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The Prevention and Treatment of Preeclampsia and Fetal Growth Restriction

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 43709

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Dr. Zaneta Kimber-Trojnar

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Guest Editor

Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland
Interests: gestational diabetes mellitus; fetal growth restriction; preeclampsia biomarkers; preterm delivery; fetal programming; excessive gestational weight gain; metabolic syndrome
Special Issues, Collections and Topics in MDPI journals

Dr. Jolanta Patro-Małysza

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Co-Guest Editor

Chair, Department of Obstetrics and Perinatology, Medical University of Lublin, Lublin, Poland
Interests: fetal growth restriction; preeclampsia; fetal programming; excessive gestational weight gain; gestational diabetes mellitus; multiple gestation; cervical ripening; cervical incompetence

Special Issue Information

Dear Colleagues,

Preeclampsia and fetal growth restriction remain the leading causes of both maternal and fetal morbidity and mortality worldwide. Although their pathogeneses remain unclear, the underlying causes are thought to overlap, since both preeclampsia and fetal growth restriction commonly occur together. A failed remodeling of the spiral arteries by trophoblasts in early pregnancy seems to be the most plausible hypothesis explaining this phenomenon. However, knowledge about the molecular mechanisms underlying the onset and maintenance of preeclampsia and fetal growth restriction is still insufficient, and prevention of preeclampsia and fetal growth restriction is still challenging because of the limited information and effective interventions available for these conditions. Since these gestational abnormalities will result in the development of life-long cardiovascular diseases in the mother, pregnancy-related morbidity has started to be a priority concern among not only obstetricians but also primary care physicians and cardiologists. On the other hand, the fetal environment is considered a key factor in the etiology of chronic non-communicable diseases during offspring’s adulthood.

This Special Issue aims to provide an overview of the latest research on the prevention, treatment, and prognosis of preeclampsia and fetal growth restriction.

Dr. Zaneta Kimber-Trojnar
Dr. Jolanta Patro-Małysza
Guest Editors

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Keywords

preeclampsia
fetal growth restriction
preeclampsia biomarkers
maternal risk factors
fetal programming
endothelial dysfunction
inflammation
oxidative stress
placental growth factor
acetylsalicylic acid

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Published Papers (9 papers)

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Research

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8 pages, 384 KiB

Open AccessArticle

Risk of Early Childhood Obesity in Offspring of Women with Preeclampsia: A Population-Based Study

by Seung-Woo Yang, Min-Jeong Oh, Keon-Vin Park, Sung-Won Han, Hee-Sun Kim, In-Sook Sohn, Han-Sung Kwon, Geum-Joon Cho and Han-Sung Hwang

J. Clin. Med. 2021, 10(16), 3758; https://doi.org/10.3390/jcm10163758 - 23 Aug 2021

Cited by 4 | Viewed by 2192

Abstract

Preeclampsia (PE) is a major disease of pregnancy, with various short- or long-term complications for both the mother and offspring. We focused on the body mass index (BMI) of offspring and compared the incidence of obesity during early childhood between PE- and non-PE-affected pregnancies. Women with singleton births (n = 1,697,432) were identified from the Korea National Health Insurance database. The outcomes of offspring at 30–80 months of age were analyzed. The effects of PE on BMI and the incidence of obesity in the offspring were compared. The incidence of low birth weight (LBW) offspring was higher in the PE group (n = 29,710) than that in the non-PE group (n = 1,533,916) (24.70% vs. 3.33%, p < 0.01). However, BMI was significantly higher in the PE-affected offspring than that in non-PE-affected offspring. After adjusting for various factors, the risk of obesity was higher in the PE-affected offspring (odds ratio = 1.34, 95% confidence interval = 1.30–1.38). The BMI and incidence of obesity were higher during early childhood in the PE-affected offspring, even though the proportion of LBW was higher. These results may support the basic hypotheses for the occurrence of various cardiovascular and metabolic complications in PE-affected offspring. In addition, early-age incidence of obesity could influence PE management and child consultation in clinical applications. Full article

(This article belongs to the Special Issue The Prevention and Treatment of Preeclampsia and Fetal Growth Restriction)

