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Journal of Clinical Medicine Apr 2023Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the... (Review)
Review
Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the phenotypic expression of gestational alloimmune liver disease (GALD). The diagnosis of NH-GALD is rarely prenatally established. In addition to providing a systematic review of the prenatal features that are identifiable using ultrasound (US) and MRI, we suggest a prenatal diagnosis algorithm for use in suspected NH during the first affected pregnancy. From a total of 586 database entries identified in PubMed, Google Scholar, and ResearchGate, we selected 18 studies published from 1993 to 2021 that reported maternal medical and obstetric history, prenatal ultrasound findings, and postpartum outcomes. We investigated the ultrasound and MRI features of these studies, along with the outcome due to this condition. A total of 74 cases were identified. The main reported prenatal US finding was fetal growth restriction (FGR) (33%), followed by oligohydramnios (13%) and hydrops fetalis (13%), with 13% cases described as uneventful. Other rare prenatal findings were fetal anemia, ascites, and abnormal fetal liver and spleen. Most pregnancies ended with fetal/perinatal death or therapeutic interruption of pregnancy. Favorable evolution with treatment (ensanguine transfusion and intravenous immunoglobulin (IVIG)) was reported for only 7% of fetuses. Using T2-weighted MRI, fetal extrahepatic siderosis confirmed prenatally in two cases and postnatally in 11 cases. IVIG treatment throughout subsequent pregnancies was found to significantly improve fetal prognosis. MRI should be indicated in selected cases of oligohydramnios, fetal hydrops, fetal hepatomegaly, ascites, or unexplained FGR or anemia after ruling out all other more frequently encountered conditions. MRI can be used to detect iron overload in the liver and extrahepatic siderosis.
PubMed: 37048762
DOI: 10.3390/jcm12072679 -
The Journal of Maternal-fetal &... Dec 2023To estimate the incremental yield of detecting pathogenic or likely pathogenic diagnostic genetic variants (DGV) by whole exome sequencing (WES) over standard karyotype... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the incremental yield of detecting pathogenic or likely pathogenic diagnostic genetic variants (DGV) by whole exome sequencing (WES) over standard karyotype and chromosomal microarray (CMA) analyses in fetuses with isolated increased nuchal translucency (NT) and normal fetal anatomy at the time of 11-14 weeks scan.
MATERIALS AND METHODS
Medline and Embase databases were searched. Inclusion criteria were fetuses with NT >95 percentile, normal karyotype and CMA and no associated structural anomalies at the time of the 11-14 weeks scan. The primary outcome was to estimate the incremental yield of detecting pathogenic or likely pathogenic genetic variants by WES over standard karyotype and CMA analyses in fetuses with isolated increased nuchal translucency. The secondary outcomes were the detection of a genetic variant of unknown significance. Sub-analysis according to different NT cutoffs (between 3.0 and 5.5 mm and > 5.5 mm) and considering fetuses with isolated NT in which fetal anatomy was confirmed to be normal at the anomaly scan were also performed. Random effects model meta-analyses of proportion were used to analyze the data.
RESULTS
Eight articles (324 fetuses) were included in the systematic review. Of the fetuses with negative standard karyotype and CMA analysis, the 8.07% (95% CI 5.4-11.3) had pathogenic or likely pathogenic genetic variants detected exclusively by WES. When stratifying the analysis according to NT cutoffs, genetic anomalies detected exclusively at WES analysis were found in 44.70% (95% CI 26.8-63.4) of fetuses with NT between 3.0 mm and 5.5 mm and 55.3% (95% CI 36.6-73.2) in those fetuses with NT >5.5 mm and positive WES results. The 7.84% (95% CI 1.6-18.2) had variants of unknown significance identified by WES. When considering fetuses with isolated increased NT and normal fetal anatomy at the anomaly scan, the rate of pathogenic or likely pathogenic genetic variants detected by WES was 3.87% (95% CI 1.6-7.1), while variants of unknown significance were detected in 4.27% (95% CI 2.2-7.0) of cases.
