Prevention Of Fetal Growth Restriction Research Articles

Pentaerythrityl tetranitrate improves the outcome of children born to mothers with compromised uterine perfusion—12-months follow-up and safety data of the double-blind randomized PETN trial

This is a follow-up study to the pentaerythrityl tetranitrate randomized controlled multicenter trial that reports neonatal outcome data of newborns admitted to neonatal intensive care units and outcome data of the offspring at 12 months of age. We present data on adverse events reported during the study to document the safety of pentaerythrityl tetranitrate treatment during pregnancy. To further evaluate the effects of pentaerythrityl tetranitrate on neonatal and long-term outcomes, we present follow up data from of 240 children at 12 months of age, including information on height, weight, head circumference, developmental milestones, and the presence of chronic disease and of 144 newborns admitted to the neonatal intensive care unit during the trial. The pentaerythrityl tetranitrate trial was a randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of the nitric oxide-donor pentaerythrityl tetranitrate in the prevention of fetal growth restriction and perinatal death in pregnancies complicated by abnormal placental perfusion. Results at 12 months demonstrated that significantly more children were age appropriately developed without impairments in the pentaerythrityl tetranitrate group (P=.018). In addition, the presence of chronic disease was lower in the pentaerythrityl tetranitrate group (P=.041). Outcome data of the 144 newborns admitted to the neonatal intensive care unit did not reveal differences between the treatment and placebo groups. There were no differences in the number or nature of reported adverse events between the study groups. The analysis shows that study children born in the pentaerythrityl tetranitrate cohort have a clear advantage compared with the placebo group at the age of 12 months, as evidenced by the increased incidence of normal development without the presence of chronic disease. Although safety has been proven, further follow-up studies are necessary to justify pentaerythrityl tetranitrate treatment during pregnancies complicated by impaired uterine perfusion.

Влияние непрерывного профилактического приема ацетилсалициловой кислоты на гистологическую картину плаценты у беременных группы высокого риска развития задержки роста плода

Background: fetal growth restriction (FGR) is the main cause of perinatal mortality. We have relatively effective methods of predicting and preventing this condition, however, it has not yet been possible to achieve a significant reduction of the FGR incidence. Acetylsalicylic acid (ASA) is the only effective pharmacological method for the prevention of FGR, but the mechanism of its action is still in doubt. Aim: to study the placental morphology in pregnant women at high risk of FGR according to the first trimester screening (FTS), depending on whether female patients took ASA for the FGR prevention or not. Patients and Methods: the study was conducted in 2019–2021. By that time, the clinical recommendations concerning «Insufficient fetal growth requiring the provision of medical care to the mother (fetal growth restriction)», developed by the Ministry of Health of the Russian Federation, had not yet come into effect. In a prospective analysis, the placental morphology of 125 pregnant women at high risk of FGR and 554 placentas of pregnant women at low risk was studied according to the FTS results. Pregnant women at high risk of FGR were divided into 2 groups: 51 female patients received ASA from 14 to 36 weeks pregnant, 74 did not receive ASA; the control group consisted of 554 pregnant women at low risk of FGR according to the FTS. The placenta was examined in 3 stages according to the conventional management scheme, including macroscopic analysis, material incisure and histology. Results: placental pathological changes (dystrophic changes, syncytial knots formation, fibrinoid deposition, disorders of placental villous maturation) in patients who did not receive ASA were significantly more common than in the control group and in the subgroup receiving ASA. Conclusion: FGR incidence decrease in patients receiving ASA was due to an improvement in the histological structure of the placenta. KEYWORDS: fetal growth restriction, small for gestational age, placenta, acetylsalicylic acid. FOR CITATION: Shamugiya V.V., Kuznetsov P.A., Dobrokhotova Yu.E. Effect of the continuous prophylaxis with acetylsalicylic acid on the placental histological image in pregnant women at high risk of fetal growth restriction. Russian Journal of Woman and Child Health. 2024;7(1):12–17 (in Russ.). DOI: 10.32364/2618-8430-2024-7-1-2.

