional e no peso no momento do parto em recém-nascidos no departamento de Guaviare-Colômbia. Metodologia: Estudo observacional, analítico, retrospectivo e transversal que buscou determinar a relação entre a exposição a altas e baixas temperaturas durante a gravidez e seu efeito na idade gestacional e no peso no momento do parto em recém-nascidos. O universo foi composto por 10.137 nascimentos. vivos, dos quais 9.932 preencheram os critérios de inclusão. O Odds Ratio foi determinado para estimar a associação entre as variáveis. Resultados:Na 3ª semana de atraso, a exposição a temperaturas máximas no percentil 90 é fator de proteção para ganho de peso OR < 1, a exposição a temperaturas mínimas no percentil 10 foi associada como fator de proteção para parto prematuro na semana. de atraso 1 e 2 OR < 1.Conclusão:Apesar do benefício das altas e baixas temperaturas durante a gravidez no ganho de peso e redução do parto prematuro, é aconselhável evitar a exposição a temperaturas extremas durante o período de gestação[AU]

Multimodal management of ectopic hepatic pregnancy: a systematic review of the literature.

PURPOSE: Ectopic pregnancies with implantation in the upper abdomen are exceptionally rare. Here we provide a systematic review of hepatic ectopic pregnancies and the corresponding management strategies. Furthermore, this report details a case of ectopic hepatic pregnancy, successfully treated with primary methotrexate (MTX) followed by a two-staged robotic-assisted resection. METHODS: Two independent investigators performed a systematic review using the online search engine PubMed and MEDLINE database. The search utilized the following terms: 'Hepatic Ectopic Pregnancy,' 'Hepatic Extrauterine Pregnancy,' 'Hepatic Abdominal Pregnancy,' and 'Ectopic Liver Pregnancy.' Cross-referencing was employed to identify possible additional publications. FINDINGS: Forty-seven case reports on hepatic pregnancies were identified. Of these, 40 provided manuscripts in the English language. Most patients with hepatic pregnancy presented with mild to moderate abdominal pain, while only a minority exhibited signs of hemodynamically relevant intraperitoneal hemorrhage. Most cases were managed through open surgical removal, although in recent years, there has been an increase in laparoscopically managed cases. Conservative approaches using methotrexate are seldom employed. CONCLUSION: Hepatic pregnancies present a rare and challenging clinical scenario. Until now, these cases have usually been treated primarily with open explorative surgery. As reported in this case, primary conservative treatment approaches with MTX before surgery hold promise as a strategy to reduce surgery-related bleeding and morbidity, particularly for asymptomatic or oligosymptomatic patients.

Double burden of gestational diabetes and pregnancy-induced hypertension in Ethiopia: A systematic review and meta-analysis of observational studies.

BACKGROUND: The coexistence of gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) amplifies the risk of maternal and perinatal mortality and complications, leading to more severe adverse pregnancy outcomes. This systematic review and meta-analysis aimed to assess the double burden of GDM and PIH (GDM/PIH) among pregnant women in Ethiopia. METHODS: A comprehensive systematic search was conducted in the databases of PubMed, Cochrane Library, Science Direct, Embase, and Google Scholar, covering studies published up to May 14, 2023. The analysis was carried out using JBI SUMARI and STATA version 17. Subgroup analyses were computed to demonstrate heterogeneity. A sensitivity analysis was performed to examine the impact of a single study on the overall estimate. Publication bias was assessed through inspection of the funnel plot and statistically using Egger's regression test. RESULT: Of 168 retrieved studies, 15 with a total of 6391 participants were deemed eligible. The pooled prevalence of GDM/PIH co-occurrence among pregnant women in Ethiopia was 3.76% (95% CI; 3.29-4.24). No publication bias was reported, and sensitivity analysis suggested that excluded studies did not significantly alter the pooled prevalence of GDM/PIH co-occurrence. A statistically significant association between GDM and PIH was observed, with pregnant women with GDM being three times more likely to develop PIH compared to those without GDM (OR = 3.44; 95% CI; 2.15-5.53). CONCLUSION: This systematic review and meta-analysis revealed a high dual burden of GDM and PIH among pregnant women in Ethiopia, with a significant association between the two morbidities. These findings emphasize the critical need for comprehensive antenatal care programs in Ethiopia to adequately address and monitor both GDM and PIH for improved maternal and perinatal health outcomes.

