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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 28101

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Prof. Dr. Agnieszka Kordek

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Guest Editor

Department of Neonatology, Medical University in Szczecin, Poland, Poland
Interests: early and late neonatal infection; microbiome; neonatal sepsis; breastfeeding
Special Issues, Collections and Topics in MDPI journals

Dr. Andrzej Torbé

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Guest Editor

Department of Obstetrics and Gynecology, Pomeranian Medical University, Szczecin, Poland
Interests: early and late neonatal infection; microbiome; neonatal sepsis; breastfeeding
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

An increasing amount of data indicate that the majority of cases of the so-called great obstetrics syndrome are caused by dysfunction of the placenta, which is caused by its impaired development or too-early functional impairment. Today, a holistic approach to maternal-fetal medicine allows us to explore the causes and primary pathogenesis of subsequent clinical syndromes.

The proposed Special Issue aims to focus on the presentation of modern approaches to pathogenesis and diagnostic methods that take advantage of the primary trophoblast impairment and allow the detection of potential threats in advance.

Pregnant women with clinical symptoms of placental insufficiency are still doomed to iatrogenic premature termination of pregnancy, and the severity of the pathology is correlated with perinatal outcomes. Therefore, it is worth looking for genetic, biochemical, and biophysical methods that can be used to monitor the course of the disease, and in some situations prevent serious complications.

In recent years, attention has been paid to the role of the microbiome in the pathogenesis of many pathological conditions. There are also studies on the microbiome in the context of maternal-fetal medicine. A relationship is sought between the type of bacteria inhabiting the gastrointestinal tract of women and the occurrence of obesity, gestational diabetes, or premature birth, as well as hypoxia and intrauterine infection. Other metabolomes, such as maternal and newborn urine, amniotic fluid, human breast milk, and meconium of the newborn, are also tested. In research on the microbiome in the newborn, the relationship with civilization diseases, infections, and eating disorders is sought. Is it possible to get closer to personalized medicine by using metabolomics?

Prof. Agnieszka Kordek
Prof. Andrzej Torbé
Guest Editors

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Keywords

trophoblast markers
preeclampsia
maternal and perinatal consequences of placental insufficiency
fetal growth restriction
prediction and diagnostics
microbiome
metabolomics
neonatal sepsis

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Published Papers (10 papers)

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Research

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15 pages, 2446 KiB

Open AccessArticle

Decreased Maternal Morbidity and Improved Perinatal Results of Magnesium-Free Tocolysis and Classical Hysterotomy in Fetal Open Surgery for Myelomeningocele Repair: A Single-Center Study

by Mateusz Zamłyński, Anita Olejek, Ewa Horzelska, Tomasz Horzelski, Jacek Zamłyński, Rafał Bablok, Iwona Maruniak-Chudek, Katarzyna Olszak-Wąsik and Agnieszka Pastuszka

Biomedicines 2023, 11(2), 392; https://doi.org/10.3390/biomedicines11020392 - 28 Jan 2023

Cited by 2 | Viewed by 1955

Abstract

Fetal and maternal risks associated with open fetal surgery (OFS) in the management of meningomyelocele (MMC) are considerable and necessitate improvement. A modified technique of hysterotomy (without a uterine stapler) and magnesium-free tocolysis (with Sevoflurane as the only uterine muscle relaxant) was implemented in our new magnesium-free tocolysis and classical hysterotomy (MgFTCH) protocol. The aim of the study was to assess the introduction of the MgFTCH protocol in reducing maternal and fetal complications. The prospective study cohort (SC) included 64 OFS performed with MgFTCH at the Fetal Surgery Centre Bytom (FSCB) (2015–2020). Fetal and maternal outcomes were compared with the retrospective cohort (RC; n = 46), and data from the Zurich Center for Fetal Diagnosis and Therapy (ZCFDT; n = 40) and the Children’s Hospital of Philadelphia (CHOP; n = 100), all using traditional tocolysis. The analysis included five major perinatal complications (Clavien-Dindo classification, C-Dc) which developed before the end of 34 weeks of gestation (GA, gestational age). None of the newborns was delivered before 30 GA. Only two women presented with grade 3 complications and none with 4th or 5th grade (C-Dc). The incidence of perinatal death (3.3%) was comparable with the RC (4.3%) and CHOP data (6.1%). MgFTCH lowers the risk of major maternal and fetal complications. Full article

(This article belongs to the Special Issue Perinatal-Related Pathology)

