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Journal of Perinatal Medicine May 2016Succinic semialdehyde dehydrogenase (SSADH) deficiency is a neurometabolic disease in which the degradation of γ-aminobutyric acid (GABA) is impaired. The purpose of... (Review)
Review
Mutation analysis and prenatal diagnosis in a Chinese family with succinic semialdehyde dehydrogenase and a systematic review of the literature of reported ALDH5A1 mutations.
AIMS
Succinic semialdehyde dehydrogenase (SSADH) deficiency is a neurometabolic disease in which the degradation of γ-aminobutyric acid (GABA) is impaired. The purpose of this study was to report two novel ALDH5A1 mutations responsible for SSADH deficiency in a Chinese family and the prenatal diagnosis of an at-risk fetus with DNA sequencing.
RESULTS
Genetic analysis of ALDH5A1, in a child with SSADH deficiency, parents, and 10 weeks' gestation at-risk fetus and 100 healthy unrelated volunteers, was performed. The coding sequence and the intron/exon junctions of ALDH5A1 were analyzed by bidirectional DNA sequencing. The proband was identified to have a compound heterozygous mutations with c.496T>C (p.W166R) and c.589G>A (p.V197M). Each of his parents carried a deleterious mutation. DNA sequencing of chorionic villus revealed the fetus was a carrier, but not affected, and this was confirmed after birth by genetic analysis of umbilical cord blood and urine organic acid analysis. A study in 2003 described 35 mutations of ALDH5A1 in 54 unrelated families, and the current study and systematic literature review identified nine additional novel mutations in eight unrelated families bringing the total number of unique mutations of ALDH5A1 resulting in SSADH deficiency to 44, and the 44 mutations occur from exon 1 to exon 10. No mutational hotspots or prevalent mutations were observed, and all mutations appeared vital for the function of SSADH.
CONCLUSIONS
Two novel ALDH5A1 mutations likely responsible for SSADH deficiency were identified, and DNA sequencing provided an accurate diagnosis for an at-risk fetus whose sibling had SSADH deficiency.
Topics: Amino Acid Metabolism, Inborn Errors; Amino Acid Sequence; Amino Acid Substitution; Asian People; Base Sequence; China; Conserved Sequence; DNA Mutational Analysis; Developmental Disabilities; Female; Genetic Testing; Heterozygote; Humans; Infant; Male; Mutation, Missense; Pregnancy; Prenatal Diagnosis; Succinate-Semialdehyde Dehydrogenase
PubMed: 25431891
DOI: 10.1515/jpm-2014-0164 -
BJOG : An International Journal of... Jul 2021Phaeochromocytoma and paraganglioma (PPGL) in pregnancy, if not diagnosed antepartum, pose a high risk for mother and child.
BACKGROUND
Phaeochromocytoma and paraganglioma (PPGL) in pregnancy, if not diagnosed antepartum, pose a high risk for mother and child.
OBJECTIVE
To examine the clinical clues of antepartum and postpartum/postmortem diagnosis of PPGL.
SEARCH STRATEGY
Case reports on PPGL in pregnancy published between 1 January 1988 and 30 June 2019 in English, German, Dutch or French.
SELECTION CRITERIA
Case reports containing a predefined minimum of clinical data on PPGL and pregnancy.
DATA COLLECTION AND ANALYSIS
Two authors independently performed data extraction and assessed data quality. We calculated odds ratios (OR) (with 95% confidence intervals) and used uni- and multivariable logistic regression analysis.
MAIN RESULTS
Maternal and fetal/neonatal mortalities were 9.0% (18/200) and 14.2% (29/204), respectively. Maternal mortality was 42-fold higher with PPGL diagnosed postpartum/postmortem (17/58; 29.3%) than antepartum (1/142; 0.7%) (adjusted OR 45.9, 95% CI 5.67-370, P = 0.0003). Offspring mortality was 2.6-fold higher with PPGL diagnosed postpartum/postmortem than antepartum (OR 3.1, 95% CI 1.38-6.91, P = 0.0044). Hypertension at admission (OR 2.29, 95% CI 1.12-4.68, P = 0.022), sweating (OR 3.14, 95% CI 1.29-7.63, P = 0.014) and a history of PPGL, a known PPGL-associated gene mutation or adrenal mass (OR 8.87, 95% CI 1.89-41.64, P = 0.0056) were independent factors of antepartum diagnosis. Acute onset of symptoms (OR 8.49, 95% CI 3.52-20.5, P < 0.0001), initial diagnosis of pre-eclampsia (OR 6.34, 95% CI 2.60-15.5, P < 0.0001), admission for obstetric care (OR 10.71, 95% CI 2.70-42.45, P = 0.0007) and maternal tachycardia (OR 2.72, 95% CI 1.26-5.85, P = 0.011) were independent factors of postpartum diagnosis.
