Plasma Exchange in Postpartum Hemorrhage (PPH)-Associated Thrombotic Microangiopathy (TMA): A Case Report.

Thrombotic microangiopathy (TMA) is a rare yet potentially life-threatening condition. The diagnosis is difficult as there are other conditions presenting with features akin to TMA during the peripartum period such as eclampsia, preeclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and antiphospholipid syndrome. A 28-year-old woman with no significant past medical history developed TMA following a massive hemorrhage after an emergency cesarean section at 41 weeks of gestation. This case was finally diagnosed as postpartum hemorrhage (PPH)-associated TMA. The patient fully recovered after plasma exchange therapy. We posit the value of accumulating case reports, given that the documentation on the efficacy of plasma exchange in PPH-associated TMA is limited.

Hypertensive states of pregnancyEstados hipertensivos del embarazo / Estados hipertensivos del embarazo

Hypertensive disorders in pregnancy (HDP) remain a leading cause of pregnancy-related maternal and foetal morbidity and mortality worldwide, including chronic hypertension, gestational hypertension, and pre-eclampsia. Affected women and newborns also have an increased risk of cardiovascular disease later in life, independent of traditional cardiovascular disease risks. Despite these risks, recommendations for optimal diagnosis and treatment have changed little in recent decades, probably due to fear of the foetal repercussions of decreased blood pressure and possible drug toxicity. In this document we review the diagnostic criteria and classification of (HDP), as well as important aspects regarding pathophysiology and early detection that allows early identification of women at risk, with the aim of preventing both immediate and long-term consequences. Prophylactic treatment with aspirin is also reviewed early and a therapeutic approach is carried out that involves close maternal and foetal monitoring, and if necessary, the use of safe drugs in each situation. This review aims to provide an updated vision for the prevention, diagnosis, and treatment of HDP that is useful in our usual clinical practice.(AU)

Los estados hipertensivos del embarazo (EHE) siguen siendo una de las principales causas de morbilidad y mortalidad materna y fetal relacionada con el embarazo en todo el mundo, incluyen la hipertensión crónica, la hipertensión gestacional y la preeclampsia. Las mujeres afectadas y los recién nacidos también tienen un mayor riesgo de sufrir enfermedades cardiovasculares en el futuro, independientemente de los riesgos tradicionales de la enfermedad cardiovascular. A pesar de estos riesgos, las recomendaciones para un diagnóstico y un tratamiento óptimo han cambiado poco en las últimas décadas, probablemente por el miedo a las repercusiones fetales de la disminución de la presión arterial y la posible toxicidad farmacológica. En ese documento revisamos los criterios diagnósticos y la clasificación de los EHE, así como aspectos importantes en cuanto a fisiopatología y la detección temprana que permita la identificación precoz de las mujeres en riesgo, con el objetivo de prevenir tanto las secuelas inmediatas como a largo plazo. También se revisa el tratamiento profiláctico con aspirina de forma precoz y se realiza una aproximación terapéutica que implica una estrecha vigilancia materna y fetal, y si es necesario, el uso de fármacos seguros en cada situación. Esta revisión pretende dar una visión actualizada para la prevención, diagnóstico y tratamiento de los EHE que sea de utilidad en nuestra práctica clínica habitual.(AU)

First-trimester uterine artery Doppler and hypertensive disorders in twin pregnancies: Use of twin versus singleton references.