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11 pages, 3027 KiB

Open AccessArticle

Fetal Growth Restriction Impairs Lung Function and Neurodevelopment in an Early Preterm Rabbit Model

by Ignacio Valenzuela, Katerina Zapletalova, Marnel Greyling, Yannick Regin, Andre Gie, David Basurto, Jan Deprest and Johannes van der Merwe

Biomedicines 2023, 11(1), 139; https://doi.org/10.3390/biomedicines11010139 - 5 Jan 2023

Cited by 3 | Viewed by 1849

Abstract

We previously reported the multi-system sequelae of fetal growth restriction, induced by placental underperfusion, in near-term born rabbits, in the immediate neonatal period and up to pre-adolescence. Herein, we describe the pulmonary and neurodevelopmental consequences of FGR in rabbits born preterm. We hypothesize that FGR has an additional detrimental effect on prematurity in both pulmonary function and neurodevelopment. FGR was induced at gestational day (GD) 25 by placental underperfusion, accomplished by partial uteroplacental vessel ligation in one uterine horn. Rabbits were delivered by cesarean section at GD 29, and placentas were harvested for histology. Neonates underwent neurobehavioral or pulmonary functional assessment at postnatal day 1, followed by brain or lung harvesting, respectively. The neurodevelopmental assessment included neurobehavioral testing and multiregional quantification of cell density and apoptosis in the brain. Lung assessment included functional testing, alveolar morphometry, and airway histology. FGR was associated with higher perinatal mortality, lower birth and placental weight, and a similar brain-to-body weight ratio compared to controls. Placental underperfusion decreased labyrinth and junction zone volumes in FGR placentas. FGR impaired pulmonary function, depicted by higher parenchymal resistance, damping, and elastance. Alveolar morphometry and airway smooth muscle content were comparable between groups. Neurobehavioral tests showed motoric and sensorial impairment in FGR rabbits. In FGR brains, cell density was globally reduced, with higher apoptosis in selected areas. In conclusion, in preterm-born rabbits, placental underperfusion leads to higher mortality, FGR, and impaired lung and brain development in early assessment. This study complements previous findings of placental, pulmonary, and neurodevelopmental impairment in near-term born rabbits in this model. Full article

(This article belongs to the Special Issue Perinatal-Related Pathology)

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10 pages, 540 KiB

Open AccessArticle

Adverse Neonatal Outcome of Pregnancies Complicated by Preeclampsia

by Piotr Tousty, Magda Fraszczyk-Tousty, Joanna Ksel-Hryciów, Beata Łoniewska, Joanna Tousty, Sylwia Dzidek, Kaja Michalczyk, Ewa Kwiatkowska, Aneta Cymbaluk-Płoska, Andrzej Torbé and Sebastian Kwiatkowski

Biomedicines 2022, 10(8), 2048; https://doi.org/10.3390/biomedicines10082048 - 22 Aug 2022

Cited by 5 | Viewed by 2327

Abstract

Despite many available treatments, infants born to preeclamptic mothers continue to pose a serious clinical problem. The present study focuses on the evaluation of infants born to preeclamptic mothers for the occurrence of early-onset complications and attempts to link the clinical status of such infants to the angiogenesis markers in maternal blood (sFlt-1, PlGF). The study included 77 newborns and their mothers diagnosed with preeclampsia. The infants were assessed for their perinatal outcomes, with an emphasis on adverse neonatal outcomes such us infections, RDS, PDA, NEC, IVH, ROP, or BPD during the hospitalization period. The cutoff point was established using the ROC curve for the occurrence of any adverse neonatal outcome and it was 204 for the sFlt-1/PlGF and 32 birth week with AOC 0.644 and 0.91, respectively. The newborns born to mothers with high ratios had longer hospitalization times and, generally, were more frequently diagnosed with any of the aforementioned adverse neonatal outcomes. Also, the neonates born prior to or at 32 wkGA with higher sFlt-1/PlGF ratios were statistically significantly more common to be diagnosed with any of the adverse neonatal outcomes compared to those with lower ratio born prior to or at 32 wkGA. The sFlt-1/PlGF ratio can be a useful tool in predicting short-term adverse neonatal outcomes. Infants born after a full 33 weeks gestation developed almost no severe neonatal complications. Appropriate screening and preventive healthcare for preeclampsia can contribute significantly to reducing the incidence of neonatal complications. Full article

(This article belongs to the Special Issue Perinatal-Related Pathology)

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21 pages, 1105 KiB

Open AccessArticle

Comparative Proteomic Assessment of Normal vs. Polyhydramnios Amniotic Fluid Based on Computational Analysis

by Rūta Navakauskienė, Sandra Baronaitė, Dalius Matuzevičius, Natalija Krasovskaja, Gražina Treigytė, Audronė Arlauskienė and Dalius Navakauskas

