Search Results (419)

Objective: To evaluate and compare fetal arterial and venous Doppler parameters in early-onset (EO) and late-onset (LO) fetal growth restriction (FGR), and to assess their performance within the study cohort and their association with composite adverse neonatal outcome (CANO). Methods: This prospective observational cohort study included 184 singleton pregnancies between 24 and 37 weeks of gestation, comprising 91 FGR cases and 93 appropriate-for-gestational-age controls. FGR was defined according to Delphi consensus criteria and classified as EO-FGR (<32 weeks) or LO-FGR (≥32 weeks). All fetuses underwent standardized Doppler assessment of the umbilical artery (UA), middle cerebral artery (MCA), uterine artery (UtA), and ductus venosus (DV). The cerebroplacental ratio (CPR) was calculated. Multivariable logistic regression models were constructed separately for EO-FGR and LO-FGR. Classification performance was evaluated using receiver operating characteristic analysis. CANO was defined as at least one of the following: 5-min Apgar score <7, respiratory distress syndrome, neonatal intensive care unit admission, or preterm birth. Results: In both EO-FGR and LO-FGR, UA PI values were significantly higher, whereas MCA PI and CPR were significantly lower than in controls. CPR demonstrated the highest discriminative performance among arterial parameters in both subgroups. DV Doppler indices were not significantly different in EO-FGR. In LO-FGR, DV S-wave and v-wave velocities were independently associated with FGR. No significant associations were observed between Doppler parameters and CANO in subgroup analyses. Conclusions: Arterial Doppler parameters, particularly CPR, showed consistent alterations in both EO- and LO-FGR. The contribution of venous Doppler parameters differed according to clinical subtype, with additional value observed in LO-FGR. Full article

Preeclampsia is a pregnancy-specific multisystem disorder and a major cause of maternal and perinatal morbidity and mortality worldwide. This narrative review summarizes current evidence on the principal risk factors and pathophysiological mechanisms involved in its development. The disease is best explained by the two-stage model: in stage 1, inadequate trophoblast invasion and incomplete spiral artery remodeling lead to placental hypoperfusion, hypoxia, and oxidative stress; in stage 2, the hypoxic placenta releases anti-angiogenic and pro-inflammatory factors, including soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), which trigger systemic endothelial dysfunction and the maternal clinical syndrome. The review highlights the central role of angiogenic imbalance, immune dysregulation, and chronic inflammation in disease progression. Particular emphasis is placed on maternal risk factors such as primiparity, advanced maternal age, obesity, diabetes mellitus, chronic hypertension, multiple pregnancy, prior preeclampsia, genetic susceptibility, and epigenetic regulation. We also emphasize the contribution of microRNAs in relation to placental hypoxia, trophoblast invasion, angiogenesis, endothelial injury and microchimerism to the development of preeclampsia. The review also examines the role of T helper 1 (Th1)/Th2/Th17/regulatory T cells (Treg) imbalance and uterine natural killer cell dysfunction at the maternal–fetal interface. Improved understanding of these interconnected mechanisms may support earlier diagnosis, better risk stratification, and the development of targeted preventive and therapeutic strategies. Full article

Background/Objectives: Neonatal sepsis remains a major contributor to neonatal morbidity and mortality worldwide, yet diagnostic uncertainty and heterogeneous clinical presentation continue to challenge early recognition and management. Early-onset sepsis (EOS), typically arising within the first 72 h of life, is strongly influenced by maternal and perinatal factors. Limited data exist on the temporal evolution of clinical system involvement during the first week of life. This study aimed to identify the predominant clinical systems involved in preterm and term neonates with suspected or confirmed sepsis and to determine maternal and neonatal risk factors associated with early disease severity, persistent sepsis, and adverse outcomes. Methods: A total of 297 neonates met the inclusion criteria. Most infants (99.3%) were admitted before 72 h of life. Clinical system involvement was recorded daily, and maternal–neonatal risk factors were analyzed to identify predictors of advanced sepsis at presentation, persistent sepsis at Day 7, and mortality. Results: Respiratory involvement was the predominant clinical system affected on Day 1 (57.2%) and remained common through Day 3. CNS, gastrointestinal, and skin involvement were infrequent. Lower gestational age (p = 0.035) and prolonged rupture of membranes >18 h (p = 0.043) independently predicted sepsis at Day 1. Advanced sepsis at admission was associated with lower birth weight, lower gestational age, older maternal age, and absence of intrapartum antibiotics (all p ≤ 0.001). Persistent sepsis at Day 7 was linked to prematurity (p = 0.008), higher mortality (p < 0.001), and prolonged hospitalization (p = 0.001). Conclusions: Respiratory involvement was the most common clinical system affected in neonates with EOS. Prematurity, low birth weight, prolonged rupture of membranes, and maternal intrapartum infection significantly increased the risk of severe disease. Understanding the evolution of clinical system involvement during the first days of life may support more precise risk stratification and reduce unnecessary antibiotic exposure. Full article

