Highlights
- •Preeclampsia is the leading cause of premature delivery worldwide.
- •Pravastatin given in the second trimester may increase the duration of early severe preeclampsia.
- •Our data suggest a role of pravastatin in stabilizing the progression of preeclampsia.
- •No differences in infant follow-up are observed between treated and not-treated pregnancies.
Abstract
Objective
Preeclampsia (PE) is the major cause of maternal morbidity and mortality and the leading
cause of premature delivery worldwide. As well as intrauterine growth restriction
(IUGR), PE is associated with pathogenic evidence of placental malperfusion and ischemia.
Recent literature has highlighted the potential of pravastatin in the prevention and
treatment of these conditions. Aim of this study is to describe perinatal outcomes
and placental histopathological findings in a small series of pregnant women with
severe PE and IUGR treated with pravastatin on compassionate grounds. Two-year follow
up of these babies is provided.
Study design
Between October 2017 and October 2019 in Fondazione Policlinico Universitario Agostino
Gemelli, IRCCS, Rome, Italy, women with singleton pregnancy between 19.6 and 27.6
gestational weeks, who presented with severe PE and IUGR were counselled for a compassionate
treatment with Pravastatin 40 mg a day. Treated women were compared with controls
identified with similar data in terms of gestational age at diagnosis, clinical maternal
data, Doppler severity findings. Neonates were followed up for two years.
Results
The median time from diagnosis to delivery was 39 days (IQR 20) for women in the pravastatin
group and 20 days (IQR 20.5) for controls. Looking to maternal blood exams, in the
group of women treated with pravastatin, maximum transaminase, creatinine levels were
lower than in controls, where the minimum platelet count was higher. Placenta examination
did not reveal any significant differences in placental histopathological findings.
No significant differences were observed in the investigated perinatal data, as well
as in infant follow-up, although an increased prenatal weight gain was found in treated
pregnancies in comparison to controls.
Conclusions
Our data did not allow us to find significant differences in pregnancy outcome and
infant follow-up, as well as in placental histological picture in preeclamptic patients
when pravastatin is administered in the late second trimester. However, we suggest
its possible role in stabilizing the disease, increasing the prenatal weight gain
and prolonging the duration of pregnancy, thus preventing the progression to a more
severe maternal disease.
Keywords
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References
- Global and regional estimates of preeclampsia and eclampsia: a systematic review.Eur J Obstet Gynecol Reprod Biol. 2013; 170: 1-7
- Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy.Placenta. 2009; 30: 473-482
Duley L, Meher S, Hunter KE, Seidler AL, Askie LM. Antiplatelet agents for preventing preeclampsia and its complications. Cochrane Database Syst Rev 2019;2019:CD004659.
- Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: a systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants.Am Heart J. 2019; 210: 18-28
Brownfoot FC, Tong S, Hannan NJ, et al. Effects of pravastatin on human placenta, endothelium, and women with severe preeclampsia. Hypertension 2015;66:687–97. discussion 445.
- Pravastatin as the statin of choice for reducing pre-eclampsia-associated endothelial dysfunction.Pregnancy Hypertens. 2020; 20: 83-91
Fox KA, Longo M, Tamayo E, et al. Effects of pravastatin on mediators of vascular function in a mouse model of soluble fms-like tyrosine kinase1-induced preeclampsia. Am J Obstet Gynecol 2011;205:366.e1–5.
Bauer AJ, Banek CT, Needham K, et al. Pravastatin attenuates hypertension, oxidative stress, and angiogenic imbalance in rat model of placental ischemia-induced hypertension. Hypertension 2013;61:1103–10.
- Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in highrisk pregnant women: a pilot randomized controlled trial.Am J Obstet Gynecol. 2016; 214: 720.e1-720.e17
- Pravastatin for early-onset pre-eclampsia: a randomised, blinded, placebo-controlled trial.BJOG. 2020; 127: 478-488
- Pravastatin for the prevention of preeclampsia in high-risk pregnant women.Obstet Gynecol. 2013; 121: 349-353
- Pravastatin is useful for prevention of recurrent severe placenta-mediated complications - a pilot study.J Matern Fetal Neonatal Med. 2021; 21: 1-7
- Evaluating the Effect of Pravastatin in Early-Onset Fetal Growth Restriction: A Nonrandomized and Historically Controlled Pilot Study.Am J Perinatol. 2020 Jul 2;
- Pravastatin therapy during preeclampsia prevents long-term adverse health effects in mice.JCI Insight. 2018; 3: e120147
- Statins reverse postpartum cardiovascular dysfunction in a rat model of preeclampsia.Hypertension. 2020; 75: 202-210
- Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis.BMJ. 2007; 335: 974
- Promoting risk identification and reduction of cardiovascular disease in women through collaboration with obstetricians and gynecologists: a presidential advisory from the American Heart Association and the American College of Obstetricians and Gynecologists.Circulation. 2018; 137
- Heart disease and stroke statistics–2009 update: a report from the American Heart Association statistics committee and stroke statistics subcommittee.Circulation. 2009; 119: 480-486
- The 2021 international society for the study of hypertesion in pregnancy classification, diagnosis & management recommendations for international practice.Pregnancy Hypertens. 2022; 27: 148-169
- Consensus definition of fetal growth restriction: a Delphi procedure.Ultrasound Obstet Gynecol. 2016; 48: 333-339
- Sonographic estimation of fetal weight. The value of femur length in addition to head and abdomen measurements.Radiology. 1984; 150: 535-540
- Normal values of Pulsatility Index from fetal vessels: a cross-sectional study on 1556 healthy fetuses.J Perinat Med. 1990; 18: 165-172
- International fetal and newborn growth consortium for the 21st century (INTERGROWTH-21st). International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.Lancet. 2014; 384: 869-879
ISUOG Practice Guidelines (updated): use of Doppler velocimetry in obstetrics. Ultrasound Obstet Gynecol 2021.