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17 pages, 2735 KiB

Open AccessArticle

Fetal Growth Restriction and Subsequent Low Grade Fetal Inflammatory Response Are Associated with Early-Onset Neonatal Sepsis in the Context of Early Preterm Sterile Intrauterine Environment

by Kyung Chul Moon, Chan-Wook Park, Joong Shin Park and Jong Kwan Jun

J. Clin. Med. 2021, 10(9), 2018; https://doi.org/10.3390/jcm10092018 - 8 May 2021

Cited by 3 | Viewed by 2536

Abstract

There is no information about whether fetal growth restriction (FGR) is an independent risk factor for low-grade fetal inflammatory response (FIR), and which is more valuable for the prediction of early-onset neonatal sepsis (EONS) between low-grade FIR or fetal inflammatory response syndrome (FIRS) in the context of human early preterm sterile intrauterine environment. We examined FIR (umbilical cord plasma (UCP) CRP concentration at birth) according to the presence or absence of FGR (birth weight < 5th percentile for gestational age (GA)) and EONS in 81 singleton preterm births (GA at delivery: 24.5~33.5 weeks) within 72 h after amniocentesis and with sterile intrauterine environment. A sterile intrauterine environment was defined by the presence of both a sterile amniotic fluid (AF) (AF with both negative culture and MMP-8 < 23 ng/mL) and inflammation-free placenta. Median UCP CRP (ng/mL) was higher in cases with FGR than in those without FGR (63.2 vs. 34.5; p = 0.018), and FGR was an independent risk factor for low-grade FIR (UCP CRP ≥ 52.8 ng/mL) (OR 3.003, 95% CI 1.024–8.812, p = 0.045) after correction for confounders. Notably, low-grade FIR (positive likelihood-ratio (LR) and 95% CI, 2.3969 (1.4141–4.0625); negative-LR and 95% CI, 0.4802 (0.2591–0.8902)), but not FIRS (positive-LR and 95% CI, 2.1071 (0.7526–5.8993); negative-LR and 95% CI, 0.8510 (0.6497–1.1145)), was useful for the identification of EONS. In conclusion, FGR is an independent risk factor for low-grade FIR, and low-grade FIR, but not FIRS, has a value for the identification of EONS in the context of the early preterm sterile intrauterine environment. Full article

(This article belongs to the Special Issue The Prevention and Treatment of Preeclampsia and Fetal Growth Restriction)

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16 pages, 1692 KiB

Open AccessArticle

MiRNAs Regulating Oxidative Stress: A Correlation with Doppler Sonography of Uteroplacental Complex and Clinical State Assessments of Newborns in Fetal Growth Restriction

by Vladislava Gusar, Mariya Ganichkina, Vitaliy Chagovets, Nataliya Kan and Gennadiy Sukhikh

J. Clin. Med. 2020, 9(10), 3227; https://doi.org/10.3390/jcm9103227 - 8 Oct 2020

Cited by 10 | Viewed by 2755

Abstract

Overproduction of reactive oxygen species (ROS) and, as a result, uncontrolled oxidative stress (OS) can play a central role in disorders of fetal hemodynamics and subsequent development of adverse perinatal outcomes in newborns with fetal growth restriction (FGR). Given the epigenetic nature of such disorders, the aim of our study was to evaluate the expression of miRNAs associated with OS and endothelial dysfunction (miR-27a-3p, miR-30b-5p, miR-125b-5p, miR-221-3p, miR-451a and miR-574-3p) in umbilical cord blood using real-time quantitative RT-PCR. ΜiRNA expression was evaluated in patients with FGR delivery before (n = 9 pregnant) and after 34 weeks of gestation (n = 13 pregnant), and the control groups corresponding to the main groups by gestational age (13 pregnant women in each group, respectively). A significant increase in miR-451a expression was detected in late-onset FGR and correlations with fetoplacental and cerebral circulation were established (increase of resistance in the umbilical artery (pulsatility index, PI UA (umbilical artery): r = −0.59, p = 0.001) and a decrease in cerebral blood flow (CPR: r = 0.48, p = 0.009)). The change in miR-125b-5p expression in the placenta is associated with reduced Doppler of cerebral hemodynamics (CPR: r = 0.73, p = 0.003; PI MCA (middle cerebral artery): r = 0.79, p = 0.0007), and newborn weight (r = 0.56, p = 0.04) in early-onset FGR. In addition, significant changes in miR-125b-5p and miR-451a expression in umbilical cord blood plasma were found in newborns with neonatal respiratory distress syndrome (NRDS) (in early-onset FGR) and very low birth weight (VLBW) (in late-onset FGR). A number of key signaling pathways have been identified in which the regulation of the studied miRNAs is involved, including angiogenesis, neurotrophin signaling pathway and oxidative stress response. In general, our study showed that changes of the redox homeostasis in the mother-placenta-fetus system in FGR and subsequent perinatal outcomes may be due to differential expression of oxidative stress-associated miRNAs. Full article