Black women in the United States experience inequities in perinatal and neonatal mortality, contributing to psychological stress during and after perinatal loss. This analysis drew on a subset of interviews from a larger qualitative dataset and explored the experiences of 22 Black women who experienced perinatal loss and were pregnant or had given birth after a loss, focusing on feeling unheard by healthcare providers. Semi-structured interviews were conducted, and data were analyzed using descriptive coding and inductive thematic analysis. Three themes emerged: unheard and dismissed concerns, biased and stratified care, and perinatal loss follow-up gaps driving self-advocacy. Women described how systemic racism intensified psychological distress, expressed as heightened anxiety and uncertainty in subsequent pregnancies after perinatal loss. Findings underscore the need for maternity settings to confront racial bias and strengthen cultural safety. Care environments that validate Black women’s concerns and act on them may help rebuild trust and improve maternal and newborn outcomes. The study calls for changes in maternity and mental healthcare aimed at addressing systemic racism and strengthening culturally responsive, equitable care. These findings have implications for perinatal public health practice and policy, including surveillance, prevention, and community-responsive approaches to maternity care during and after perinatal loss. Full article

Neonatal infections remain a leading cause of morbidity and mortality worldwide, particularly among preterm and low-birth-weight infants and in low- and middle-income countries. This burden has intensified with the global increase in multidrug-resistant (MDR) bacteria, especially in neonatal intensive care units, where prolonged hospitalization, invasive interventions, and exposure to broad-spectrum antibiotics promote colonization, transmission, and invasive infection. In this narrative review, we explore the epidemiology and microbiological characteristics of MDR bacterial infections in newborns, alongside their associated risk factors, diagnostic challenges, treatment outcomes, and prevention strategies. Across different settings, Gram-negative pathogens, particularly Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii, account for a substantial proportion of severe neonatal infections, whereas methicillin-resistant Staphylococcus aureus remains important in selected units. The risk of MDR infection is driven by a complex interplay of factors, ranging from maternal and perinatal exposures to the inherent immunological vulnerability of newborns, hospital-based transmission, antibiotic selection pressure, and structural deficiencies in healthcare infrastructure. Diagnosis remains challenging because clinical presentations are nonspecific and culture-based methods are constrained by low blood volumes, prior antimicrobial exposure, and delayed turnaround times. Treatment is increasingly complicated due to resistance to standard empirical regimens, substantial regional variation in susceptibility profiles, and limited neonatal pharmacokinetic and safety data for reserve agents. Current evidence mainly supports surveillance-informed empirical therapy, susceptibility-guided treatment adjustment, antimicrobial stewardship, and strict infection prevention measures. Future progress will require neonatal-specific clinical trials, harmonized surveillance systems, stronger molecular epidemiology, and more equitable access to microbiological diagnostics and effective treatment. Full article