Biomedicines 2022, 10(8), 1821; https://doi.org/10.3390/biomedicines10081821 - 28 Jul 2022

Viewed by 2105

Abstract

Mass spectrometry-based proteomics have become a valued tool for conducting comprehensive analyses in amniotic fluid samples with pathologies. Our research interest is the finding and characterization of proteins related to normal vs. polyhydramnios (non-immune hydrops) pregnancy. Proteomic analysis was performed on proteins isolated from fresh amniotic fluid samples. Proteins were fractionated by 2DE using a different pI range (pI 3–11, pI 4–7) and analyzed with MALDI-TOF-MS. Furthermore, by using computational analysis, identified proteins in protein maps specific to normal vs. polyhydramnios pregnancy were compared and the quantities of expressed proteins were evaluated mathematically. Comparative analysis of proteome characteristic for the same polyhydramnios pregnancy fractionated by 2DE in different pI range (3–11 and 4–7) was performed and particular protein groups were evaluated for the quantification of changes within the same protein level. Proteins of normal and polyhydramnios pregnancies were fractionated by 2DE in pI range 3–11 and in pI range 4–7. Mass spectrometry analysis of proteins has revealed that the quantity changes of the main identified proteins in normal vs. polyhydramnios pregnancy could be assigned to immune response and inflammation proteins, cellular signaling and regulation proteins, metabolic proteins, etc. Specifically, we have identified and characterized proteins associated with heart function and circulatory system and proteins associated with abnormalities in prenatal medicine. The following are: serotransferrin, prothrombin, haptoglobin, transthyretin, alpha-1-antitrypsin, zinc-alpha-2-glycprotein, haptoglobin kininogen-1, hemopexin, clusterin, lumican, afamin, gelsolin. By using computational analysis, we demonstrated that some of these proteins increased a few times in pathological pregnancy. Computer assistance analysis of 2DE images suggested that, for the better isolation of the proteins’ isoforms, those levels increased/decreased in normal vs. polyhydramnios pregnancy, and the fractionation of proteins in pI rage 3–11 and 4–7 could be substantial. We analyzed and identified by MS proteins specific for normal and polyhydramnios pregnancies. Identified protein levels increased and/or modification changed in case of non-immune hydrops fetus and in cases of cardiovascular, anemia, growth restriction, and metabolic disorders. Computational analysis for proteomic characterization empower to estimate the quantitative changes of proteins specific for normal vs. polyhydramnios pregnancies. Full article

(This article belongs to the Special Issue Perinatal-Related Pathology)

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12 pages, 1663 KiB

Open AccessArticle

Identification of LOC101927355 as a Novel Biomarker for Preeclampsia

by Reyna Peñailillo, Lara J. Monteiro, Stephanie Acuña-Gallardo, Felipe García, Victoria Velásquez, Paula Correa, Pilar Díaz, Patricia P. Valdebenito, Cristina Navarro, Roberto Romero, Mario Sánchez, Sebastián E. Illanes and Gino Nardocci

Biomedicines 2022, 10(6), 1253; https://doi.org/10.3390/biomedicines10061253 - 27 May 2022

Cited by 5 | Viewed by 2975

Abstract

Preeclampsia, a disorder with a heterogeneous physiopathology, can be attributed to maternal, fetal, and/or placental factors. Long non-coding RNAs (lncRNAs) refer to a class of non-coding RNAs, the essential regulators of biological processes; their differential expression has been associated with the pathogenesis of multiple diseases. The study aimed to identify lncRNAs, expressed in the placentas and plasma of patients who presented with preeclampsia, as potential putative biomarkers of the disease. In silico analysis was performed to determine lncRNAs differentially expressed in the placentas of patients with preeclampsia, using a previously published RNA-Seq dataset. Seven placentas and maternal plasma samples collected at delivery from preterm preeclamptic patients (≤37 gestational weeks of gestation), and controls were used to validate the expression of lncRNAs by qRT-PCR. Six lncRNAs were validated and differentially expressed (p < 0.05) in the preeclampsia and control placentas: UCA1 and HCG4 were found upregulated, and LOC101927355, LINC00551, PART1, and NRAD1 downregulated. Two of these lncRNAs, HCG4 and LOC101927355, were also detected in maternal plasma, the latter showing a significant decrease (p = 0.03) in preeclamptic patients compared to the control group. In silico analyses showed the cytoplasmic location of LOC101927355, which suggests a role in post-transcriptional gene regulation. The detection of LOC101927355 in the placenta and plasma opens new possibilities for understanding the pathogenesis of preeclampsia and for its potential use as a biomarker. Full article

