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Virulence Dec 2019In 2015-2016, in the Americas, and especially in northeast Brazil, a significant number of cases of microcephaly and other congenital brain abnormalities were linked... (Review)
Review
In 2015-2016, in the Americas, and especially in northeast Brazil, a significant number of cases of microcephaly and other congenital brain abnormalities were linked with an outbreak of Zika virus (ZIKV) infection in pregnant women. While maternal symptoms of ZIKV are generally mild and self-limiting, clinical presentation in fetuses and newborns infected is extensive and includes microcephaly, decreased cortical development, atrophy and hypoplasia of the cerebellum and cerebellar vermis, arthrogryposis, and polyhydramnios. The term congenital ZIKV syndrome (CZS) was introduced to describe the range of findings associated with maternal-fetal ZIKV transmission. ZIKV is primarily transmitted by mosquitoes, however non-vector-dependent routes are also possible. Mechanisms of maternal-fetal transmission remain unknown, and the trans-placental route has been extensively studied in animal models and in human samples. The aim of this review was to summarize recent studies that helped to elucidate the mechanism of CZS in animal models and observational studies. There are still challenges in the diagnosis and prevention of CZS in humans, due to the large gap that remains in translating ZIKV research to clinical practice. Translational research linking governments, local health workers, scientists and industry is fundamental to improve care for mothers and children.
Topics: Aedes; Animals; Brazil; Female; Host Microbial Interactions; Humans; Infectious Disease Transmission, Vertical; Mice; Microcephaly; Mosquito Vectors; Placenta; Pregnancy; Pregnancy Complications, Infectious; Zika Virus; Zika Virus Infection
PubMed: 31451049
DOI: 10.1080/21505594.2019.1656503 -
Journal of Pediatric Surgery Nov 2023Prenatal diagnosis of congenital malformations is considered favorable. Esophageal atresia (EA) is prenatally detected in 10-40% of patients. The aims of our study were...
BACKGROUND
Prenatal diagnosis of congenital malformations is considered favorable. Esophageal atresia (EA) is prenatally detected in 10-40% of patients. The aims of our study were to assess factors influencing the prenatal detection rate and to study the outcome in EA patients with and without prenatal diagnosis.
METHOD
We included 136 patients in two time periods, group 1 (1996-2002, n = 68) and group 2 (2014-2020, n = 68). We registered clinical variables; prenatal signs, perinatal and postnatal outcome from the electronic patient record.
RESULTS
Twenty-five patients (18%) had a prenatal diagnosis of EA, significantly more during 2014-2020 (28%), than during 1996-2002 (9%). Patients with EA type A or B and with associated anomalies had increased likelihood of prenatal diagnosis, odds ratio (OR) 9.00 (1.99-40.69) and 3.53 (1.24-10.06), respectively. Among the 25 patients with prenatal diagnosis all had polyhydramnios and 16 had small/absent stomach. Prenatally diagnosed patients arrived significantly earlier at the surgical unit (median 2 h (2 h-1 days) vs 21 h (2 h-1275 days)), had more delayed primary anastomosis (OR 8.80 (2.68-28.92)) and anastomotic stricture (OR 3.11 (1.20-8.04)), longer length of stay (median 62 days (11-212 days) vs 20 days (2-270 days)) and longer time on ventilator (median 5 days (1-25 days) vs 1.5 days (0.5-33 days)) compared to patients without prenatal diagnosis. In multivariate analysis prenatal diagnosis predicts length of stay.
CONCLUSION
Prenatally diagnosed EA patients have more; type A and B malformations, associated anomalies and neonatal morbidity. Consequences of the assumed benefits of prenatal diagnosis; opportunity of early arrival to surgical care and prenatal counselling, must be further studied.
PubMed: 37407414
DOI: 10.1016/j.jpedsurg.2023.05.015 -
Diagnostics (Basel, Switzerland) Nov 2023Klippel-Trenaunay syndrome (KTS) is a very rare vascular malformation syndrome also referred to as a capillary-lymphatic-venous malformation with unknown aetiology. The...
