Pulmonary Embolism in Pregnancy.

Pulmonary embolism during and after pregnancy remains a significant contributor to maternal morbidity and mortality. Symptoms that would be a clear indicator of a pulmonary embolus in the nonpregnant population can be masked by pregnancy and its routine pregnancy-related symptoms. To affect a reduction in this severe maternal mortality indicator, physicians need to maintain a high degree of suspicion coupled with expedient testing.

Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.

Clinical Stratification of Pregnant COVID-19 Patients based on Severity: A Single Academic Center Experience.

OBJECTIVE: This study aimed to describe baseline characteristics of a cohort of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determine if these correlate with disease severity and perinatal outcomes. STUDY DESIGN: This was a retrospective cohort trial conducted at the University of Texas Medical Branch Galveston, Texas. All pregnant women presented to our medical center, who were screened and tested positive for SARS-CoV-2 virus, were included. We stratified our study population in three groups: asymptomatic, symptomatic not requiring oxygen therapy, and patients requiring oxygen support to maintain oxygen saturation >94%. Relevant population characteristics, laboratory data, and maternal and neonatal outcomes were abstracted. A p-value <0.05 was considered statistically significant. RESULTS: Between March and July 2020, 91 women tested positive for SARS-CoV-2 upon admission to our labor and delivery unit. Among these, 61.5% were asymptomatic, 34.1% were symptomatic, and 4.4% required oxygen support. Our population was mainly Hispanic (80.2%), multiparous (76.9%), obese (70.3%), and with a median age of 27 years. Median gestational age at symptom onset or diagnosis was 36 weeks. Significant differences were found between gestational age and disease severity. Maternal characteristics including age, body mass index (BMI), and presence of comorbid conditions did not appear to influence severity of SARS-CoV-2 infection. Significant laboratory findings associated with increasing disease severity included decreasing hemoglobin and white blood cell count, lymphopenia, and increasing levels of inflammatory markers including CRP, ferritin, and procalcitonin. Maternal and neonatal outcomes did not differ among groups. No SARS-CoV-2 was detected by polymerase chain reaction testing in neonates of mothers with COVID-19. CONCLUSION: Pregnant patients with COVID-19 infection are predominantly asymptomatic. Patients appear to be at increased risk for more severe infection requiring oxygen support later in pregnancy. KEY POINTS: · The majority of pregnant patients with COVID-19 are asymptomatic and <1 in 20 require oxygen support.. · Women in the later stages of pregnancy may be at increased risk for severe infection.. · Anemia, leukopenia, CRP, ferritin, and procalcitonin are associated with increasing severity..

The impact of low-dose versus high-dose antibiotic prophylaxis regimens on surgical site infection rates after cesarean delivery.

OBJECTIVE: The objective of this study was to determine if high-dose antibiotic prophylaxis with cefazolin decreases the risk of surgical site infection (SSI) after a cesarean delivery. METHODS: We performed a retrospective cohort study of women who underwent a cesarean section. Two preoperative antibiotic regimens were compared: low dose versus high dose. The primary outcome was SSI. A sample size of 343 patients per group was calculated for a 50% reduction in risk for SSI. RESULTS: Seven hundred and thirty women were included with an incidence of SSI of 5%. Women who received the high-dose antibiotic regimen had lower rates of risk factors for SSI. The only exception was skin incision closure with staples. The rate of SSI did not differ between the low-dose and high-dose groups, even after adjusting for confounding variables [aOR 1.78, 95% CI (0.82-3.9)]. CONCLUSIONS: Higher doses of antibiotic prophylaxis did not decrease the rates of SSI after cesarean delivery.

Pfannenstiel versus Vertical Skin Incision for Cesarean Delivery in Women with Class III Obesity: A Randomized Trial.