OBJECTIVE: To determine the association of first-trimester uterine artery Doppler with hypertensive disorders of pregnancy in twin pregnancies. METHODS: This was a retrospective cohort study of twin pregnancies followed at the University Hospital Center of Central Lisbon, Portugal, between January 2010 and December 2022. First-trimester uterine artery pulsatility index (UtA-PI) was determined and compared between twin pregnancies (n = 454) and singleton pregnancies (n = 908), matched to maternal and pregnancy characteristics. Maternal characteristics and mean UtA-PI were analyzed for gestational age, birth weight, gestational hypertension, early- and late-onset pre-eclampsia, HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, and preterm birth. Univariable and multivariable logistic regression models were used. RESULTS: The mean first-trimester UtA-PI was significantly lower in dichorionic twins than in singletons (P < 0.001). To study hypertensive disorders of pregnancy in twins, 390 pregnancies were included: 311 (79.7%) dichorionic and 79 (20.3%) monochorionic twins. The observed rates of early- and late-onset pre-eclampsia, gestational hypertension, and HELLP syndrome were 1.0%, 4.4%, 7.4%, and 1.5%, respectively. We achieved a 100% detection rate for early-onset pre-eclampsia using the UtA-PI 90th centile for twins. However, when singleton references were considered, the detection rate decreased to 50%. UtA-PI at or above the 95th centile was associated with increased odds for preterm birth before 32 weeks (adjusted odds ratio 4.1, 95% confidence interval 1.0-16.7, P = 0.043). CONCLUSIONS: Unless other major risk factors for hypertensive disorders are present, women with low UtA-PI will probably not benefit from aspirin prophylaxis. Close monitoring of all twin pregnancies for hypertensive disorders is still recommended.

An Observational Study of Maternal and Perinatal Outcome in Preeclampsia Cases in a Tertiary Care Center.

INTRODUCTION: Preeclampsia, a hypertensive disorder in pregnancy, is a multisystem disease of unknown etiology and is associated with an increased risk of maternal mortality and morbidity. Infants from preeclampsia mothers have significantly higher incidence of prematurity, somatic growth retardation, thrombocytopenia, low birth weight, respiratory distress syndrome, and long duration of admission to neonatal intensive care (NICU). AIMS AND OBJECTIVES: This study was done to study the maternal mortality and morbidity and foetal outcome in pregnant women with severe preeclampsia. METHOD: This observational study was done in the Department of Obstetrics and Gynaecology, of a tertiary care centre, from the period October 2015 to October 2017. Data was collected from all 130 women attending the antenatal clinic of tertiary care hospital and ward admission and all details such as demographic details, obstetrics examination, and all clinical findings were noted and from that made results.  Result: After applying inclusion and exclusion criteria all 130 women were observed in this study. Among 130 women 47 were diagnosed with preeclampsia. Mainly primigravida women were diagnosed with preeclampsia in the 21-25 years group. Among 47 preeclampsia women, 39 women had a BMI of 19-25 kg/m2. Thirty-two of 47 (68.09%) women were diagnosed with preeclampsia around 36-39 weeks. Among all preeclampsia, 28 women out of 47 (59.5%) women delivered babies vaginally, 18 of 47 (38.3%) women delivered through cesarean section, and one of 47 (2.13%) underwent preterm vaginal delivery. In preeclampsia, women's babies were delivered mostly (25/47, 53.19%) ≤2.5 kg weight and only one baby was shifted to NICU because of low birth weight. Preeclampsia increases maternal mortality and morbidity but in this study mortality was not done because our hospital is a tertiary care center with all ICU (intensive care unit) and NICU setup. CONCLUSION: Preterm births and cesarean deliveries were the mild to severe outcomes that were noted. ICU and NICU hospitalizations as a result of severe complications place a heavy demand on medical facilities. There are firm guidelines for the management of pregnancy-induced hypertension and its complications. For appropriate management, there is careful consideration of various factors, and individual case studies are required.

Hemolysis, Elevated Liver Enzymes and Low Platelet Count Syndrome Complicated by Disseminated Intravascular Coagulation and Posterior Reversible Encephalopathy Syndrome: A Case Report.

A 22-year-old pregnant woman was transferred from an external medical facility after experiencing an eclamptic seizure linked to hemolysis, elevated liver enzymes and low platelet count syndrome (HELLP) syndrome, and posterior reversible encephalopathy syndrome (PRES). Her situation was further complicated by intrauterine fetal demise and disseminated intravascular coagulation, necessitating a comprehensive multidisciplinary approach. This report details the diagnostic process and challenges in managing this complex patient with diverse medical requirements. Emphasis is placed on the observed hemostatic abnormalities, and we delineate the nuances in our approach compared to managing a similar condition in a nonpregnant patient. Heightened awareness among healthcare professionals is imperative for prompt diagnosis and effective intervention in such uncommon neurological complications during pregnancy.