(This article belongs to the Special Issue The Prevention and Treatment of Preeclampsia and Fetal Growth Restriction)

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13 pages, 706 KiB

Open AccessArticle

The Influence of Various Smoking Categories on The Risk of Gestational Hypertension and Pre-Eclampsia

by Małgorzata Lewandowska and Barbara Więckowska

J. Clin. Med. 2020, 9(6), 1743; https://doi.org/10.3390/jcm9061743 - 4 Jun 2020

Cited by 18 | Viewed by 4021

Abstract

The relationship between smoking and the risk of pregnancy-induced hypertension (PIH) is not clearly established. Therefore, we conducted an analysis of cigarette smoking in a Polish cohort of women, recruited in the first trimester of a single pregnancy in 2015–2016. We evaluated the women who subsequently developed PIH (n = 137) (gestational hypertension—GH (n = 113) and pre-eclampsia—PE (n = 24)), and the women who remained normotensive (n = 775). The diseases odds ratios (and 95% CI—confidence intervals) were calculated in a multivariate logistic regression. In the PIH cases (vs. normotensive women) we found more smokers (25.6% vs. 17.2%, p = 0.020) including smokers in the first trimester (14.6% vs. 4.8%, p < 0.001). The average number of cigarettes smoked daily per smokers in the first trimester was 11.2 (range 2–30), and the average number of years of smoking was 11.6 (range 2–25). The number of years of smoking was a stronger risk factor for GH and PE than the number of cigarettes/day. Compared to the women who have never smoked, smoking ever before pregnancy was associated with a higher GH risk (AOR = 1.68; p = 0.043), and with no effect on PE risk (OR = 0.97; p = 0.950). Smokers in the first trimester had a higher odds ratio of GH (AOR = 4.75; p < 0.001) and PE (OR = 2.60; p = 0.136). Quitting smoking before pregnancy (ex-smokers) was associated with a lower odds ratio of GH (AOR = 0.83; p = 0.596) and PE (OR = 0.33; p = 0.288). However, quitting smoking during pregnancy was associated with a higher risk of GH (AOR = 11.63; p < 0.0001) and PE (OR = 3.57; p = 0.238). After dissection of the cohort into pre-pregnancy body–mass index (BMI) categories, smoking in the first trimester was associated with the higher hypertension risk in underweight women (OR = 22.00, p = 0.024). Conclusions: The factors that increased the risk of GH and PE were smoking in the first trimester and (paradoxically and more strongly) smoking cessation during pregnancy. Our results suggest that women of childbearing potential should be encouraged to quit smoking before pregnancy. Full article

(This article belongs to the Special Issue The Prevention and Treatment of Preeclampsia and Fetal Growth Restriction)

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10 pages, 631 KiB

Open AccessArticle

Developmental Evaluation of Infants Who Have Received Tadalafil in Utero for Fetal Growth Restriction

by Shintaro Maki, Ineko Kato, Naosuke Enomoto, Sho Takakura, Masafumi Nii, Kayo Tanaka, Hiroaki Tanaka, Shinsuke Hori, Kana Matsuda, Yukito Ueda, Hirofumi Sawada, Masahiro Hirayama, Akihiro Sudo and Tomoaki Ikeda