The influence of education by using 5J pregnancy nutrition guidebook for the prevention of fetal growth restriction and maternal nutritional sufficiency

Background: Stunting is a growth and development disorder experienced by children due to poor nutrition, recurring infections, and inadequate psychosocial stimulation. If not addressed with proper nutrition, it can lead to reduced child growth. According to the Indonesian Ministry of Health, stunting is influenced by several factors, including maternal, infant, and toddler factors, as well as social, economic, and environmental conditions. According to Global Nutrition, by 2025, it is estimated that children aged ≤ 5 years will experience stunting, with an increase of 171-314 million individuals worldwide, with 90% originating from countries in Africa and Asia. The province of Lampung has shown improvement, with a stunting prevalence of 15.2% in 2022, aiming to reach the national target of around 14%. Based on nutritional status monitoring in 2017, the prevalence of stunting was 35.20%, and according to the Indonesia Nutrition Status Study (INSS) and Community-Based Nutrition Recording and Reporting (CBNRP), the prevalence of stunting in Pesawaran in 2022 was 3.50%.Purpose: To determine the impact of using the 5J Pregnancy Nutrition Guidebook in educating pregnant mothers about preventing fetal growth restriction on the knowledge, attitudes, and behaviors of mothers in the working area of Gedong Tataan Community Health Center, Pesawaran, Lampung.Method: This quantitative research employed an analytical survey design with a quasi-experimental one-group pretest-posttest method. The dependent variables in this study were the level of knowledge, attitude, and behavior of mothers, while the independent variable was education using the 5J guidebook. The research was conducted in the Gedong Tataan Community Health Center, Pesawaran, Lampung in August 2023 with a sample size of 30 using total sampling technique, and a paired sample t-test was performed.Results: Knowledge improved by 2.37 points after receiving education, with an increase difference of 1.24, and the Wilcoxon statistical test yielded a p-value of 0.000 (<0.05). Respondents' attitudes increased by 1.93 points after receiving education, although this value was in the low range, it saw a rise with a difference of 0.9, and the p-value was 0.000 (<0.05). Behavior after receiving education increased to 1.23 with an increase difference of 0.2, and the Wilcoxon statistical test showed an improvement with a p-value of 0.000 (<0.05). The test results indicate the influence of education using the 5J guidebook on maternal knowledge, attitude, and behavior.Conclusion: Educational media using the 5J guidebook has a significant influence on maternal knowledge, attitude, and behavior regarding nutrition management in the prevention of stunting.

Что нового в предотвращении и терапии задержки роста плода? Роль оксида азота

Fetal growth restriction (FGR) is an integral term for a group of conditions in which the fetus does not reach the size potentially embedded in its genome. FGR is the main cause of perinatal mortality. Commonly, FGR develops due to placental insufficiency. At the same time, there are very few levers of control on this pathology by obstetricians and gynecologists. The authors present preclinical and clinical study review concerning drugs for the FGR prevention and its therapy, as well as the role of nitric oxide (NO). Currently, it is possible to determine the risk group based on the history and data from the first trimester screening, as well as to use acetylsalicylic acid (ASA) for the preventive measures. During the study, there are several drugs that can potentially not only prevent FGR but also improve the condition course with, when the diagnose is already established. Conducting randomized clinical trials, where the primary endpoint would be the FGR, will allow to assess the safety and efficacy of the proposed medicines and advance them into clinical practice. KEYWORDS: fetal growth restriction, prevention, acetylsalicylic acid, nitric oxide, randomized clinical trials, small for gestational age. FOR CITATION: Osipov R.S., Kuznetsov P.A., Dzhokhadze L.S., Shuginin I.O. What's new in the prevention and therapy of fetal growth restriction? Role of nitric oxide. Russian Journal of Woman and Child Health. 2023;6(3):258–264 (in Russ.). DOI: 10.32364/2618-8430- 2023-6-3-7.

Ferritin screening and Iron treatment for maternal anemia and fetal growth restriction prevention - A multicenter randomized controlled trial (FAIR Study).