CONCLUSION
Several clinical clues can assist clinicians in considering an antenatal diagnosis of PPGL in pregnancy, thus potentially improving outcome.
TWEETABLE ABSTRACT
Systematic review of 204 pregnant patients with phaeochromocytoma identified clinical clues for a timely antepartum diagnosis.
Topics: Adrenal Gland Neoplasms; Early Diagnosis; Female; Humans; Infant; Infant Mortality; Infant, Newborn; Paraganglioma; Pheochromocytoma; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prenatal Diagnosis; Prognosis; Risk Factors
PubMed: 33342020
DOI: 10.1111/1471-0528.16635 -
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 -
Clinical Genetics Dec 2021Exome sequencing (ES) enhanced the diagnostic yield of genetic testing, but has also increased the possibility of uncertain findings. Prenatal ES is increasingly being...
Exome sequencing (ES) enhanced the diagnostic yield of genetic testing, but has also increased the possibility of uncertain findings. Prenatal ES is increasingly being offered after a fetal abnormality is detected through ultrasound. It is important to know how to handle uncertainty in this particularly stressful period. This systematic review aimed to provide a comprehensive overview of guidelines available for addressing uncertainty related to prenatal chromosomal microarray (CMA) and ES. Ten uncertainty types associated with prenatal ES and CMA were identified and defined by an international multidisciplinary team. Medline (all) and Embase were systematically searched. Laboratory scientists, clinical geneticists, psychologists, and a fetal medicine specialist screened the papers and performed the data extraction. Nineteen papers were included. Recommendations generally emphasized the importance of trio analysis, clinical information, data sharing, validation and re-analysis, protocols, multidisciplinary teams, genetic counselling, whether to limit the possible scope of results, and when to report particular findings. This systematic review helps provide a vocabulary for uncertainties, and a compass to navigate uncertainties. Prenatal CMA and ES guidelines provide a strong starting point for determining how to handle uncertainty. Gaps in guidelines and recommendations were identified and discussed to provide direction for future research and policy making.
Topics: Clinical Decision-Making; Disease Management; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genomics; Health Policy; Humans; Practice Guidelines as Topic; Pregnancy; Prenatal Diagnosis; Uncertainty
PubMed: 34155632
DOI: 10.1111/cge.14010 -
Prenatal Diagnosis Oct 2017The objective of the study is to compare outcomes of ultrasound-guided aspiration of fetal ovarian cysts with conservative management. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective of the study is to compare outcomes of ultrasound-guided aspiration of fetal ovarian cysts with conservative management.
METHOD
A systematic review of MEDLINE and Web of Science included studies reporting outcomes (prenatal and postnatal torsion, spontaneous resolution and surgery) of fetuses with ovarian cysts. Subgroup analysis was performed according to cyst diameter at diagnosis and cysts ≥40 mm.
RESULTS
Ninety-two non-randomised studies reported on 380 cysts (324 observed and 56 aspirated in utero) in 365 fetuses. All studies were case reports or series with high heterogeneity and risk of bias. The overall spontaneous resolution rate of conservatively managed cysts was 46%, yet decreased with increasing cyst size. Risk of prenatal ovarian torsion in conservatively managed cases depended on cyst size and was particularly important in the range 30 to 59 mm (15-34%). The rate of prenatal torsion in simple cysts ≥40 mm was lower in aspirated than conservatively managed cysts (0% vs 10%, p = 0.03). Aspirated cysts had lower rates of postnatal surgery (7%) compared with conservatively managed cysts (49%, p < 0.001).
CONCLUSION
Cysts 30 to 59 mm were at highest risk of torsion. Simple cysts >40 mm had lower rates of torsion when aspirated prenatally. Randomised studies and safety data are needed prior to routine prenatal ovarian cyst aspiration. © 2017 John Wiley & Sons, Ltd.