Klippel-Trenaunay syndrome (KTS) is a very rare vascular malformation syndrome also referred to as a capillary-lymphatic-venous malformation with unknown aetiology. The aim of our paper is to highlight interesting images, regarding a rare case of foetal Klippel-Trenaunay syndrome diagnosed prenatally in our department and confirmed postnatally with a favourable evolution during the gestation and neonatal periods. This case was diagnosed at 26 weeks gestation and characterised through ultrasound by the presence of superficial multiple cystic structures of different sizes spreading over the left leg with hemihypertrophy and reduced mobility. The cystic lesions were spreading to the left buttock and the pelvic area. The right leg and upper limbs had normal appearance with good mobility. There were no signs of hyperdynamic circulation or foetal anaemia, but mild polyhydramnios was associated. The ultrasound findings were confirmed postnatally, the left leg presented multiple cystic lesions and port wine stains, and there was hypertrophy and fixed position, with favourable evolution at 6 months of life, when the size of the lesions began to decrease and the mobility of the leg improved.
PubMed: 37998536
DOI: 10.3390/diagnostics13223400 -
Children (Basel, Switzerland) Oct 2022Idiopathic polyhydramnios is a controversial clinical condition, as data on perinatal outcomes are conflicting and vary depending on the severity of the condition. The...
Idiopathic polyhydramnios is a controversial clinical condition, as data on perinatal outcomes are conflicting and vary depending on the severity of the condition. The aim of the present study was to compare obstetric and neonatal outcomes between pregnant women with mild idiopathic polyhydramnios and a control population. : A retrospective cohort study was performed at a single university hospital comparing the obstetrics and neonatal outcomes of pregnancies with mild idiopathic polyhydramnios ( = 109) and control pregnancies ( = 2550). : Cesarean section (CS) was significantly increased in the group with polyhydramnios compared to controls (46% vs. 32%, respectively, = 0.047) due to a higher rate of emergency CS in the polyhydramnios group ( = 0.041) because of abnormal cardiotocography (7.3% vs. 2.9%; = 0.018) or labor dystocia (8.2% vs. 2.9%; = 0.006). No statistically significant difference was found in the Apgar score, in the rate of neonatal hypoxia, or in the incidence of macrosomia between groups. In four cases, additional diagnoses of anomalies were made after birth, with a rate of 3.2%, which is comparable to the general population. : Besides an increased risk of CS, patients with mild idiopathic polyhydramnios should be reassured regarding maternal and feto-neonatal outcomes. The management of pregnancies with stable mild idiopathic polyhydramnios should not differ from uncomplicated pregnancies, except for the need for increased labor surveillance.
PubMed: 36360352
DOI: 10.3390/children9111624 -
Antioxidants (Basel, Switzerland) Apr 2021Gestational diabetes mellitus (GDM) represents a challenging pregnancy complication in which women present a state of glucose intolerance. GDM has been associated with... (Review)
Review
Gestational diabetes mellitus (GDM) represents a challenging pregnancy complication in which women present a state of glucose intolerance. GDM has been associated with various obstetric complications, such as polyhydramnios, preterm delivery, and increased cesarean delivery rate. Moreover, the fetus could suffer from congenital malformation, macrosomia, neonatal respiratory distress syndrome, and intrauterine death. It has been speculated that inflammatory markers such as tumor necrosis factor-alpha (TNF-α), interleukin (IL) 6, and C-reactive protein (CRP) impact on endothelium dysfunction and insulin resistance and contribute to the pathogenesis of GDM. Nutritional patterns enriched with plant-derived foods, such as a low glycemic or Mediterranean diet, might favorably impact on the incidence of GDM. A high intake of vegetables, fibers, and fruits seems to decrease inflammation by enhancing antioxidant compounds. This aspect contributes to improving insulin efficacy and metabolic control and could provide maternal and neonatal health benefits. Our review aims to deepen the understanding of the impact of a plant-based diet on oxidative stress in GDM.
PubMed: 33918528
DOI: 10.3390/antiox10040557 -
Genes Feb 2023Pathogenic variants in are typically associated with a clinical condition called "capillary malformation-arteriovenous malformation" (CM-AVM) syndrome, an autosomal...
Pathogenic variants in are typically associated with a clinical condition called "capillary malformation-arteriovenous malformation" (CM-AVM) syndrome, an autosomal dominant genetic disease characterized by a broad phenotypic variability, even within families. In CM-AVM syndrome, multifocal capillary and arteriovenous malformations are mainly localized in the central nervous system, spine and skin. Although CM-AVM syndrome has been widely described in the literature, only 21 cases with prenatal onset of clinical features have been reported thus far. Here, we report four pediatric cases of molecularly confirmed CM-AVM syndrome which manifested during the prenatal period. Polyhydramnios, non-immune hydrops fetalis and chylothorax are only a few possible aspects of this condition, but a correct interpretation of these prenatal signs is essential due to the possible fatal consequences of unrecognized encephalic and thoracoabdominal deep vascular malformations in newborns and in family members carrying the same variant.
