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BJOG : An International Journal of... Mar 2024Observational studies have described associations between obesity and adverse outcomes of pregnancy but observational results are liable to influence by residual...
OBJECTIVE
Observational studies have described associations between obesity and adverse outcomes of pregnancy but observational results are liable to influence by residual confounding. Mendelian randomisation (MR) leverages the 'natural' genetic randomisation to risk of an exposure occurring at allele assortment and conception. Similar to randomisation in a clinical trial, this limits the potential for the influence of confounding.
DESIGN
A two-sample MR study.
SETTING
Summary statistics from published genome wide association studies (GWAS) in European ancestry populations.
POPULATION OR SAMPLE
Instrumental variants for body mass index (BMI) were obtained from a study on 434 794 females.
METHODS
Inverse-variance weighted MR was used to assess the association between BMI and all outcomes. Sensitivity analyses with weighted median and MR-Egger were also performed.
MAIN OUTCOME MEASURES
Female-specific genetic association estimates for outcomes were extracted from the sixth round of analysis of the FINNGEN cohort data.
RESULTS
Higher genetically predicted BMI was associated with higher risk of pre-eclampsia (odds ratio [OR] per standard deviation 1.68, 95% confidence interval [CI] 1.46-1.94, P = 8.74 × 10 ), gestational diabetes (OR 1.67, 95% CI 1.46-1.92, P = 5.35 × 10 ), polyhydramnios (OR 1.40, 95% CI 1.00-1.96, P = 0.049). There was evidence suggestive of a potential association with higher risk of premature rupture of membranes (OR 1.16, 95% CI 1.00-1.36, P = 0.050) and postpartum depression (OR 1.12, 95% CI 0.99-1.27, P = 0.062).
CONCLUSIONS
Higher genetically predicted BMI is associated with marked increase in risk of pre-eclampsia, gestational diabetes and polyhydramnios. The relation between genetically predicted BMI and premature rupture of membranes and postpartum depression should be assessed in further studies. Our study supports efforts to target BMI as a cardinal risk factor for maternal morbidity in pregnancy.
Topics: Pregnancy; Humans; Female; Body Mass Index; Pre-Eclampsia; Genome-Wide Association Study; Diabetes, Gestational; Depression, Postpartum; Polyhydramnios; Polymorphism, Single Nucleotide
PubMed: 37667670
DOI: 10.1111/1471-0528.17650 -
American Journal of Medical Genetics.... Jan 2020Kabuki syndrome (KS) is a disorder of epigenetic dysregulation due to heterozygous mutations in KMT2D or KDM6A, genes encoding a lysine-specific methyltransferase or...
Kabuki syndrome (KS) is a disorder of epigenetic dysregulation due to heterozygous mutations in KMT2D or KDM6A, genes encoding a lysine-specific methyltransferase or demethylase, respectively. The phenotype is highly variable, including congenital cardiac and renal anomalies, developmental delay, hypotonia, failure to thrive, short stature, and immune dysfunction. All affected individuals have characteristic facial features. As KS natural history has not been fully delineated, limited information exists on its prenatal and perinatal history. Two tertiary centers collected retrospective data from individuals with KS (N = 49) using a questionnaire followed by review of medical records. Data from 49 individuals (age range: 7 months-33 years; 37% male; 36 with KMT2D mutations, 2 with KDM6A mutations, and 11 diagnosed clinically) were examined. Polyhydramnios affected 16 of 39 (41%) pregnancies. Abnormal quad screens in four out of nine (44%) pregnancies and reduced placental weights also complicated KS pregnancies. These data comprise the first large dataset on prenatal and perinatal history in individuals with confirmed (genetically or clinically) KS. Over a third of pregnancies were complicated by polyhydramnios, possibly secondary to abnormal craniofacial structures and functional impairment of swallowing. The differential diagnosis for polyhydramnios in the absence of intrauterine growth retardation should include KS.
Topics: Abnormalities, Multiple; Adolescent; Adult; Child; Child, Preschool; DNA-Binding Proteins; Diagnosis, Differential; Face; Female; Fetal Growth Retardation; Hematologic Diseases; Histone Demethylases; Humans; Infant; Male; Mutation; Neoplasm Proteins; Phenotype; Polyhydramnios; Pregnancy; Vestibular Diseases; Young Adult
PubMed: 31654559
DOI: 10.1002/ajmg.a.61387 -
The Laryngoscope Apr 2021Detection of fetal airway compromise through imaging raises the possible need for ex utero intrapartum treatment (EXIT) procedures. Despite EXIT procedures involving...
OBJECTIVE
Detection of fetal airway compromise through imaging raises the possible need for ex utero intrapartum treatment (EXIT) procedures. Despite EXIT procedures involving massive resource utilization and posing increased risk to the mother, decisions for EXIT are usually based on anecdotal experience. Our objectives were to analyze prenatal consultations with potential fetal airway obstruction for imaging and obstetric findings used to determine management strategy.
