Search Results (433)

Background/Objectives: Hypertensive disorders of pregnancy (HDP) remain a significant cause of maternal and perinatal morbidity worldwide. In some healthcare settings, access to angiogenic testing is limited, underscoring the need for affordable biomarkers to guide risk assessment. NT-proBNP, a marker of myocardial wall stress and cardio-renal dysfunction, may offer complementary prognostic value to the angiogenic sFlt-1/PlGF ratio. Methods: In this prospective multicenter observational study, we enrolled 180 pregnant women and categorized them into preeclampsia (PE, n = 95), non-PE HDP (gestational or chronic hypertension, n = 25), and healthy controls (n = 60). NT-proBNP and sFlt-1/PlGF levels were measured at enrollment, after 20 weeks of gestation, predominantly during the second and third trimesters. Associations with proteinuria, uric acid, creatinine, and maternal–fetal complications were examined using multivariable logistic regression adjusted for maternal age, BMI, and gestational age. Discrimination was assessed using receiver operating characteristic (ROC) curve analysis, and the incremental value of NT-proBNP beyond the sFlt-1/PlGF ratio was evaluated using ΔAUC and net reclassification improvement (NRI). Results: Median NT-proBNP levels were significantly higher in PE compared with non-PE HDP and controls (p < 0.01). NT-proBNP ≥200 pg/mL independently predicted maternal–fetal complications (adjusted OR 3.12, 95% CI 1.41–6.90, p = 0.005) and correlated with proteinuria (r = 0.47), creatinine (r = 0.43), and uric acid (r = 0.40) (all p < 0.001). sFlt-1/PlGF alone yielded an AUC of 0.84 (95% CI 0.77–0.89), while NT-proBNP alone demonstrated an AUC of 0.78 (0.71–0.84). Combining both biomarkers improved discrimination (AUC 0.88, 95% CI 0.82–0.92), with a ΔAUC of 0.04 (p = 0.02) and a continuous NRI of 0.21 (p = 0.03). The 200 pg/mL threshold for NT-proBNP achieved 80% sensitivity and 71% specificity (p < 0.001). Conclusions: NT-proBNP provides independent and complementary prognostic value to the sFlt-1/PlGF ratio in predicting maternal–fetal complications in HDP. A practical threshold of 200 pg/mL aids risk assessment, and integrating NT-proBNP into angiogenic models improves prediction. Further multicenter studies are needed to validate multimarker strategies and their cost-effectiveness. Full article

Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with oxidative stress and mitochondrial dysfunction. NRF1 and NRF2 are transcription factors that regulate mitochondrial activity and antioxidant defense. This study investigated their expression patterns in placentas from preeclamptic and severe preeclamptic pregnancies by immunohistochemical and bioinformatical methods. Methods: Placentas from 40 healthy controls, 40 PE, and 40 sPE patients were analyzed by histological and immunohistochemical techniques. Protein–protein interaction networks for NRF1, NRF2, and PE-related proteins were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape software, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis performed via ShinyGO, with significance set at false discovery rate (FDR) < 0.05. Results: NRF1 expression was significantly decreased in PE and sPE groups compared to controls, with notably negative staining in syncytial knots and fibrinoid areas. Conversely, NRF2 expression significantly increased, showing intense positivity in syncytiotrophoblasts, stromal cells, and vascular structures. Pathway analysis revealed that decreased NRF1 expression was associated with glutathione metabolism, hypoxia inducible factor-1 (HIF-1) signaling, and AMP-Activated Protein Kinase (AMPK) signaling pathways. Increased NRF2 expression was associated predominantly with inflammatory and immune response pathways, including AGE-RAGE signaling and pathogen–response pathways. Conclusions: Differential expressions of NRF1 and NRF2 in preeclamptic placentas reflect distinct yet interconnected responses to oxidative stress and inflammation. These transcription factors have potential clinical relevance as biomarkers for PE severity assessment and as targets for future therapeutic interventions. Full article