J. Clin. Med. 2020, 9(5), 1448; https://doi.org/10.3390/jcm9051448 - 13 May 2020

Cited by 4 | Viewed by 2699

Abstract

To assess the long-term effects of tadalafil, a therapeutic agent for fetal growth restriction (FGR), we evaluated the developmental progress of 1.5-year-old infants whose mothers had taken tadalafil during pregnancy. Twenty-four infants were assessed. We evaluated infant body weight, height, and head circumference, and performed the Kyoto Scale of Psychological Development (KSPD) test, a standardized developmental assessment covering Postural–Motor (P–M), Cognitive–Adaptive (C–A), and Language-Social (L–S) functions. The sum score was converted to a developmental quotient (DQ). The mean gestational week of the included cases was 36.1 (29–39) weeks, and the mean birth weight was 1841 (874–2646) g. Twenty-one and 20 out of the 24 cases, respectively, attained body weight and height similar to those of age-matched normal infants (within the 3rd percentile); all cases caught up in head circumference. KSPD was performed for 18 cases at 1.5 years of corrected age. The mean DQ scores were 87 (in total): 82 in P–M, 90 in C–A, and 88 in L–S. The total DQ score in one case (5.6%) was less than 70, and ranged from 70 to 85 in five cases (27.7%), and was more than 85 in 11 cases (61.1%). The growth and development of infants born of tadalafil-treated mothers seem to show good progress at a corrected age of 1.5 years. Full article

(This article belongs to the Special Issue The Prevention and Treatment of Preeclampsia and Fetal Growth Restriction)

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7 pages, 1538 KiB

Open AccessArticle

Who Is at Risk for Preeclampsia? Risk Factors for Developing Initial Preeclampsia in a Subsequent Pregnancy

by Tamar Wainstock, Ruslan Sergienko and Eyal Sheiner

J. Clin. Med. 2020, 9(4), 1103; https://doi.org/10.3390/jcm9041103 - 13 Apr 2020

Cited by 19 | Viewed by 4918

Abstract

Background: The incidence of preeclampsia, which may cause significant maternal and perinatal morbidity, has risen in recent years, therefore it is critical to identify women at risk for preeclampsia. We aimed to identify risk factors in the first pregnancy (not complicated by preeclampsia) for preeclampsia in the subsequent pregnancy. Methods: A retrospective population-based nested case-control study was conducted, including all women with first (P1) and second (P2) singleton consecutive deliveries. Women who had experienced preeclampsia in their first pregnancy were excluded. Cases were defined as women with preeclampsia in their second pregnancy, and were compared to the controls, defined as women without this diagnosis in second pregnancy. Characteristics and complications of the first pregnancy were compared between cases and controls, and multivariable regression models were used to study the association between pregnancy complications (in the first pregnancy) and preeclampsia (in the subsequent pregnancy), while adjusting for confounders. Results: A total of 40,673 women were included in the study, 1.5% of second pregnancies were diagnosed with preeclampsia (n = 627, i.e., Cases). Cases, as compared to controls were older in their 1st pregnancy, with longer inter-pregnancy interval, and were more likely to have the following complications in their first pregnancy: preterm delivery (15.0% vs. 7.7%), low birthweight (17.9% vs. 10.3%), perinatal mortality (3.2% vs. 1.1%), and gestational diabetes (7.0% vs. 2.7%). In the multivariable model, adjusted for maternal age, obesity and inter-pregnancy interval, either one of these first pregnancy complications were independently associated with an increased risk for preeclampsia (adjusted OR for either of first pregnancy complication =1.73; 95% CI 1.37–2.14, <0.001), and the risk was greater for each additional complication (adjusted OR for ≥2 risk factors =3.54; 95% CI 2.28–5.52, p < 0.001). Conclusions: Complications in first pregnancy, including preterm delivery, perinatal mortality and gestational diabetes, are risk factors for primary preeclampsia in second pregnancy. First pregnancy may serve as a window of opportunity to identify women at risk for future preeclampsia and other morbidities later in life. Full article

(This article belongs to the Special Issue The Prevention and Treatment of Preeclampsia and Fetal Growth Restriction)

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Review

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17 pages, 355 KiB

Open AccessReview

Preeclampsia and Cardiovascular Risk for Offspring

by Wiktor Wojczakowski, Żaneta Kimber-Trojnar, Filip Dziwisz, Magdalena Słodzińska, Hubert Słodziński and Bożena Leszczyńska-Gorzelak

