Search Results (233)

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by systemic inflammation, endothelial dysfunction, and placental insufficiency. While inadequate trophoblast invasion and impaired spiral artery remodeling have long been recognized as central to its pathogenesis, emerging evidence underscores the critical roles of dysregulated iron metabolism and its crosstalk with immune responses, particularly macrophage-mediated inflammation, in driving PE development. This review systematically explores the dynamic changes in iron metabolism during pregnancy, including increased maternal iron demand, placental iron transport mechanisms, and the molecular regulation of placental iron homeostasis. We further explore the contribution of ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, to trophoblast dysfunction and pregnancy-related diseases, including PE. Macrophages, pivotal immune regulators at the maternal–fetal interface, exhibit distinct polarization states that shape tissue remodeling and immune tolerance. We outline their origin, distribution, and polarization in pregnancy, and emphasize their aberrant phenotype and function in PE. The bidirectional crosstalk between iron and macrophages is also dissected: iron shapes macrophage polarization and function, while macrophages reciprocally modulate iron homeostasis. Notably, excessive reactive oxygen species (ROS) and pro-inflammatory cytokines secreted by M1-polarized macrophages may exacerbate trophoblast ferroptosis, amplifying placental injury. Within the context of PE, we delineate how iron overload and macrophage dysfunction synergize to potentiate placental inflammation and oxidative stress. Key iron-responsive immune pathways, such as the HO-1/hepcidin axis and IL-6/TNF-α signaling, are discussed in relation to disease severity. Finally, we highlight promising therapeutic strategies targeting the iron–immune axis, encompassing three key modalities—iron chelation therapy, precision immunomodulation, and metabolic reprogramming interventions—which may offer novel avenues for PE prevention and treatment. Full article

Background/Objectives: As the incidence of diabetes mellitus (DM) is increasing rapidly worldwide, it is anticipated that an increasing number of women will enter pregnancy with pregestational diabetes mellitus (PGDM) in the future. Compelling evidence suggests that hyperglycemia in pregnancy is related to multiple adverse perinatal outcomes. This systematic review and meta-analysis aims to assess and quantify the association of PGDM with a range of adverse perinatal outcomes, providing a comprehensive understanding of its impact on pregnancy. Methods: The data sources of this systematic review and meta-analysis were Medline/PubMed, Scopus and Cochrane Library (January 1999 to August 2023), complemented by hand-searching for additional references. Observational studies reporting perinatal outcomes of pregnancies with PGDM diagnosed before pregnancy versus control pregnancies were eligible for inclusion. A systematic review and meta-analysis were conducted as per the PRISMA guidelines. Pooled estimate odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to determine the risk of adverse pregnancy outcomes between PGDM and control pregnancies. Results: The systematic search of the literature yielded 81 observational studies meeting inclusion criteria and in total, 137,237,640 pregnancies were included in the analysis. A total of 19 adverse perinatal outcomes were assessed, revealing a significant association with PGDM. In pregnancies with PGDM there was an increased risk of adverse perinatal outcomes, including gestational hypertension (OR 3.16, 95% CI 2.65–3.77), preeclampsia (OR 4.46, 95% CI 3.94–5.05), preterm delivery (OR 3.46, 95% CI 3.06–3.91), cesarean delivery (OR 3.12, 95% CI 2.81–3.47), induction of labor (OR 2.92, 95% CI 2.35–3.63), macrosomia (OR 2.23, 95% CI 1.76–2.83), LGA neonates (OR 3.95, 95% CI 3.47–4.49), low 5-min Apgar score (OR 2.49, 95% CI 2.07–2.99), shoulder dystocia (OR 3.05, 95% CI 2.07–4.50), birth trauma (OR 1.40, 95% CI 1.22–1.62), polyhydramnios (OR 5.06, 95% CI 4.33–5.91), oligohydramnios (OR 1.61, 95% CI 1.19–2.17), neonatal hyperbilirubinemia (OR 3.45, 95% CI 2.51–4.74), neonatal hypoglycemia (OR 19.19, 95% CI 2.78–132.61), neonatal intensive care unit (NICU) admission (OR 4.54, 95% CI 3.87–5.34), congenital malformations (OR 2.44, 95% CI 1.96–3.04), stillbirth (OR 2.87, 95% CI 2.27–3.63) and perinatal mortality (OR 2.94, 95% CI 2.18–3.98). Subgroup analyses indicated a higher risk of neonatal hypoglycemia, stillbirth and perinatal mortality in T1DM pregnancies compared with T2DM pregnancies. Conclusions: This study provides a robust synthesis of evidence underlying the strong association between PGDM and several adverse perinatal outcomes. Early detection, optimal glycemic control during the periconceptional and pregnancy periods, and proper antenatal care are critical to mitigate these risks. Full article