Background: Preterm birth, the leading cause of neonatal mortality, is associated with reduced nephron endowment and an increased risk of kidney disease in later life. In preterm infants, the interruption of nephrogenesis leads to a lower nephron number and structural abnormalities. Prenatal factors such as intrauterine growth restriction, and postnatal factors including nephrotoxic medications, patent ductus arteriosus, perinatal asphyxia, and infections contribute to this deficit. Ultrasound is a key tool for assessing renal volume at birth and can, when indexed to body weight, be used to estimate nephron endowment, which is known to vary widely among individuals. Methods: This study analyzed 52 preterm infants with birth weight < 1000 g, assessing combined renal volume (sum of right and left kidney volumes) indexed to body weight. Results: The mean combined kidney volume-to-body weight ratio was 12.12 (SD = 2.03). Values below the 10th percentile (9.46) or more than one standard deviation below the mean (10.11) may indicate nephron deficiency at birth. Conclusions: Standardized ultrasound-based parameters enable the early identification of neonates at risk for nephron deficit, supporting targeted preventive strategies. Long-term follow-up is essential to detect early renal functional impairment and reduce the risk of chronic kidney disease. Full article

Introduction: Placental malaria increases the risk of adverse birth outcomes. Current preventive measures are undermined by poor coverage, growing resistance to chemo-preventive and therapeutic drugs, and vector eliminating insecticides. Candidate placental malaria (PM) vaccines (PAMVAC and PRIMVAC) have shown safety and immunogenicity in Phase I trials, but empirical evidence on their potential population-level value is lacking. This study modelled the expected cost-effectiveness of a PM vaccine administered before pregnancy. Methods: A decision-analytic model compared two strategies from the provider’s perspective: vaccinating women of childbearing age versus no vaccination. The model incorporated gravidity-specific risks of PM, neonatal mortality and the malaria attributable fractions from the literature. Since the efficacy of a PM vaccine for malaria prevention is unknown, we assumed a 40% efficacy and varied this estimate widely in sensitivity analyses. Primary outcomes were incremental cost-effectiveness ratios (ICERs) per perinatal disability adjusted life years (DALYs) averted. Baseline, best-case, and worst-case scenarios were analysed. One-way and probabilistic sensitivity analyses were used to assess parameter uncertainty. Cost-effectiveness was defined as an ICER below half of sub- Saharan Africa’s 2025 GDP per capita ($1556). Results: The vaccine was most cost-effective among primigravidae. Under baseline assumptions (40% efficacy; 30% uptake; $5 dose price), the ICER was $321 per perinatal DALY averted for primigravidae versus $4444 for multigravidae. Best-case assumptions further improved cost-effectiveness ($225 vs. $3148). Sensitivity analyses showed robust cost-effectiveness for primigravidae across all plausible parameter ranges, while ICERs in multigravidae were highly sensitive to programme costs and vaccine efficacy. Cost-effectiveness acceptability curves demonstrated that vaccination becomes favourable for primigravidae at relatively low willingness-to-pay thresholds. Conclusions: A placental malaria vaccine delivered before pregnancy has high potential to be cost-effective in endemic areas when targeted to protect primigravidae. These findings support prioritised deployment strategies and highlight the value of early economic modelling to inform vaccine development and policy planning. Full article

Background/Objectives: Hypertensive disorders of pregnancy (HDPs) affect approximately one in seven hospital deliveries in the United States and increase the risk of pregnancy-associated mortality. Home blood pressure monitoring (HBPM) for patients with HDPs has emerged as a model of care poised to improve ascertainment of blood pressure and triage of care during pregnancy and postpartum periods. However, the strength of evidence supporting HBPM approaches has been variable. This rapid review aimed to understand how HBPM approaches for pregnant and postpartum populations with HDPs have been evaluated in order to strengthen future research. Methods: Search criteria included peer-reviewed literature in English and French published during 2018–2024 that assessed HBPM approaches for pregnant and postpartum populations in high-income countries. A total of 370 records were screened and reviewed to identify 52 eligible articles. Key study characteristics, methodologies, and outcome measures were extracted. Identified outcome measures were mapped by outcome type (implementation, health service, and client) to assess gaps in evaluation of HBPM approaches. Results: A range of study designs were employed to evaluate HBPM approaches: experimental (17%), observational (52%), qualitative (10%), mixed method (10%), and economic (11%) designs. Over a third employed a comparison group, most of which compared HBPM approaches to usual antepartum or postpartum care. Only 11 studies reported on impact outcomes (long-term blood pressure control, adverse maternal and perinatal outcomes). Significant gaps were identified among the implementation outcomes examined. While patient engagement measures were common, assessment of provider adherence and engagement was limited. Hospital admissions and emergency department visits were often employed as proxies to measure HBPM effectiveness, efficiency, and safety. However, no studies adequately reported effectiveness measures for remote patient triage. Conclusions: Our results call for improved HBPM metrics to ensure patients are receiving high-quality care responsive to their clinical condition. Future studies on HBPM approaches should prioritize more transparent reporting on health actor engagement. A composite measure including both patient and provider adherence to monitoring and triage processes will provide stronger evidence on the effectiveness of HBPM for pregnant and postpartum patients and share impactful learning for health systems interested in adopting HBPM approaches. Full article

