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Diagnosis, Treatment and Prevention of Fetal Diseases and Fetal Risk Factors for Non-Communicable Diseases

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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 (31 August 2019) | Viewed by 80603

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Prof. Dr. Michael Skilton

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Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
Interests: nutrition; life course; cardiovascular diseases; non-communicable diseases
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Dear Colleagues,

Diseases of the fetal period include chorioamnionitis, fetal growth restriction, preterm birth, and congenital heart diseases amongst others, in addition to emerging threats such as those secondary to Zika virus. These diseases of the fetal period have a disproportionately large impact on the burden of disease and disability across the life course.

There are distinct challenges in the diagnosis, treatment and prevention of diseases of the fetal period. Diagnosis, particularly in the early stage of disease, is often challenging; treatments often lack effectiveness; and there are inherent risks associated with prevention strategies implemented during pregnancy.

Furthermore, beyond immediate disease outcomes in the fetal and perinatal periods, there is evidence that a variety of intrauterine exposures can influence the risk of non-communicable diseases across the life course. While most evidence has focused on cardiovascular diseases, allergic diseases, obesity and diabetes, there is emerging evidence of links between early life exposures and a number of cancers.

Evidence from animal models, epidemiology, applied and clinical research, particularly clinical trials, are required to advance the science, prevention, diagnosis and treatment within this field.

Dr. Michael Skilton
Guest Editor

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Keywords

Fetus
Pregnancy
Fetal diseases
Prevention
Treatment
Developmental origins of disease
Non-communicable diseases

Published Papers (9 papers)

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Research

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9 pages, 1121 KiB

Open AccessArticle

Quality Assurance of Non-Invasive Prenatal Screening (NIPS) for Fetal Aneuploidy Using Positive Predictive Values as Outcome Measures

by Wendy DiNonno, Zachary Demko, Kimberly Martin, Paul Billings, Melissa Egbert, Susan Zneimer, Dianne Keen-Kim and Peter Benn

J. Clin. Med. 2019, 8(9), 1311; https://doi.org/10.3390/jcm8091311 - 26 Aug 2019

Cited by 16 | Viewed by 11753

Abstract

Non-invasive prenatal screening (NIPS) based on the analysis of cell-free DNA in maternal plasma has been shown to have high sensitivity and specificity. We gathered follow-up information for pregnancies in women with test-positive NIPS results from 2014–2017 with quarterly assessments of positive predictive values (PPVs). A non-inferiority analysis with a minimum requirement of 70%/80% of expected performance for trisomy 21 and 18 was used to ensure testing met expectations. PPVs were evaluated in the context of changes in the population receiving testing. For all quarters, PPVs for trisomies 21 and 18 exceeded the requirement of > 70% of the reference PPV. Overall observed PPVs for trisomy 21, 18, 13 and monosomy X were similar for women aged <35 (90.9%, 95% Confidence Interval (CI) 88.6–92.7%) compared to women with advanced maternal age (94.5%, 95% CI 93.1–95.6%). Despite significant declines in test-positive rates from 1.18% to 0.62% for trisomy 21, and from 0.75% to 0.48% for trisomies 18, 13 and monosomy X combined, PPVs remained stable through the four-year interval. We conclude that quarterly evaluation of PPV provides an overview of past testing and helps demonstrate long-term consistency in test performance, even in the setting of increasing use by women with lower a priori risks. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prevention of Fetal Diseases and Fetal Risk Factors for Non-Communicable Diseases)

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13 pages, 1094 KiB

Open AccessArticle

Blood Pressure Abnormalities Associated with Gut Microbiota-Derived Short Chain Fatty Acids in Children with Congenital Anomalies of the Kidney and Urinary Tract