Background: Previous research has examined the idea of the healthy immigrant effect and its potential application to pregnancy-related hypertensive disorders, particularly inracial and ethnic minority groups. The aim of this study is to examine how nativity, race, and ethnicity are related to prevalence of pregnancy-related hypertensive disorders. Methods: A retrospective cohort study was conducted using data from the PRAMS CDC dataset. These data were analyzed via Χ² comparisons of prevalence of pregnancy-related hypertensive disorders in foreign and US-born mothers, including subgroup analyses for Black and Hispanic women. Results: A sample size of 63,648 was analyzed, and revealed significant differences in the prevalence of gestational hypertension between US-born vs. foreign-born Black mothers (12.6% vs. 8.0%, Χ² (1, N = 12,046) = 36.92, p < 0.001), Hispanic mothers (9.5% vs. 7.2%, Χ² (1, N = 11,524) = 18.236, p < 0.001), and the larger sample of mothers across all reported racial and ethnic backgrounds (11.0% vs. 7.0%, Χ² (1, N = 63,648) = 163.835, p < 0.001). The results also revealed a significant difference in the prevalence of hypertension eclampsia between US-born and foreign-born Hispanic mothers (0.8% vs. 0.3%, Χ² (1, N = 11,152) = 8.480, p = 0.004). Conclusions: The study results showed evidence of significantly lower prevalence of pregnancy-related hypertensive disorders among foreign-born mothers as compared to their US-born counterparts, both in the full study sample and specifically in the subsamples of women who self-identified as Black and women who self-identified as Hispanic. These variances by nativity, race, and ethnicity provide further insight into how the healthy immigrant effect can apply to pregnancy-related hypertensive disorders, particularly for women of racial and ethnic minorities. Full article

Background: The Fibroblast Growth Factor (FGF) 19 subfamily plays a key role in the regulation of metabolic and growth processes, and their dysregulation can lead to fetal growth disorders, such as small for gestational age (SGA) and large for gestational age (LGA), as well as to pathogenesis and development of gestational diabetes and gestational hypertension. Methods: We conducted a narrative review using the PRISMA2020 statement. Two electronic databases were searched: PubMed and Web of Science until October 2024. The search terms were as follows: (FGF-21 OR fibroblast growth factor-21 OR FGF-23 OR fibroblast growth factor-23 OR FGF-19 OR fibroblast growth factor-19) AND (human fetus development OR fetal growth OR infancy). We only included original papers that analysed the effect of FGF-19,21,23 on pre- and postnatal development. Results: Only 6 out of 203 studies met the inclusion criteria. There were higher concentrations of FGF-21 among patients with gestational diabetes mellitus (GDM) compared to healthy females, but no differences were found in FGF-21 values in newborn’s umbilical cord blood. Interestingly, higher FGF-21 concentrations were observed in females than males born to patients with GDM. FGF-19 was linked to fetal development by its association with chronic insulin secretion levels during fetal life, particularly in female newborns, but no significant correlation with GDM was found. The evaluation of the role of FGF-23 has shown that its low level could be related to gestational hypertension and fetal growth restriction. Conclusions: In conclusion, all the studies discussed suggest that FGF-19 subfamily factors may play an important role in fetal and neonatal growth and development, particularly in pregnancies complicated by metabolic disorders, such as gestational diabetes or gestational hypertension. Differences in FGF-19 and FGF-21 concentrations based on gender and gestational disorders suggest the need for further research in order to fully understand the effects of these proteins and their potential clinical applications. Full article