Background/Objectives: In low-resource settings, diagnostic delays and limited specialist access worsen health inequalities, making hypertensive disorders of pregnancy (HDPs) defined by new-onset blood pressure ≥ 140/90 mmHg after 20 weeks of gestation, with or without proteinuria, a major cause of maternal morbidity and mortality. This study evaluated the diagnostic effectiveness of a rural-applicable clinical model for detecting HDPs in a real-world population from Hospital General San Felipe (Tegucigalpa, Honduras). Methods: A cross-sectional diagnostic accuracy study was conducted on 147 consecutive pregnant women in February 2025. Clinical documentation from the initial appointment defined HDP. We modeled HDP risk using penalized logistic regression and common factors such maternal age, gestational age, blood pressure, BMI, primary symptoms, semi-quantitative proteinuria, and medical history. Median imputation was utilized for missing numbers and stratified five-fold cross-validation assessed performance. We assessed AUROC, AUPRC, Brier score, calibration, and operational utility at a data-driven threshold. Results: Of patients, 27.9% (41/147) had HDP. The model had an AUROC of 0.614, AUPRC of 0.461 (cross-validation averages), and Brier score of 0.253. The threshold with the highest F1-score (0.474) had a sensitivity of 0.561, specificity of 0.679, positive predictive value of 0.404, and negative predictive value of 0.800. HDP had higher meaning systolic/diastolic/mean arterial pressure (130.7/82.9/98.9 vs. 120.5/76.1/90.9 mmHg) and ordinal proteinuria (0.59 vs. 0.36 units). Conclusions: The model had moderate but clinically meaningful discriminative performance using low-cost, commonly obtained variables, excellent calibration, and a good negative predictive value for first exclusion. These findings suggest modification of predictors, a larger sample size, and clinical usefulness assessment using decision curves and process outcomes, including quick referral and prophylaxis. This approach aligns with contemporary developments in the 2023–2025 European Society of Cardiology (ESC) and 2024 American Heart Association (AHA) guidelines, which emphasize earlier identification and risk-stratified management of hypertensive disorders during pregnancy as a cornerstone of women’s cardiovascular health. Full article

Background: Folic acid supplementation (FAS) before and in early pregnancy prevents neural tube defects, but the benefits of extending FAS to late pregnancy on pregnancy outcomes remain unclear. We aimed to investigate the associations between duration of FAS and a spectrum of pregnancy outcomes, and to determine whether the associations were modified by maternal age or pre-pregnancy body mass index (BMI). Methods: This prospective multicenter study included 15,694 singleton pregnancies. We used mixed-effects log-binomial regression models to estimate the adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for gestational diabetes mellitus (GDM), gestational hypertensive disorders (GHDs), pre-eclampsia, preterm birth, macrosomia, small (SGA) and large for gestational age (LGA), and the interaction effects of advanced maternal age and pre-pregnancy BMI. Results: Of 15,694 women, 4523 (28.8%) did not take FAS before or during pregnancy, 2854 (18.2%) took FAS only during peri-pregnancy, 921 (5.9%) took FAS from peri- to mid-pregnancy, and 7396 (47.1%) took it through late pregnancy. Compared with women without FAS, those supplemented until mid-pregnancy were associated with lower risks of GHDs (aRR 0.84, 95% CI 0.74, 0.96) and pre-eclampsia (aRR 0.81, 95% CI 0.67, 0.97). Supplementation until late pregnancy was associated with lower risks of preterm birth (aRR 0.67, 95% CI 0.59, 0.76), SGA (aRR 0.74, 95% CI 0.63, 0.87), and LGA (aRR 0.88, 95% CI 0.79, 0.97). Among women of advanced maternal age or with overweight/obesity, supplementation until mid-pregnancy was associated with higher risk of GDM. Conclusions: Extending FAS until mid-pregnancy is associated with lower risks of GHDs and preeclampsia, and extending it until late pregnancy is associated with lower risks of preterm birth, SGA, and LGA. However, women of advanced maternal age or with overweight/obesity should be cautious about prolonging FAS. Full article