Non-anemic iron deficiency precedes iron deficiency anaemia and has an estimated prevalence of 1-2 billion worldwide. Few studies have comprehensively researched the idea of treating non-anemic iron deficiency (NAID) with iron to improve the outcome of the mother and the offspring. FAIR will be a multicenter randomized controlled trial that will be conducted in multiple clinical academic obstetrics units in Lahore (including Services Institute of Medical Sciences, Lahore, Allama Iqbal Medical College, Lahore and Fatima Jinnah Medical University). Pregnant women at gestational age <20 weeks with hemoglobin 11-13 g/L and ferritin below the threshold (<30 ng/ml) will be invited to take part in the study. Randomization will be done by computer based generated random numbers. One group (usual care or oral group) will be offered routine care prophylactic dose of oral iron (30-45 mg/day) and the other group (intervention arm or IV group) will be offered therapeutic dose of IV iron (dose calculated by Ganzoni formula) in addition to usual care. All patients will be followed up till delivery. Primary maternal outcome will be hemoglobin at 36 weeks' gestation. Secondary outcomes are fetal birthweight or small for gestational age, preterm birth, preeclampsia, multidimensional fatigue inventory, breast feeding initiation, blood transfusion, and fetal cord ferritin and hemoglobin. The study will generate evidence as to whether screening serum ferritin in non-anemic pregnant women and replenishing their iron stores will likely reduce the rate of predelivery anemia in pregnant women, improve birthweight and preventing perinatal complications. Tayyiba Wasim is principal Investigator and other members of data management team are Natasha Bushra, Shamsa Humayoun, Khalid Saeed Khan, Fatima Shehbaz, Saba Rasool, Anam Riaz and Sonia Irshad. Principal investigator will assume the full responsibility of Fair trial including training of research assistants, administration of informed consent and protecting participants confidentiality. Data management team will help in the management, development and execution of trial. Khadija Irfan Khawaja is the operational lead for fair trial´s technology team comprising of Aziz Fatima and Zubia Zafar, responsible for gathering requirements from study teams and supporting the operational implementation of technology to drive the collection of high-quality study data. Protocol contributors are Gynae unit I of Services Institute of Medical Sciences/ Services hospital, Lahore, Gynae Unit II of Allama Iqbal Medical College/ Jinnah hospital, Lahore and Gynae unit 1 of Fatima Jinnah Medical College/ Sir Ganga Ram hospital, Lahore. These coordinating centres will recruit patients (sample size=600) and will discuss their progress in trial management meetings quarterly. has an independent chair Prof Samia Malik, one expert member Prof Faiza Bashir and Ms Neelam to represent patients, public and consumers. Trial steering committee with independent chair and member with a patient representative will oversee the study. Chair of steering committee has the authority to stop the trial whenever needed in case of positive or negative results. Steering committee meetings will be held on annual basis. comprises of Dr. Shehnoor Azhar as chair and Prof Ejaz Hussain and Dr. Shehla Javed Akram as members. Data monitoring committee will assess the progress, data safety and if needed critical efficacy points of the clinical study and will show their results quarterly in data interim meetings. The committee will focus on integrity of the whole process and compliance of all sites with all aspects of the protocol. It will perform confidential interim analyses quarterly, which may be used to determine if an effect is observed and if the study should continue to its planned sample size. Data monitoring committee will report to the Chair of the steering committee.

Does Aspirin Prescribed to Women Deemed High Risk for Preterm Pre-Eclampsia at 11–13+6 Weeks Gestation Affect the Prevalence of Small for Gestational Age Neonates?

(Abstracted from Aust N Z J Obstet Gynaecol 2021;61:347–353) Previous studies have reported that aspirin can be used to reduce the prevalence of both early-onset preeclampsia (ePET) and fetal growth restriction (FGR). The prevention of FGR would improve both pregnancy and infant outcomes and could also reduce costs to the health care system.