Uncomplicated hypertension (UH) during pregnancy represents a common condition, worsening maternal and fetal prognosis. However, no single biomarker has proven optimal for determining the risk of UH. We developed an early risk multivariate model for UH, integrating hemodynamics with biochemistry, focusing on the relationship between blood pressure (BP) indices, uric acid (UA), and angiogenesis-related factors (AF). We collected and analyzed data on 24 h ambulatory BP monitoring, demographic, epidemiological, clinical, and laboratory variables from 132 pregnancies. The main predictors were BP indices and serum UA and AF levels. Uncomplicated hypertension, defined as the presence of gestational hypertension or worsening of essential hypertension beyond the 20th week, was the main outcome. The combined second-degree polynomial transformation of UA and the AF (sFlt-1/PIGF) ratio, called the UA-AF Index, consistently showed a positive association with UH. The models incorporating nighttime BP indices combined with the UA-AF Index outperformed the others, with the best-performing model based on the nocturnal systolic BP (SBP). Specifically, in the best-fitting model (nighttime SBP + UA-AF Index as predictors), each 1 mmHg increase in nocturnal SBP was associated with a 10% higher risk of UH, while each one-unit increase in the UA-AF Index raised the likelihood of UH by more than twofold (accuracy: 0.830, AUC 0. 874, SE 0.032, p-value < 0.001, 95%CI 0.811–0.938). The combination of nighttime blood pressure indices, serum uric acid, and angiogenesis-related factors may provide added value in the assessment of uncomplicated hypertension during pregnancy. Full article

Background: Hypertensive disorders of pregnancy (HDPs) are a major cause of maternal morbidity and mortality worldwide. Very little progress has been made in reducing HDP-related maternal deaths in low- and middle-income countries (LMICs), including South Africa, over the past decade. Aim: The aim of this study was to describe maternal deaths arising from HDPs at tertiary/quaternary hospital in Johannesburg, South Africa, with specific focus on maternal characteristics, management, timing of death, causes, and avoidable factors and to use the information to inform clinical practice. Methods: We conducted a retrospective review of patient clinical records covering the period 1 January 2015 to 31 December 2018. Data on maternal demographic and pregnancy characteristics, management, causes, and timing of death were extracted from the clinical records and transferred into a Microsoft Excel^® Spreadsheet and analysed using descriptive statistics. Results: During the study period, 70 maternal deaths were recorded, of which 23 (32.8%) were due to HDP-related complications. The majority of the maternal deaths, 20 (86.9%), occurred during the postpartum period, predominantly affecting Black African women, 23 (100%), with a median age of 27 years. Notably, 18 (78.2%) of the deceased had booked early and attended antenatal care (ANC). Eclampsia emerged as the most common final cause of death. Key avoidable factors included non-adherence to established protocols, particularly failure to initiate aspirin prophylaxis in at-risk women, as well as incorrect or inadequate administration of antihypertensive therapy and magnesium sulphate (MgSO₄) prophylaxis. Conclusions: HDP-related maternal deaths are largely preventable. They primarily result from poor quality of care due to a lack of adherence to evidence-based protocol. Full article