CONCLUSIONS
Pathogenic and likely pathogenic genetic variants detected by WES are present in a significant proportion of fetuses with increased NT but normal standard karyotype and CMA analysis, also when no anomalies are detected at the anomaly scan. Further large studies sharing objective protocols of imaging assessment are needed to confirm these findings and to elucidate which gene panels should be assessed in fetuses with isolated increased NT to rule out associated genetic anomalies, which may potentially impact post-natal outcomes.
Topics: Pregnancy; Female; Humans; Nuchal Translucency Measurement; Exome Sequencing; Fetus; Karyotyping; Karyotype; Prenatal Diagnosis
PubMed: 37019452
DOI: 10.1080/14767058.2023.2193285 -
American Journal of Obstetrics and... May 2023Green-stained amniotic fluid, often referred to as meconium-stained amniotic fluid, is present in 5% to 20% of patients in labor and is considered an obstetric hazard.... (Review)
Review
Green-stained amniotic fluid, often referred to as meconium-stained amniotic fluid, is present in 5% to 20% of patients in labor and is considered an obstetric hazard. The condition has been attributed to the passage of fetal colonic content (meconium), intraamniotic bleeding with the presence of heme catabolic products, or both. The frequency of green-stained amniotic fluid increases as a function of gestational age, reaching approximately 27% in post-term gestation. Green-stained amniotic fluid during labor has been associated with fetal acidemia (umbilical artery pH <7.00), neonatal respiratory distress, and seizures as well as cerebral palsy. Hypoxia is widely considered a mechanism responsible for fetal defecation and meconium-stained amniotic fluid; however, most fetuses with meconium-stained amniotic fluid do not have fetal acidemia. Intraamniotic infection/inflammation has emerged as an important factor in meconium-stained amniotic fluid in term and preterm gestations, as patients with these conditions have a higher rate of clinical chorioamnionitis and neonatal sepsis. The precise mechanisms linking intraamniotic inflammation to green-stained amniotic fluid have not been determined, but the effects of oxidative stress in heme catabolism have been implicated. Two randomized clinical trials suggest that antibiotic administration decreases the rate of clinical chorioamnionitis in patients with meconium-stained amniotic fluid. A serious complication of meconium-stained amniotic fluid is meconium aspiration syndrome. This condition develops in 5% of cases presenting with meconium-stained amniotic fluid and is a severe complication typical of term newborns. Meconium aspiration syndrome is attributed to the mechanical and chemical effects of aspirated meconium coupled with local and systemic fetal inflammation. Routine naso/oropharyngeal suctioning and tracheal intubation in cases of meconium-stained amniotic fluid have not been shown to be beneficial and are no longer recommended in obstetrical practice. A systematic review of randomized controlled trials suggested that amnioinfusion may decrease the rate of meconium aspiration syndrome. Histologic examination of the fetal membranes for meconium has been invoked in medical legal litigation to time the occurrence of fetal injury. However, inferences have been largely based on the results of in vitro experiments, and extrapolation of such findings to the clinical setting warrants caution. Fetal defecation throughout gestation appears to be a physiologic phenomenon based on ultrasound as well as in observations in animals.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Meconium Aspiration Syndrome; Meconium; Amniotic Fluid; Chorioamnionitis; Pregnancy Complications; Inflammation; Heme
PubMed: 37012128
DOI: 10.1016/j.ajog.2022.11.1283 -
Journal of Medical Internet Research Mar 2023Increasing prenatal screening options and limited consultation time have made it difficult for pregnant women to participate in shared decision-making. Interactive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Increasing prenatal screening options and limited consultation time have made it difficult for pregnant women to participate in shared decision-making. Interactive digital decision aids (IDDAs) could integrate interactive technology into health care to a facilitate higher-quality decision-making process.
OBJECTIVE
The objective of this study was to assess the effectiveness of IDDAs on pregnant women's decision-making regarding prenatal screening.