Combined prevention of fetal growth restriction based on determination of diagnostic markers

Due to the morbidity of mothers and newborns caused by fetal growth restriction (FGR) and preeclampsia, preventive measures should be taken, especially in women at high risk of developing these conditions. Many studies have been conducted on the prevention of FGR and preeclampsia in high-risk women, especially anticoagulants, aspirin, paravastatin, nitric oxide, microelements (L-arginine, folic acid, vitamins E and C, phytonutrients, vitamin D) and calcium.&#x0D; The aim is to improve perinatal consequences by preventing FGR in high-risk women.&#x0D; Materials and methods: A prospective study of 137 pregnant women in the period of 110–136 weeks was conducted at the Perinatal Center in Kyiv. Pregnant women were divided into 3 groups. The main group included 47 women at high risk of FGR who received therapy (low doses of aspirin, low molecular weight heparin (LMWH) and vitamin and micro elements drugs). The comparison group included 45 women who had a high risk of FGR but did not receive treatment. The control group consisted of 45 women who were not at risk of FGR. The frequency of FGR and placental dysfunction were analyzed as well as a fetal distress was analyzed ante- and intranatally.&#x0D; Results: Therapy with low doses of aspirin, LMWH and a complex preparation of vitamins and micro elements improves the course of pregnancy and gestational complications. In the main group FGR was detected in 8.5 %, in the comparison group – in 17.8 %, in the control group – 4.4 %. Placental dysfunction was detected in 13.3 % in the control group, and only 6.4 % in the main group that was close to the control group – 2.2 %. Similar tendencies were found for fetal distress ante- and intranatally.&#x0D; Conclusions: The proposed prophylactic measures can improve maternal outcomes by reducing the level of gestational complications in pregnant women with biochemical signs of risk of FGR development. In addition, these preventive measures can reduce the frequency of children births with growth restriction, which significantly reduces early neonatal and perinatal morbidity and mortality.

Pharmacological Interventions for the Prevention of Fetal Growth Restriction: A Systematic Review and Network Meta-Analysis.

The prevention of fetal growth restriction (FGR) is challenging in clinical practice. To date, no meta-analysis summarized evidence on the relative benefits and harms of pharmacological interventions for FGR prevention. We performed a systematic review and network meta-analysis (NetMA), searching PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until November 2019. We included clinical trials and observational studies on singleton gestating women evaluating antiplatelet, anticoagulant, or other treatments, compared between each other or with controls (placebo or no treatment), and considering the pregnancy outcome FGR (primary outcome of the NetMA). Secondary efficacy outcomes included preterm birth, placental abruption, and fetal or neonatal death. Safety outcomes included bleeding and thrombocytopenia. Network meta-analyses using a frequentist framework were conducted to derive odds ratios (ORs) and 95% confidence intervals (CIs). Of 18,780 citations, we included 30 studies on 4,326 patients. Low molecular weight heparin (LMWH), alone or associated with low-dose aspirin (LDA), appeared more efficacious than controls in preventing FGR (OR 2.00, 95% CI 1.27-3.16 and OR 2.67, 95% CI 1.21-5.89 for controls vs. LMWH and LDA+LMWH, respectively). No difference between active treatments emerged in terms of FGR prevention, but estimates for treatments other than LMWH +/- LDA were imprecise. Only the confidence in the evidence regarding LMWH vs. controls was judged as moderate, according to the Confidence in Network Meta-Analysis framework. No treatment was associated with an increased risk of bleeding, although estimates were precise enough only for LMWH. These results should inform clinicians on the benefits of active pharmacological prophylaxis for FGR prevention.

Aspirin for prevention of preeclampsia and fetal growth restriction.

For the past decades, growing attention has been given to aspirin use during pregnancy. It favors placentation by its proangiogenic, antithrombotic, and anti-inflammatory effects. Therefore, low doses of aspirin are prescribed in the prevention of placenta-mediated complications, mainly preeclampsia and fetal growth restriction. However, questions regarding its clinical application are still debated. Aspirin is effective in preventing preeclampsia in a high-risk population. Most guidelines recommend that risk stratification should rely on medical history. Nevertheless, screening performances dramatically improve if biochemical and biophysical markers are included. Concerning the appropriate timing and dose, latest studies suggest aspirin should be started before 16 weeks of pregnancy and at a daily dose of 100 mg or more. Further studies are needed to improve the identification of patients likely to benefit from prophylactic aspirin. Besides, the role of aspirin in the prevention of fetal growth restriction is still questioned.