Background: Nausea and Vomiting in Pregnancy (NVP) and Hyperemesis Gravidarum (HG) are common pregnancy-related conditions that can significantly impair maternal quality of life and, in severe cases, impact pregnancy outcomes. This study aimed to assess the prevalence of NVP and HG, evaluate their association with pregnancy progression and neonatal outcomes, and investigate the role of pharmacological therapy. Methods: A prospective observational study was conducted at the University Hospital of Siena between September 2023 and September 2024. Seventy-nine pregnant women aged 28–34 years were enrolled and followed throughout pregnancy. Symptom severity was assessed using the PUQE questionnaire during scheduled outpatient visits. Patients with NVP received pharmacological treatment with doxylamine succinate/pyridoxine hydrochloride. Results: Nausea and Vomiting in Pregnancy was reported by 59% of patients, with all cases categorized as mild or moderate; no severe HG cases were observed. Symptoms resolved by the third trimester. A significant association was observed between NVP and a positive family history of the condition (OR: 3.66, 95% CI: 1.20–11.21; p = 0.025). Logistic regression analysis also revealed that NVP was associated with an increased risk of gestational hypertension (15% vs. 0%, p = 0.04), and a decreased likelihood of gestational diabetes (OR: 0.24, 95% CI: 0.07–0.86) and cesarean section (OR: 0.34, 95% CI: 0.13–0.87). No significant differences were found in neonatal outcomes, including birth weight, Apgar scores, or fetal complications. Conclusions: While NVP may influence maternal outcomes, the condition does not significantly affect neonatal health. Early pharmacological treatment improves maternal well-being and may reduce hospitalization rates. Larger multicenter studies are needed to confirm these findings. Full article

Background/Objectives: Adverse pregnancy outcomes (APOs), which include hypertensive disorders of pregnancy (gestational hypertension, preeclampsia, and related disorders), gestational diabetes, preterm birth, fetal growth restriction, low birth weight, small-for-gestational-age newborn, placental abruption, and stillbirth, are health risks for pregnant women that can have fatal outcomes. This study’s aim is to investigate the usefulness of artificial intelligence (AI) in improving these outcomes and includes changes in the utilization of ultrasound, continuous monitoring, and an earlier prediction of complications, as well as being able to individualize processes and support clinical decision-making. This study evaluates the use of AI in improving at least one APO. Methods: PubMed, Web of Science, and Scopus databases were searched and limited to the English language, humans, and between 2020 and 2024. This scoping review included peer-reviewed articles across any study design. However, systematic reviews, meta-analyses, unpublished studies, and grey literature sources (e.g., reports and conference abstracts) were excluded. Studies were eligible for inclusion if they described the use of AI in improving APOs and the associated ethical issues. Results: Five studies met the inclusion criteria and were included in this scoping review. Although this review initially aimed to evaluate AI’s role across a wide range of APOs, including placental abruption and stillbirth, the five selected studies focused primarily on preterm birth, hypertensive disorders of pregnancy, and gestational diabetes. None of the included studies addressed placental abruption or stillbirth directly. The studies primarily utilized machine-learning models, including extreme gradient boosting (XGBoost) and random forest (RF), showing promising results in enhancing prenatal care and supporting clinical decision-making. Ethical considerations, including algorithmic bias, transparency, and the need for regulatory oversight, were highlighted as critical challenges. Conclusions: The application of these tools can improve prenatal care by predicting obstetric complications, but ethics and transparency are pivotal. Empathy and humanization in healthcare must remain fundamental, and flexible training mechanisms are needed to keep up with rapid innovation. AI offers an opportunity to support, not replace, the doctor–patient relationship and must be subject to strict legislation if it is to be used safely and fairly. Full article