METHODS
We searched Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, World Health Organization International Clinical Trials Registry Platform, Google Scholar, and reference lists of included studies until August 2021. We included the randomized controlled trials (RCTs) that compared the use of IDDAs (fulfilling basic criteria of International Patient Decision Aid Standards Collaboration and these were interactive and digital) as an adjunct to standard care with standard care alone and involved pregnant women themselves in prenatal screening decision-making. Data on primary outcomes, that is, knowledge and decisional conflict, and secondary outcomes were extracted, and meta-analyses were conducted based on standardized mean differences (SMDs). Subgroup analysis based on knowledge was performed. The Cochrane risk-of-bias tool was used for risk-of-bias assessment.
RESULTS
Eight RCTs were identified from 10,283 references, of which 7 were included in quantitative synthesis. Analyses showed that IDDAs increased knowledge (SMD 0.58, 95% CI 0.26-0.90) and decreased decisional conflict (SMD -0.15, 95% CI -0.25 to -0.05). Substantial heterogeneity in knowledge was identified, which could not be completely resolved through subgroup analysis.
CONCLUSIONS
IDDAs can improve certain aspects of decision-making in prenatal screening among pregnant women, but the results require cautious interpretation.
Topics: Pregnancy; Female; Humans; Decision Support Techniques; Prenatal Diagnosis; Patient Participation
PubMed: 36917146
DOI: 10.2196/37953 -
Campbell Systematic Reviews Dec 2022The consequences for children born with birth defects and developmental disabilities encompassed by foetal alcohol spectrum disorder (FASD) are profound, affecting all... (Review)
Review
BACKGROUND
The consequences for children born with birth defects and developmental disabilities encompassed by foetal alcohol spectrum disorder (FASD) are profound, affecting all areas of social, behavioural and cognitive functioning. Given the strong evidence for a core deficit in executive functioning, underpinned by impaired self-regulation skills, there has been a growing focus on the development of interventions that enhance or support the development of executive functions (EFs).
OBJECTIVES
The primary objective of this review is to synthesise the evidence for structured psychological interventions that explicitly aim to improve EF in children. The review also sought to ascertain if the effectiveness of interventions were influenced by characteristics of the intervention, participants or type of EF targeted by the intervention.
SEARCH METHODS
Sixteen databases, 18 grey literature search locations and 9 trial registries were systematically searched to locate eligible studies (up to December 2020). These searches were supplemented with reference harvesting, forward citation searching, hand searches of topic-relevant journals and contact with experts.
SELECTION CRITERIA
Studies were included in the review if they reported on an impact evaluation of a psychological intervention aiming to improve EF in children 3-16 years who either had confirmed prenatal alcohol exposure or a formal diagnosis falling under the umbrella term of FASDs. Eligible study designs included randomised controlled trials (RCTs) and quasi-experimental designs with either no treatment, wait list control or an alternative treatment as a comparison condition. Single-group pre-post designs were also included.
DATA COLLECTION AND ANALYSIS
Standard methodological procedures expected by the Campbell Collaboration were used at all stages of this review. Standardised mean differences (SMDs) were used to estimate intervention effects, which were combined with random effects meta-analysis (data permitting). Risk of bias was assessed using the Cochrane Risk of Bias Tool (RoB2) and Cochrane Risk of Bias in Non-Randomised Studies-Interventions tool (ROBINS-I).