Background: Congenital heart disease (CHD) represents a major cause of perinatal morbidity and mortality, and fetal echocardiography is essential for its early diagnosis and management. Maternal smoking has been suggested as a potential teratogenic factor affecting fetal cardiovascular development; however, findings regarding its association with CHD remain inconsistent. This study aimed to evaluate the relationship between maternal smoking during pregnancy and the risk of CHD. Methods: A total of 2715 pregnant women and 2784 fetuses who underwent fetal echocardiography at ≥20 weeks’ gestation between 1 January 2024 and 1 November 2025 were analyzed. Pregnancies complicated by known chromosomal or syndromic abnormalities, significant teratogenic exposure, duplicate assessments, or nonstandard examinations were excluded. Maternal smoking status during pregnancy was recorded and categorized according to daily cigarette consumption. The prevalence of CHD and the distribution of CHD subtypes were evaluated and compared according to smoking status. Fetal cardiac diagnoses were classified based on the classical morphological classification system. Results: A total of 2715 pregnancies (2784 fetuses) were analyzed, including 2530 fetuses in the non-smoking group and 254 in the smoking group. Congenital heart disease was detected in 12.5% of fetuses in the non-smoking group and 14.2% in the smoking group, with no statistically significant difference (p = 0.442). According to the classical morphological classification, the distribution of fetal echocardiographic pathologies did not differ significantly between groups (p = 0.607). Septal defects were the most common subtype in both groups. Although conotruncal defects were proportionally more frequent in the smoking group, this difference did not reach statistical significance. After reclassifying daily cigarette consumption into four exposure categories, no association was detected between maternal smoking and CHD risk (OR = 1.04; 95% CI: 0.86–1.26; p = 0.691). Conclusion: In this cohort referred for fetal echocardiographic evaluation, no association was detected between maternal smoking during pregnancy and the risk of congenital heart disease or alterations in CHD subtype distribution. No consistent dose–response relationship was observed. These findings suggest that no association was detected between maternal smoking exposure and CHD. Further large-scale prospective studies are needed to clarify phenotype-specific associations. Full article

Background: Pregnancy in women with liver cirrhosis is considered a rare clinical condition due to the decreased fertility commonly associated with chronic liver disease. Hormonal disturbances, anovulation and impaired hepatic function contribute to the lower conception rates observed in this population. However, when pregnancy occurs, it is associated with a significantly increased risk of maternal and fetal complications. Maternal risks include hepatic decompensation, variceal bleeding, ascites, coagulopathy and a higher rate of hypertensive disorders during pregnancy and related complications. Fetal complications involve prematurity, intrauterine growth restriction, and increased perinatal mortality. Methods: We present the clinical case of a woman with idiopathic liver cirrhosis who experienced four consecutive pregnancies with different clinical courses and outcomes. Results: The case highlights the complexity of managing pregnancy in patients with chronic liver disease and underscores the importance of individualized clinical assessment and multidisciplinary management. This report also reviews current management strategies and discusses key considerations for optimizing care in pregnant women with liver cirrhosis. Conclusions: Advances in multidisciplinary care and improved management strategies have contributed to better pregnancy outcomes in recent years. Careful monitoring during pregnancy, appropriate management of portal hypertension, and coordinated care between obstetricians, hepatologists, and neonatologists are essential to minimizing potential complications, ensuring favorable maternal and fetal outcomes. Full article