Pharmacological interventions for the prevention of fetal growth restriction: protocol for a systematic review and network meta-analysis.

IntroductionFetal growth restriction (FGR) includes different conditions in which a fetus fails to reach the own full growth, and accounts for 28%–45% of non-anomalous stillbirths. The management of FGR is based on the prolongation of pregnancy long enough for fetal organs to mature while preventing starvation. As for pharmacological management, most guidelines recommend treatment with low-dose aspirin and/or with heparin, although this approach is still controversial and innovative promising therapies are under investigation. As no firm evidence exists to guide clinicians towards the most effective therapeutic intervention, this protocol describes methods for a systematic review and network meta-analysis (NetMA) of pharmacological treatments for FGR prevention.Methods and analysisWe will search MEDLINE and Embase for clinical trials and observational studies performed on gestating women with clinically diagnosed risk of FGR. Experimental interventions will include heparin and low-molecular-weight heparin, acetylsalicylic acid, antiplatelet agents, phosphodiesterase type 3 and 5 inhibitors, maternal vascular endothelial growth factor gene therapy, nanoparticles, microRNA, statins, nitric oxide donors, hydrogen sulphide, proton pump inhibitors, melatonin, creatine and N-acetylcysteine, and insulin-like growth factors, compared between each other or to placebo or no treatment. Primary efficacy outcome is FGR. Secondary efficacy outcomes will be preterm birth, fetal or neonatal death and neonatal complications. For the safety outcome, all adverse events reported in included studies and experienced by either mothers, fetuses or newborns will be considered. Two review authors will independently screen title, abstract and full paper text, and will independently extract data from included studies. Where possible and appropriate, for primary and secondary efficacy outcomes, a NetMA will be performed using a random-effects model within a frequentist framework. Adverse events will be narratively described.Ethics and disseminationResults will be disseminated through a peer-reviewed scientific journal, and by scientific congresses and meetings.PROSPERO registration numberCRD42019122831.

Proteomics analysis of fetal growth restriction and taurine‑treated fetal growth restriction rat brain tissue by 2DDIGE and MALDI‑TOF/TOF MS analysis.

Fetal growth restriction (FGR) is caused by placental insufficiency and can lead to short and long-term neurodevelopmental delays. Taurine, one of the most abundant amino acids in the brain, is critical for the normal growth and development of the nervous system; however, the mechanistic role of taurine in neural growth and development remains unknown. The present study investigated the role of taurine in FGR. Specifically, we explored the proteomic profiles of fetal rats at 6 h postpartum by two-dimensional difference gel electrophoresis combined with matrix assisted laser desorption ionization-time-of-flight (TOF)/TOF tandem mass spectrometry; the findings were verified via reverse transcription-quantitative polymerase chain reaction. A total of 31 differentially expressed protein spots were selected. Among these, 31 were matched, including dihydropyrimidinase-related protein 2 and, CRK and peroxiredoxin 2. Functional analysis using the Gene Ontology database and Ingenuity Pathway Analysis demonstrated that the differentially expressed proteins were mainly associated with neuronal differentiation, 'metabolic process', 'biological regulation' and developmental processes. The present study identified several proteins that were differentially expressed in rats with FGR in the presence or absence of taurine administration. The results of the present study suggest a potential role for taurine in the treatment and prevention of FGR.

Variation in outcome reporting in randomized controlled trials of interventions for prevention and treatment of fetal growth restriction.