Patient-centered pregnancy planning in multiple sclerosis: evidence for a new era.

A few decades ago, women diagnosed with multiple sclerosis were discouraged from becoming pregnant. However, with new knowledge about the disease and treatments, this recommendation has changed, and it is pregnancy after the diagnosis of the disease is no longer contraindicated, with family planning being essential in this process. This review aims to provide a comprehensive overview of the family planning process for people with multiple sclerosis.

Até recentemente, a gravidez nas pacientes com o diagnóstico de esclerose múltipla era contraindicada. O avanço no conhecimento sobre a doença e os tratamentos alterou essa recomendação, e agora a gravidez após o diagnóstico da doença não é mais contraindicada; contudo, o planeamento familiar é essencial nesse processo. Esta revisão tem como objetivo fornecer uma visão abrangente do processo de planejamento familiar para pacientes com esclerose múltipla.

Prenatal Diagnosis and Clinical Outcomes of Isolated Mega Cisterna Magna.

Objective: The study aimed to investigate the clinical outcomes of fetuses diagnosed with isolated mega cisterna magna in utero. Methods: A multicenter retrospective cohort study was conducted across 18 university hospitals from 2010 to 2019. Cases diagnosed with isolated mega cisterna magna, defined as a cisterna magna >10 mm with a normal cerebellar vermis and no cystic dilation of the fourth ventricle, were included. Cases with other central nervous system (CNS) anomalies, extra-central nervous system anomalies, chromosomal abnormalities, or congenital infections were excluded. Maternal demographics, prenatal findings, delivery outcomes, and postnatal outcomes were analyzed. Results: The mean gestational age at initial diagnosis was 28.6 ± 3.9 weeks, and the mean anteroposterior diameter of the cisterna magna was 12.5 ± 3.2 mm. Of the 71 cases initially assessed, 48 (67.6%) showed self-regression in utero. Postnatally, 13 cases (18.3%) had persistent isolated mega cisterna magna, whereas 10 cases (14.1%) were diagnosed with other central nervous system anomalies. Among the persistent isolated mega cisterna magna cases, one child exhibited delayed neurodevelopment. There was a higher incidence of isolated mega cisterna magna in male fetuses, which exhibited a significantly larger mean cisterna magna diameter compared with female fetuses (P = .045). Conclusion: Male fetuses exhibited a higher incidence of isolated mega cisterna magna compared with female fetuses and had larger anteroposterior diameters of the cisterna magna. The study demonstrated favorable neurodevelopmental outcomes associated with isolated mega cisterna magna, with self-regression observed in two-thirds of the cases. However, consecutive prenatal and postnatal evaluations for additional central nervous system or extra-central nervous system malformations need to be performed, considering the differences between prenatal and postnatal diagnoses.

Disease Activity in Pregnant and Postpartum Women With Multiple Sclerosis Receiving Ocrelizumab or Other Disease-Modifying Therapies.