by Chien-Ning Hsu, Pei-Chen Lu, Chih-Yao Hou and You-Lin Tain

J. Clin. Med. 2019, 8(8), 1090; https://doi.org/10.3390/jcm8081090 - 24 Jul 2019

Cited by 25 | Viewed by 3641

Abstract

Both kidney disease and hypertension can originate from early life. Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of chronic kidney disease (CKD) in children. Since gut microbiota and their metabolite short chain fatty acids (SCFAs) have been linked to CKD and hypertension, we examined whether gut microbial composition and SCFAs are correlated with blood pressure (BP) load and renal outcome in CKD children with CAKUT. We enrolled 78 children with CKD stage G1–G4. Up to 65% of children with CAKUT had BP abnormalities on 24 h ambulatory blood pressure monitoring (ABPM). CKD children with CAKUT had lower risk of developing BP abnormalities and CKD progression than those with non-CAKUT. Reduced plasma level of propionate was found in children with CAKUT, which was related to increased abundance of phylum Verrucomicrobia, genus Akkermansia, and species Bifidobacterium bifidum. CKD children with abnormal ABPM profile had higher plasma levels of propionate and butyrate. Our findings highlight that gut microbiota-derived SCFAs like propionate and butyrate are related to BP abnormalities in children with an early stage of CKD. Early assessments of these microbial markers may aid in developing potential targets for early life intervention for lifelong hypertension prevention in childhood CKD. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prevention of Fetal Diseases and Fetal Risk Factors for Non-Communicable Diseases)

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18 pages, 1466 KiB

Open AccessArticle

Pregnant Women’s Risk Perception of the Teratogenic Effects of Alcohol Consumption in Pregnancy

by Isabel Corrales-Gutierrez, Ramon Mendoza, Diego Gomez-Baya and Fatima Leon-Larios

J. Clin. Med. 2019, 8(6), 907; https://doi.org/10.3390/jcm8060907 - 25 Jun 2019

Cited by 12 | Viewed by 8368

Abstract

There is ample evidence of the teratogenic effects of prenatal alcohol exposure, with long-term consequences throughout the entire life cycle. Nevertheless, research on risk perception of alcohol consumption among pregnant women is scarce. In order to analyze risk perception of alcohol consumption during pregnancy, a cross-sectional study was conducted with a random sample of 426 pregnant women (in their 20th week of gestation) receiving care at the outpatient clinics of a public university hospital in the southern European city of Seville (Spain). Data were collected through structured face-to-face interviews conducted by trained health professionals using a customized questionnaire. Data analysis included structural equation modeling. Only 48.1% of the sample indicated that the sequelae from alcohol consumption during pregnancy were life-long. The structural equation model showed that a lower risk perception about beer and wine consumption, and a lower educational level, were related to more frequent alcohol consumption. Younger participants showed lower risk perception concerning beer consumption. Higher levels of education were related to a greater risk perception of beer. Healthcare institutions should articulate programs that facilitate health advice regarding alcohol consumption during pregnancy, particularly when providing care for women with low educational levels. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prevention of Fetal Diseases and Fetal Risk Factors for Non-Communicable Diseases)

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17 pages, 1241 KiB

Open AccessArticle

Safety Evaluation of Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER): Results from the Phase II Trial

by Shintaro Maki, Hiroaki Tanaka, Makoto Tsuji, Fumi Furuhashi, Shoichi Magawa, Michiko K. Kaneda, Masafumi Nii, Kayo Tanaka, Eiji Kondo, Satoshi Tamaru, Toru Ogura, Yuki Nishimura, Masayuki Endoh, Tadashi Kimura, Tomomi Kotani, Akihiko Sekizawa and Tomoaki Ikeda

J. Clin. Med. 2019, 8(6), 856; https://doi.org/10.3390/jcm8060856 - 15 Jun 2019

Cited by 23 | Viewed by 4648

Abstract

Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor with a long half-life, high selectivity, and rapid onset of action. Because the safety of using PDE5 inhibitors as therapeutic agents for fetal growth restriction (FGR) has been a problem worldwide, this paper primarily focuses on the safety assessments performed in the Tadalafil Treatment for Fetuses with Early-Onset Growth Restriction (TADAFER) II population. Neonatal and maternal adverse events were analyzed, in addition to fetal, neonatal, and infant death cases, six months after stopping the trial. Eighty-nine pregnant women with FGR were studied between September 2016 and March 2018 (45 and 44 in the tadalafil and conventional treatment groups, respectively). Seven (16%) deaths (four fetal, one neonatal, and two infant) in the control group, whereas only one neonatal death occurred in the tadalafil group. Although headache, facial flushing, and nasal hemorrhage occurred more frequently in the tadalafil group, these symptoms were Grade 1 and transient. In conclusion, this trial showed that tadalafil decreased the fetal and infant deaths associated with FGR. This is thought to be primarily due to pregnancy prolongation. Further studies are warranted to evaluate the efficacy of tadalafil in treating early-onset FGR. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prevention of Fetal Diseases and Fetal Risk Factors for Non-Communicable Diseases)