Pregnancy orchestrates profound neurological, hormonal, and anatomical transformations in the maternal brain, preparing it for caregiving and infant bonding. Neuroimaging reveals structural changes such as gray matter reductions and white matter reorganization during pregnancy, followed by partial recovery postpartum. These adaptations are modulated by fluctuating levels of estradiol, progesterone, prolactin, and oxytocin, which coordinate neuroplasticity and behavioral readiness. At the molecular and cellular levels, pregnancy hormones drive synaptic remodeling, neurogenesis, and glial activity. Together, these changes support maternal motivation, attachment, and responsiveness, highlighting the maternal brain’s dynamic plasticity across gestation and the postpartum period. Also, pregnancy induces profound physiological changes, particularly in vascular, hormonal, and neurologic systems, to support maternal and fetal health. While these adaptations are essential, they can predispose pregnant individuals to various neurologic and ophthalmic pathologies. This review explores how pregnancy-related changes—including hypercoagulability, pituitary enlargement, hormonal fluctuations, and immunological modulation—contribute to conditions such as stroke, idiopathic intracranial hypertension, preeclampsia-associated visual disturbances, and demyelinating disorders like neuromyelitis optica spectrum disorder and multiple sclerosis. Additionally, ocular manifestations of systemic diseases like diabetic retinopathy and thyroid orbitopathy are discussed. Understanding these complex interactions is critical for prompt recognition, accurate diagnosis, and appropriate management of vision-threatening and neurologically significant complications during pregnancy. Nevertheless, many aspects of physiological and pathological changes during and after pregnancy remain unknown and warrant further investigation. Full article

Splanchnic vein thrombosis (SVT) is a heterogeneous group of disorders affecting the portal, mesenteric, splenic, and hepatic veins. While frequently associated with liver cirrhosis and malignancy, SVT also occurs in non-cirrhotic, non-neoplastic patients. This narrative review evaluates the epidemiology and risk factors for SVT in this population. The prevalence and incidence of SVT in non-cirrhotic, non-neoplastic patients remain incompletely characterized, with estimates varying widely across studies. The clinical significance of SVT relates to potential complications, including intestinal ischemia, portal hypertension, and a possible underlying systemic disorder. Risk factors for SVT can be categorized into local abdominal conditions, thrombophilias, and systemic disorders. Local factors include inflammatory bowel disease, pancreatitis, abdominal surgery, and trauma. Thrombophilias, both inherited and acquired, are significant contributors to SVT risk. Systemic conditions associated with SVT include autoimmune disorders, pregnancy, hematological diseases, and infections. The complex interplay of these risk factors highlights the need for a comprehensive evaluation of SVT patients. Early recognition and management of these conditions can prevent potentially life-threatening complications and guide decisions regarding anticoagulation and long-term follow-up. Full article

Background: Obesity is a complicated, chronic condition that has a major impact on reproductive health, leading to infertility, anovulation, and poor pregnancy outcomes. It alters the hypothalamic–pituitary–ovarian (HPO) axis, promotes insulin resistance, and causes persistent low-grade inflammation, all of which result in hormonal abnormalities that compromise normal ovarian function. Because standard weight loss procedures frequently fail to provide significant and long-term reproductive benefits, bariatric surgery is becoming increasingly popular as a therapeutic option for obese women trying to conceive. However, continuous research is being conducted to determine the degree of its advantages and potential hazards to fertility and pregnancy outcomes. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and entered into the PROSPERO database. Comprehensive searches in the PubMed, Scopus, and Web of Science databases turned up relevant studies. Studies that examined the effects of bariatric surgery on female fertility, ovulatory function, pregnancy rates, and neonatal outcomes were considered. Methodological quality and risk of bias were evaluated using the Newcastle–Ottawa Scale (NOS) for observational studies and the Cochrane Risk of Bias Tool for randomized controlled trials. Results: This review comprised 34 studies. More than 75% of the studies analyzed showed improvements in ovulatory function, monthly regularity, or spontaneous pregnancy after bariatric surgery. Post-surgical pregnancies are related to a lower incidence of gestational diabetes, hypertension, and macrosomia. However, several studies raised concerns about nutritional inadequacies and the possibility of small-for-gestational-age newborns, particularly following Roux-en-Y gastric bypass. Studies suggest delaying conception for 12 to 18 months after surgery to reduce nutritional hazards and improve pregnancy outcomes. Variability in study design, follow-up duration, and surgical methods reduces the generalizability of findings, emphasizing the importance of uniform research protocols. Conclusions: Bariatric surgery is a highly effective treatment for increasing fertility and pregnancy outcomes in obese women, particularly those with PCOS. However, rigorous preconception planning, postoperative nutritional monitoring, and multidisciplinary follow-up are required to reduce the related hazards. Future research should concentrate on long-term reproductive outcomes, standardizing fertility assessment criteria, and improving clinical guidelines for managing post-bariatric pregnancies. These findings support the incorporation of bariatric surgery into fertility treatment regimens for obese women, and they may shape future revisions to clinical guidelines on reproductive care following weight loss surgery. Full article

