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American Journal of Obstetrics and... Jul 2017Women with a history of previous cesarean delivery, presenting with a placenta previa, have become the largest group with the highest risk for placenta previa accreta. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Women with a history of previous cesarean delivery, presenting with a placenta previa, have become the largest group with the highest risk for placenta previa accreta.
OBJECTIVE
The objective of the study was to evaluate the accuracy of ultrasound imaging in the prenatal diagnosis of placenta accreta and the impact of the depth of villous invasion on management in women presenting with placenta previa or low-lying placenta and with 1 or more prior cesarean deliveries.
STUDY DESIGN AND DATA SOURCES
We searched PubMed, Google Scholar, clinicalTrials.gov, and MEDLINE for studies published between 1982 and November 2016.
STUDY ELIGIBILITY CRITERIA
Criteria for the study were cohort studies that provided data on previous mode of delivery, placenta previa, or low-lying placenta on prenatal ultrasound imaging and pregnancy outcome. The initial search identified 171 records, of which 5 retrospective and 9 prospective cohort studies were eligible for inclusion in the quantitative analysis.
STUDY APPRAISAL AND SYNTHESIS METHODS
The studies were scored on methodological quality using the Quality Assessment of Diagnostic Accuracy Studies tool.
RESULTS
The 14 cohort studies included 3889 pregnancies presenting with placenta previa or low-lying placenta and 1 or more prior cesarean deliveries screened for placenta accreta. There were 328 cases of placenta previa accreta (8.4%), of which 298 (90.9%) were diagnosed prenatally by ultrasound. The incidence of placenta previa accreta was 4.1% in women with 1 prior cesarean and 13.3% in women with ≥2 previous cesarean deliveries. The pooled performance of ultrasound for the antenatal detection of placenta previa accreta was higher in prospective than retrospective studies, with a diagnostic odds ratios of 228.5 (95% confidence interval, 67.2-776.9) and 80.8 (95% confidence interval, 13.0-501.4), respectively. Only 2 studies provided detailed data on the relationship between the depth of villous invasion and the number of previous cesarean deliveries, independently of the depth of the villous invasion. A cesarean hysterectomy was performed in 208 of 232 cases (89.7%) for which detailed data on management were available. Positive correlations were found in the largest prospective studies between the cumulative rates of the more invasive forms of accreta placentation and the sensitivity and specificity of ultrasound imaging but not with diagnostic odds ratio values. We found no data on the ultrasound screening of placenta accreta at the routine midtrimester ultrasound examination from the nonexpert ultrasound units.
CONCLUSION
Planning individual management for delivery is possible only with accurate evaluation of prenatal risk of accreta placentation in women presenting with a low-lying placenta/previa and a history of prior cesarean delivery. Ultrasound is highly sensitive and specific in the prenatal diagnosis of accreta placentation when performed by skilled operators. Developing a prenatal screening protocol is now essential to further improve the outcome of this increasingly more common major obstetric complication.
Topics: Cesarean Section; Female; Humans; Hysterectomy; MEDLINE; Placenta Accreta; Placenta Previa; Placentation; Pregnancy; Pregnancy Outcome; Prospective Studies; Retrospective Studies; Risk Factors; Sensitivity and Specificity; Ultrasonography, Prenatal
PubMed: 28268196
DOI: 10.1016/j.ajog.2017.02.050 -
The Journal of Maternal-fetal &... Dec 2022The present systematic review aims to investigate the diagnosis, prognosis, delivery assistance, pregnancy results and postnatal management in gastroschisis.
OBJECTIVES
The present systematic review aims to investigate the diagnosis, prognosis, delivery assistance, pregnancy results and postnatal management in gastroschisis.
STUDY DESIGN
The following data sources were evaluated: The CINAHL, Embase and MEDLINE/PubMed databases were searched, observational and intervention studies published over the past 20 years. The quality of the studies was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE).
RESULTS
A total of 3770 infants diagnosed with gastroschisis were included (44 studies); 1534 fetuses were classified as simple gastroschisis and 288 as complex gastroschisis. Intrauterine fetal demise occurred in 0.47% and elective termination occurred in 0.13%. Preterm delivery occurred in 23.23% and intrauterine growth restriction in 4.43%. Cesarean section delivery was performed in 54.6%. Neonatal survival was 91.29%. The main neonatal complications were: sepsis (11.78%), necrotizing enterocolitis (2.33%), short bowel syndrome (1.37%), bowel obstruction (0.79%), and volvulus (0.23%). Immediate surgical repair was performed in 80.1% with primary closure in 69%. The average to oral feeding was 33 (range: 11-124.5) days. Average hospital duration was 38 days and 89 days in neonates with simple and complex grastroschisis, respectively.