MAIN RESULTS
The systematic search identified 3820 unique records. After title/abstract and full-text screening, 11 eligible studies (reported in 21 eligible documents) were deemed eligible, with a combined 253 participants. Of the 11 studies, 6 were RCTs, 1 was a quasi-experiment and 4 were single-group pre-post intervention designs. All studies were rated as having an overall high or serious risk of bias, with some variation across domains for RCTs. For RCT and quasi-experimental studies, the overall effect of EF interventions on direct and indirect measures of EF generally favoured the experimental condition, but was not statistically significant. There was no difference between intervention and comparison groups on direct measures of auditory attention ( = 3; SMD = 0.06, 95% confidence interval [CI] = -1.06, 1.18), visual attention ( = 2; SMD = 0.90, 95% CI = -1.41, 3.21), cognitive flexibility ( = 2; SMD = 0.23, 95% CI = -0.40, 0.86), attentional inhibition ( = 2; SMD = 0.04, 95% CI = -0.58, 0.65), response inhibition ( = 3; SMD = 0.47, 95% CI = -0.04, 0.99), or verbal working memory ( = 1; = 0.6827; 95% CI = -0.0196, 1.385). Significant heterogeneity was found across studies on measures of auditory attention and visual attention, but not for measures of cognitive flexibility, attentional inhibition or response inhibition. Available data prohibited further exploration of heterogeneity. There was no statistical difference between intervention and comparison groups on indirect measures of global executive functioning ( = 2; SMD = 0.21, 95% CI = -0.40, 0.82), behavioural regulation ( = 2; SMD = 0.18, 95% CI = -0.43, 0.79), or emotional control ( = 3; SMD = 0.01, 95% CI = -0.33, 0.36). Effect sizes were positive and not significant for meta-cognition ( = 1; SMD = 0.23, 95% CI = -0.72, 1.19), shifting ( = 2; SMD = 0.04, 95% CI = -0.35, 0.43), initiation ( = 1; SMD = 0.04, 95% CI = -0.40, 0.49), monitoring ( = 1; SMD = 0.25, 95% CI = -0.20, 0.70) and organisation of materials ( = 1; SMD = 0.25, 95% CI = -0.19, 0.70). Effect sizes were negative and not statistically different for effortful control ( = 1; SMD = -0.53, 95% CI = -1.50, 0.45), inhibition ( = 2; SMD = -0.08, 95% CI = -0.47, 0.31), working memory ( = 1; SMD = 0.00, 95% CI = -0.45, 0.44), and planning and organisation ( = 1; SMD = -0.10, 95% CI = -0.55, 0.34). No statistically significant heterogeneity was found for any of the syntheses of indirect measures of EF. Based on pre-post single-group designs, there was evidence for small to medium sized improvements in EF based on direct measures (cognitive flexibility, verbal working memory and visual working memory) and indirect measures (behavioural regulation, shifting, inhibition and meta-cognition). However, these results must be interpreted with caution due to high risk of bias.
AUTHORS' CONCLUSIONS
This review found limited and uncertain evidence for the effectiveness of interventions for improving executive functioning in children with FASD across 8 direct and 13 indirect measures of EF. The findings are limited by the small number of high-quality studies that could be synthesised by meta-analysis and the very small sample sizes for the included studies.
PubMed: 36908848
DOI: 10.1002/cl2.1258 -
Prenatal Diagnosis May 2023The aim of this study was to determine the diagnostic yield of exome sequencing (ES) above that of chromosomal microarray analysis (CMA) or karyotyping in fetuses with... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to determine the diagnostic yield of exome sequencing (ES) above that of chromosomal microarray analysis (CMA) or karyotyping in fetuses with isolated fetal growth restriction (FGR). This was a systematic review conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Selected studies included those with (a) only fetuses with FGR in the absence of fetal structural anomalies and (b) negative CMA or karyotyping results. Only positive variants classified as likely pathogenic or pathogenic determined as causative of the fetal phenotype were considered. A negative CMA or karyotype result was treated as the reference standard. Eight studies with data on ES diagnostic yield, including 146 fetuses with isolated FGR, were identified. Overall, a pathogenic variant determined as potentially causative of the fetal phenotype was found in 17 cases, resulting in a 12% (95% CI: 7%-18%) incremental performance pool of ES. The vast majority were studied before 32 weeks'gestation. In conclusion, a monogenic disorder was prenatally found in association with apparently isolated FGR in 12% of these fetuses.