Acute liver failure in pregnancy.

Liver function abnormalities are noted in a minority of pregnancies with multiple causes for the same. A small proportion of these develop severe liver injury and progress to acute liver failure (ALF). There is a discrete set of etiology for ALF in pregnancy and comprehensive understanding will help in urgent evaluation. Certain diseases such as acute fatty liver of pregnancy, hemolysis, elevated liver enzyme, low platelet (HELLP) syndrome and pre-eclampsia are secondary to pregnant state and can present as ALF. Quick and targeted evaluation with urgent institution of etiology-specific management, especially urgent delivery in patients with pregnancy-associated liver diseases, is the key to avoiding maternal deaths. Pregnancy, as also the fetal life, imparts a further layer of complication in assessment, prognosis and management of these sick patients with ALF. Optimal management often requires a multidisciplinary approach in a well-equipped centre. In this review, we discuss evaluation, assessment and management of pregnant patients with ALF, focussing on approach to pregnancy-associated liver diseases.

First clinical reports of acute hantavirus and dengue infections among pregnant women in the Caribbean.

BACKGROUND: Hantavirus and dengue virus infections lead to diseases causing economic and public health concerns. Acute hantavirus infections can lead to similar clinical haemorrhagic signs as other endemic diseases including dengue and leptospirosis. METHODS: Using a retrospective case analysis of pregnant dengue and hantavirus disease patients with clinical reports and compatible clinical laboratory information during pregnancy, we report the first evidence of dengue and hantavirus infections and a case of dual dengue and hantavirus infection among pregnant women in the Caribbean. Laboratory testing by enzyme-linked immunosorbent assay (ELISA) and non-structural protein 1 (NS1) for DENV and for hantavirus infection pseudotype focus reduction neutralisation tests (pFRNT), ELISA and immunochromatographic (ICG) strips. RESULTS: Four pregnant cases with acute DENV infections were identified; however, only one out of the four cases (25%) had a detailed medical record to permit abstraction of clinical data. Six hantavirus infected pregnant cases were identified with gestation periods ranged from 36 to 39 weeks; none of the reported patients exhibited previous pregnancy complications prior to hospitalisation and infection. Acute liver damage was observed in three of the six cases (AST readings) who were subsequently diagnosed with hepatitis in pregnancy and variable clinical outcomes were observed with term and pre-term deliveries. CONCLUSIONS: Whilst hantavirus infection in pregnancy is rare, consideration should be given to differential diagnosis with fever, kidney involvement, liver involvement, haemorrhagic symptoms and thrombocytopenia in endemic areas with clinically similar diseases such as dengue and leptospirosis.HighlightsFirst recorded case of hantavirus and dengue co-infection in a pregnant woman.First detailed report of clinical hantavirus infection in pregnant women in the Caribbean.First published report of clinical dengue infection in pregnant woman in the Caribbean.Possible complications of pregnancy following hantavirus infection.Pre-term birth and low birth weights.Clinical course of hantavirus infection in a Caribbean population.

Delayed versus early delivery leads to similar outcome in selected cases of preeclampsia in the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) cohort.