Background: Preeclampsia (PE) and gestational diabetes mellitus (GDM) are complex pregnancy disorders characterized by hypertension, proteinuria, increased blood glucose levels, and metabolic dysfunction. Methods: We investigated lymphocyte proliferation, immune function, key antioxidants, and metabolic and mitochondrial enzyme activities in women with PE and PE with GDM compared to normotensive pregnant (NP) controls. Lymphocyte proliferation was assessed following phytohemagglutinin (PHA) stimulation at varying concentrations (0.5, 2.5, and 5 µg/mL). Activities of key antioxidant enzymes, metabolic enzymes, and mitochondrial enzymes were measured. Other stress markers, including nitric oxide (NO) production and lipid peroxidation (TBARS), along with acetylcholine esterase (AChE) activity, and proinflammatory cytokine assays (IL-6 and TNF-α) were also evaluated from the PHA-induced lymphocytes. Results: Lymphocyte proliferation in response to PHA was significantly increased in PE and PE with GDM groups compared to NP, although low-dose PHA (0.5 and 2.5 µg/mL) moderately enhanced proliferation in NP. IL-6 and TNF-α levels were notably elevated in both disease groups. Antioxidant activities of SOD, GST, GPx and AChE, Citrate synthase, Cytochrome c oxidase, and NO production were significantly reduced in PE and PE with GDM, while hexokinase activity involved in glycolysis was elevated in both groups. Further, TBARS levels were elevated in the disease groups, particularly in PE with GDM. Conclusions: The findings arise from a clinical cross-sectional study and highlight significant immune alterations, oxidative stress, and mitochondrial impairment in PE and PE with GDM. The observed elevation in proinflammatory cytokines further underscore the role of immune activation in the pathogenesis of these complications, emphasizing the integrated immunometabolic shifts identified in this study, as potential molecular indicators for early intervention. Full article

Background: With advances in cancer diagnosis and therapy, survival after childhood and young-adult cancers has improved markedly. As survivorship extends, understanding long-term health sequelae, including obstetric outcomes, has become increasingly important. However, the reproductive safety of pregnancy following cancer remains insufficiently characterized. This systematic review and meta-analysis aims to provide a comprehensive evaluation of obstetric outcomes following pregnancy in survivors of childhood and young-adult cancers. Methods: We conducted a systematic review and meta-analysis (PROSPERO: CRD42024573707) of PubMed, Embase, and Cochrane databases to identify controlled studies assessing obstetric complications among female cancer survivors, published between 1 January 2000 and 31 June 2024. Random effects meta-analyses were used to estimate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity, subgroup analyses, and meta-regression were performed to identify sources of variation. Results: Of 6032 records screened, 16 studies involving 89,123 survivors and 21,569,191 controls were included. Cancer survivorship was associated with higher risks of preeclampsia (RR 1.37, 95% CI 1.17–1.62), gestational diabetes (RR 1.29, 95% CI 1.05–1.59), and miscarriage (RR 1.16, 95% CI 1.01–1.35), but not with anemia in pregnancy (RR 1.16, 95% CI 0.98–1.39) or hypertensive disorders (RR 1.21, 95% CI 0.99–1.49). Cancer type emerged as a potential prognostic factor for preeclampsia. Conclusions: Female cancer survivors are at significantly increased risk of major obstetric complications, underscoring the need for anticipatory preconception counselling and enhanced antenatal surveillance. Future research should delineate cancer- and treatment-specific risks to inform precision reproductive care in this growing survivorship population. Full article