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12 pages, 458 KiB

Open AccessArticle

FABP4 in Gestational Diabetes—Association between Mothers and Offspring

by Jolanta Patro-Małysza, Marcin Trojnar, Żaneta Kimber-Trojnar, Radzisław Mierzyński, Jacek Bartosiewicz, Jan Oleszczuk and Bożena Leszczyńska-Gorzelak

J. Clin. Med. 2019, 8(3), 285; https://doi.org/10.3390/jcm8030285 - 27 Feb 2019

Cited by 17 | Viewed by 3320

Abstract

Fetuses exposed to gestational diabetes mellitus (GDM) have a higher risk of abnormal glucose homeostasis in later life. The molecular mechanisms of this phenomenon are still not fully understood. Fatty acid binding protein 4 (FABP4) appears to be one of the most probable candidates involved in the pathophysiology of GDM. The main aim of the study was to investigate whether umbilical cord serum FABP4 concentrations are altered in term neonates born to GDM mothers. Two groups of subjects were selected—28 healthy controls and 26 patients with GDM. FABP4, leptin, and ghrelin concentrations in the umbilical cord serum, maternal serum, and maternal urine were determined via an enzyme-linked immunosorbent assay. The umbilical cord serum FABP4 levels were higher in the GDM offspring and were directly associated with the maternal serum FABP4 and leptin levels, as well as the prepregnancy body mass index (BMI) and the BMI at and after delivery; however, they correlated negatively with birth weight and lipid parameters. In the multiple linear regression models, the umbilical cord serum FABP4 concentrations depended positively on the maternal serum FABP4 and negatively on the umbilical cord serum ghrelin levels and the high-density lipoprotein cholesterol. There are many maternal variables that can affect the level of FABP4 in the umbilical cord serum, thus, their evaluation requires further investigation. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prevention of Fetal Diseases and Fetal Risk Factors for Non-Communicable Diseases)

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12 pages, 455 KiB

Open AccessArticle

Body Fatness and Cardiovascular Health in Newborn Infants

by Hasthi U. Dissanayake, Rowena L. McMullan, Yang Kong, Ian D. Caterson, David S. Celermajer, Melinda Phang, Camille Raynes-Greenow, Jaimie W. Polson, Adrienne Gordon and Michael R. Skilton

J. Clin. Med. 2018, 7(9), 270; https://doi.org/10.3390/jcm7090270 - 11 Sep 2018

Cited by 11 | Viewed by 3848

Abstract

Birth weight is associated with cardiovascular disease, with those at both ends of the spectrum at increased risk. However, birth weight is a crude surrogate of fetal growth. Measures of body composition may more accurately identify high risk infants. We aimed to determine whether aortic wall thickening, cardiac autonomic control, and cardiac structure/function differ in newborns with high or low body fatness compared to those with average body fatness. 189 healthy singleton term born neonates were recruited and stratified by body fat percentiles (sex and gestation-specific). Infants with low body fat had higher aortic intima-media thickness (43 µm (95% confidence interval (CI) 7, 78), p = 0.02), lower heart rate variability (log total power, −0.5 (95% CI −0.8, −0.1), p = 0.008), and thicker ventricular walls (posterior wall thickness, 3.1 mm (95% CI 1.6, 4.6), p < 0.001) compared to infants with average body fatness. Infants with high body fat showed no differences in aortic intima-media thickness (−2 µm (95% CI −37, 33), p = 0.91) or cardiac structure compared to average body fatness, although stroke volume (−0.3 mL/kg (95% CI −0.6, −0.0), p = 0.003) and heart rate variability were lower (log total power, −0.8 (95% CI −1.1, −0.5), p < 0.001). The non-linear association of body fatness with heart rate variability was independent of birth weight. Infants born with low or high body fat have altered markers of cardiovascular health. Assessment of body fatness alongside birth weight may assist in identifying high risk individuals. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prevention of Fetal Diseases and Fetal Risk Factors for Non-Communicable Diseases)