OBJECTIVE: To compare Pfannenstiel versus vertical skin incision for the prevention of cesarean wound complications in morbidly obese women. STUDY DESIGN: Women with body mass index ≥ 40 kg/m2 undergoing cesarean delivery (CD) were randomly allocated to Pfannenstiel or vertical skin incision. The primary outcome was a wound complication within 6 weeks. Due to a low consent rate, we limited enrollment to a defined time period for feasibility. We conducted a traditional frequentist analysis with log-binomial regression to obtain relative risks (RRs), and a Bayesian analysis to estimate the probability of treatment benefit. A priori, we decided that a ≥60% probability of treatment benefit for either incision type would be convincing evidence to pursue a larger trial. RESULTS: A total of 648 women were approached, 228 were consented, and 91 were randomized. The primary outcome rate was 19% in the Pfannenstiel group and 21% in the vertical group (RR: 1.18; 95% confidence interval: 0.49-2.85). Bayesian analysis revealed a 59% probability that Pfannenstiel had a lower primary outcome rate. CONCLUSION: In the first published randomized trial to compare skin incision types for obese women undergoing CD, we were unable to demonstrate differences in clinical outcomes. Our trial suggests that a larger study would have a low probability for different findings. TRIAL REGISTRATION: NCT 01897376 (www.clinicaltrials.gov).

The Effect of Distraction during Labor Induction on Timing of Analgesia Request: A Randomized Clinical Trial.

OBJECTIVE: To assess whether distraction using music and/or video games influences timing of analgesia request and improves pain outcomes in women undergoing labor induction. STUDY DESIGN: A total of 219 pregnant women with singleton gestation undergoing labor induction with a Foley bulb (FB) at term were randomized to distraction with music and video games via iPod (n = 109) or no iPod (n = 110). The primary outcome was the time from FB placement to request for pain medication. Secondary outcomes included number of patients requesting pain medication within 6 and 12 hours, type of pain medication received, pain visual analog scale scores, and patient satisfaction. Mann-Whitney's, chi-square, Kaplan-Meier's curves, and Pearson's product moment correlation were used for statistical analysis (significance: p < 0.05). RESULTS: Baseline characteristics were similar between the two groups. There was no difference in the time from FB placement until pain medication request between the groups. There were no significant differences in secondary outcomes. Increased per cent time of iPod use correlated with a longer time until pain medication request (R 2 = 0.22, p = 0.03). CONCLUSION: We were not able to show that distraction using music and video games delays timing of analgesia request or improve pain outcomes in pregnant women undergoing mechanical labor induction at term.

The Effect of Wearing White Coats on Patients' Appreciation of Physician Communication during Postpartum Rounds: A Randomized Controlled Trial.

OBJECTIVE: Wearing a white coat (WC) has been associated with risk of colonization and transmission of resistant pathogens. Also, studies have shown that physicians' attire in general affects patients' confidence in their physician and the patient-physician relationship. Our objective is to evaluate the hypothesis that not wearing a WC during physician postpartum rounds does not affect patient-physician communication scores. MATERIALS AND METHODS: This is an unblinded, randomized, parallel arms, controlled trial of postpartum women at a single university hospital. Women were randomly assigned to having their postpartum physicians' team wear a WC or not (no-WC) during rounds. Our primary outcome was "patient-physician communication" score. Univariable and multivariable analysis were used where appropriate. RESULTS: One hundred and seventy-eight patients were enrolled (87 in WC and 91 in no-WC groups). Note that 40.4% of patients did not remember whether the physicians wore a WC or not. There was no difference in the primary outcome (p = 0.64) even after adjusting for possible confounders. CONCLUSION: Not wearing a WC during postpartum rounds did not affect the patient-physician communication or patient satisfaction scores. In the setting of prior reports showing a risk of WC pathogen transmission between patients, our findings cannot support the routine wearing of WCs during postpartum rounds.

Long-Term Effect of Lactation on Maternal Cardiovascular Function and Adiposity in a Murine Model.