Background and Objectives: Pre-eclampsia (PE) is a serious pregnancy complication defined by the onset of hypertension and multi-organ dysfunction occurring after 20 weeks of gestation. Studies have indicated the correlation between diabetes mellitus (DM) and PE, but the causal relationship remains unclear. Materials and Methods: The two-sample Mendelian randomization (MR) approach, including the inverse variance weighted random effects (IVW-RE) model and the traditional sensitivity model, was employed to assess the causal effects of pre-pregnancy type 1 diabetes (T1D) and type 2 diabetes (T2D) on PE using summary-level data obtained from genome-wide association studies. Additionally, diabetes-related factors, such as glycated hemoglobin (HbA1c) levels, fasting insulin levels, and body mass index (BMI), were evaluated for their potential causal effects on the risk of PE. Pleiotropy-robust and multivariable Mendelian randomization (MVMR) methods were further used because of the intricate associations among the traits. Insulin and metformin use was also assessed for their causal role in PE risk. Results: Our findings show that genetically predicted T1D (OR = 1.06, 95% CI: 1.03–1.09, p < 0.001), T2D (OR = 1.09, 95% CI: 1.04–1.14, p < 0.001), and BMI (OR = 1.64, 95% CI 1.49 to 1.80, p < 0.001) had causal effects on the incidence of PE, while the effects of HbA1c (OR = 0.77, 95% CI 0.59 to 1.02, p = 0.064) and fasting insulin levels (OR = 1.35, 95% CI 0.89 to 2.05, p = 0.153) on the occurrence of PE were not significant. The results were verified by MVMR analysis. Additionally, insulin use increased the risk of pre-eclampsia (OR = 1.11, 95% CI 1.05–1.17, p < 0.001). Conclusions: Our findings demonstrate a causal relationship between pre-pregnancy diabetes (DM) and obesity and the risk of PE from a genetic epidemiological perspective. Adverse maternal factors, including DM and obesity prior to pregnancy, should be considered in mechanistic studies of PE. In addition, comprehensive interventions for risk factors such as pre-pregnancy DM and obesity should be emphasized in clinical practice. Full article

Pre-eclampsia is a severe pregnancy complication affecting 5–8% of pregnancies worldwide, marked by high blood pressure and organ damage typically occurring after 20 weeks of gestation. It is a leading cause of maternal and fetal morbidity and mortality. Though its exact cause is unknown, it involves placental abnormalities and improper blood vessel development. Risk factors include a history of pre-eclampsia, chronic hypertension, diabetes, obesity, and autoimmune disorders. Symptoms include high blood pressure, proteinuria, headaches, vision changes, and abdominal pain. Untreated, it can lead to seizures, stroke, preterm birth, or death. Delivery is the definitive treatment, with management strategies such as monitoring and blood pressure control. Pre-eclampsia significantly increases long-term cardiovascular disease (CVD) risks, including hypertension, ischemic heart disease, and stroke, linked to shared mechanisms like endothelial dysfunction and inflammation. Women with severe or recurrent pre-eclampsia have heightened risks, often developing chronic hypertension within a decade postpartum. It also impacts offspring, with daughters at elevated risk for pre-eclampsia and CVD. Hypertensive disorders of pregnancy, including pre-eclampsia, induce changes like left ventricular hypertrophy and diastolic dysfunction, raising risks for heart failure with preserved ejection fraction and coronary atherosclerosis. Overlapping with peripartum cardiomyopathy, pre-eclampsia underscores a spectrum of pregnancy-related cardiovascular disorders. Long-term monitoring and lifestyle interventions are crucial for managing risks, with research into genetic and biological mechanisms offering the potential for targeted prevention. Full article