METHODS
Retrospective chart review was performed for prenatal abnormal fetal airway consults between 2004-2019 at a quaternary pediatric facility. Data collected included demographics, imaging characteristics, delivery information, and airway management. Our primary outcome was EXIT performance and the secondary outcome was postnatal airway management. Fisher's exact test was used to compare management decisions, outcomes, and imaging findings.
RESULTS
Thirty-seven patients met inclusion criteria. The most common diagnoses observed were lymphatic malformation, teratoma, and micrognathia. Of the imaging findings collected, only midline neck mass location was associated with EXIT procedure performance. Factors associated with invasive airway support at birth were mass-induced in-utero neck extension and neck vessel compression, polyhydramnios, and micrognathia.
CONCLUSIONS
Multidisciplinary input and interpretation of prenatal imaging can guide management of fetal airway-related pathology. EXIT is an overall safe procedure and can decrease risk due to airway obstruction at birth. We identified in-utero neck extension, neck vessel compression, micrognathia, and polyhydramnios as better indicators of a need for invasive airways measures at birth and suggest use of these criteria in combination with clinical judgement when recommending EXIT.
LEVEL OF EVIDENCE
4 Laryngoscope, 131:E1357-E1362, 2021.
Topics: Adult; Airway Management; Airway Obstruction; Cesarean Section; Female; Fetal Diseases; Gestational Age; Humans; Lymphatic Abnormalities; Male; Micrognathism; Neck; Pregnancy; Retrospective Studies; Teratoma; Ultrasonography, Prenatal
PubMed: 32770766
DOI: 10.1002/lary.28959 -
Computational Intelligence and... 2022To explore the prenatal ultrasonographic characteristics and pregnancy outcomes of fetal meconium peritonitis (FMP).
OBJECTIVE
To explore the prenatal ultrasonographic characteristics and pregnancy outcomes of fetal meconium peritonitis (FMP).
METHODS
Nine patients diagnosed with FMP by routine prenatal examination between January 2015 and December 2020 were identified. Both prenatal ultrasonographic characteristics and pregnancy outcomes associated with these patients were retrospectively analyzed.
RESULTS
The mean gestational age at the time of FMP diagnosis was 31.3 ± 4.8 weeks, and the mean gestational age of delivery was 35.1 ± 5.1 weeks. Prenatal ultrasonographic findings at the time of diagnosis in these patients included intestinal dilatation (9/9, 100%), intraperitoneal calcification (8/9, 88.9%), fetal ascites (5/9, 55.6%), intraperitoneal pseudocyst (5/9, 55.6%), and polyhydramnios (6/9, 66.7%). Analyses of the etiological basis for meconium peritonitis in 5 of the 8 live births that underwent surgical treatment revealed 4 cases of congenital volvulus and 1 case of jejunal atresia.
CONCLUSION
The prenatal ultrasound manifestations of fetal meconium peritonitis are diverse, and the different grades of prenatal ultrasound manifestations can provide important information for the treatment of perinatal infants.
Topics: Female; Fetal Diseases; Humans; Infant; Infant, Newborn; Meconium; Peritonitis; Pregnancy; Pregnancy Outcome; Retrospective Studies; Ultrasonography, Prenatal
PubMed: 35669660
DOI: 10.1155/2022/8658999 -
American Journal of Perinatology Sep 2023Shallow placental implantation (SPI) features placental maldistribution of extravillous trophoblasts and includes excessive amount of extravillous trophoblasts,...
OBJECTIVE
Shallow placental implantation (SPI) features placental maldistribution of extravillous trophoblasts and includes excessive amount of extravillous trophoblasts, chorionic microcysts in the membranes and chorionic disc, and decidual clusters of multinucleate trophoblasts. The histological lesions were previously and individually reported in association with various clinical and placental abnormalities. This retrospective statistical analysis of a large placental database from high-risk pregnancy statistically compares placentas with and without a composite group of features of SPI.
STUDY DESIGN
Twenty-four independent abnormal clinical and 44 other than SPI placental phenotypes were compared between 4,930 placentas without (group 1) and 1,283 placentas with one or more histological features of SPI (composite SPI group; group 2). Placentas were received for pathology examination at a discretion of obstetricians. Placental lesion terminology was consistent with the Amsterdam criteria, with addition of other lesions described more recently.
RESULTS
Cases of group 2 featured statistically and significantly ( < 0.001after Bonferroni's correction) more common than group 1 on the following measures: gestational hypertension, preeclampsia, oligohydramnios, polyhydramnios, abnormal Dopplers, induction of labor, cesarean section, perinatal mortality, fetal growth restriction, stay in neonatal intensive care unit (NICU), congenital malformation, deep meconium penetration, intravillous hemorrhage, villous infarction, membrane laminar necrosis, fetal blood erythroblastosis, decidual arteriopathy (hypertrophic and atherosis), chronic hypoxic injury (uterine and postuterine), intervillous thrombus, segmental and global fetal vascular malperfusion, various umbilical cord abnormalities, and basal plate myometrial fibers.