OBJECTIVE: Epidemiological studies suggest that lactation is associated with long-term maternal health benefits. To avoid confounders in human studies, we used a previously characterized murine model to investigate the long-term effect of lactation on both cardiovascular function and adiposity. STUDY DESIGN: After the delivery of the pups, CD-1 female mice were randomly divided into two groups: lactated and nonlactated (NL). Before pregnancy and at 9 months postdelivery, blood pressure was measured using a tail cuff, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were assessed by computed tomography (CT), echocardiography was performed using microultrasound, and cholesterol panels and fasting blood glucose were measured. The data were analyzed using Student's t-test (significance at p < 0.05). RESULTS: There were no differences in baseline parameters between the two groups. At 9 months postdelivery, the NL group weighed significantly more (p = 0.03) and demonstrated a significantly lower cardiac output (p = 0.05) and ejection fraction (p = 0.03). The mice in the NL group also had higher VAT (p < 0.01) and SAT percentiles (p = 0.03). Fasting glucose (p = 0.01) and low-density lipoprotein (p = 0.01) were significantly higher in the NL group at 9 months. CONCLUSION: Our results show the benefit of lactation is not just limited to the immediate postpartum period but it also extends into midlife in a murine model.

Zika Virus and Pregnancy: A Review of the Literature and Clinical Considerations.

The latest Zika virus (ZIKV) outbreak has reached epidemic proportions as it spreads throughout South and Central America. In November 2015, the Brazilian Ministry of Health reported a 20-fold increase in the number of cases of neonatal microcephaly, which corresponds geographically and temporally to the ZIKV outbreak. Case reports have provided some evidence of a causal link between maternal ZIKV infection, fetal microcephaly, and intracranial calcifications. The sparse data regarding ZIKV in pregnancy come solely from case reports and personal communications, and recommendations for management of ZIKV exposure during pregnancy are rapidly evolving. Our objective is to review and synthesize the current literature regarding ZIKV as it pertains to pregnancy and provide some assistance to clinicians who may have to manage a pregnant patient with potential exposure to ZIKV. We will also explore certain aspects of related viruses in pregnancy in hopes to shed light on this little-known topic.

Relation between birth weight and weight and height at the age of 2 in children born preterm.

OBJECTIVE: The aim of the study was to evaluate associations between fetal growth and weight at 2 years in infants born preterm using a customized approach for birth weight. STUDY DESIGN: This is a secondary analysis of a multicenter trial that included a 2-year follow-up of children born prematurely. Customized birth weight percentiles were calculated using the Gardosi model for a U.S. population, and the relation between customized percentile and weight and height at 2 years (adjusted for gender using z-score) was determined using regression analysis and by comparing z-scores for children with birth weight <10th versus ≥10th percentile. RESULTS: Weight z-score at 2 years was significantly lower in the <10th than in the ≥10th percentile group (median [interquartile range, IQR]: -0.66 [-1.58, -0.01] vs. -0.23 [-1.05, 0.55]; p < 0.001), and remained after adjusting for maternal education (p < 0.001). A similar relationship was noted for height z-score between groups (median [IQR]: -0.56 [-1.29, 0.19] vs. -0.24 [-0.99, 0.37]; p < 0.001). Positive relationships between customized birth weight percentile and weight and height at 2 years were noted (p < 0.001 for both), but were not strong (R (2) = 0.04 and 0.02, respectively). CONCLUSION: Customized birth weight percentile is a minor determinant of weight at 2 years among children born preterm.

Effect of lactation on maternal postpartum cardiac function and adiposity: a murine model.