Topics: Female; Humans; Infant, Newborn; Child; Pregnancy; Mutation; p120 GTPase Activating Protein; Port-Wine Stain; Arteriovenous Malformations; GTPase-Activating Proteins
PubMed: 36980822
DOI: 10.3390/genes14030549 -
Australasian Journal of Ultrasound in... Aug 2021Polyhydramnios is common; the majority of cases are idiopathic, but maybe associated with fetal abnormality. Literature suggests the volume of amniotic fluid...
INTRODUCTION
Polyhydramnios is common; the majority of cases are idiopathic, but maybe associated with fetal abnormality. Literature suggests the volume of amniotic fluid discriminates idiopathic from pathological polyhydramnios but is not unanimous. We assessed fetal anomaly incidence amongst women with polyhydramnios and the role of discriminatory variables in identifying pathological cases.
METHODS
Retrospective observational cohort study at an inner-city London fetal medicine centre. Records for patients referred and/or diagnosed with polyhydramnios were reviewed as well as maternal/fetal demographics, amongst singleton pregnancies using the Astraia™ database from January 2015-2016. Estimated fetal weight was calculated using the Hadlock model (biometry undertaken at diagnosis). Student's t-test/one-way ANOVA compared means; chi-squared tests compared proportions.
RESULTS
120 cases were identified. 36 (30%) had fetal abnormality. There was no difference in AFI between fetuses with an abnormality and without (26.7 vs 25.2 cm, P = 0.22). AFI was normalised for weight (AFI (cm)/estimated fetal weight (kg)): AFI/kg was significantly different between cases with fetal abnormality and without (24.4 vs 16.7 cm/kg, P < 0.001) - incidence of abnormality increased with increasing AFI/kg (P = 0.007). Early gestational diagnosis was associated with higher rates of anomaly (P = 0.004). Differences in AFI/kg between those with and without abnormality were not significant when adjusted for gestation. AFI was significantly higher in cases of abnormality diagnosed at later gestation (P = 0.005).
CONCLUSION
Excess volume of amniotic fluid alone does not denote abnormality. Earlier gestations and higher AFI/kg corresponded with significantly increased rates of anomaly. However, the latter is a result of confounding by gestation, which is closely correlated with fetal weight.
PubMed: 34765423
DOI: 10.1002/ajum.12247 -
Maedica Sep 2019Polyhydramnios is frequently seen in patients with diabetes in pregnancy, as well as in cases of fetal malformations. The aim of our paper is to present a rare case of a...
Polyhydramnios is frequently seen in patients with diabetes in pregnancy, as well as in cases of fetal malformations. The aim of our paper is to present a rare case of a fetus with anomalies of the precordial veins (absent ductus venosus, intracardiac drainage of the umbilical vein, persistent left superior vena cava) and upper intestinal tract obstruction. The mother developed gestational diabetes and polyhydramnios, in this case. The 29-year-old patient was admitted to our hospital at 35 weeks of gestation with ruptured membranes. Cesarean section was performed. A live baby boy, 2400 g, with multiple congenital abnormalities (including esophageal atresia) was delivered. Our case illustrates the diagnostic approach to polyhydramnios and the difficulty to prenatally diagnose esophageal atresia, in the context of a fetus with multiple malformations.
PubMed: 31798750
DOI: 10.26574/maedica.2019.14.3.301 -
Molecular Genetics & Genomic Medicine Jun 2023Wolf-Hirschhorn syndrome (WHS) is a congenital malformation syndrome with poor prognosis. It is associated with a heterozygous deletion of chromosome 4p16.3. Adequate... (Review)
Review
OBJECTIVE
Wolf-Hirschhorn syndrome (WHS) is a congenital malformation syndrome with poor prognosis. It is associated with a heterozygous deletion of chromosome 4p16.3. Adequate knowledge of prenatal phenotypes and proper prenatal counseling are essential for intrauterine diagnosis.