- Development of a new fetal growth curve from a large sample of Italian population.Minerva Pediatr. 2017; 69
- Placenta weight percentile curves for singleton and twins deliveries.Placenta. 2011; 32: 58-62
Khong T.Y., Mooney E.E., Ariel I. et al. Sampling and definitions of placental lesions. Amsterdam placental workshop group consensus statement. Archives of Pathology and Laboratory Medicine. Vol 140. ; 2016:698-713.
- Placental pathology: a systematic approach with clinical correlations.Placenta. 2008; 29: 86-91
- Classification of placental lesions.Am J Obstet Gynecol. 2015; 213: S21-S28
- A synoptic framework and future directions for placental pathology reporting.Placenta. 2018; 2019: 46-57
F. C. Brownfoot , S. Tong, N. J. Hannan, R. Hastie, P. Cannon and Tu’uhevaha J. Kaitu’u-Lino. Effects of simvastatin, rosuvastatin and pravastatin on soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sENG) secretion from human umbilical vein endothelial cells, primary trophoblast cells and placenta. BMC Pregnancy and Childbirth (2016) 16:117.
- Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model.PNAS. 2011; 108: 1451-1455
- Mechanistic and epidemiologic considerations in the evaluation of adverse birth outcomes following gestational exposure to statins.Am J Med Genetics Part A. 2004; 131: 287-298
- Risk of statin use during pregnancy: a systematic review.J Obstet Gynaecol Can. 2007; 29: 906
- Risk of congenital anomalies in pregnant users of statin drugs.Br J Clin Pharmacol. 2007; 64: 496
- Prenatal exposure to HMG-CoA reductase inhibitor: effects on fetal and neonatal outcomes.Repro Tox. 2008; 26: 175
Petersen. Maternal Exposure to Statins and Risk for Birth Defects. Am J Med Gen. 2008; 146A: 2701–2705.
- Statins and pregnancy: between supposed risks and theoretical benefits.Drugs. 2012; 72: 773-788
Devin D. Smith, MD; Maged M. Costantine, MD. The role of statins in the prevention of preeclampsia. Am J Obstet Gynecol, 2020 Aug 17;S0002-9378(20)30868-1.
- Pravastatin improves pregnancy outcomes in obstetric antiphospholipid syndrome refractory to antithrombotic therapy.J Clin Invest. 2016; 126: 2933-2940
- Pravastatin for prevention of HELLP syndrome: a case report.Medicine (Baltimore). 2017; 96: e8229
S. Tong, Tu’uhevaha J. Kaitu’u-Lino, R. Hastie, F. Brownfoot, C. Cluver, N. Hannan. Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia. Am J Obstet Gynecol , 2020 Sep 16;S0002-9378(20)31071-1.
Biography
Stefano Fruci Stefano Fruci is a doctor specialized in Gynecology and Obstetrics. His clinical activity is mainly aimed at the study of maternal-fetal medicine with particular attention to some maternal problems, in particular hypertensive disorders such as chronic hypertension, gestational hypertension and preeclampsia (PE) and to some fetal problems such as fetal growth restriction (FGR). Together with his team colleagues, he has focused on some specific topics including: use of pravastatin in the treatment of early onset PE and FGR, maternal hemodynamics using USCOM (Ultrasonic Cardiac Output Monitor), analysis of proangiogenic and antiangiogenic biomarkers on maternal blood.
Biography
Silvia Salvi Education: Degree in Medicine and Surgery at Catholic University of Sacred Heart in Rome; Speciality Degree in Obstetrics and Gynecology; PhD in Cellular and Molecular Clinical Research at the Catholic University of the Sacred Heart, Rome. Career: Research Fellow in Obstetrics and Gynecology at the Policlinico A. Gemelli in Rome. Publications: Several International publications. She has an H-index of 14, and 821 citations (Scopus, 2023). Her main topic of interest is the feto-maternal medicine, moving from maternal disease (in particular hypertensive disorders, autoimmune diseases, cardiac problems in pregnancy) to related fetal problems (fetal growth disorders), from bench (placental in vitro studies) to bedside (maternal haemodynamic assessment).