Topics: Female; Fetal Diseases; Humans; MEDLINE; Ovarian Cysts; Ovarian Diseases; Pregnancy; Risk Factors; Suction; Torsion Abnormality; Treatment Outcome; Ultrasonography, Prenatal
PubMed: 28886226
DOI: 10.1002/pd.5143 -
Ultrasound in Obstetrics & Gynecology :... Jan 2011Array comparative genomic hybridization (CGH) is transforming clinical cytogenetics with its ability to interrogate the human genome at increasingly high resolution. The... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Array comparative genomic hybridization (CGH) is transforming clinical cytogenetics with its ability to interrogate the human genome at increasingly high resolution. The aim of this study was to determine whether array CGH testing in the prenatal population provides diagnostic information over conventional karyotyping.
METHODS
MEDLINE (1970 to December 2009), EMBASE (1980 to December 2009) and CINAHL (1982 to December 2009) databases were searched electronically. Studies were selected if array CGH was used on prenatal samples or if array CGH was used on postnatal samples following termination of pregnancy for structural abnormalities that were detected on an ultrasound scan. Of the 135 potential articles, 10 were included in this systematic review and eight were included in the meta-analysis. The pooled rate of extra information detected by array CGH when the prenatal karyotype was normal was meta-analyzed using a random-effects model. The pooled rate of receiving an array CGH result of unknown significance was also meta-analyzed.
RESULTS
Array CGH detected 3.6% (95% CI, 1.5-8.5) additional genomic imbalances when conventional karyo-typing was 'normal', regardless of referral indication. This increased to 5.2% (95% CI, 1.9-13.9) more than karyotyping when the referral indication was a structural malformation on ultrasound.
CONCLUSIONS
There appears to be an increased detection rate of chromosomal imbalances, compared with conventional karyotyping, when array CGH techniques are employed in the prenatal population. However, some are copy number imbalances that are not clinically significant. This carries implications for prenatal counseling and maternal anxiety.
Topics: Chromosome Aberrations; Chromosome Disorders; Comparative Genomic Hybridization; Female; Genome, Human; Humans; Karyotyping; Oligonucleotide Array Sequence Analysis; Pregnancy; Prenatal Diagnosis
PubMed: 20658510
DOI: 10.1002/uog.7754 -
Ultrasound in Obstetrics & Gynecology :... Jul 2017To explore the outcome of fetuses with a prenatal diagnosis of ovarian cyst. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To explore the outcome of fetuses with a prenatal diagnosis of ovarian cyst.
METHODS
The electronic databases MEDLINE and EMBASE were searched using keywords and word variants for 'ovarian cysts', 'ultrasound' and 'outcome'. The following outcomes in fetuses with a prenatal diagnosis of ovarian cyst were explored: resolution of the cyst, change of ultrasound pattern of the cyst, occurrence of ovarian torsion and intracystic hemorrhage, need for postnatal surgery, need for oophorectomy, accuracy of prenatal ultrasound examination in correctly identifying ovarian cyst, type of ovarian cyst at histopathological analysis and intrauterine treatment. Meta-analyses using individual data random-effects logistic regression and meta-analyses of proportions were performed. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale.
RESULTS
Thirty-four studies (954 fetuses) were included. In 53.8% (95% CI, 46.0-61.5%) of cases for which resolution of the cyst was evaluated (784 fetuses), the cyst regressed either during pregnancy or after birth. The likelihood of resolution was significantly lower in complex vs simple cysts (odds ratio (OR), 0.15 (95% CI, 0.10-0.23)) and in cysts measuring ≥ 40 mm vs < 40 mm (OR, 0.03 (95% CI, 0.01-0.06)). Change in ultrasound pattern of the cyst was associated with an increased risk of ovarian loss (surgical removal or autoamputation) (pooled proportion, 57.7% (95% CI, 42.9-71.8%)). The risk of ovarian torsion was significantly higher for cysts measuring ≥ 40 mm compared with < 40 mm (OR, 30.8 (95% CI, 8.6-110.0)). The likelihood of having postnatal surgery was higher in patients with cysts ≥ 40 mm compared with < 40 mm (OR, 64.4 (95% CI, 23.6-175.0)) and in complex compared with simple cysts, irrespective of cyst size (OR, 14.6 (95% CI, 8.5-24.8)). In cases undergoing prenatal aspiration of the cyst, rate of recurrence was 37.9% (95% CI, 14.8-64.3%), ovarian torsion and intracystic hemorrhage were diagnosed after birth in 10.8% (95% CI, 4.4-19.7%) and 12.8% (95% CI, 3.8-26.0%), respectively, and 21.8% (95% CI, 0.9-40.0%) had surgery after birth.