(This article belongs to the Special Issue Perinatal-Related Pathology)

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Review

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15 pages, 859 KiB

Open AccessReview

Mitochondrial Dysfunction, Mitophagy and Their Correlation with Perinatal Complications: Preeclampsia and Low Birth Weight

by Raziye Melike Yildirim, Yagmur Ergun and Murat Basar

Biomedicines 2022, 10(10), 2539; https://doi.org/10.3390/biomedicines10102539 - 12 Oct 2022

Cited by 8 | Viewed by 4550

Abstract

Mitochondria are essential organelles and crucial for cellular survival. Mitochondrial biogenesis and mitophagy are dynamic features that are essential for both maintaining the health of the mitochondrial network and cellular demands. The accumulation of damaged mitochondria has been shown to be related to a wide range of pathologies ranging from neurological to musculoskeletal. Mitophagy is the selective autophagy of mitochondria, eliminating dysfunctional mitochondria in cells by engulfment within double-membraned vesicles. Preeclampsia and low birth weight constitute prenatal complications during pregnancy and are leading causes of maternal and fetal mortality and morbidity. Both placental implantation and fetal growth require a large amount of energy, and a defect in the mitochondrial quality control mechanism may be responsible for the pathophysiology of these diseases. In this review, we compiled current studies investigating the role of BNIP3, DRAM1, and FUNDC1, mediators of receptor-mediated mitophagy, in the progression of preeclampsia and the role of mitophagy pathways in the pathophysiology of low birth weight. Recent studies have indicated that mitochondrial dysfunction and accumulation of reactive oxygen species are related to preeclampsia and low birth weight. However, due to the lack of studies in this field, the results are controversial. Therefore, mitophagy-related pathways associated with these pathologies still need to be elucidated. Mitophagy-related pathways are among the promising study targets that can reveal the pathophysiology behind preeclampsia and low birth weight. Full article

(This article belongs to the Special Issue Perinatal-Related Pathology)

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Other

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16 pages, 2060 KiB

Open AccessSystematic Review

Current Evidence on Vasa Previa without Velamentous Cord Insertion or Placental Morphological Anomalies (Type III Vasa Previa): Systematic Review and Meta-Analysis

by Yuki Takemoto, Shinya Matsuzaki, Satoko Matsuzaki, Mamoru Kakuda, Misooja Lee, Harue Hayashida, Michihide Maeda and Shoji Kamiura

Biomedicines 2023, 11(1), 152; https://doi.org/10.3390/biomedicines11010152 - 7 Jan 2023

Cited by 11 | Viewed by 4975

Abstract

Vasa previa carries a high risk of severe fetal morbidity and mortality due to fetal hemorrhage caused by damage to unprotected fetal cord vessels upon membrane rupture. Vasa previa is generally classified into types I and II. However, some cases are difficult to classify, and some studies have proposed a type III classification. This study aimed to review the current evidence on type III vasa previa. A systematic literature search was conducted, and 11 articles (2011–2022) were included. A systematic review showed that type III vasa previa accounts for 5.7% of vasa previa cases. Thirteen women with type III vasa previa were examined at a patient-level analysis. The median age was 35 (interquartile range [IQR] 31.5–38) years, and approximately 45% were assisted reproductive technology (ART) pregnancies. The median gestational week of delivery was 36 (IQR 34–37) weeks; the antenatal detection rate was 84.6%, and no cases reported neonatal death. The characteristics and obstetric outcomes (rate of ART, antenatal diagnosis, emergent cesarean delivery, gestational age at delivery, and neonatal mortality) were compared between types I and III vasa previa, and all outcomes of interest were similar. The current evidence on type III vasa previa is scanty, and further studies are warranted. Full article

(This article belongs to the Special Issue Perinatal-Related Pathology)

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17 pages, 1441 KiB

Open AccessSystematic Review

The Characteristics and Obstetric Outcomes of Type II Vasa Previa: Systematic Review and Meta-Analysis

by Shinya Matsuzaki, Yutaka Ueda, Satoko Matsuzaki, Mamoru Kakuda, Misooja Lee, Yuki Takemoto, Harue Hayashida, Michihide Maeda, Reisa Kakubari, Tsuyoshi Hisa, Seiji Mabuchi and Shoji Kamiura

Biomedicines 2022, 10(12), 3263; https://doi.org/10.3390/biomedicines10123263 - 15 Dec 2022