Objective: The objective of this study is to examine the detailed pregnancy and neonatal outcomes of women without male partners undergoing intrauterine insemination (IUI) compared to women with male partners. Methods: This is a retrospective cohort study of all patients who completed an IUI cycle from 2017 to 2023. 2414 cycles were included in the study: 149 cycles for women without male partners (including single and lesbian women) and 2265 cycles for women with male partners. Primary outcomes were the rates of clinical pregnancy, miscarriage, and live birth. Secondary outcomes were obstetric complication rates and neonatal outcomes. Results: Women without male partners undergoing IUI were significantly older than the reference cohort (median age 42 years versus 38 years, p < 0.0001). 84.1% of women without male partners did not have a diagnosis of the common causes of female infertility. Both cohorts had similar cycle characteristics and number of IUI cycles until pregnancy and live birth. The mean clinical pregnancy rate per cycle for women without male partners was 11.4% versus 12.5% for the reference group (p = 0.56), and the mean live birth rate was 8.1% versus 8.2% (p = 0.95). Multiple pregnancy, cumulative pregnancy, and clinical miscarriage rates were also similar. Similarities persisted after adjusting for confounders: age, BMI, race, and infertility diagnosis. Importantly, there were no statistically significant differences in obstetric complications (such as hypertensive disorders of pregnancy, gestational diabetes, placental disorders) and neonatal outcomes. Conclusions: Compared to women with male partners undergoing IUI, women without male partners had similar rates of clinical pregnancy (per cycle and cumulative), miscarriage, and live birth; there were no significant differences in obstetric complications or neonatal outcomes. Full article

Background/Objectives: HIV-exposed uninfected (HEU) infants experience increased severe respiratory syncytial virus lower respiratory tract illness (RSV-LRTI) rates compared with HIV-unexposed infants. Maternal bivalent RSVpreF vaccination can prevent infant RSV-LRTI but data from HEU infants are lacking. Methods: This phase 3 randomized, double-blinded trial assessed RSVpreF safety and immunogenicity in pregnant participants from South Africa living with HIV and their infants. Maternal participants with stable HIV disease taking antiretroviral therapy received RSVpreF or placebo (24–36 weeks’ gestation). Primary safety endpoints included reactogenicity through 7 days after vaccination (maternal participants), adverse events (AEs) through 1 month after vaccination (maternal participants) or birth (infants), and serious AEs (SAEs) throughout the study (maternal participants) or through 6 months after birth (infants). Immune responses were evaluated by 50% RSV-A and RSV-B neutralizing titers prevaccination and at delivery (maternal participants) or birth (infants). Results: Overall, 343 maternal participants received RSVpreF (n = 172) or placebo (n = 171). Most reactogenicity events were mild/moderate. AEs and SAEs were generally reported at similar frequencies in maternal RSVpreF and placebo groups including percentages of hypertensive disorders of pregnancy. There were no safety concerns in infants; percentages of reported AEs and SAEs were generally similar between RSVpreF and placebo groups and no difference in preterm birth. RSVpreF elicited high maternal neutralizing RSV-A and RSV-B immune responses, with efficient RSV antibody transplacental transfer to infants demonstrated by levels greater than the placebo group at birth (geometric mean ratios (GMRs) of RSVpreF to placebo were 7.8 for RSV-A and 6.8 for RSV-B) and by comparison with a cohort of HIV-unexposed infants from the pivotal phase 3 efficacy trial (GMRs of HEU to HIV-unexposed infants were 0.86 for RSV-A and 0.72 for RSV-B). Conclusions: These results support maternal RSVpreF vaccination among those living with stable HIV for preventing RSV-LRTI in HEU infants. (NCT06325657). Full article