BACKGROUND AND OBJECTIVES: Women with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods. METHODS: We performed a retrospective cohort study using data from the MSBase Registry including pregnancies conceived after December 31, 2010, from women aged 18 years and older, with relapsing-remitting MS or clinically isolated syndrome. Women were classified by preconception exposure to DMTs, including OCR, rituximab (RTX), natalizumab (NAT), stratified into active (NAT-A; continued ≥28 weeks of gestation, restarted ≤1 month postpartum) or conservative (NAT-C; continued ≤4 weeks of gestation, restarted >1 month postpartum) strategies, dimethyl fumarate (DMF) or low-efficacy DMTs (interferon-beta, glatiramer acetate). Annualized relapse rates (ARRs) were calculated for 12-month prepregnancy, pregnancy, and 6-month postpartum periods. RESULTS: A total of 2,009 live births from 1,744 women were analyzed, including 73 live births from 69 women treated with preconception OCR. For OCR, no within-pregnancy relapse was observed and 3 women (4.1%) experienced 1 relapse in the postpartum period (ARR 0.09 [95% CI 0.02-0.27]). For NAT-A, 3 (3.7%) of 82 women relapsed during pregnancy (0.05 [0.01-0.15]) and 4 (4.9%) relapsed during postpartum (0.10 [0.03-0.26]). However, for NAT-C, 13 (15.9%) of 82 women relapsed within pregnancy (0.32 [0.20-0.51]) and 25 (30.5%) relapsed during postpartum (0.74 [0.50-1.06]). In the low-efficacy DMT group, 101 (7.6%) of 1,329 women experienced within-pregnancy relapse (0.12 [0.10-0.14]), followed by an increase in postpartum relapse activity with 234 women (17.6%) relapsing (0.43 [0.38-0.48]). This was similarly seen in the DMF group with 13 (7.9%) of 164 women experiencing within-pregnancy relapse (0.12 [0.06-0.20]) and 25 (15.2%) of 164 relapsing postpartum (0.39 [0.26-0.57]). Our RTX cohort had 0 of 24 women experiencing within-pregnancy relapse and 3 (12.5%) of 24 experiencing postpartum relapse. DISCUSSION: Women treated with OCR or NAT-A were observed to have low relapse rates during pregnancy and postpartum. NAT-C was associated with increased risk of relapses. There was no within-pregnancy relapse in our RTX cohort, although we caution overinterpretation due to our sample size. An effective DMT strategy with a favorable safety profile for the mother and infant should be discussed and implemented well in advance of planning a family. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for women with relapsing-remitting MS or clinically isolated syndrome who become pregnant, ocrelizumab, rituximab, and natalizumab (continued ≥28 weeks of gestation and restarted ≤1 month postpartum) were associated with reduced risk of relapses, compared with other therapeutic strategies.

The Impact of Undetected Hyperglycaemia During Pregnancy on Maternal and Neonatal Outcomes.

BACKGROUND: Despite clear diagnostic criteria for hyperglycaemia first detected in pregnancy, many pregnant women do not have the proper diagnosis. The following paper analyses the course of the perinatal period in pregnant women with undetected hyperglycaemia and their newborns. MATERIALS AND METHODS: Medical data of patients hospitalized in the Department of Perinatology between 2020 and 2022 was verified: 1st group: 40 patients with undetected hyperglycaemia, 2nd group: 40 with the diagnosis of gestational diabetes during pregnancy and adequate therapeutic management. The course of the perinatal period, abnormalities in the oral glucose tolerance test (OGTT) and the compliance with recommended postpartum tests were analysed. RESULTS: There were significant differences in the newborn weights (p=0.039) - in the 1st group 15% large for gestational age (LGA) vs. 0% in the 2nd, and the occurrence of neonatal hyperbilirubinemia requiring phototherapy (p=0.007) - 22.5% in the 1st group vs. 2.5% in the 2nd. The most common mistake in the OGTT was evaluation of fasting plasma glucose. In the 1st group, no effect on incidence of hypertensive disorders, time or the route of delivery was observed. 75% from the 1st group and 36% from the 2nd did not perform postpartum OGTT (p=0.003). CONCLUSION: Hyperglycaemia in pregnancy is often undetected, which has a negative impact, especially on the neonates. In our study, LGA and hyperbilirubinaemia were significantly more common in neonates of mothers with undetected hyperglycaemia. These women had significantly more careless attitude to the postpartum diagnostic, which may influence future health and course of subsequent pregnancies. New and more effective methods of educating practitioners need to be implemented.

Case Report-Severe Hyponatremia at Birth in a Premature Infant.