Although fetal growth restriction (FGR) is well known to be associated with adverse outcomes for the mother and offspring, effective interventions for the management of FGR are yet to be established. Trials reporting interventions for the prevention and treatment of FGR may be limited by heterogeneity in the underlying pathophysiology. The aim of this study was to conduct a systematic review of outcomes reported in randomized controlled trials (RCTs) assessing interventions for the prevention or treatment of FGR, in order to identify and categorize the variation in outcome reporting. MEDLINE, EMBASE and The Cochrane Library were searched from inception until August 2018 for RCTs investigating therapies for the prevention and treatment of FGR. Studies were assessed systematically and data on outcomes that were reported in the included studies were extracted and categorized. The methodological quality of the included studies was assessed using the Jadad score. The search identified 2609 citations, of which 153 were selected for full-text review and 72 studies (68 trials) were included in the final analysis. There were 44 trials relating to the prevention of FGR and 24 trials investigating interventions for the treatment of FGR. The mean Jadad score of all studies was 3.07, and only nine of them received a score of 5. We identified 238 outcomes across the included studies. The most commonly reported were birth weight (88.2%), gestational age at birth (72.1%) and small-for-gestational age (67.6%). Few studies reported on any measure of neonatal morbidity (27.9%), while adverse effects of the interventions were reported in only 17.6% of trials. There is significant variation in outcome reporting across RCTs of therapies for the prevention and treatment of FGR. The clinical applicability of future research would be enhanced by the development of a core outcome set for use in future trials. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Evaluation of magnesium sulfate effects on fetus development in experimentally induced surgical fetal growth restriction in rat

Objective: The objective of this study was to evaluate the effect of magnesium sulfate in the prevention of fetal growth restriction due to the impaired uterine blood supply in the rat model.Methods: A total number of 24 female rats were used in this study. They were mated overnight and randomly divided into control and treatment groups. After anesthesia and incising abdominal midline in day 17 of gestation, the uterine artery was occluded by an atraumatic clamp for 60 min. The rats of the control group received normal saline after surgery and the rats of treatment group received magnesium sulfate subcutaneously. The laparotomy was repeated on day 21 of gestation, and the number of alive and dead fetuses was counted in each horn. The viability of fetuses was evaluated. The weight of the placenta and fetuses and the distance between the head and tail as well as back to the abdomen of the fetuses were also measured. Samples of the amniotic fluid (AF) were collected during both surgeries for biochemical analyses of the glucose, urea, lactate, and pyruvate levels by an AutoAnalyzer.Results: Among the total fetuses in ischemic horn, only 50% survived in the control group. Dead fetuses had less body consistency and had a dark color. In contrary, only 7.6% of the fetuses in the treatment group were absorbed and 92.4% were completely healthy and developed. Parameters related to placenta weight, fetus weight, fetus length, and fetus width had significant differences and those of the treatment group were higher. Glucose and lactate levels of the AF in the treatment group were significantly lower and urea level was significantly higher than the control group in day 21 of gestation. The changes in pyruvate levels were not significant.Conclusion: In conclusion, magnesium sulfate may counteract with the effects of temporary uterine ischemia in pregnant rats and prevent intrauterine growth restriction.

The use of folates for the prevention of fetal growth restriction during pregnancy

Purpose of the study: Rational for the use of folates for the prevention of fetal growth restriction on the basis of the identification of a MTHFR polymorphism.Material and methods: 200 patients (case-control) were enrolled in the study. The (main) group I included 100 patients with fetal growth restriction (FGR), the (control) group II included 100 conditionally healthy patients. The features of the anamnesis, the initial clinical characteristics, the course of pregnancy, childbirth and the postpartum period in patients with placental insufficiency were studied in detail, and the features of the early neonatal period were analysed comprehensively. At the second stage, the polymorphism of the MMP2, MMP3, MMP9, and MTHFR genes was studied and their dependence with the development of the FGR was established. Statistical processing of the results was carried out on a personal computer using the SPSS Statistics 17.0 for Windows software package.Results:The clinical risk factors for the development of FGR include: chronic pyelonephritis, medium degree myopia, varicose veins, threat of abortion, ultrasound-detected subchorionic hemorrhage in the I trimester of gestation, anemia. Along with clinical risk factors for ZRP, the carriage of MTGFR (677 C&gt; T) polymorphism is also considered, which justifies its identification in patients at risk.Conclusion: The data obtained make it possible to use the identification of MTHFR polymorphism as a predictor of placental abnormalities during pregnancy and to start taking folic acid supplements at the preconception stage in good time. Femibion 1 vitaminmineral complex has proved to be an effective product that is suitable for women in the period of preparation for pregnancy and in the first trimester of gestation, reducing the risk of fetal malformations and endothelial dysfunction caused by a violation of folic acid metabolism. 