Introduction: Both preeclampsia (PE) and prediabetes (PD) are known hypertensive disorders of pregnancy, and a correlation has been shown between these two diseases. A recent study in our laboratory has shown that pregestational PD is a risk factor for developing PE during pregnancy, as pregestational PD increased antiangiogenic factors. However, pregestational PD antiangiogenic release has not been shown to be associated with liver dysfunction. Therefore, this study seeks to investigate pregestational PD as a risk factor for hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome. Materials and Methods: Animals were divided into a normal pregnant group (ND), a preeclamptic pregnant group (PE), and a prediabetic pregnant group (PD). On gestational day (GND) 19, animals were sacrificed, and blood and liver tissues were collected to measure antioxidant protection and lipid peroxidation parameters, liver TGs, liver enzymes, TNF-α, IL-6, and hematology parameters. Results: The results showed significant increases in liver TGs, liver enzymes, TNF-α, IL-6, and hematology parameters in the PE and PD pregnant groups compared to the ND group. Conclusions: These findings suggest that pregestational PD predisposes patients to metabolic and inflammatory changes associated with HELLP syndrome. To our knowledge, this is the first study to demonstrate a link between pregestational PD and HELLP syndrome-related complications in a preclinical model, highlighting the importance of monitoring metabolic health before pregnancy. Full article

Background: Hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia, affect up to 10% of pregnancies worldwide and remain a leading cause of maternal and perinatal morbidity and mortality. These conditions are associated with adverse fetal outcomes, including preterm birth, growth restriction, and maternal complications such as stroke, eclampsia, multi-organ dysfunction, and a higher risk of long-term cardiovascular complications. Current management relies largely on intermittent blood pressure monitoring and assessment of symptoms, approaches that provide limited insight into the complex hemodynamic alterations underlying HDP. Objective: This narrative review aims to synthesize the available evidence on noninvasive cardiography through thoracic electrical bioimpedance (TEB) as a tool for maternal hemodynamic monitoring in pregnancy, with a focus on hypertensive disorders. Specifically, we (1) describe maternal cardiovascular adaptations in normal gestations and their disruption in HDP, (2) provide an overview of thoracic electrical bioimpedance cardiac output (TEBCO) technology, (3) summarize validation studies in pregnant populations, (4) explore potential clinical applications, including diagnostic support, therapeutic guidance, fluid management and postpartum surveillance, and (5) identify key limitations and research priorities for future practice. Conclusions: Noninvasive cardiography through thoracic electrical bio-impedance is an underutilized tool in the medical field. As an alternative to invasive assessment, TEBCO can identify underlying pathologic hemodynamic changes susceptible to treatment and allow monitoring of hemodynamic trends. The implementation of TEBCO would allow pathophysiologic-based treatments, improve clinical response to therapy, and lead to potential prolongations of pregnancy and cost-savings in healthcare. Current evidence is limited by small sample sizes, device variability, and lack of outcome-based trials. Future research should focus on standardized validation, multicenter studies, and interventional trials to determine whether non-invasive cardiography-guided care can improve maternal and neonatal outcomes. Full article

Gestational obesity, defined as obesity during pregnancy or a pre-pregnancy BMI ≥30, is a growing global health challenge with profound implications for both maternal and offspring health. This narrative review synthesizes current evidence on the mechanistic pathways by which maternal obesity affects pregnancy outcomes and intergenerational health trajectories. For mothers, gestational obesity increases the risk of gestational diabetes, hypertensive disorders, cesarean delivery, and postpartum weight retention. Offspring exposed to maternal obesity face higher risks of obesity, metabolic syndrome, cardiovascular disease, and neurodevelopmental disorders, many of which persist across the lifespan. The underlying mechanisms include metabolic dysregulation, insulin resistance, chronic inflammation, oxidative stress, and alterations in placental function. Epigenetic modifications, such as DNA methylation, histone changes, and non-coding RNA expression, play central roles in fetal programming, while maternal gut dysbiosis and alterations in breast milk microbiota further shape infant health outcomes. Importantly, maternal obesity not only influences pregnancy and early life but also perpetuates an intergenerational cycle of obesity and related comorbidities. Preventive strategies targeting preconception and prenatal health, combined with interventions to optimize lactation and maternal diet, may mitigate long-term risks. Future research should prioritize longitudinal and mechanistic studies to refine interventions aimed at disrupting the transmission of obesity-related disease across generations. Full article