OBJECTIVE: Lactation is associated with reduction in maternal metabolic disease and hypertension later in life; however, findings in humans may be confounded by socioeconomic factors. We sought to determine the independent contribution of lactation on cardiovascular parameters and adiposity in a murine model. STUDY DESIGN: Following delivery, CD-1 female mice were randomly divided into 2 groups: lactated (L; nursed pups for 3 weeks, n = 10), and nonlactated (NL; pups were removed after birth, n = 12). Blood pressure (BP) was assessed prepregnancy and at 1 and 2 months' postpartum. Visceral and subcutaneous adipose tissue determined by computed tomography and left ventricular ejection fraction, cardiac output, and the E/A ratio determined by microultrasound were evaluated at 1 and 2 months' postpartum. The results were analyzed using a Student t test (significance at P < .05). RESULTS: We observed a significantly different maternal BP at 2 months' postpartum with relatively greater BP in NL (systolic BP: NL, 122.2 ± 7.2 vs L, 96.8 ± 9.8 mm Hg; P = .04; diastolic BP: NL, 87.0 ± 6.8 vs L, 65.9 ± 6.2 mm Hg; P = .04). Visceral adipose tissue was significantly increased in NL mice at 1 (22.0 ± 4.1% vs 10.7 ± 1.8%, P = .04) and 2 months' postpartum (22.9 ± 3.5% vs 11.2 ± 2.2%, P = .02), whereas subcutaneous adipose tissue did not differ between the groups. At 2 months' postpartum, ejection fraction (51.8 ± 1.5% vs 60.5 ± 3.8%; P = .04), cardiac output (14.2 ± 1.0 vs 18.0 ± 1.3 mL/min; P = .02) and mitral valve E/A ratio (1.38 ± 0.06 vs 1.82 ± 0.13; P = .04) were significantly lower in NL mice than L mice. CONCLUSION: Our data provide evidence that interruption of lactation adversely affects postpartum maternal cardiovascular function and adiposity.

Therapeutic Exercise Approaches to Nonoperative and Postoperative Management of Femoroacetabular Impingement Syndrome.

Femoroacetabular impingement syndrome (FAIS) is characterized by premature contact of the femur and acetabulum during hip motion. Morphologic variations of FAIS present as either aspherical femoral deformity (cam femoroacetabular impingement) or overcoverage (pincer femoroacetabular impingement) or both. Patients with FAIS often describe discomfort with hip flexion, adduction, and internal rotation. The use of hip arthroscopy to treat FAIS has risen substantially over the last 15 years. Given that one practice domain of the athletic training profession involves injury prevention and wellness protection, optimal FAIS treatment and management strategies warrant discussion. Sports medicine professionals often help patients with FAIS explore nonoperative exercise strategies and direct rehabilitation exercises for those who pursue surgery. Both approaches demonstrate key pillars of exercise program design, which include postural control, core stabilization, hip strength and motor control, and mobility. The purpose of this article is 2-fold: to present an overview of FAIS, including common diagnostic strategies, and commonalities in therapeutic approaches between nonoperative and postoperative rehabilitation for the treatment and management of patients with FAIS.

Lactation Leads to Modifications in Maternal Renin-Angiotensin System in Later Life.

The objective of this study was to evaluate whether the renin-angiotensin system (RAS) is associated with maternal cardioprotective phenotype observed in post-lactated mice later in life. Following the delivery, CD-1 female mice were randomized to one of the following groups: lactated (nursed pups for 3 weeks, n = 10) or non-lactated (pups were removed after birth, n = 10). The mice were sacrificed 6 months after the delivery, and tissues were collected. Protein levels of angiotensinogen, angiotensin type 1 and 2 receptors (AT1R, AT2R), angiotensin converting enzymes (ACE, ACE2), and MAS receptor were determined using Western blot. Results were analyzed using Student's t-test and Mann-Whitney test as appropriate (significance: P < 0.05). Angiotensinogen levels were significantly lower in the liver (P = 0.0002), and ACE was significantly decreased in the lungs (P = 0.04) and kidney (P = 0.001) from lactated mice as compared to non-lactated. The levels of AT2R in the kidney (P = 0.02) and visceral adipose tissue (VAT, P = 0.04), the ACE 2 in the VAT (P = 0.03) and heart (P = 0.04), and MAS receptor in VAT (P = 0.02) were significantly elevated in tissues from lactated mice. No other differences were found. Lactation led to the upregulation and downregulation of selected RAS components in lactated mice as compared to non-lactated group and may be a contributing factor to maternal cardioprotective phenotype later in life. Further studies are needed to dissect the mechanisms between lactation and the long-term maternal cardiometabolic benefits, which could lead to the therapies to prevent cardiovascular disease in women.