BACKGROUND: Given the role of the placenta in maintaining maternal-fetal equilibrium, changes in maternal sodium levels affect the fetus. Clinicians must also account for the direct impact of maternal conditions and medications on the neonate. Gestational hyponatremia develops in approximately one-third of mothers with preeclampsia with severe features. Additionally, the use of selective antidiuretic (V2 receptor) agonist 1-deamino-8-D-arginine-vasopressin, commonly known as DDAVP, during pregnancy leads to maternal hyponatremia by inhibiting maternal diuresis. We present a case of severe hyponatremia in a premature infant born to a mother with preeclampsia with severe features who was taking DDAVP for von Willebrand Disease (VWD). CASE: A preterm female infant was born at 34 weeks gestation to a mother with pre-eclampsia with severe features treated with magnesium sulfate, and the use of DDAVP for VWD was found to have severe hyponatremia (122 mmol/L). Causes of hyponatremia were explored, such as mineralocorticoid deficiency, renal tubular dysfunction, inappropriate secretion of antidiuretic hormone (SIADH), and renal failure. Initial investigation of the neonatal hyponatremia prompted obtaining a maternal serum sodium level, which also demonstrated severe hyponatremia (122 mmol/L), identical to the infant's serum sodium level. The infant was managed with fluid restriction and close monitoring of serial serum and urine chemistries. Gradually, serum sodium levels increased and normalized by day 4 of life. We speculate that severe maternal hyponatremia induced by preeclampsia with severe features, along with the use of DDAVP during pregnancy, led to fetal and neonatal hyponatremia. CONCLUSION: DDAVP during pregnancy to treat VWD is associated with maternal hyponatremia and subsequent neonatal hyponatremia. It is important to monitor electrolytes in neonates born to mothers treated with DDAVP to promptly correct electrolyte abnormalities.

Clinical value of transperineal ultrasound in evaluating the effects of different delivery methods on the primipara pelvic floor structure and function.

To evaluate the effects of different delivery methods on the pelvic floor structure and function among primiparas by transperineal ultrasound, with a view to providing guidance for early postpartum intervention. Primiparas who underwent postpartum examination with transperineal ultrasound were recruited. Subjects were divided according to mode of delivery (vaginal and cesarean delivery). General information (including age, pre-pregnancy BMI and neonatal weight) were collected, and transperineal ultrasound was performed to measure such indicators as the levator hiatus areas in resting, constrictive anal and maximum Valsalva states, the posterior vesicourethral angles and distances between vesical neck and posterior inferior margin of pubic symphysis in resting and maximum Valsalva states, as well as the vesical neck mobility and urethral rotation angle in maximum Valsalva state. The inter-group differences in ultrasound indicators between the resting and Valsalva states were compared to analyze the postpartum incidences of pelvic floor dysfunctions like stress urinary incontinence, urethral funnel formation, bladder prolapse and uterine prolapse in primiparas. The levator hiatus areas in resting, constrictive anal and maximum Valsalva states were all larger in the vaginal delivery group than in the cesarean delivery group (P < 0.05). Compared to the cesarean delivery group, the vaginal delivery group exhibited larger posterior vesicourethral angles in resting and maximum Valsalva states (P < 0.05). The distances between vesical neck and posterior inferior margin of pubic symphysis were greater in the cesarean delivery group than in the vaginal delivery group at both resting and maximum Valsalva, with that at maximum Valsalva showing significant inter-group difference (P < 0.05). The vaginal delivery group exhibited greater vesical neck mobility and urethral rotation angle at maximum Valsalva compared to the cesarean delivery group (P < 0.05). The incidences of stress urinary incontinence, urethral funnel formation, bladder prolapse and uterine prolapse were all higher in the vaginal delivery group than in the cesarean delivery group, with the stress urinary incontinence and bladder prolapse incidences showing significant inter-group differences (P < 0.05). With transperineal ultrasound, various pelvic floor indicators of primiparas can be clearly measured and, through these ultrasound indicators, the effects of different delivery methods on the pelvic floor function can be evaluated, which is conducive to early clinical detection and intervention of postpartum pelvic floor dysfunctions, thus facilitating the early postpartum treatment.

Evaluation of the phase-specific antibody response in water buffalo (Bubalus bubalis) after two doses of an inactivated phase I Coxiella burnetii vaccine.