Topics: Pregnancy; Humans; Female; Fetal Growth Retardation; Exome Sequencing; Ultrasonography, Prenatal; Karyotyping; Microarray Analysis
PubMed: 36869857
DOI: 10.1002/pd.6339 -
Ultrasound in Obstetrics & Gynecology :... Jun 2023It is debated whether fetal endoscopic tracheal occlusion (FETO) is beneficial to fetuses with congenital diaphragmatic hernia (CDH) and whether FETO has different... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
It is debated whether fetal endoscopic tracheal occlusion (FETO) is beneficial to fetuses with congenital diaphragmatic hernia (CDH) and whether FETO has different effects in moderate and severe CDH. We conducted a systematic review and meta-analysis including the latest evidence to assess the overall effects of FETO on clinical outcomes of CDH.
METHODS
We searched PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database and Wanfang Database to retrieve eligible studies published before 8 September 2022. No language or study design restrictions were applied. Studies were included if CDH fetuses underwent FETO surgery and were compared with a cohort that underwent expectant management, with at least one outcome reported. The primary outcomes were mortality at 1, 6 and 12 months after birth, rates of pulmonary hypertension, use of extracorporeal membrane oxygenation (ECMO) and prematurity. Meta-analysis was conducted to obtain pooled odds ratios (ORs) and mean differences. The quality of included studies and pooled evidence was also assessed.
RESULTS
A total of 1187 CDH fetuses from 20 studies were included in the quantitative synthesis. FETO significantly reduced 1-month (OR, 0.56 (95% CI, 0.34-0.93); P = 0.02, number needed to treat (NNT) = 7.67) and 6-month (OR, 0.34 (95% CI, 0.18-0.65); P = 0.0009, NNT = 5.26) CDH mortality (moderate/low quality of evidence). Subgroup analysis suggested that the effects of FETO on the rates of pulmonary hypertension and ECMO usage were significant in severe CDH (low/moderate quality of evidence) but not in moderate CDH (low/very low quality of evidence). FETO was also associated with an increased risk of preterm prelabor rupture of membranes before 37 weeks' gestation (OR, 4.94 (95% CI, 2.25-10.88); P < 0.0001, number needed to harm (NNH) = 3.13) and preterm birth before 37 weeks (OR, 5.24 (95% CI, 3.33-8.23); P < 0.00001, NNH = 2.79) (high/moderate quality of evidence). However, FETO was not associated with severe complications, such as preterm birth before 32 weeks, placental abruption or chorioamnionitis (very low/low quality of evidence).
CONCLUSIONS
FETO is associated with a reduction in mortality, rate of pulmonary hypertension and ECMO usage in severe CDH, while it reduces only the risk of mortality in moderate CDH. Although FETO increases the risk of late prematurity, it does not result in extreme prematurity. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Infant, Newborn; Female; Humans; Pregnancy; Hernias, Diaphragmatic, Congenital; Fetoscopy; Hypertension, Pulmonary; Premature Birth; Placenta; Fetus; Trachea
PubMed: 36704940
DOI: 10.1002/uog.26164 -
Diagnostics (Basel, Switzerland) Jan 2023It is rare to detect echogenic content in the fetal gallbladder. The etiology, natural course, and prognosis of this condition remain unclear. In addition to providing a... (Review)
Review
It is rare to detect echogenic content in the fetal gallbladder. The etiology, natural course, and prognosis of this condition remain unclear. In addition to providing a systematic review of this topic, we suggest a plan for patient follow-up. From a total of 100 database entries identified in PubMed, EMBASE, and ICTRP reviews, we selected 34 studies in which we investigated the ultrasound features and outcome of this condition. There were 226 fetuses with gallbladder echogenic content identified. Seventy-two fetuses were found to have biliary sludge; thirty cases had a single hyperechogenic focus, and one hundred fetuses had multiple foci in the gallbladder. There were 16 cases of distal shadowing, 37 fetuses with comet tail and twinkling, and 26 cases with no acoustic artifacts. Nine cases of spontaneous resolution before birth have been documented; nine fetuses exhibited no echogenic content at birth, and 138 cases of resolution of echogenic content within the first year of life have been described. Typically, the condition resolves spontaneously during the postnatal period. After adequately reassuring the parents, the patients should be monitored for spontaneous resolution; medical or surgical intervention is not indicated. Asymptomatic patients can be managed with a wait-and-see strategy.