OBJECTIVES: Most guidelines recommend induction of labor after 37 weeks of gestation in preeclampsia. This study assessed the effect of interval between diagnosis of preeclampsia and delivery on maternal and perinatal outcomes. STUDY DESIGN: A cohort of 1637 women with preeclampsia recruited at five university hospitals in Finland was studied. Outcomes were compared in two groups according to the time interval between diagnosis of PE and delivery: delivery in less than 10 days (the early delivery group) and delivery at 10 days or later after the diagnosis (the delayed delivery group). MAIN OUTCOME MEASURES: Maternal outcomes included significantly preterm delivery (delivery before 34 weeks of gestation), placental abruption, eclampsia and maternal intensive care or intensive monitoring for more than 24 h. Neonatal outcomes included small for gestational age, Apgar score of less than seven at the age of five minutes, umbilical artery pH < 7.05 and fetal death. RESULTS: No differences in frequency of preterm deliveries or maternal need for intensive care were observed between groups. Eclampsia and fetal death were rare, and their incidence did not differ between the groups. No maternal deaths were observed. Low Apgar score at five minutes of age was reported more commonly in the early delivery group, but there was no difference in fetal acidemia between groups. CONCLUSION: Early and delayed delivery lead to comparable outcomes in this cohort. Expectant management could be beneficial in women with an unripe cervix or preterm preeclampsia without severe features.

Catastrophic antiphospholipid syndrome after pregnancy complicated by hemolysis, elevated liver enzymes and low platelets syndrome.

Background: Antiphospholipid syndrome (APLS) is rarely complicated by catastrophic antiphospholipid syndrome (CAPS). Peripartum CAPS is rarer still and can masquerade as other obstetric disorders. A high degree of suspicion is critical for early diagnosis and specific management given the significant morbidity and mortality associated with this disorder. Case: We report a case of a 27-year-old at 22 week's gestation with a history of APLS found to have severe hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, resulting in termination of pregnancy. Further workup revealed the diagnosis of CAPS followed by prompt treatment with triple therapy leading to clinical improvement. Conclusion: CAPS should be considered within the differential in an obstetric patient with a history of APLS who has evidence of multiorgan involvement with macro- or microvascular thrombosis. Although this may mimic alternative disorders, prompt diagnosis is imperative for appropriate therapy and reduction in maternal morbidity and mortality.

Obstetrical outcomes of women with new-onset isolated proteinuria diagnosed after 24 weeks' gestation.

PURPOSE: To assess a possible association between marked proteinuria and the risk of preeclampsia with severe features, as defined by the American College of Obstetricians and Gynecologists. METHODS: This retrospective study included data recorded at a tertiary university-affiliated hospital between 2017 and 2022. Women at or beyond 24 weeks of gestation with proteinuria (protein levels > 300 mg in a 24 h urine collection) and normal blood pressure during the initial 48 h of admission were included. Obstetrical and neonatal outcomes were compared between women with mild proteinuria (300-1000 mg/24 h) and marked proteinuria (≥ 1000 mg/24 h). RESULTS: Among the women with marked proteinuria (n = 48) compared to those with mild proteinuria (n = 108), the incidences were higher of preeclampsia (50.0% vs. 22.2%, p = 0.001) and of preeclampsia with severe features (18.8% vs. 2.8%, p < 0.001). In multivariate analysis that adjusted for maternal age, primiparity, multiple pregnancy, uric acid level > 6 mg/dL and aspirin treatment, marked proteinuria was a risk factor for preeclampsia with severe features (adjusted odds ratio [aOR] = 10.2, confidence interval [CI] 95% 1.9-54.0, p = 0.007) and for small-for-gestational-age infants (aOR = 2.4, 95% CI 1.02-5.6, p = 0.001). Among women with marked compared to mild proteinuria, rates were also higher of labor induction (58.3% vs. 25.9%, p < 0.001), indicated preterm delivery (41.7% vs. 25.0%, p = 0.04) and admission to the neonatal intensive care unit (44.1% vs. 25.8%, p = 0.017). CONCLUSIONS: Women with marked compared to mild isolated proteinuria showed higher risk of developing preeclampsia with severe features and of delivering small-for-gestational-age neonates.

Hepatic infarction in pregnancy: a systematic review.