Prevention of fetal growth restriction in placental insufficiency

The occurrence and development of such complications of pregnancy as preeclampsia, placental insufficiency, fetal growth restriction can be mediated by the systemic vascular damage. Understanding the pathophysiological mechanisms in the mother-placenta-fetus system contributes to the improvement of diagnostic methods and the selection of pathogenetically valid therapy for certain obstetric complications. In the systemic inflammatory response syndrome accompanying obstetric complications, the uncontrolled and excessive activation of proinflammatory mediators occurs, which leads to generalized tissue damage and development of multiple organ failure.The use of antiplatelet agents at a preventive dose in pregnant women with high risk of placental insufficiency and fetal growth restriction contributes to the reduction of systemic and placental blood flow disorders by affecting the vascular endothelium, increasing the synthesis of prostacyclin and nitric oxide, thereby implementing its angioprotective properties and increasing blood flow in the arteries and existing collaterals.The obtained data showed that adding of dipyridamole to the algorithm for managing pregnant women with high risk of placental insufficiency and fetal growth restriction, starting from the II trimester of gestation allows to reduce the risk of endotheliopathy and thrombophilia, improve obstetric and perinatal outcomes. 

Prevention of fetal growth restriction in pregnancy

Living in large cities, environmentally unfriendly background, smoking during pregnancy are associated with increasing number of complications, such as premature birth, intrauterine growth restriction, stillbirth and low birth weight. Pathogenetic mechanisms of these complications include oxidative stress, which can be combated by adding vitamin supplements with antioxidant activity to the daily routine of a pregnant woman. Smokers have a lower serum level of such important antioxidants as vitamins E, C and omega-3 fatty acids. The additional intake of vitamin complexes containing omega-3 fatty acids by pregnant women living in large megacities, adverse ecological regions and/or abusing smoking, has a preventive effect and can reduce the risk of premature delivery and fetal growth restriction among this cohort of patients.

Hydroxychloroquine for the prevention of fetal growth restriction and prematurity in lupus pregnancy: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that primarily affects women of childbearing age. While the impact of hydroxychloroquine (HCQ) on SLE activity and neonatal lupus occurrence has been evaluated in several studies, its role on prematurity and intrauterine growth restriction (IUGR) remains uncertain. The aim of this study was to assess the impact of HCQ exposure on prematurity and IUGR during pregnancy in women with SLE. We conducted a systematic review and a meta-analysis comparing prematurity and IUGR in SLE pregnancies exposed or not exposed to HCQ. The odds ratio of IUGR and prematurity were calculated and compared between pregnancies in each group according HCQ treatment. Six studies were included (3 descriptive cohort studies and 3 case series) totalling 870 pregnancies. Of the SLE pregnancies, 308 were exposed to HCQ and were compared to 562 not exposed to HCQ. There was no statistical difference for prematurity or IUGR between groups. This meta-analysis failed to prove the efficacy of HCQ in the prevention of prematurity as well as IUGR during SLE pregnancies. Due to the heterogeneity of the studies, these results should be interpreted cautiously.

Low dose aspirin for preventing fetal growth restriction: a randomised trial.

Abstract The purpose of this study was to investigate when in pregnancy to stop the administration of low dose aspirin (150 mg/daily) so as to prevent fetal growth restriction (FGR) A randomised, placebo-controlled study was designed. The patients were all screened positive using the Fetal Medicine Foundation (FMF) early pregnancy screening test for preeclampsia (PE) and FGR prediction. One hundred and fifty patients were enrolled and divided equally into three groups: A – the controls who received placebo treatment; B – those who received aspirin till 32 weeks of gestation and C – those who received aspirin till 36 weeks of gestation. The mean gestational age at enrollment was similar for all the groups (12.4 weeks). The growth curves, fetal and maternal Doppler measurements and amniotic fluid index (AFI) were monitored every 4 weeks. Also, the outcome of the pregnancy was noted and all the results were compared between the groups. FGR was defined as a fetal weight below the 10th centile for gestational age. In group C, there were less cases of FGR compared with the other groups: 6% vs. 10% in group B vs. 24% in controls. Also, there was a significant birth weight improvement in this group with a median of 3180 g compared with 2950 g in group B and 2760 g in group A (P=0.01). The gestational age at delivery was similar in all the groups (39 weeks in group C/39.2 weeks in group B/38.6 weeks in group A). In conclusion, low dose aspirin improves the outcome in the selected population and should be offered for prevention of FGR from 12 to 36 weeks.