The control and management of Q fever outbreaks in ruminants are currently based on vaccination. Although buffalo (Bubalus bubalis) are intensively farmed in several countries and represent a reservoir for Coxiellosis, no evidence has been described regarding the efficacy of vaccination in this species. This work aimed to evaluate the humoral response, using appropriate phase-specific ELISAs, and the effects on abortion rate in buffalo by a field study. A total of 15 seropositive and 20 seronegative animals were vaccinated twice, three weeks apart, with a commercial phase I vaccine, and phase-specific antibodies were determined in the course of vaccination. Although anti-phase II antibody reactivity predominated after vaccination compared to phase I, both anti-phase I- and -phase II-antibody-reactivity significantly increased after the first (p = 0.001) and again after the second vaccination (p = 0.05). Seroconversion did not significantly depend on age or natural infection status. Once the vaccination cycle was completed, the herd study observed a reduced rate of abortion and placenta retention. Our data demonstrated that the vaccine principally induced a similar antibody response as in goats and sheep. These preliminary data appeared to support vaccination in buffalo, even in seropositive animals, although further studies are needed to better define the dynamics concerning seroconversion in this species.

Dexamethasone as an emerging environmental pollutant: Disruption of cholesterol-dependent synaptogenesis in the hippocampus and subsequent neurobehavioral impacts in offspring.

When fetuses are exposed to abnormally high levels of glucocorticoids in utero, irreversible damage to neuronal synaptogenesis occurs, leading to long-term cognitive and emotional behavioral abnormalities after birth. In this study, we investigated how maternal exposure to a novel environmental pollutant-synthetic glucocorticoid dexamethasone-affects offspring cognitive and emotional behaviors enduringly. We noted that offspring subjected to maternal dexamethasone exposure (MDE) displayed cognitive and emotional neurobehavioral deficits beginning in infancy, and these impairments persisted into adulthood. The principal mechanism involves MDE-induced damage to hippocampal neuronal synapse formation in the offspring, primarily due to a cholesterol deficiency which destabilizes neuronal membranes, thereby affecting normal synapse formation and ultimately leading to cognitive and emotional deficiencies. Specifically, we demonstrated abnormal activation of glucocorticoid receptors in hippocampal astroglial cells of MDE offspring, which triggers changes in the miR-450a-3p/HAT1/ABCG1 signaling axis, causing impaired cholesterol efflux in astroglial cells and insufficient cholesterol supply to neurons, further impairing synaptogenesis. This research not only underscores the significant impact of prenatal environmental pollutants on long-term health outcomes in offspring but also broadens our understanding of how prenatal exposure to glucocorticoids affects brain development in the progeny, providing new insights for interventions in neurodevelopmental and psychiatric disorders of fetal origin.

ALKBH5 modulation of ferroptosis in recurrent miscarriage: implications in cytotrophoblast dysfunction.