CONCLUSION
Size and ultrasound appearance are the major determinants of perinatal outcome in fetuses with ovarian cysts. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Female; Humans; Ovarian Cysts; Predictive Value of Tests; Pregnancy; Ultrasonography, Prenatal
PubMed: 27325566
DOI: 10.1002/uog.16002 -
Gynecologie, Obstetrique, Fertilite &... Oct 2019To investigate prenatal diagnosis characteristics and pregnancy outcomes associated with isolated right aortic arch (RAA).
OBJECTIVE
To investigate prenatal diagnosis characteristics and pregnancy outcomes associated with isolated right aortic arch (RAA).
METHODS
A retrospective study including fetuses with isolated RAA, managed between January 2010 and February 2018. Cases were identified from the ultrasound databases of the expert pediatric cardiologists, who made the aforementioned diagnosis. All fetuses were examined by a fetal medicine imaging expert to exclude any extracardiac abnormality. A systematic review was performed to assess the prenatal diagnosis and outcomes of fetuses with isolated RAA.
RESULTS
Fifty-six fetuses were diagnosed with an isolated RAA. An isolated double aortic arch (DAA) was diagnosed in one fetus. Mean gestational age at diagnosis was 24 weeks. The sex ratio (boy/girl) was 0.89. No significant abnormality was detected in invasive tests (karyotype and FISH or microarray). Only one fetus was misdiagnosed with isolated RAA. He was the only symptomatic (stridor) newborn baby and was later diagnosed with DAA. Four studies were included in our systematic review representing 115 cases of isolated RAA. One significant chromosomal abnormality was detected: a 22q11 deletion in a newborn baby who had a postnatal finding of a soft palate cleft. There was one major obstetric complication: an intrauterine fetal demise at 41 gestational weeks.
CONCLUSION
Diagnosis of isolated RAA can be challenging. Invasive tests are to be discussed. The diagnosis of isolated RAA should not change obstetric monitoring. Nevertheless, an echocardiography should be performed systematically in these new newborn babies within their first month of life.
Topics: Adult; Aortic Arch Syndromes; Cleft Palate; Echocardiography; Female; Gene Deletion; Humans; Infant, Newborn; Male; Palate, Soft; Pregnancy; Pregnancy Outcome; Retrospective Studies; Ultrasonography, Prenatal
PubMed: 31494313
DOI: 10.1016/j.gofs.2019.09.002 -
Obstetrics and Gynecology Sep 2023To determine the causes and potential preventability of perinatal deaths in prenatally identified cases of vasa previa.
OBJECTIVE
To determine the causes and potential preventability of perinatal deaths in prenatally identified cases of vasa previa.
DATA SOURCES
Reports of prenatally identified cases of vasa previa published in the English language literature since 2000 were identified in Medline and ClinicalTrials.gov with the search terms "vasa previa," "abnormal cord insertion," "velamentous cord," "marginal cord," "bilobed placenta," and "succenturiate lobe."
METHODS OF STUDY SELECTION
All cases from the above search with an antenatally diagnosed vasa previa present at delivery in singleton or twin gestations with perinatal mortality information were included.
TABULATION, INTEGRATION, AND RESULTS
Cases meeting inclusion criteria were manually abstracted, and multiple antenatal, intrapartum, and outcome variables were recorded. Deaths and cases requiring neonatal transfusion were analyzed in relation to plurality, routine hospitalization, and cervical length monitoring. A total of 1,109 prenatally diagnosed cases (1,000 singletons, 109 twins) were identified with a perinatal mortality rate attributable to vasa previa of 1.1% (95% CI 0.6-1.9%). All perinatal deaths occurred with unscheduled deliveries. The perinatal mortality rate in twin pregnancies was markedly higher than that in singleton pregnancies (9.2% vs 0.2%, P <.001), accounting for 80% of overall mortality despite encompassing only 9.8% of births. Compared with individuals with singleton pregnancies, those with twin pregnancies are more likely to undergo unscheduled delivery (56.4% vs 35.1%, P =.01) despite delivering 2 weeks earlier (33.2 weeks vs 35.1 weeks, P =.006). An institutional policy of routine hospitalization is associated with a reduced need for neonatal transfusion (0.9% vs 6.0%, P <.001) and a reduction in the perinatal mortality rate in twin pregnancies (0% vs 25%, P =.002) but not in singleton pregnancies (0% vs 0.5%, P =.31).