The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction.

Fetal growth restriction and related placental pathologies such as preeclampsia, stillbirth, and placental abruption are believed to arise in early pregnancy when inadequate remodeling of the maternal spiral arteries leads to persistent high-resistance and low-flow uteroplacental circulation. The consequent placental ischaemia, reperfusion injury, and oxidative stress are associated with an imbalance in angiogenic/antiangiogenic factors. Many interventions have centered on the prevention and/or treatment of preeclampsia with results pertaining to fetal growth restriction and small-for-gestational-age pregnancy often included as secondary outcomes because of the common pathophysiology. This renders the study findings less reliable for determining clinical significance. For the prevention of fetal growth restriction, a recent large-study level meta-analysis and individual patient data meta-analysis confirm that aspirin modestly reduces small-for-gestational-age pregnancy in women at high risk (relative risk, 0.90, 95% confidence interval, 0.81-1.00) and that a dose of ≥100 mg should be recommended and to start at or before 16 weeks of gestation. These findings support national clinical practice guidelines. Invitro and invivo studies suggest that low-molecular-weight heparin may prevent fetal growth restriction; however, evidence from randomized control trials is inconsistent. A meta-analysis of multicenter trial data does not demonstrate any positive preventative effect of low-molecular-weight heparin on a primary composite outcome of placenta-mediated complications including fetal growth restriction (18% vs 18%; absolute risk difference, 0.6%; 95% confidence interval, 10.4-9.2); use of low-molecular-weight heparin for the prevention of fetal growth restriction should remain in the research setting. There are even fewer treatment options once fetal growth restriction is diagnosed. At present the only management option if the risk of hypoxia, acidosis, and intrauterine death is high is iatrogenic preterm birth, with the use of peripartum maternal administration of magnesium sulphate for neuroprotection and corticosteroids for fetal lung maturity, to prevent adverse neonatal outcomes. The pipeline of potential therapies use different strategies, many aiming to increase fetal growth by improving poor placentation and uterine blood flow. Phosphodiesterase type 5 inhibitors that potentiate nitric oxide availability such as sildenafil citrate have been extensively researched both in preclinical and clinical studies; results from the Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction consortium of randomized control clinical trials are keenly awaited. Targeting the uteroplacental circulation with novel therapeutics is another approach, the most advanced being maternal vascular endothelial growth factor gene therapy, which is being translated into the clinic via the doEs Vascular endothelial growth factor gene therapy safEly impRove outcome in seveRe Early-onset fetal growth reSTriction consortium. Other targeting approaches include nanoparticles and microRNAs to deliver drugs locally to the uterine arterial endothelium or trophoblast. Invitro and invivo studies and animal models have demonstrated effects of nitric oxide donors, dietary nitrate, hydrogen sulphide donors, statins, and proton pump inhibitors on maternal blood pressure, uteroplacental resistance indices, and angiogenic/antiangiogenic factors. Data from human pregnancies and, in particular, pregnancies with fetal growth restriction remain very limited. Early research into melatonin, creatine, and N-acetyl cysteine supplementation in pregnancy suggests they may have potential as neuro- and cardioprotective agents in fetal growth restriction.

P08.03: Low‐dose aspirin for prevention of fetal growth restriction and pre‐eclampsia in twins: the GAP pilot randomised trial

P08.03: Low‐dose aspirin for prevention of fetal growth restriction and pre‐eclampsia in twins: the GAP pilot randomised trial