PubMed: 36673040
DOI: 10.3390/diagnostics13020230 -
Diagnostics (Basel, Switzerland) Jan 2023Methodological advancements, such as relative haplotype and relative mutation dosage analyses, have enabled non-invasive prenatal diagnosis of autosomal recessive and... (Review)
Review
BACKGROUND
Methodological advancements, such as relative haplotype and relative mutation dosage analyses, have enabled non-invasive prenatal diagnosis of autosomal recessive and X-linked diseases. Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by progressive proximal muscular dystrophy and a high mortality rate before the age of twenty. We aimed to systematically present obtainable data regarding a non-invasive prenatal diagnosis of DMD and provide a comprehensive resume on the topic. The emphasis was given to the comparison of different available protocols and molecular methods used for fetal inheritance deduction, as well as their correlation with prognostic accuracy.
METHODS
We searched the Scopus and PubMed databases on 11 November 2022 and included articles reporting a non-invasive prenatal diagnosis of DMD in families at risk using relative dosage analysis methods.
RESULTS
Of the 342 articles identified, 7 met the criteria. The reported accuracy of NIPT for DMD was 100% in all of the studies except one, which demonstrated an accuracy of 86.67%. The combined accuracy for studies applying indirect RHDO, direct RHDO, and RMD approaches were 94.74%, 100%, and 100%, respectively. Confirmatory results by invasive testing were available in all the cases. Regardless of the technological complexity and low prevalence of the disease that reduces the opportunity for systematic research, the presented work demonstrates substantial accuracy of NIPT for DMD.
CONCLUSIONS
Attempts for its implementation into everyday clinical practice raise many ethical and social concerns. It is essential to provide detailed guidelines and arrange genetic counseling in order to ensure the proper indications for testing and obtain informed parental consent.
PubMed: 36672993
DOI: 10.3390/diagnostics13020183 -
Prenatal Diagnosis May 2023Aetiological understanding and screening methods for congenital heart disease (CHD) are limited. Maternal metabolomic assessment offers the potential to identify risk... (Review)
Review
Aetiological understanding and screening methods for congenital heart disease (CHD) are limited. Maternal metabolomic assessment offers the potential to identify risk factors and biomarkers. We performed a systematic review (PROSPERO CRD42022308452) investigating the association between fetal/childhood CHD and endogenous maternal metabolites. Ovid-MEDLINE, Ovid-EMBASE and Cochrane Library were searched between inception and 06/09/2022. Case control studies included analysing maternal blood or urine metabolites in pregnancy or postpartum where there was foetal/childhood CHD. Risk of bias assessment utilised the Scottish Intercollegiate Guidelines Network methodology checklist and narrative synthesis was performed. A total of 134 records were screened with eight eligible studies (n = 3242 pregnancies, n = 842 CHD-affected offspring). Five studies performed metabolomic analysis in pregnancy. Metabolites distinguishing case and control groups spanned lipid, glucose and amino-acid pathways, with the development of sensitive risk prediction models. No single metabolite consistently distinguished cases and controls across studies. Three studies performed targeted analysis postnatally with altered lipid and amino acid metabolites and raised homocysteine and markers of oxidative stress identified in cases. Included studies reported small sample sizes, analysing different biosamples at variable time points using differing techniques. At present, there is not enough evidence to confidently associate maternal metabolomic profiles with offspring CHD risk. However, several identified pathways warrant further investigation.
Topics: Female; Pregnancy; Humans; Child; Heart Defects, Congenital; Metabolomics; Family; Case-Control Studies; Lipids
PubMed: 36617630
DOI: 10.1002/pd.6301