Background: As one of the most common and abundant internal modifications of eukaryotic mRNA, N6-methyladenosine (m6A) modifications are closely related to placental development. Ferroptosis is a newly discovered form of programmed cell death. During placental development, placental trophoblasts are susceptible to ferroptosis. However, the interactions of m6A and ferroptosis in trophoblast physiology and injury are unclear. Methods: Recurrent miscarriage (RM) was selected as the main gestational disease in this study. Published data (GSE76862) were used to analyze the gene expression profiles in patients with RM. The extent of m6A modification in total RNA of villous tissues between patients with RM and healthy controls (HC) was compared. ALKBH5 (encoding AlkB homolog 5, RNA demethylase) was selected as the candidate gene for further research. Quantitative real-time reverse transcription PCR, western blotting, and immunohistochemistry (IHC) confirmed the elevated expression of ALKBH5 in the cytotrophoblasts of patients with RM. Then, cell counting kit-8 assays, glutathione disulfide/glutathione quantification, 2',7'-dichlorfluorescein-diacetate staining, and malonaldehyde assays were used to explore the alterations of ferroptosis-related characteristics following RAS-selective lethal (RSL3) stimulation after overexpression of ALKBH5. Thereafter, we re-analyzed the published RNA sequencing data upon knockdown of ALKBH5, combined with published tissue RNA-seq data, and FTL (encoding ferritin light chain) was identified as the ferroptosis-related gene in cytotrophoblasts of patients with RM that is regulated by ALKBH5. Finally, western blotting and IHC confirmed the increased expression of FTL in the cytotrophoblasts from patients with RM. Results: Total m6A levels were decreased in patients with RM. The most significant differentially m6A-related gene was ALKBH5, which was increased in patients with RM. In vitro cell experiments showed that treatment with RSL3 resulted in increased cell death and upregulated ALKBH5 expression. Overexpression of ALKBH5 alleviated RSL3-induced HTR8 cell death and caused decreased levels of intracellular oxidation products. Published transcriptome sequencing revealed that FTL was the major ferroptosis-related gene regulated by ALKBH5 in the villous tissues of patients with RM. Consistent with the expression of ALKBH5, FTL was increased by RSL3-induction and increased in patients with RM. Conclusion: Elevated ALKBH5 alleviated RSL3-induced cytotrophoblast cell death by promoting the expression of FTL in patients with RM. Our results supported the view that ALKBH5 is an important regulator of the ferroptosis-related etiology of RM and suggested that ALKBH5 could be responsible for epigenetic aberrations in RM pathogenesis.

Cardiovascular responses to heat and cold exposure are altered by preterm birth in guinea pigs.

Adversity early in life can modify the trajectory for disease risk extending decades beyond the event. Preterm birth produces persistent cardiovascular alterations that may appear maladaptive in adulthood. We have previously hypothesized that those born preterm may exhibit cardiovascular vulnerability in the climate change context. Further, this vulnerability may be present as early as childhood. We aimed to identify the early signs of cardiovascular dysfunction at childhood-equivalent age using our animal model of preterm birth. Using a whole-body thermal stress test, guinea pigs aged 35-d and 38-d (equivalent to 8-10-year-old children) and born at term or preterm gestations were exposed to progressive hyper- (TC = 41.5°C) and hypo-thermia (TC = 34°C; normothermia TC = 39°C). Comprehensive cardiovascular monitoring included ECG, blood pressure, microvascular perfusion, blood gas, and catecholamine profile, as well as skin and core body temperature. Preterm-born animals exhibited attenuated vascular responses to hyperthermic stress, and a significant elevation in systolic blood pressure in response to hypothermic stress. Such responses are similar to those observed in elderly populations and indicate the presence of cardiovascular dysfunction. This is the first study to demonstrate the impact of preterm birth on the cardiovascular response to both heat and cold stress. Further, this dysfunction has been observed at an earlier age than that achievable using traditional stress testing techniques. The present findings warrant further investigation.

Assessing Pubic Symphysis Evolution in Guinea Pigs (Cavia procellus): Insights From Computer Tomography on Primiparous and Non-Breeding Females.

In guinea pigs (Cavia porcellus), dystocia is a common occurrence. Several factors have been identified in the literature, including the ossification of the pubic symphysis following failure to breed before 9-12 months of age. The objective of this study was to investigate the ossification of pubic symphysis and its evolution during growth in two groups of females. The first group consisted of non-breeding females, while the second group comprised females introduced to breeding at 4-6 months of age. Twelve pairs of sows were selected for comparison, with one non-breeding and one breeding sow in each pair. Symphysis width and tissue density were assessed using micro-computed tomography. Measurements included the distance between the acetabula, width and bone density of the pubic symphysis. Serial computed tomography scans were performed on each sow over several months, both before and after parturition. The results revealed a significantly higher symphysis width in females that had bred. In addition, symphysis ossification was absent in both breeding and non-breeding sows, contrary to previous descriptions of this species. Therefore, dystocia in guinea pigs may not be attributable to ossification of the pubic symphysis.

On placental and lactational transfer of IgG-based therapeutic proteins - Current understanding and knowledge gaps from a clinical pharmacology perspective.