Cardiovascular diseases increase among pregnant women and complicate 1–4% of pregnancies worldwide. The incidence of maternal deaths due to cardiovascular causes has increased dramatically, rising from 3% three decades ago to 15% in recent years. The aim of this study is to provide a comprehensive overview of the current status of knowledge in sudden maternal death (SMD) described in the literature and to present two cases of autopsy findings in sudden cardiac death in pregnant women. Among the most common causes of sudden maternal deaths are peripartum cardiomyopathies, aortic dissection, acute myocardial infarction, arrhythmias, ischemic heart disease, and coronary artery dissection, and among the less common causes, we list coronary artery dissection, congenital heart diseases, valvulopathies, hypertension, fibroelastosis, and borderline myocarditis. The Centers for Disease Control and Prevention (CDC) reported that over 80% of pregnancy-related deaths were preventable. To reduce the number of maternal deaths caused by cardiovascular diseases, the implementation of specialized multidisciplinary teams has been proposed. Molecular biology techniques are proving their effectiveness in forensic medicine. PCR or DNA sequencing can be utilized in “molecular autopsy”, which holds particular value in cases of sudden death where the forensic autopsy is negative but there is a suspicion that death was caused by arrhythmia. Susceptibility genes can be analyzed, such as KCNQ1, KCNH2, KCNE1, and KCNE2, which are involved in long QT syndrome, the RYR2 gene implicated in catecholaminergic polymorphic ventricular tachycardia type 1, or the SCN5A gene associated with Brugada syndrome. Early identification of risk factors involved in sudden maternal death prenatally and during pregnancy is essential. At the same time, genetic determinations and molecular biology techniques are absolutely necessary to prevent the occurrence of sudden deaths among close relatives. Full article

Background/Objectives: Hypertensive disorders of pregnancy are a leading cause of pregnancy-related deaths in the United States, accounting for 7% of maternal mortality. Labetalol and nifedipine are the first-line drugs for the management of hypertension in pregnancy, but there are little data guiding the choice of one drug over the other. The current pilot longitudinal study aims to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of labetalol stereoisomers throughout pregnancy and postpartum. Methods: This is a single-center clinical study recruiting up to 40 pregnant individuals ≥ 18 years of age at the time of enrollment, taking labetalol as per the standard of care. The exclusion criteria include any pathophysiology impacting the PK of labetalol, e.g., liver failure. Maternal plasma, urine, amniotic fluid, cord blood, and breast milk will be collected, and labetalol stereoisomers will be measured using a validated LC-MS/MS assay. Heart rate and blood pressure will be measured as the PD endpoints. These may be assessed throughout a participant’s dosing interval at scheduled PK study visits, which will occur every 6–10 weeks during pregnancy, at delivery, during the 1st week postpartum, and up to 20 weeks postpartum. The primary aim is to characterize the PK and PD of labetalol during pregnancy and in the postpartum period. The secondary aim is to determine the extent of breast milk excretion of and infant exposure to labetalol from breast milk. The data will be analyzed using population PK modeling to evaluate the PK/PD relationship and ultimately develop trimester-specific dosing recommendations. Results/Conclusions: To our knowledge, this is the first study aiming to characterize the PK of labetalol stereoisomers across pregnancy and postpartum, utilizing individual stereoisomer data to evaluate the PK/PD relationship, and collecting postpartum samples, including breast milk, to model infant exposure to labetalol through breast milk. This study will provide important PK/PD data and knowledge which will be combined with large multi-center clinical trial data to develop trimester-specific dosing regimens for anti-hypertensive agents. Full article