Preeclampsia remains a major cause of maternal and perinatal morbidity and mortality worldwide, yet progress in biomarker discovery and predictive modeling has translated only modestly into clinically meaningful risk stratification. Over the past two decades, numerous biomarkers and predictors reflecting placental–angiogenic dysfunction, maternal cardiovascular maladaptation, and inflammatory–metabolic stress have been proposed, alongside increasingly sophisticated statistical and machine learning approaches. However, many predictive strategies continue to treat preeclampsia as a single disease entity and rely on static thresholds applied at isolated gestational time points. Accumulating biological and clinical evidence instead suggests that preeclampsia represents a heterogeneous syndrome composed of partially overlapping mechanistic phenotypes whose relative contributions vary across pregnancy and across individuals. In this narrative review, we argue that further progress in prediction is likely to depend less on the identification of additional biomarkers and more on how biological heterogeneity and temporal dynamics are integrated into predictive frameworks. We synthesize current evidence supporting multimarker approaches, phenotype-informed frameworks, and longitudinal risk trajectories that conceptualize prediction as a dynamic process rather than a binary classification task. We also examine the complementary roles of classical statistical models and machine learning, emphasizing that calibration, external validation, interpretability, transportability, and clinical usability are essential, alongside discrimination, for successful clinical implementation. Finally, we outline key research priorities for the next generation of predictive studies, including mechanistically grounded phenotyping, dynamic risk updating across gestation, rigorous evaluation across diverse populations, and explicit linkage of risk stratification to preventive interventions and clinical decision-making. Together, these directions support a shift toward an integrative, longitudinal, and clinically anchored approach to preeclampsia prediction. Full article

Background: Pre-eclampsia (PE) is a significant cause of maternal and perinatal morbidity and mortality globally and is characterized by impaired endothelial function and disturbances in coagulation pathways. The effects of Human Immunodeficiency Virus (HIV) on the immune and coagulation systems have been investigated during pregnancy, but there are few reports on anticoagulant factors in pregnant women who are infected with HIV and develop PE. This investigation compares plasma protein C levels in pregnant women with pre-eclampsia and those without pre-eclampsia, and compares the results based on their HIV status. Methods: A hospital-based cross-sectional study design was used for the current research, which was carried out at Charlotte Maxeke Johannesburg Academic Hospital, South Africa. A total of 83 pregnant women participated in the study and were categorized into one of four groups: normotensive HIV-negative (n = 36); normotensive HIV-positive (n = 18); pre-eclamptic HIV-negative (n = 21); and pre-eclamptic HIV-positive (n = 8). Data collected included demographic information and clinical characteristics that were abstracted from maternity records. Plasma protein C concentrations were determined by ELISA (enzyme-linked immunosorbent assay). Nonparametric statistical methods were used to compare the mean values of plasma protein C between each of the four groups, and significance was set at p < 0.05. Subgroup analyses, particularly for the pre-eclamptic HIV-positive group (n = 8), were considered exploratory due to small sample sizes. Results: As would be anticipated, both systolic and diastolic blood pressure values were significantly elevated in the pre-eclamptic group when compared to the normotensive control subjects (p < 0.0001). There were no statistically significant differences in plasma protein C concentration between the normotensive and pre-eclamptic groups, nor between the HIV-negative and HIV-positive groups. Similarly, there were no significant differences in plasma protein C concentration when comparing all four study groups (Kruskal–Wallis test p = 0.2295). Conclusions: Plasma protein C concentrations did not vary significantly according to the presence of pre-eclampsia or HIV status in this cohort. These findings suggest that protein C concentrations were not measurably altered between groups within this study population. However, due to the small sample size in key subgroups, these findings should be considered preliminary and interpreted with caution. Larger, adequately powered studies are required to further investigate potential associations between HIV infection, pre-eclampsia, and anticoagulant pathways during pregnancy. Full article

Fetal MRI has been increasingly used in diagnosis and assessment of congenital anomalies and conditions by providing detailed structural information. However, such information is only part of the whole landscape of these genetic disorders. Given that genetic disorders are associated with significant morbidity and mortality in infants, multidisciplinary team management is essential for perinatal management and parental counseling. In the past two decades, there are advances in both fetal MRI and genetic testing for prenatal diagnosis of genetic disorders. This narrative review consolidates the current literature and aims to provide a systematic overview of fetal MRI applications in genetic disorders affecting the central nervous system, craniofacial structures, skeletal system, lungs, and urinary system. Understanding embryological and genetic basis as well as imaging phenotypes of genetic disorders are important in improving perinatal diagnosis and management. Full article