J. Clin. Med. 2021, 10(14), 3154; https://doi.org/10.3390/jcm10143154 - 16 Jul 2021

Cited by 39 | Viewed by 4398

Abstract

There is growing evidence of long-term cardiovascular sequelae in children after in utero exposure to preeclampsia. Maternal hypertension and/or placental ischaemia during pregnancy increase the risk of hypertension, stroke, diabetes, and cardiovascular disease (CVD) in the offspring later in life. The mechanisms associated with CVD seem to be a combination of genetic, molecular, and environmental factors which can be defined as fetal and postnatal programming. The aim of this paper is to discuss the relationship between pregnancy complicated by preeclampsia and possibility of CVD in the offspring. Unfortunately, due to its multifactorial nature, a clear dependency mechanism between preeclampsia and CVD is difficult to establish. Full article

(This article belongs to the Special Issue The Prevention and Treatment of Preeclampsia and Fetal Growth Restriction)

24 pages, 1373 KiB

Open AccessReview

Prevention of Hypertensive Disorders of Pregnancy—Is There a Place for Metformin?

by Elżbieta Poniedziałek-Czajkowska, Radzisław Mierzyński, Dominik Dłuski and Bożena Leszczyńska-Gorzelak

J. Clin. Med. 2021, 10(13), 2805; https://doi.org/10.3390/jcm10132805 - 25 Jun 2021

Cited by 6 | Viewed by 4846

Abstract

The possibility of prophylaxis of hypertensive disorders of pregnancy (HDPs) such as preeclampsia (PE) and pregnancy-induced hypertension is of interest due to the unpredictable course of these diseases and the risks they carry for both mother and fetus. It has been proven that their development is associated with the presence of the placenta, and the processes that initiate it begin at the time of the abnormal invasion of the trophoblast in early pregnancy. The ideal HDP prophylaxis should alleviate the influence of risk factors and, at the same time, promote physiological trophoblast invasion and maintain the physiologic endothelium function without any harm to both mother and fetus. So far, aspirin is the only effective and recommended pharmacological agent for the prevention of HDPs in high-risk groups. Metformin is a hypoglycemic drug with a proven protective effect on the cardiovascular system. Respecting the anti-inflammatory properties of metformin and its favorable impact on the endothelium, it seems to be an interesting option for HDP prophylaxis. The results of previous studies on such use of metformin are ambiguous, although they indicate that in a certain group of pregnant women, it might be effective in preventing hypertensive complications. The aim of this study is to present the possibility of metformin in the prevention of hypertensive disorders of pregnancy with respect to its impact on the pathogenic elements of development Full article

(This article belongs to the Special Issue The Prevention and Treatment of Preeclampsia and Fetal Growth Restriction)

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25 pages, 3222 KiB

Open AccessReview

Preeclampsia Is a Syndrome with a Cascade of Pathophysiologic Events

by Wilfried Gyselaers

J. Clin. Med. 2020, 9(7), 2245; https://doi.org/10.3390/jcm9072245 - 15 Jul 2020

Cited by 37 | Viewed by 14117

Abstract

This review integrates the currently available information on the molecular, cellular, and systemic mechanisms involved in the pathophysiology of preeclampsia. It highlights that the growth, protection, and promotion of the conceptus requires the modulation of an intact maternal immune system, communication between the mother and fetus, and adaptation of the maternal organic functions. A malfunction in any of these factors, on either side, will result in a failure of the cascade of events required for the normal course of pregnancy. Maladaptive processes, initially aiming to protect the conceptus, fail to anticipate the gradually increasing cardiovascular volume load during the course of pregnancy. As a result, multiple organ dysfunctions install progressively and eventually reach a state where mother and/or fetus are at risk of severe morbidity or even mortality, and where the termination of pregnancy becomes the least harmful solution. The helicopter view on pathophysiologic processes associated with preeclampsia, as presented in this paper, illustrates that the etiology of preeclampsia cannot be reduced to one single mechanism, but is to be considered a cascade of consecutive events, fundamentally not unique to pregnancy. Full article

(This article belongs to the Special Issue The Prevention and Treatment of Preeclampsia and Fetal Growth Restriction)

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