Maternal medication use may expose the developing fetus through placental transfer or the infant through lactational transfer. Because pregnant and lactating individuals have been historically excluded from early drug development trials, there is often limited to no human data available to inform pharmacokinetics (PK) and safety in these populations at the time of drug approval. We describe the known mechanisms of placental or lactational transfer of IgG-based therapeutic proteins and use clinical examples to highlight the potential for fetal or infant exposure during pregnancy and lactation. Placental transfer of IgG-based therapeutic proteins may result in systemic exposure to the developing fetus. A lactational transfer may be associated with local gastrointestinal (GI) exposure in the infant and may also result in systemic exposure, although data are very limited as proteins have shown instability in the GI tract. Understanding of PK and pharmacodynamic (PD) effects of IgG-based therapeutic proteins in infants exposed in utero as well as the potential exposure through human milk and its clinical implications is critical for developing treatment strategies for pregnant or lactating individuals. We share the current knowledge gaps and considerations for future evaluations to inform PK, PD, and the safety of IgG-based therapeutic proteins for safe use during pregnancy and lactation. With the increasing use of IgG-based therapeutic proteins in treating chronic diseases during pregnancy and lactation, there is a need to improve the quantity and quality of data to inform the safe use in pregnant and lactating individuals.

Outcomes After Loss to Follow-Up for Pregnant and Postpartum Women Living With HIV and Their Children in Kenya: A Prospective Cohort Study.

BACKGROUND: Many prevention of vertical transmission (PVT) studies assess outcomes within 12 months postpartum and exclude those lost to follow-up (LTFU), potentially biasing outcomes toward those retained in care. SETTING: Five public facilities in western Kenya. METHODS: We recruited women living with HIV (WLH) ≥18 years enrolled in antenatal clinic (ANC). WLH retained in care (RW) were recruited during pregnancy and followed with their children through 6 months postpartum; WLH LTFU (LW, last visit >90 days) after ANC enrollment and ≤6 months postpartum were recruited through community tracing. Recontact at 3 years was attempted for all participants. Primary outcomes were retention and child HIV-free survival. Generalized linear regression was used to estimated risk ratios (RRs) for associations with becoming LTFU by 6 months postpartum, adjusting for age, education, facility, travel time to facility, gravidity, income, and new vs. known HIV positive at ANC enrollment. RESULTS: Three hundred thirty-three WLH (222 RW, 111 LW) were recruited from 2018 to 2019. More LW versus RW were newly diagnosed with HIV at ANC enrollment (49.6% vs. 23.9%) and not virally suppressed at study enrollment (40.9% vs. 7.7%). 6-month HIV-free survival was lower for children of LW (87.9%) versus RW (98.7%). At 3 years, 230 WLH were retained in care (including 51 previously LTFU before 6 months), 30 transferred, 70 LTFU, and 3 deceased. 3-year child HIV-free survival was 81.9% (92.0% for children of RW, 58.6% for LW), 3.7% were living with HIV, 3.7% deceased, and 10.8% had unknown HIV/vital status. Being newly diagnosed with HIV at ANC enrollment was the only factor associated with becoming LTFU (aRR 1.21, 95% CI: 1.11 to 1.31). CONCLUSIONS: Outcomes among those LTFU were worse than those retained in care, underscoring the importance of retention in PVT services. Some, but not all, LW re-engaged in care by 3 years, suggesting the need for PVT services must better address the barriers and transitions women experience during pregnancy and postpartum.

Sociodemographic inequalities in the uptake of prenatal HIV testing in Ethiopia: Systematic review and meta-analysis.