Biography
Sascia Moresi Sascia Moresi is a doctor specialized in Gynecology and Obstetrics and he works at the Policlinico Agostino Gemelli in Rome. His clinical activity develops in the field of maternal-fetal medicine and involves the study of some maternal pathologies, in particular hypertensive disorders of pregnancy and preeclampsia (PE) and the clinical management of some fetal complications including fetal growth restriction (FGR). Together with the team colleagues we are carrying out various research protocols that make use of USCOM (ultrasonic cardiac output monitor), drugs such as pravastatin for the compassionate treatment of PE, markers for endothelial dysfunction and placental histology.
Biography
Francesca Gallini Prof. Francesca Gallini, MD is Assistant Professor in Pediatrics, Neonatology, Catholic University of Rome, IRCSS-Fondazione Gemelli. Education: degree in Medicine and Surgery in 1989; advanced Professional Degree in Pediatrics in 1993. From 2001 she is Researcher in Pediatrics- Neonatology and now Assistant Professor. From 2004 she is the Director of the Neonatal Follow-up Program. She has an H-index of 20, and 1235 citations (Scopus).
Biography
Marco dell’Aquila Graduated from Sapienza University of Rome in 2016, specializing in Pathology at the University of the Sacred Heart. His scientific and professional interests are mainly directed to the histopathology of tumors and to fetoplacental pathology, perinatal autopsy and clinical autopsy. He is currently a PhD student at Catholic University of the Sacred Heart.
Biography
Vincenzo Arena Dr. Vincenzo Arena is a pathologist at the IRCCS Fondazione Policlinico Universitario A.Gemelli (Italy). A well known cardiovascular pathology expert, his major areas of clinical practice include autopsy pathology, feto-placental pathology, breast and colon pathology. His research contributions include the expression of ancillary prognosticators in human malignancies. He has authored>200 peer reviewed manuscripts. Degrees: MD, Catholic University of Rome – School of Medicine (2001). Residencies: Catholic University of Rome – School of Medicine (2006).
Biography
Enrico Di Stasio Prof. Enrico Di Stasio, MD is Adjunct Professor in Biochemistry, Catholic University of Rome, IRCSS-Fondazione Gemelli. His research was focused on biophysics and biochemistry of ligand binding theory, mechanical statistics and thermodynamics of protein aggregation and chaos theory in biological systems. He principally worked on coagulation processes and cryoglobulins aggregation. Moreover he serves as statistician for many projects in medical field. Author of over 200 peer-reviewed publications, he has an H-index of 38.
Biography
Sergio Ferrazzani Sergio Ferrazzani was born on June 6, 1952 in Viterbo. Italy. On November 4, 1977: he graduated in Medicine and Surgery at the Catholic University of Rome. On 6 November 1981: he obtained the specialization diploma in Obstetrics and Gynecology. From November 1, 1988: he was winner of the competition for University Researcher at the Institute of Obstetrics and Gynecology. Since 1 January 1998 he has been 1st level Medical Director at the Division of Obstetrics and Gynecology. Since 1 November 2001 he has been Associate Professor in Gynecology and Obstetrics at the same University. He has been retired since 1 November 2022.
Biography
Sara De Carolis Prof. Sara De Carolis, MD is Adjunct Professor in Obstetrics and Medical Manager (UOS) at High-Risk Pregnancy Unit, Catholic University of Rome, IRCSS-Fondazione Gemelli. She has received several research awards. Her research tracks are investigation on the role of antiphospholipid antibodies in pregnancy (treatment, obstetrical management and outcome, risk factors), autoimmune disease in pregnancy, pregnancy management of blood disorders (inherited thrombophilia, immune thrombocytopenia, coagulopathies), cancer in pregnancy, preeclampsia, twin pregnancy, fetal growth, preterm delivery, coeliac disease and pregnancy, and recurrent abortion. Author of almost 130 peer-reviewed publications, she has an H-index of 34, and 3.593citations (Scopus).
Biography
Antonio Lanzone Degree in Medicine; Speciality Degree in Obstetrics and Gynecology; from 2012 to present Head of the High Risk Pregnancy Department at Fondazione Policlinico Univ. A. Gemelli in Rome. From November 2010 he was appointed President of the Degree Course in Medicine and Surgery at the Catholic University of the Sacred Heart in Rome. From 2018: Director of Woman’s Health – Department of Woman and Child Health Sciences and Public Health. Author of>500 publications. H index: 46 (Scopus) 2023.
Article info
Publication history
Published online: February 01, 2023
Accepted:
January 30,
2023
Received in revised form:
January 18,
2023
Received:
September 10,
2021
Identification
Copyright
© 2023 Elsevier B.V. All rights reserved.