OBJECTIVE: Hepatic infarction is a rare complication of pregnancy most often associated with hemolysis, elevated liver enzymes, and low platelets syndrome. The objective of this review is to identify risk factors, present signs and symptoms, identify methods of diagnosis, and identify best management practices on the basis of published case reviews. DATA SOURCES: PubMed and MEDLINE (Ovid) databases were searched for citations regarding hepatic infarction in pregnancy or the postpartum period from database inception until the study date of December 18, 2023. Key words included "liver infarction" or "hepatic infarction" and "pregnancy" or "obstetrics." STUDY ELIGIBILITY CRITERIA: Case reviews or case series published in the English language were included. Our study was registered with the Prospective Register of Systematic Reviews (registration number CRD42023488176) and was conducted in accordance with the published Prospective Register of Systematic Reviews and Meta-analyses Of Observational Studies in Epidemiology guidelines. METHODS: Included papers were evaluated for bias using a previously published tool. RESULTS: A total of 38 citations documenting 50 pregnancies published between 1979 and 2023 were included. Of these, 34% had a history of hypertensive disease, 26% had antiphospholipid syndrome, and 22% had a history of thrombus. Of those without a preexisting diagnosis of antiphospholipid syndrome, 24% tested positive during hospitalization. Most patients presented with epigastric or right upper quadrant pain (78%), and 32% and 16% had severe blood pressure or mild blood pressure, respectively. Sixty-four percent of patients presented with transaminitis. Forty-six percent of patients delivered preterm, and 32% of pregnancies ended in intrauterine fetal demise, abortion, or early termination of pregnancy for maternal benefit. Computed tomography scans were used to confirm diagnosis of hepatic infarction in 58% of cases, magnetic resonance imaging in 14%, and ultrasound in 6%. In cases that described management, treatment was always multimodal, including antihypertensives (18%), therapeutic anticoagulation (45%), blood product transfusion (36%), plasma exchange or intravenous immunoglobulin (20%), and steroids (39%). Transfer to the intensive care unit was required in 20% of cases. CONCLUSION: Hepatic infarction should be considered in all cases of hemolysis, elevated liver enzymes, and low platelets syndrome, but specifically in patients with a history of antiphospholipid syndrome who present with epigastric or right upper quadrant pain. The diagnosis can usually be confirmed with a computed tomography scan alone, and management should be prompt with supportive care, therapeutic anticoagulation, and steroids.

Magnesium sulfate in preeclampsia: Broad indications, not only in neurological symptoms.

The role of magnesium sulfate for treatment of eclampsia is well established. The medication proved to be superior to other anticonvulsants to reduce the incidence of recurrent convulsions among women with eclampsia. Additionally, magnesium sulfate has been indicated for women with preeclampsia with different severe features. However, despite these recommendations, many clinicians are still not confident with the use of magnesium sulfate, even in settings with high incidence of preeclampsia and unacceptable rates of maternal mortality. This review brings basic science and clinical information to endorse recommendations to encourage clinicians to use magnesium sulfate for patients with all severe features of preeclampsia, not only for women with neurological symptoms. Additionally, other benefits of magnesium sulfate in anesthesia and fetal neuroprotection are also presented. Finally, a comprehensive algorithm presents recommendations to manage patients with preeclampsia with severe features between 34 and 36+6 weeks.

Hepatic Rupture Associated With HELLP (Hemolysis, Elevated Liver Enzymes, and Low Platelets) Syndrome: A Report of Two Cases and Literature Review.

Hepatic rupture is a rare complication of severe preeclampsia. A high index of suspicion is required in the presence of abdominal pain accompanied by hemodynamic decompensation in a pregnant woman. Hepatic rupture constitutes a medical emergency that demands immediate intervention, often with the support of other medical disciplines, in a highly specialized hospital setting. Unruptured hepatic hematomas can be managed conservatively. Immediate delivery and surgical repair of the liver are necessary for maternal survival. Spontaneous liver rupture in pregnancy is often unrecognized, highly lethal, and not completely understood with few cases having been reported in the literature. Therefore, we present two cases of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome with hepatic rupture, emphasizing their clinical presentation and therapeutic approaches.

Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in Patients with Preeclampsia/HELLP Syndrome Compared to Healthy Pregnancies: An Observational Case-Controlled Study.