The association of hyperuricemia and immediate postpartum hypertension in women without a diagnosis of chronic hypertension.

Our objective was to determine if elevated uric acid (UA) is associated with postpartum hypertension (PP HTN) in women without chronic hypertension. This is a secondary analysis of a randomized trial. We compared those with elevated UA to those with normal UA. Logistic regression was conducted to determine the association of elevated UA with PP HTN. Five hundred and fifty-six women met criteria. An UA level ≥ 5.2 mg/dL was associated with immediate PP HTN (adjusted odds ratio 2.44, 95% CI 1.63-3.64). The association was stronger among overweight and obese women. We conclude that hyperuricemia is associated with PP HTN, especially among obese women.

Neurocysticercosis in Pregnancy.

The normal physiologic changes during pregnancy contribute to nutritional, metabolic, and immunologic adjustments, which can have an impact on the presentation of several diseases. New onset seizures during pregnancy and the postpartum can be attributed to several etiologies. Patient demographic data as well as personal and social histories are key in determining the etiology of new onset seizures. Neurocysticercosis (NCC), a commonly overlooked etiology, must be included in the differential diagnosis of patients with new onset seizures coming from NCC endemic areas. The diagnosis is based on a combination of clinical findings, exposure history, imaging, and serology. We present two cases of patients with NCC that became symptomatic during pregnancy or postpartum period. We will review the epidemiology, clinical manifestations, and management of NCC in pregnancy.

A multi-institutional effort for temporary training of residents displaced by disaster: lessons from Katrina.

OBJECTIVE: This study was undertaken to describe a comprehensive, collaborative temporary residency training curriculum after disaster. STUDY DESIGN: The Texas Southeast Alliance was created in response to the Katrina Disaster by regional obstetric/gynecology programs. Principles were devised to guide development of a temporary training curriculum. Learning opportunities were identified and pooled. Affected program directors were contacted who expressed interest in the curriculum which had been approved by institutional officials and appropriate regulatory bodies. RESULTS: In total, 41 different training opportunities were made available to the Tulane residents. Twenty-four residents completed 92 rotations in total. Residents met weekly with their program director. Free psychiatric consultative services were provided through resident counseling services. Housing was facilitated wherever possible. CONCLUSION: Consolidation of resources by the Texas Southeast Alliance provided temporary training experiences for Tulane obstetric and gynecology residents displaced by Hurricane Katrina. Effective training can be maintained after disaster by coordinating institutional efforts and establishing governing principles.

Adipose Tissue Insulin Resistance in Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance (IR) and altered glucose-lipid metabolism. We propose that ectonucleotide pyrophosphate phosphodiesterase-1 (ENPP1), a protein known to induce adipocyte IR, is a determinant of GDM. Our objective was to study ENPP1 expression in adipose tissue (AT) of obese pregnant women with or without GDM, as well as glucose tolerance in pregnant transgenic (Tg) mice with AT-specific overexpression of human ENPP1. METHODS: AT biopsies and blood were collected from body mass index-matched obese pregnant women non-GDM (n = 6), GDM (n = 7), and nonpregnant controls (n = 6) undergoing cesarian section or elective surgeries, respectively. We measured the following: (1) Expression of key molecules involved in insulin signaling and glucose-lipid metabolism in AT; (2) Plasma glucose and insulin levels and calculation of homeostasis model assessment of IR (HOMA-IR); (3) Intraperitoneal glucose tolerance test in AtENPP1 Tg pregnant mice. RESULTS: We found that: (1) Obese GDM patients have higher AT ENPP1 expression than obese non-GDM patients, or controls (P = 0.01-ANOVA). (2) ENPP1 expression level correlated negatively with glucose transporter 4 (GLUT4) and positively with insulin receptor substrate-1 (IRS-1) serine phosphorylation, and to other adipocyte functional proteins involved in glucose and lipid metabolism (P < 0.05 each), (3) AT ENPP1 expression levels were positively correlated with HOMA-IR (P = 0.01-ANOVA). (4) Pregnant AT ENPP1 Tg mice showed higher plasma glucose than wild type animals (P = 0.046-t test on area under curve [AUC]glucose). CONCLUSIONS: Our results provide evidence of a causative link between ENPP1 and alterations in insulin signaling, glucose uptake, and lipid metabolism in subcutaneous abdominal AT of GDM, which may mediate IR and hyperglycemia in GDM.