CONCLUSIONS
The present systematic review provides scientific data for counseling families with fetal gastroschisis.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Gastroschisis; Cesarean Section; Prognosis; Ultrasonography, Prenatal; Fetal Growth Retardation; Retrospective Studies
PubMed: 33899664
DOI: 10.1080/14767058.2021.1909563 -
The Cochrane Database of Systematic... Sep 2017During pregnancy, fetal cells suitable for genetic testing can be obtained from amniotic fluid by amniocentesis (AC), placental tissue by chorionic villus sampling... (Review)
Review
BACKGROUND
During pregnancy, fetal cells suitable for genetic testing can be obtained from amniotic fluid by amniocentesis (AC), placental tissue by chorionic villus sampling (CVS), or fetal blood. A major disadvantage of second trimester amniocentesis is that the results are available relatively late in pregnancy (after 16 weeks' gestation). Earlier alternatives are chorionic villus sampling (CVS) and early amniocentesis, which can be performed in the first trimester of pregnancy.
OBJECTIVES
The objective of this review was to compare the safety and accuracy of all types of AC (i.e. early and late) and CVS (e.g. transabdominal, transcervical) for prenatal diagnosis.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (3 March 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP; 3 March 2017), and reference lists of retrieved studies.
SELECTION CRITERIA
All randomised trials comparing AC and CVS by either transabdominal or transcervical route.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach.
MAIN RESULTS
We included a total of 16 randomised studies, with a total of 33,555 women, 14 of which were deemed to be at low risk of bias. The number of women included in the trials ranged from 223 to 4606.Studies were categorized into six comparisons: 1. second trimester AC versus control; 2. early versus second trimester AC; 3. CVS versus second trimester AC; 4. CVS methods; 5. Early AC versus CVS; and 6. AC with or without ultrasound.One study compared second trimester AC with no AC (control) in a low risk population (women = 4606). Background pregnancy loss was around 2%. Second trimester AC compared to no testing increased total pregnancy loss by another 1%. The confidence intervals (CI) around this excess risk were relatively large (3.2% versus 2.3 %, average risk ratio (RR) 1.41, 95% CI 0.99 to 2.00; moderate-quality evidence). In the same study, spontaneous miscarriages were also higher (2.1% versus 1.3%; average RR 1.60, 95% CI 1.02 to 2.52; high-quality evidence). The number of congenital anomalies was similar in both groups (2.0% versus 2.2%, average RR 0.93, 95% CI 0.62 to 1.39; moderate-quality evidence).One study (women = 4334) found that early amniocentesis was not a safe early alternative compared to second trimester amniocentesis because of increased total pregnancy losses (7.6% versus 5.9%; average RR 1.29, 95% CI 1.03 to 1.61; high-quality evidence), spontaneous miscarriages (3.6% versus 2.5%, average RR 1.41, 95% CI 1.00 to 1.98; moderate-quality evidence), and a higher incidence of congential anomalies, including talipes (4.7% versus 2.7%; average RR 1.73, 95% CI 1.26 to 2.38; high-quality evidence).When pregnancy loss after CVS was compared with second trimester AC, there was a clinically significant heterogeneity in the size and direction of the effect depending on the technique used (transabdominal or transcervical), therefore, the results were not pooled. Only one study compared transabdominal CVS with second trimester AC (women = 2234). They found no clear difference between the two procedures in the total pregnancy loss (6.3% versus 7%; average RR 0.90, 95% CI 0.66 to 1.23, low-quality evidence), spontaneous miscarriages (3.0% versus 3.9%; average RR 0.77, 95% CI 0.49 to 1.21; low-quality evidence), and perinatal deaths (0.7% versus 0.6%; average RR 1.18, 95% CI 0.40 to 3.51; low-quality evidence). Transcervical CVS may carry a higher risk of pregnancy loss (14.5% versus 11.5%; average RR 1.40, 95% CI 1.09 to 1.81), but the results were quite heterogeneous.Five studies compared transabdominal and transcervical CVS (women = 7978). There were no clear differences between the two methods in pregnancy losses (average RR 1.16, 95% CI 0.81 to 1.65; very low-quality evidence), spontaneous miscarriages (average RR 1.68, 95% CI 0.79 to 3.58; very low-quality evidence), or anomalies (average RR 0.68, 95% CI 0.41 to 1.12; low-quality evidence). We downgraded the quality of the evidence to low due to heterogeneity between studies. Transcervical CVS may be more technically demanding than transabdominal CVS, with more failures to obtain sample (2.0% versus 1.1%; average RR 1.79, 95% CI 1.13 to 2.82, moderate-quality evidence).Overall, we found low-quality evidence for outcomes when early amniocentesis was compared to transabdominal CVS. Spontaneous miscarriage was the only outcome supported by moderate-quality evidence, resulting in more miscarriages after early AC compared with transabdominal CVS (2.3% versus 1.3%; average RR 1.73, 95% CI 1.15 to 2.60). There were no clear differences in pregnancy losses (average RR 1.15, 95% CI 0.86 to 1.54; low-quality evidence), or anomalies (average RR 1.14, 95% CI 0.57 to 2.30; very low-quality evidence).We found one study that examined AC with or without ultrasound, which evaluated a type of ultrasound-assisted procedure that is now considered obsolete.