CONCLUSION
SPI placentas were statistically and significantly associated with 48% abnormal independent clinical and 51% independent abnormal placental phenotypes such as acute and chronic hypoxic lesions, fetal vascular malperfusion, umbilical cord abnormalities, and basal plate myometrial fibers among others. Therefore, SPI should be regarded as a category of placental lesions related to maternal vascular malperfusion and the "Great Obstetrical Syndromes."
KEY POINTS
· SPI reflects abnormal distribution of extravillous trophoblasts.. · SPI features abnormal clinical and placental phenotypes.. · SPI portends increased risk of complicated perinatal outcome..
Topics: Humans; Pregnancy; Female; Placenta; Placentation; Retrospective Studies; Cesarean Section; Placenta Diseases
PubMed: 34587634
DOI: 10.1055/s-0041-1735554 -
Journal of Clinical Medicine Nov 2021Although gastroschisis is often diagnosed by prenatal ultrasound, there is still a gap in the literature about which prenatal ultrasound markers can predict complex... (Review)
Review
Although gastroschisis is often diagnosed by prenatal ultrasound, there is still a gap in the literature about which prenatal ultrasound markers can predict complex gastroschisis. This systematic review and meta-analysis aimed to investigate the ultrasound markers that characterize complex gastroschisis. A systematic review of the literature was conducted according to the guidelines of PRISMA. The protocol was registered (PROSPERO ID CRD42020211685). Meta-analysis was displayed graphically on Forest plots, which estimate prevalence rates and risk ratios, with 95% confidence intervals, using STATA version 15.0. The combined prevalence of intestinal complications in fetuses with complex gastroschisis was 27.0%, with a higher prevalence of atresia (about 48%), followed by necrosis (about 25%). The prevalence of deaths in newborns with complex gastroschisis was 15.0%. The predictive ultrasound markers for complex gastroschisis were intraabdominal bowel dilatation (IABD) (RR 3.01, 95% CI 2.22 to 4.07; I = 15.7%), extra-abdominal bowel dilatation (EABD) (RR 1.55, 95% CI 1.01 to 2.39; I = 77.1%), and polyhydramnios (RR 3.81, 95% CI 2.09 to 6.95; I = 0.0%). This review identified that IABD, EABD, and polyhydramnios were considered predictive ultrasound markers for complex gastroschisis. However, evidence regarding gestational age at the time of diagnosis is needed.
PubMed: 34830497
DOI: 10.3390/jcm10225215 -
Annals of Human Genetics Mar 2021To assess the experience on prenatal diagnosis of Miller-Dieker syndrome (MDS) to further delineate the fetal presentation of this syndrome.
OBJECTIVE
To assess the experience on prenatal diagnosis of Miller-Dieker syndrome (MDS) to further delineate the fetal presentation of this syndrome.
METHODS
This was a retrospective study. Fetal MDS was diagnosed prenatally by chromosomal microarray (CMA). Clinical data were reviewed for these cases, including maternal characteristics, indications for prenatal diagnosis, sonographic findings, CMA results, and pregnancy outcomes.
RESULTS
Four cases were diagnosis as MDS by CMA. The most common sonographic features were ventriculomegaly (3/4) and polyhydramnios (2/4). Deletion sizes ranged from 1.5 to 5.4 Mb. All microdeletions were located at the MDS critical region and showed haploinsufficiency of the YWHAE, CRK, and PAFAH1B1. All patients chose to terminate the pregnancy. Parental chromosome analysis were preformed in three cases and demonstrated that two cases were de novo and one case was caused by inherited derivative chromosomes from parental balanced translocations.
CONCLUSION
The most common prenatal ultrasound findings of MDS were ventriculomegaly and polyhydramnios. CMA can improve diagnostic precision for detecting MDS.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; 14-3-3 Proteins; Adult; Chromosomes; Classical Lissencephalies and Subcortical Band Heterotopias; Female; Haploinsufficiency; Humans; Hydrocephalus; Microarray Analysis; Microtubule-Associated Proteins; Polyhydramnios; Pregnancy; Prenatal Diagnosis; Proto-Oncogene Proteins c-crk; Ultrasonography; Young Adult
PubMed: 33026665
DOI: 10.1111/ahg.12407 -
Best Practice & Research. Clinical... 2022Congenital enteropathies (CE) are a group of rare inherited diseases with a typical onset early in life. They involve defects in enterocyte structure or differentiation.... (Review)
Review
Congenital enteropathies (CE) are a group of rare inherited diseases with a typical onset early in life. They involve defects in enterocyte structure or differentiation. They can cause a severe condition of intestinal failure (IF). The diagnostic approach is based first on clinical presentation (consanguinity, prenatal expression, polyhydramnios, early neonatal onset, aspect of stools, persistence at bowel rest, associated extra-digestive manifestations….) and histo-pathological analyses. These rare intestinal diseases cause protracted diarrhea that might resolve, for a few, with a dietetic approach. However, protracted or permanent IF may require long term parenteral nutrition and, in limited cases, intestinal transplantation. With the progresses in both clinical nutrition and genetics, many of these CE are nowadays associated with recognized gene mutations. It improved our knowledge and the understanding in the patho-physiology of these diseases, thus, leading potentially to therapeutic perspectives. These review cover most of the early onset CE and excludes the immune related diarrhea.