Background/Objectives: Placental vascular malperfusion, on both the maternal (MVM) and fetal (FVM) side, is a key mechanism linking hypertensive disorders of pregnancy, fetal growth restriction (FGR), stillbirth, preterm neonatal death and neonatal encephalopathy. Nevertheless, clinical use and medico-legal interpretation of placental findings remain inconsistent. To summarize recent evidence on the relationship between placental vascular malperfusion, perinatal mortality and neonatal brain injury, integrating standardized placental pathology with Doppler and angiogenic biomarkers, and to outline the main medico-legal implications. Methods: A PubMed search using the string “((placenta OR placental pathology) AND (stillbirth OR fetal death) AND (maternal vascular malperfusion OR fetal vascular malperfusion))” yielded 118 records. After excluding reviews, meta-analyses, case reports (except one illustrative SARS-CoV-2 placentitis case), non-human studies and papers without original histopathology, 33 studies were included: observational cohorts and case–control studies with standardized placental assessment, autopsy series, biomarker/Doppler cohorts, mechanistic work, one randomized trial protocol and a small number of focused clinical commentaries. Results: Across these studies, MVM emerges as the dominant placental lesion in pre-eclampsia, FGR and a large proportion of stillbirths, especially in early-onset disease and in association with maternal hypertension. FVM is strongly linked to stillbirth and term neonatal encephalopathy, and specific combinations of MVM, FVM and inflammatory lesions correspond to distinct patterns of brain injury. Large population-based cohorts confirm that maternal hypertensive disorders and placental malperfusion are major upstream causes of intrauterine hypoxia and preterm neonatal death. Doppler velocimetry and angiogenic biomarkers (PlGF, sFlt-1 and their ratio) are strongly associated with an increased likelihood of underlying MVM and adverse neonatal outcomes, although their predictive performance remains probabilistic and context-dependent rather than diagnostic. Mechanistic studies suggest roles for placental genomic instability and altered decidual immunity in defective placentation. Conclusions: Maternal and fetal vascular malperfusion represent converging pathways to FGR, stillbirth, preterm neonatal death and neonatal encephalopathy. Routine, standardized placental examination, interpreted together with Doppler and biomarker data, substantially improves causal attribution and timing of injury, with direct consequences for counselling, prevention and medico-legal assessment. Full article

Background/Objectives: Preeclampsia (PE) is the primary cause of maternal and perinatal morbidity and mortality on a global scale. It is driven by a multifactorial aetiology, in which genetic factors involved in blood pressure regulation, including the endothelial nitric oxide synthase (eNOS) gene, play an important role. This study aimed to investigate the association between eNOS gene polymorphisms and the development and severity of PE in an Algerian cohort. Methods: A total of 305 Algerian women, comprising 124 patients with PE and 181 healthy controls, were genotyped for two polymorphisms: intron 4 variable number tandem repeat (VNTR) (4a/4b) and the −786 T>C promoter variant. Genotyping was performed using standard polymerase chain reaction (PCR) for VNTR and polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) for the −786 T>C variant. Results: Our results revealed no significant difference in the allelic or genotypic frequencies of the −786 T>C polymorphism between the cases and controls (p > 0.05). Interestingly, the frequency of the protective “4b” allele was significantly lower in cases than in controls (odds ratio (OR) = 0.400 [0.278–0.575]; p < 0.0001). However, the “4a” allele and the 4a/4a genotype were significantly associated with an increased risk of preeclampsia (OR = 2.50 [1.74–3.59], p < 0.0001; and OR = 6.20 [2.85-13.50], p < 0.0001, respectively). Furthermore, they were correlated with disease severity (allelic: OR = 2.76 [1.60–4.75], p = 0.0002; and genotypic: OR = 4.64 [1.83-11.78], p = 0.0003). Conclusions: These findings support the potential role of the eNOS VNTR 4a/4b polymorphism in both the risk and severity of preeclampsia in the Algerian population. Full article