Anxiety symptoms during pregnancy and postpartum.

This cross-sectional study compared the distribution of anxiety symptoms among pregnant, non-pregnant, and postpartum women of lower socioeconomic status. Participants were 807 women who were pregnant (24-36 weeks), postpartum (2-8 weeks), or not pregnant. Anxiety and depressive symptoms were assessed by the state-trait anxiety index and the Beck depression inventory, respectively. English and Spanish versions of the instrument were available. Group differences in anxiety were evaluated using analysis of variance. Multivariate regression was performed to evaluate differences in anxiety while controlling for marital status, education, race/ethnicity, employment, cohabitation, income, parity, history of depression/anxiety, and depressive symptoms. Anxiety scores were lower among postpartum women relative to pregnant and non-pregnant women (both P < 0.001), who did not differ (P = 0.99). After controlling for depressive symptoms and patient characteristics, anxiety remained lowest among postpartum women. Additionally, history of depression/anxiety and depressive symptoms were significant predictors of anxiety in the multivariate analysis. Comparatively low anxiety and depressive symptoms were observed among women who were 2-8 weeks postpartum. Anxiety symptoms that occur postpartum may not appear until later in the postpartum period.

Pravastatin Effects on Placental Prosurvival Molecular Pathways in a Mouse Model of Preeclampsia.

OBJECTIVE: Using an animal model of preeclampsia induced by overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1), we previously showed that pravastatin prevents the development of a preeclampsia phenotype. Our objective is to determine whether pravastatin treatment may be explained by its effects on apoptotic/survival pathways in the placenta. METHODS: Pregnant CD1 mice at day 8 of gestation (length of gestation 19 days) were randomly allocated to injection via tail vein with either adenovirus carrying sFlt-1 or adenovirus carrying the murine immunoglobulin G2α Fc fragment (mFc virus control group). Mice from the sFlt group were randomly assigned to receive pravastatin (5 mg/kg/d) in their drinking water from day 9 until killing (sFlt-1 + Pravastatin) or water (sFlt-1). The mFc control received water only. Mice were killed on day 18, and the placentas were collected. Protein mitogen-activated protein kinase (MAPK) pathway substrates were assayed using Bioplex Multiplex Immunoassay (Bio-Rad, Hercules, California). Data are reported as mean ± standard error of the mean or median (interquartile range) when appropriate. One-way analysis of variance followed by post hoc analysis was performed. Two-sided P value < .05 was considered statistically significant. RESULTS: The sFlt-1 + Pravastatin mice had significantly higher placental protein concentrations of prosurvival/ antiapoptotic factors (activating transcription factor 2, pp38, phosphorylated c-jun N-terminal kinase, and phosphorylated extracellular signal-regulated kinase) and of heat-shock protein 27 and signal transducer and activator of transcription 3, 2 factors crucial for embryonic and placental development during oxidative stress, compared to sFlt-1 mice (P < .05) and similar to the mFc control group. No differences were noted in substrates of the proapoptotic pp53 pathway. CONCLUSION: Pravastatin ability to prevent preeclampsia phenotype may be mediated through pleiotropic mechanisms involving a prosurvival/ antiapoptotic MAPK pathway in the placenta. Our results further support continued research in the role for statins in the prevention of preeclampsia.