Topics: Diarrhea; Enterocytes; Humans; Infant, Newborn; Intestinal Diseases; Intestines; Parenteral Nutrition
PubMed: 35331396
DOI: 10.1016/j.bpg.2021.101784 -
The Pediatric Infectious Disease Journal Jan 2024The diagnostic yield of TORCH screening for obstetrical indications is unclear. We evaluated TORCH testing results among women with intrauterine growth restriction... (Observational Study)
Observational Study
BACKGROUND
The diagnostic yield of TORCH screening for obstetrical indications is unclear. We evaluated TORCH testing results among women with intrauterine growth restriction (IUGR), polyhydramnios and oligohydramnios; and associations with congenital infections in neonates.
METHOD
This retrospective single-center study included all the women diagnosed with IUGR, polyhydramnios or oligohydramnios who underwent serological TORCH testing during 2010-2019. TORCH screening included Toxoplasma, cytomegalovirus (CMV), rubella IgM and IgG. The data, which were cross-referenced with data of neonates with congenital TORCH infections during the same period, included indications for neonatal testing, sonographic findings and neonatal ophthalmologic and hearing findings.
RESULT
Six women of 771 (0.8%) were diagnosed with primary TORCH infection: 4 (0.5%) with toxoplasmosis, and 2 (0.3%) with CMV. None had a confirmed congenital infection. The rates of positive maternal TORCH screening in IUGR and polyhydramnios were 2.1% and 0.6%, respectively. Maternal TORCH infection was not identified in any woman with oligohydramnios or severe polyhydramnios. None of the neonates with congenital infection were screened for TORCH during pregnancy due to polyhydramnios, oligohydramnios or IUGR. Among the neonates with congenital CMV, the most common indication for performing neonatal CMV polymerase chain reaction was suspected primary maternal infection during pregnancy due to symptomatic CMV. No incidences of congenital rubella were noted in the last decade in our medical center.
CONCLUSION
Our results suggest that routine TORCH screening in pregnancies complicated with IUGR, polyhydramnios or oligohydramnios should be avoided. Suggestive maternal symptoms and specific fetal sonographic features should prompt testing for CMV and Toxoplasma infection.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Retrospective Studies; Polyhydramnios; Oligohydramnios; Communicable Diseases; Rubella; Infant, Newborn, Diseases; Cytomegalovirus Infections; Fetal Growth Retardation; Cytomegalovirus; Toxoplasma; Pregnancy Complications, Infectious
PubMed: 37725823
DOI: 10.1097/INF.0000000000004107 -
European Journal of Obstetrics,... Feb 2024To analyze the risk for genetic aberrations and pregnancy outcomes in pregnancies with isolated polyhydramnios.
OBJECTIVE
To analyze the risk for genetic aberrations and pregnancy outcomes in pregnancies with isolated polyhydramnios.
STUDY DESIGN
This was a retrospective study of singleton pregnancies complicated by isolated polyhydramnios that underwent genetic amniocentesis between 2016 and 2021. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, chromosomal microarray results, and pregnancy outcomes.
RESULTS
A total of 94 singleton pregnancies were included. Three (3.2%) cases with chromosomal abnormalities were detected, including 2 case of trisomy 21 and 1 of 22q21.1 microdeletion. One case was diagnosed as Prader-Willi syndrome caused by maternal uniparental disomy of chromosome 15. Perinatal death occurred in 1 case with severe polyhydramnios, and was retrospectively diagnosed as Bartter syndrome. Of the 90 infants survived, two were identified to have single gene disorders after birth by whole exome sequencing.
CONCLUSION
We first attempted to determine the value of exome sequencing in pregnancies with isolated polyhydramnios. Our results warrant more studies to evaluate advanced genetic testing technologies used in such pregnancies.
Topics: Humans; Pregnancy; Female; Retrospective Studies; Polyhydramnios; Chromosome Aberrations; Pregnancy Outcome; Amniocentesis
PubMed: 38141485
DOI: 10.1016/j.ejogrb.2023.12.030