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20 pages, 3334 KiB

Open AccessArticle

A Comprehensive Feature Analysis of the Fetal Heart Rate Signal for the Intelligent Assessment of Fetal State

by Zhidong Zhao, Yang Zhang and Yanjun Deng

J. Clin. Med. 2018, 7(8), 223; https://doi.org/10.3390/jcm7080223 - 20 Aug 2018

Cited by 37 | Viewed by 5230

Abstract

Continuous monitoring of the fetal heart rate (FHR) signal has been widely used to allow obstetricians to obtain detailed physiological information about newborns. However, visual interpretation of FHR traces causes inter-observer and intra-observer variability. Therefore, this study proposed a novel computerized analysis software of the FHR signal (CAS-FHR), aimed at providing medical decision support. First, to the best of our knowledge, the software extracted the most comprehensive features (47) from different domains, including morphological, time, and frequency and nonlinear domains. Then, for the intelligent assessment of fetal state, three representative machine learning algorithms (decision tree (DT), support vector machine (SVM), and adaptive boosting (AdaBoost)) were chosen to execute the classification stage. To improve the performance, feature selection/dimensionality reduction methods (statistical test (ST), area under the curve (AUC), and principal component analysis (PCA)) were designed to determine informative features. Finally, the experimental results showed that AdaBoost had stronger classification ability, and the performance of the selected feature set using ST was better than that of the original dataset with accuracies of 92% and 89%, sensitivities of 92% and 89%, specificities of 90% and 88%, and F-measures of 95% and 92%, respectively. In summary, the results proved the effectiveness of our proposed approach involving the comprehensive analysis of the FHR signal for the intelligent prediction of fetal asphyxia accurately in clinical practice. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prevention of Fetal Diseases and Fetal Risk Factors for Non-Communicable Diseases)

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Review

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22 pages, 733 KiB

Open AccessReview

Preeclampsia: Risk Factors, Diagnosis, Management, and the Cardiovascular Impact on the Offspring

by Rachael Fox, Jamie Kitt, Paul Leeson, Christina Y.L. Aye and Adam J. Lewandowski

J. Clin. Med. 2019, 8(10), 1625; https://doi.org/10.3390/jcm8101625 - 04 Oct 2019

Cited by 164 | Viewed by 33169

Abstract

Hypertensive disorders of pregnancy affect up to 10% of pregnancies worldwide, which includes the 3%–5% of all pregnancies complicated by preeclampsia. Preeclampsia is defined as new onset hypertension after 20 weeks’ gestation with evidence of maternal organ or uteroplacental dysfunction or proteinuria. Despite its prevalence, the risk factors that have been identified lack accuracy in predicting its onset and preventative therapies only moderately reduce a woman’s risk of preeclampsia. Preeclampsia is a major cause of maternal morbidity and is associated with adverse foetal outcomes including intra-uterine growth restriction, preterm birth, placental abruption, foetal distress, and foetal death in utero. At present, national guidelines for foetal surveillance in preeclamptic pregnancies are inconsistent, due to a lack of evidence detailing the most appropriate assessment modalities as well as the timing and frequency at which assessments should be conducted. Current management of the foetus in preeclampsia involves timely delivery and prevention of adverse effects of prematurity with antenatal corticosteroids and/or magnesium sulphate depending on gestation. Alongside the risks to the foetus during pregnancy, there is also growing evidence that preeclampsia has long-term adverse effects on the offspring. In particular, preeclampsia has been associated with cardiovascular sequelae in the offspring including hypertension and altered vascular function. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prevention of Fetal Diseases and Fetal Risk Factors for Non-Communicable Diseases)

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20 pages, 1730 KiB

Open AccessReview

Natural History of Atherosclerosis and Abdominal Aortic Intima-Media Thickness: Rationale, Evidence, and Best Practice for Detection of Atherosclerosis in the Young

by Michael R. Skilton, David S. Celermajer, Erich Cosmi, Fatima Crispi, Samuel S. Gidding, Olli T. Raitakari and Elaine M. Urbina

J. Clin. Med. 2019, 8(8), 1201; https://doi.org/10.3390/jcm8081201 - 12 Aug 2019

Cited by 48 | Viewed by 5968

Abstract

Atherosclerosis underlies most myocardial infarctions and ischemic strokes. The timing of onset and the rate of progression of atherosclerosis differ between individuals and among arterial sites. Physical manifestations of atherosclerosis may begin in early life, particularly in the abdominal aorta. Measurement of the abdominal aortic intima-media thickness by external ultrasound is a non-invasive methodology for quantifying the extent and severity of early atherosclerosis in children, adolescents, and young adults. This review provides an evidence-based rationale for the assessment of abdominal aortic intima-media thickness—particularly as an age-appropriate methodology for studying the natural history of atherosclerosis in the young in comparison to other methodologies—establishes best practice methods for assessing abdominal aortic intima-media thickness, and identifies key gaps in the literature, including those that will identify the clinical relevance of this measure. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Prevention of Fetal Diseases and Fetal Risk Factors for Non-Communicable Diseases)

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