Cited by 8 | Viewed by 2332

Abstract

Vasa previa is a rare fetal life-threatening obstetric disease classified into types I and II. This study aimed to examine the characteristics and obstetric outcomes of type II vasa previa. A systematic review was performed, and 20 studies (1998–2022) were identified. The results from six studies showed that type II vasa previa accounted for 21.3% of vasa previa cases. The characteristics and obstetric outcomes (rate of assisted reproductive technology (ART), antenatal diagnosis, emergent cesarean delivery, maternal transfusion, gestational age at delivery, and neonatal mortality) were compared between type I and II vasa previa, and all outcomes of interest were similar. The association between ART and abnormal placenta (bilobed placenta or succenturiate lobe) was examined in three studies, and the results were as follows: (i) increased rate of succenturiate lobes (ART versus non-ART pregnancy; OR (odds ratio) 6.97, 95% confidence interval (CI) 2.45–19.78); (ii) similar rate of abnormal placenta (cleavage-stage versus blastocyst embryo transfer); (iii) increased rate of abnormal placenta (frozen versus fresh embryo transfer; OR 2.97, 95%CI 1.10–7.96). Although the outcomes of type II vasa previa appear to be similar to those of type I vasa previa, the current evidence is insufficient for a robust conclusion. Full article

(This article belongs to the Special Issue Perinatal-Related Pathology)

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9 pages, 2210 KiB

Open AccessCase Report

Multispecialty Approach to a Very Large Congenital Head and Neck Cystic Lymphatic Malformation in an Infant Born by SARS-CoV-2 Positive Mother—A Case Report

by Greta Sibrecht, Katarzyna Wróblewska-Seniuk, Jakub Kornacki, Daniel Boroń, Jarosław Szydłowski, Anna Kłosowska, Ewa Bień, Ewa Wender-Ożegowska and Tomasz Szczapa

Biomedicines 2022, 10(10), 2422; https://doi.org/10.3390/biomedicines10102422 - 28 Sep 2022

Cited by 1 | Viewed by 1722

Abstract

Masses of the head and neck are often diagnosed prenatally and require special care due to the risk of airway obstruction. The EXIT procedure is a preferable mode of delivery. A congenital cystic lymphatic malformation is one of the most common lesions of the cervical region described in neonates. The treatment consists of different strategies and involves the cooperation of multiple specialists. Up to now, no guidelines or protocols are available. We report a case of a congenital cystic lymphatic malformation of the head and neck delivered during the EXIT procedure by a mother who was SARS-CoV-2 positive. We analyzed clinical characteristics, radiologic features, and treatment with injections of sclerotic agents and orally administrated sirolimus. Sirolimus seems a valuable and safe therapeutic option for treating lymphatic malformations, especially with adjunct therapies. Full article

(This article belongs to the Special Issue Perinatal-Related Pathology)

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21 pages, 4216 KiB

Open AccessSystematic Review

Assisted Reproductive Technique and Abnormal Cord Insertion: A Systematic Review and Meta-Analysis

by Shinya Matsuzaki, Yutaka Ueda, Satoko Matsuzaki, Yoshikazu Nagase, Mamoru Kakuda, Misooja Lee, Michihide Maeda, Hiroki Kurahashi, Harue Hayashida, Tsuyoshi Hisa, Seiji Mabuchi and Shoji Kamiura

Biomedicines 2022, 10(7), 1722; https://doi.org/10.3390/biomedicines10071722 - 17 Jul 2022

Cited by 11 | Viewed by 2224

Abstract

Abnormal cord insertion (ACI) is associated with adverse obstetric outcomes; however, the relationship between ACI and assisted reproductive technology (ART) has not been examined in a meta-analysis. This study examines the association between ACI and ART, and delivery outcomes of women with ACI. A systematic review was conducted, and 16 studies (1990–2021) met the inclusion criteria. In the unadjusted pooled analysis (n = 10), ART was correlated with a higher rate of velamentous cord insertion (VCI) (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.64–2.79), marginal cord insertion (n = 6; OR 1.58, 95%CI 1.26–1.99), and vasa previa (n = 1; OR 10.96, 95%CI 2.94–40.89). Nevertheless, the VCI rate was similar among the different ART types (blastocyst versus cleavage-stage transfer and frozen versus fresh embryo transfer). Regarding the cesarean delivery (CD) rate, women with VCI were more likely to have elective (n = 3; OR 1.13, 95%CI 1.04–1.22) and emergent CD (n = 5; OR 1.93, 95%CI 1.82–2.03). In conclusion, ART may be correlated with an increased prevalence of ACI. However, most studies could not exclude confounding factors; thus, further studies are warranted to characterize ART as a risk factor for ACI. In women with ACI, elective and emergent CD rates are high. Full article

(This article belongs to the Special Issue Perinatal-Related Pathology)

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