Acute liver injury during pregnancy is rare and predominantly associated with pregnancy-related conditions including acute fatty liver of pregnancy; Hemolysis, Elevated Liver Enzymes and Low Platelets syndrome; intrahepatic cholestasis of pregnancy; and preeclampsia. Drug-induced liver injury (DILI) is a less common and often overlooked cause of acute liver injury in pregnant patients. A literature search on acute liver injury during pregnancy and therapeutic plasma exchange was conducted, revealing the most common causative factors and syndromes. A 39-year-old woman was diagnosed with acute liver injury in the 23rd week of her third pregnancy and, upon extensive differential diagnoses, a suspicion of DILI occurred after the use of methyldopa. Methyldopa, the drug of choice for the treatment of hypertensive disorders of pregnancy, has a high safety profile for the developing fetus and is well tolerated by pregnant women, yet, in susceptible individuals, a hepatotoxic effect may occur. The drug was discontinued and symptomatic treatment with ursodeoxycholic acid and prednisone was implemented with marginal effect. Upon a multidisciplinary joint consultation, plasmapheresis procedures were introduced, granting a significant improvement in the patient’s liver function and enabling the continuation of the pregnancy. Plasmapheresis treatment was safely and effectively used for the first time in the therapeutic process in a pregnant patient with DILI. Interdisciplinary cooperation of specialists with gastroenterology, nephrology, and obstetrics expertise is crucial to achieving a timely diagnosis and begin effective treatment for pregnant patients with acute liver injury. Full article

Background: Preeclampsia (PE) is a multicomplex disorder occurring during pregnancy, characterized by the onset of hypertension and proteinuria, or hypertension accompanied by organ dysfunction (such as impaired liver function, renal insufficiency, pulmonary edema, or cerebral and visual impairment), with or without proteinuria in the latter half of pregnancy or postpartum. It impacts around 5% of all pregnancies, resulting in considerable fetal and maternal mortality and morbidity. A properly regulated inflammatory response is crucial for achieving a successful pregnancy; nevertheless, an excessive reaction appears to contribute to the onset of this syndrome. This review sought to investigate the role and correlation of interleukins (IL)-15, IL-16, IL-17, and IL-35 in the pathogenesis of PE, along with the prospective application of biomarkers in predicting and monitoring this illness. Methods: A thorough investigation was performed in the PubMed/Medline, Scopus, and Google Scholar electronic databases up to September 2025, employing the terms PE, Pregnancy, IL-15, IL-16, IL-17, IL-35, Inflammatory Response, and Cytokines. Women at the time of diagnosis were matched with normotensive counterparts of similar gestational age. Results: A total of 30 full-text articles were obtained following a thorough assessment. The majority of the published data showed that women with preeclampsia have significantly higher levels of IL-15 and IL-17 in their plasma compared to normotensive women, whereas IL-35 levels were mainly decreased, respectively. Moreover, IL-16 levels were elevated across all the studies, primarily correlating with condition severity. Conclusions: Collectively, IL-15, IL-16, IL-17, and IL-35 are markedly linked to the immunopathology of preeclampsia, with elevated maternal serum levels corresponding with the presence and severity of the disease. These cytokines demonstrate potential as biomarkers for diagnosis, prognosis, and disease surveillance. Future study, including the examination of cytokine profiles in placental and amniotic fluid, as well as additional intriguing cytokines, is essential to clarify their prognostic importance and mechanistic roles. Full article