METHOD
We retrospectively analyzed 11 prenatal cases of WHS diagnosed using low-depth whole-genome sequencing (copy number variation sequencing) performed at our hospital from May 2017 to September 2022 and reviewed their prenatal ultrasound reports in detail. We also analyzed WHS cases (including prenatal and postnatal) with abnormal prenatal ultrasound findings in the published literature over the past 20 years.
RESULTS
Among the 11 fetuses with a prenatal diagnosis of WHS in our hospital, four cases showed abnormal prenatal ultrasound findings, including shrunken kidneys, ventricular septal defect, a small stomach, fetal growth restriction (FGR), enlarged posterior fossa, and soft ultrasonic markers. Our four cases were combined with 114 published WHS cases with prenatal ultrasound abnormalities from other medical institutions. Of the 118 cases, 59.3% (70 of 118) were multiple malformations. The most frequent ultrasound features observed in all 118 cases were FGR (76.3%, 90 of 118), followed by facial anomalies (28.8%, 34 of 118), central nervous system anomalies (27.1%, 32 of 118), and soft ultrasound markers (23.7%, 28 of 118). Other less common phenotypes included cardiac anomalies (19.5%, 23 of 118), genitourinary anomalies (19.5%, 23 of 118), increased NT/NF (12.7%, 15 of 118), skeletal anomalies (11.9%, 14 of 118), a single umbilical artery (10.2%, 12 of 118), gastrointestinal anomalies (9.3%, 11 of 118), oligohydramnios (8.5%, 10 of 118), cystic hygroma (5.1%, six of 118), hydrops/pleural effusion/ascites (2.5%, three of 118), and polyhydramnios (2.5%, three of 118).
CONCLUSION
This study improved our understanding of the prenatal presentation of WHS by analyzing prenatal ultrasound abnormalities. The timely identification of prenatal ultrasound abnormalities can provide accurate consultation for pregnant women, improve the prenatal detection of WHS, and enable early prenatal management and intervention of WHS.
Topics: Female; Humans; Pregnancy; Wolf-Hirschhorn Syndrome; Retrospective Studies; DNA Copy Number Variations; Chromosome Deletion; Phenotype; Fetal Growth Retardation
PubMed: 36849216
DOI: 10.1002/mgg3.2155 -
British Journal of Clinical Pharmacology Jan 2022Indomethacin is used for the treatment of preterm labour, short cervices and idiopathic polyhydramnios during pregnancy. Few studies have described the pharmacokinetics...
AIMS
Indomethacin is used for the treatment of preterm labour, short cervices and idiopathic polyhydramnios during pregnancy. Few studies have described the pharmacokinetics (PK) of indomethacin during pregnancy. This study aimed to determine maternal and fetal PK of indomethacin during different trimesters of pregnancy using physiologically based PK (PBPK) modelling and simulations.
METHODS
Full PBPK simulations were performed in nonpregnant subjects and pregnant subjects from each trimester of pregnancy at steady state using Simcyp's healthy volunteers and pregnancy PBPK model, respectively. The fetal exposures were predicted using a fetoplacental pregnancy PBPK model. The models were verified by comparing PBPK-based predictions with observed PK profiles.
RESULTS
Predicted exposure (AUC ) and clearance of indomethacin in nonpregnant women and pregnant women are similar to the clinical observations. AUC of indomethacin is approximately 14, 24 and 32% lower, consistent with 18, 34 and 52% higher clearance in the first, second and third trimesters of pregnancy, respectively, compared to nonpregnant women. Predicted fetal plasma exposures increased by approximately 30% from the second trimester to the third trimester of pregnancy.
CONCLUSION
A mechanistic PBPK model adequately described the maternal and the fetal PK of indomethacin during pregnancy. As the pregnancy progresses, a modest decrease (≤32%) in systemic exposures in pregnant women and a 33% increase in fetal exposures to indomethacin were predicted. Higher fetal exposures in the third trimester of pregnancy may pose safety risks to the fetus. Additional studies are warranted to understand the exposure-response relationship and provide appropriate dosing recommendations during pregnancy that consider both safety and efficacy.
Topics: Female; Fetus; Humans; Indomethacin; Infant, Newborn; Models, Biological; Pregnancy; Pregnancy Trimester, Third; Pregnancy Trimesters
PubMed: 34185331
DOI: 10.1111/bcp.14960