Preeclampsia is a progressive multi-systemic disorder characterized by proteinuria, critical organ damage, and new-onset hypertension. It can be further complicated by HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), resulting in critical liver or renal damage, disseminated coagulation, and grand mal seizures. This study aimed to examine the involvement of ADAMTS13, von Willebrand, and the complement system in the pathogenesis of preeclampsia/HELLP syndrome. We studied 30 Caucasian preeclamptic pregnant women and a control group of 15 healthy pregnancies. Genetic sequencing of ADAMTS13 and complement regulatory genes (MiniSeq System, Illumina) was performed. The modified Ham test was used to check for complement activation, ADAMTS13 activity, von Willebrand antigen (vWFAg) levels, and soluble C5b-9 levels were measured. Patients with preeclampsia had a decreased ADAMTS13 activity and increased C5b-9 levels. The vWFAg was significantly correlated with ADAMTS13 activity (r = 0.497, p = 0.003). Risk-factor variants were found in the genes of ADAMTS13, C3, thrombomodulin, CFB, CFH, MBL2, and, finally, MASP2. A portion of pregnant women with preeclampsia showed a decline in ADAMTS13 activity, correlated with vWFAg levels. These patients also exhibited an elevated complement activation and high-risk genetic variants in regulatory genes. Further research is needed to determine if these factors can serve as reliable biomarkers.

Multidisciplinary management of a pregnant woman with hepatic rupture complicated with HELLP syndrome.

A 32-year-old woman with preeclampsia who presented with persistent severe hypertension and epigastric pain underwent an emergency cesarean section for fetal distress and was diagnosed with hepatic rupture and HELLP (hemolysis, elevated liver enzymes, and a low platelet) syndrome. After the operation, the patient was transferred to the intensive care unit for supportive treatment and management of complications. Diagnosis and treatment decisions were made through multidisciplinary management. The patient received plasma exchange and continuous renal replacement therapy. One week after the operation, the patient developed deep vein thrombosis and received anticoagulant therapy, which triggered rebleeding. Conservative treatment was taken, including halving the dosage of anticoagulant medication and performing a blood transfusion, and the patient's condition gradually stabilized. The patient was discharged 44 days after the operation. Early diagnosis, effective treatment, and multidisciplinary management can help patients with this critical presentation achieve good clinical outcomes.

Severe hemolysis, elevated liver enzymes, and low platelet syndrome requiring differentiation of thrombotic microangiopathy: Four cases from a nationwide survey in Japan.

Severe cases of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome requiring plasma exchange or dialysis should be differentiated from other thrombotic microangiopathy (TMA) and treated appropriately. To evaluate the prevalence and clinical characteristics of such cases in Japan, a questionnaire-based survey was conducted among obstetricians who are members of the Perinatal Research Network Group in Japan. There were a total of 335 cases of HELLP syndrome over a 3-year period in the 48 facilities that responded to the survey. Four patients required plasma exchange or dialysis, of which two were diagnosed with atypical hemolytic uremic syndrome and two with TMA secondary to systemic lupus erythematosus. Although such severe HELLP syndrome is rare, identifying the clinical features and making accurate differential diagnosis are critical for optimal clinical outcomes for mothers and neonates.

HELLP Syndrome at 20 Gestational Weeks Managed Using the Mississippi Protocol: A Case Report.

Hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome is one of the most severe complications of hypertensive disorders of pregnancy. HELLP syndrome occurring before 22 gestational weeks (GWs) is extremely rare, and patients prevalently exhibit underlying maternal diseases or fetal abnormalities. Here, we report the case of a pregnant woman who had HELLP syndrome at 20 GWs without any obvious underlying maternal diseases or fetal abnormalities. A 38-year-old pregnant woman was referred to Kobe University Hospital from another hospital at 19 + 5/7 GWs for hypertension, proteinuria, generalized edema, and fetal growth restriction. She was diagnosed with partial HELLP syndrome according to the Mississippi classification at 20 + 2/7 GWs. The patient was managed following the Mississippi protocol, including intravenous dexamethasone, magnesium sulfate, and antihypertensive drugs. She received intensive blood pressure and laboratory data monitoring using an arterial line and additional treatments, including platelet transfusion, intravenous haptoglobin infusion, and human atrial natriuretic peptide. The pregnancy ended in an induced delivery at 20 + 3/7 GWs, and she was discharged without complications 10 days postnatal. We performed laboratory tests for diagnosing underlying diseases but identified no obvious underlying diseases. This report indicates that early and intensive treatment of patients with HELLP syndrome occurring before 22 GWs according to the Mississippi protocol may enable clinicians to complete pregnancy termination without maternal complications and provide useful information to clinical practitioners in perinatal medicine.

Caring for Patients with Gestational Hypertensive Disorders: Essential Takeaways.

Hypertensive disorders in pregnancy (HDP) are a group of conditions-including chronic hypertension, gestational hypertension, preeclampsia with and without end-organ damage, and acute complications, which include HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome and eclampsia-that could lead to severely adverse outcomes for both mother and fetus. The incidence of HDP has increased, affecting one out of seven delivery hospitalizations. Physicians should be aware of HDP for early identification and proper treatment to improve patient outcomes.

Maternal immune suppression during pregnancy does not prevent abnormal behavior in offspring.

BACKGROUND: Offspring of hypertensive disorders of pregnancy are at an increased risk of developing neurodevelopmental and neurobehavioral disorders compared to offspring from non-affected pregnancies. Using rodent models of Preeclampsia (PreE; new onset of hypertension after 20 weeks gestation) and HELLP (hemolysis, elevated liver enzymes, and low platelets), we studied the behavioral outcome of their offspring in adolescence. METHODS: A subset of dams received Orencia, a T-cell activation inhibitor, as T cells have been associated with the induction of hypertension and inflammation during pregnancy. We hypothesized that offspring from hypertensive dams would experience adverse behavioral outcomes in social, cognitive, locomotor, and anxiety tests, and offspring from dams treated with Orencia would demonstrate less adverse behaviors. RESULTS: Male offspring of PreE + Orencia dams (p < 0.05) and female offspring from HELLP + Orencia dams (p < 0.05) spent more time playing compared to normal pregnant offspring. All offspring from hypertensive and Orencia-treated dams performed worse on the Barnes Maze test compared to normal pregnant. We also measured adult (postnatal day > 60) myelin basic protein (MBP) and NeuN expression in both the prefrontal cortex and hippocampus. In the hippocampus and prefrontal cortex, there was no difference in expression of either MBP or NeuN in all groups regardless of sex. CONCLUSION: The results from this study suggest that offspring of hypertensive disorders of pregnancy have behavioral changes, specifically cognitive differences. This study has shown that there is a sex dependent difference in offspring neurobehavioral development, influenced in part by the type of hypertensive disorder of pregnancy, and alterations in the maternal immune system.

Children of pregnancies that are complicated by hypertensive disorders of pregnancy (HDP) such as Preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome have an increased risk of having behavioral deficits and changes in brain development. Both Preeclampsia and HELLP have been shown to activate the immune and inflammation systems in the body of the mother. In this study, we used offspring of rat models of Preeclampsia and HELLP to study their behavior including anxiety-like behaviors and memory deficits. We also compared offspring of rat models of Preeclampsia and HELLP that were given Orencia, which minimizes immune responses by blocking the activation of T cells. We also studied two regions of the brain (prefrontal cortex and hippocampus) to measure two proteins (myelin basic protein (MBP) and NeuN) involved in brain function. Our study found that offspring from dams that were treated with Orencia during pregnancy with HDP had sex differences in time playing. All offspring, regardless of the HDP dam being treated with or without Orencia, had evidence of spatial learning deficits. When sexes and groups were compared there was no difference in MBP or NeuN expression in the prefrontal cortex or hippocampus.