Background: Cardiovascular disease (CVD) in pregnancy is a major cause of maternal morbidity and mortality, accounting for nearly one-third of pregnancy-related deaths worldwide. Physiological adaptations—expanded plasma volume, increased cardiac output, and a prothrombotic state—represent a natural cardiovascular stress test that may precipitate decompensation or unmask subclinical disease. Aim: This review critically examines contemporary evidence and international guidelines on the management of pregnancy-related cardiovascular disorders, focusing on pathophysiological mechanisms, diagnostic challenges, and therapeutic controversies. Content: The discussion centers on three high-impact clinical domains: (1) peripartum and preexisting cardiomyopathies, emphasizing mechanisms, prognosis, and the role of bromocriptine; (2) anticoagulation management in women with mechanical prosthetic valves, balancing maternal safety and fetal protection; and (3) hypertensive disorders of pregnancy, highlighting recent evidence from the CHAP and WILL trials and their implications for long-term cardiovascular prevention. Comparative analysis of ESC 2025 and AHA 2020 recommendations reveals broad consensus but persistent discrepancies in anticoagulation targets, postpartum surveillance, and follow-up strategies. Perspectives: Endothelial dysfunction, angiogenic imbalance, and systemic inflammation emerge as shared mechanisms linking diverse pregnancy-related cardiovascular conditions. Strengthening multidisciplinary care through Pregnancy Heart Teams, integrating obstetric and cardiologic expertise, and establishing structured postpartum follow-up pathways are essential to improve outcomes. Full article

Serine protease inhibitor A3 (SERPINA3), also called α-1-antichymotrypsin, is a serine protease involved in placental dysfunction. This study examines SERPINA3 polymorphisms and haplotypes for associations with maternal hypertensive disorders of pregnancy (HDPs) and preeclampsia with severe features (sPE) or Hemolysis, Elevated Liver Enzymes, and Low Platelet (HELLP) syndrome in mother–baby dyads (HDP) and mother–father–baby triads (sPE/HELLP). This retrospective case–control study examined two patient cohorts, HDPs and severe PE/HELLP syndrome. The HDP population included cases (n = 142) and controls (n = 168) of mother–baby dyads recruited from a large, urban, safety-net hospital in Los Angeles. The sPE/HELLP syndrome population included cases (n = 189) and controls (n = 28) of mother–father–baby triads recruited through HELLP syndrome research websites. Cases were verified by medical chart abstraction when possible. Two SERPINA3 SNPs, rs4934 and rs1884082, were genotyped from saliva samples, mouthwash, or buccal swabs. The Haplin package in R was used to perform genetic association analyses. No evidence of increased risk related to individual SERPINA3 SNPs or haplotypes for the developing HDPs or sPE/HELLP was found in individual nor combined cohorts. In the HDP cohort, the g-a haplotype (relative to T-G haplotype) was borderline significant for increased risk of HDPs when carried by the child (double dose: RR = 1.58, 95% CI: (1.00, 2.52), p = 0.05). We observed significant parent-of-origin (PoO) effects in the combined cohort: specifically, an increased risk of HDPs/sPE/HELLP if the mother carries a double copy for both rs4934 (RR = 3.03, 95% CI (1.50, 6.09), p < 0.01) and rs1884082 (RR = 2.38, 95% CI (1.22, 4.71), p = 0.01). A reduced risk of HDPs/sPE/HELLP was observed for rs4934 (RR = 0.54, 95% CI (0.31, 0.98), p = 0.04) and rs1884082 (RR = 0.52, 95% CI (0.30, 0.91), p = 0.02) with child carriage of the maternally inherited allele. In contrast, child carriage of a paternally inherited copy of the variant allele for rs4934 increased risk of HDPs/sPE/HELLP (RR = 1.54, 95% CI (1.09, 2.20), p = 0.02). There was no evidence that SERPINA3 gene polymorphisms and haplotypes were associated with risk of HDPs or sPE/HELLP. However, significant PoO effects were observed in the combined cohort analysis, with child carriage of rs4934 that is maternally inherited decreasing HDPs/sPE/HELLP risk while a paternally inherited copy increases risk, suggesting a role for maternal–fetal genomic incompatibility. Full article