CONCLUSION
Routine hospitalization and earlier delivery of twins may result in a reduction in the perinatal mortality rate. A smaller benefit from routine admission of individuals with singleton pregnancies cannot be excluded. There is currently insufficient evidence to recommend the routine use of cervical length measurements to guide clinical management.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Vasa Previa; Perinatal Death; Perinatal Mortality; Retrospective Studies; Prenatal Diagnosis; Pregnancy, Twin; Ultrasonography, Prenatal
PubMed: 37535966
DOI: 10.1097/AOG.0000000000005296 -
Ultrasound in Obstetrics & Gynecology :... Jun 2016To explore the outcome in fetuses with prenatal diagnosis of posterior fossa anomalies apparently isolated on ultrasound imaging. (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of isolated posterior fossa malformations on prenatal ultrasound imaging (part 1): nomenclature, diagnostic accuracy and associated anomalies.
OBJECTIVE
To explore the outcome in fetuses with prenatal diagnosis of posterior fossa anomalies apparently isolated on ultrasound imaging.
METHODS
MEDLINE and EMBASE were searched electronically utilizing combinations of relevant medical subject headings for 'posterior fossa' and 'outcome'. The posterior fossa anomalies analyzed were Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC) and vermian hypoplasia (VH). The outcomes observed were rate of chromosomal abnormalities, additional anomalies detected at prenatal magnetic resonance imaging (MRI), additional anomalies detected at postnatal imaging and concordance between prenatal and postnatal diagnoses. Only isolated cases of posterior fossa anomalies - defined as having no cerebral or extracerebral additional anomalies detected on ultrasound examination - were included in the analysis. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. We used meta-analyses of proportions to combine data and fixed- or random-effects models according to the heterogeneity of the results.
RESULTS
Twenty-two studies including 531 fetuses with posterior fossa anomalies were included in this systematic review. The prevalence of chromosomal abnormalities in fetuses with isolated DWM was 16.3% (95% CI, 8.7-25.7%). The prevalence of additional central nervous system (CNS) abnormalities that were missed at ultrasound examination and detected only at prenatal MRI was 13.7% (95% CI, 0.2-42.6%), and the prevalence of additional CNS anomalies that were missed at prenatal imaging and detected only after birth was 18.2% (95% CI, 6.2-34.6%). Prenatal diagnosis was not confirmed after birth in 28.2% (95% CI, 8.5-53.9%) of cases. MCM was not significantly associated with additional anomalies detected at prenatal MRI or detected after birth. Prenatal diagnosis was not confirmed postnatally in 7.1% (95% CI, 2.3-14.5%) of cases. The rate of chromosomal anomalies in fetuses with isolated BPC was 5.2% (95% CI, 0.9-12.7%) and there was no associated CNS anomaly detected at prenatal MRI or only after birth. Prenatal diagnosis of BPC was not confirmed after birth in 9.8% (95% CI, 2.9-20.1%) of cases. The rate of chromosomal anomalies in fetuses with isolated VH was 6.5% (95% CI, 0.8-17.1%) and there were no additional anomalies detected at prenatal MRI (0% (95% CI, 0.0-45.9%)). The proportions of cerebral anomalies detected only after birth was 14.2% (95% CI, 2.9-31.9%). Prenatal diagnosis was not confirmed after birth in 32.4% (95% CI, 18.3-48.4%) of cases.
CONCLUSIONS
DWM apparently isolated on ultrasound imaging is a condition with a high risk for chromosomal and associated structural anomalies. Isolated MCM and BPC have a low risk for aneuploidy or associated structural anomalies. The small number of cases with isolated VH prevents robust conclusions regarding their management from being drawn. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Chromosome Aberrations; Cranial Fossa, Posterior; Dandy-Walker Syndrome; Female; Gestational Age; Humans; Magnetic Resonance Imaging; Nervous System Malformations; Pregnancy; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 25970099
DOI: 10.1002/uog.14900