BACKGROUND: In order to attain the ambitious 95-95-95 UNAIDS goals, HIV testing serves as the pivotal starting point and plays a crucial role in preventing, treating, and managing HIV. Equal access to HIV testing is crucial to stop the spread of the virus. Measuring healthcare disparities is vital for promoting fairness in health services and achieving global goals for HIV prevention and treatment. Ethiopia is actively engaged in efforts to achieve these goals and is dedicated to combating HIV/AIDS. To the best of our knowledge, no previous systematic review or meta-analysis has been conducted on sociodemographic inequalities in prenatal HIV testing in Ethiopia. Hence, this study aims to assess sociodemographic inequalities in prenatal HIV testing in Ethiopia. METHODS: We conducted an extensive search across various databases, such as PubMed, Scopus, Google Scholar, and Embase, to collect articles and reports. The data we gathered was then exported to R software for further analysis. Our analysis involved performing a meta-analysis of proportions using a random effect model. To assess the variability among the included studies, we used statistical measures such as I2 statistics and the Cochran's Q test. The results of the pooled prenatal HIV testing, along with its corresponding 95% confidence interval, were presented using a forest plot. RESULTS: A comprehensive analysis of 20 research papers on prenatal HIV testing in Ethiopia revealed that the overall pooled prevalence of testing was 69% (95% CI [60.0-80.0]). Factors such as higher education, urban residence, income, a positive attitude towards testing, marriage, and discussions about testing during antenatal care (ANC) were found to positively influence testing rates. CONCLUSION: The prevalence of prenatal HIV testing among antenatal care attendees in Ethiopia falls short of the UNAIDS target. In order to enhance the testing rates, it is advised to implement targeted initiatives within Ethiopia's public health programs. To ensure effectiveness, these initiatives should adopt a sustainable and customized approach that takes into account the specific needs and circumstances of women, particularly those who are economically disadvantaged. Ethiopia can make significant strides in enhancing the prenatal HIV testing landscape by effectively implementing policies and programs that prioritize the welfare of the less privileged. LIMITATIONS: As limitation this systematic review did not include longitudinal and qualitative studies that might have provided different results. CLINICAL TRIAL REGISTRATION: Trial registration in PROSPERO with ID: CRD42024550564.

Dietary patterns during pregnancy in relation to maternal dietary intake: The Mutaba'ah Study.

AIM: To relate adherence to healthy dietary patterns, evaluated by different dietary indices, to the intake of nutrients and food groups among pregnant women in the United Arab Emirates. METHODS: The analyses included 1122 pregnant women from the Mutaba'ah Study. Dietary intake was assessed using a semi-quantitative Food Frequency Questionnaire. Adherence to three dietary pattern indices was assessed; Alternate Healthy Eating Index for Pregnancy (AHEI-P), Alternate Mediterranean Diet (aMED) and Dietary Approaches to Stop Hypertension (DASH). Associations between adherence (score >median) to the three dietary indices and intake of nutrients and food groups were analyzed using logistic regression analysis. RESULTS: Women with higher intake of polyunsaturated fatty acids, fiber, vegetables, fruits, legumes, and nuts and lower intake of saturated fatty acids, red meat, and sweetened beverages had significantly higher odds of adherence to all three dietary patterns (p<0.05). Associations between intakes of nutrients and food groups with odds of adherence to the dietary patterns differed for total fat (only with AHEI-P, [odds ratio [OR]: 0.96; 95% confidence interval [CI]: 0.94-0.98]) and monounsaturated fatty acids (only with aMED, [OR: 1.06; 95% CI: 1.02-1.10]), dairy (with AHEI-P [OR: 0.89; 95% CI: 0.84-0.95] and aMED [OR: 0.86; 95% CI: 0.81-0.91], and with DASH [OR: 1.10; 95% CI: 1.04-1.17]), whole grain (only with aMED [OR: 2.19; 95% CI: 1.61-2.99] and DASH [OR: 4.27; 95% CI: 3.04-5.99]) and fish (with AHEI-P [OR: 1.36; 95% CI: 1.02-1.80] and aMED [OR: 1.79; 95% CI: 1.35-2.38], and with DASH [OR: 0.67; 95% CI: 0.52-0.86]). CONCLUSION: Adherence to the three dietary pattern indices was generally associated with a favorable intake of nutrients and food groups. However, the indices captured slightly different aspects of dietary intake. These results show that dietary indices that assess adherence to healthy dietary patterns cannot be used interchangeably.