AUTHORS' CONCLUSIONS
Second trimester amniocentesis increased the risk of pregnancy loss, but it was not possible to quantify this increase precisely from only one study, carried out more than 30 years ago.Early amniocentesis was not as safe as second trimester amniocentesis, illustrated by increased pregnancy loss and congenital anomalies (talipes). Transcervical chorionic villus sampling compared with second trimester amniocentesis may be associated with a higher risk of pregnancy loss, but results were quite heterogeneous.Diagnostic accuracy of different methods could not be assessed adequately because of incomplete karyotype data in most studies.
Topics: Amniocentesis; Chorionic Villi Sampling; Congenital Abnormalities; Female; Humans; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Randomized Controlled Trials as Topic
PubMed: 28869276
DOI: 10.1002/14651858.CD003252.pub2 -
BMJ (Clinical Research Ed.) Apr 2016To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤ 16 weeks' gestation to estimate a woman's risk of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤ 16 weeks' gestation to estimate a woman's risk of pre-eclampsia.
DESIGN
Systematic review and meta-analysis of cohort studies.
DATA SOURCES
PubMed and Embase databases, 2000-15.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Cohort studies with ≥ 1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤ 16 weeks' gestation.
DATA EXTRACTION
Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors.
RESULTS
There were 25,356,688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors.
CONCLUSIONS
There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at "high risk" of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.
Topics: Aspirin; Body Mass Index; Chronic Disease; Cohort Studies; Early Diagnosis; Female; Humans; Hypertension, Pregnancy-Induced; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy in Diabetics; Prenatal Diagnosis; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted; Risk Factors
PubMed: 27094586
DOI: 10.1136/bmj.i1753 -
Molecular Genetics and Metabolism Jan 2019Menkes disease is a rare X-linked neurodegenerative disorder caused by defect in copper metabolism. Parenteral copper supplementation has been used as a potential...
Menkes disease is a rare X-linked neurodegenerative disorder caused by defect in copper metabolism. Parenteral copper supplementation has been used as a potential disease-modifying treatment of Menkes disease for decades. However, recent evidence suggests its efficacy only when treatment is started within days after birth, which also has important implications related to the techniques that enable early diagnosis. We aim at proposing a guideline for prenatal and neonatal diagnosis and for disease-modifying treatment of Menkes disease, guided by a systematic review of the literature, and built in conjunction with medical experts, methodologists and patient representatives. Thirteen articles were used for our recommendations that were based on GRADE system. Reviewed evidence suggests that prenatal genetic diagnosis in families with previous diagnosis of Menkes disease is feasible; analysis of plasma catecholamine levels is accurate for neonatal diagnosis of Menkes disease; treatment with copper-histidine is effective to increase survival and reduce neurologic burden of the disease if initiated in the neonatal period; and, treatment indication should not be guided by patient's genotype. In conclusion, our guideline can contribute to standardize some aspects of the clinical care of patients with Menkes disease, especially reducing disease burden and mortality and providers' and families' anxiety.
Topics: Catecholamines; Clinical Trials as Topic; Copper; Early Diagnosis; Female; Humans; Male; Menkes Kinky Hair Syndrome; Mutation; Practice Guidelines as Topic; Pregnancy; Prenatal Diagnosis
PubMed: 30594472
DOI: 10.1016/j.ymgme.2018.12.005 -
Acta Obstetricia Et Gynecologica... Jun 2019The primary aim of this systematic review was to quantify the diagnostic performance of ultrasound, magnetic resonance imaging and amniotic fluid analysis in detecting... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The primary aim of this systematic review was to quantify the diagnostic performance of ultrasound, magnetic resonance imaging and amniotic fluid analysis in detecting esophageal atresia prenatally. The secondary aim was to explore the accuracy of individual imaging signs in identifying this anomaly.
MATERIAL AND METHODS
MEDLINE, Embase and Cochrane databases were searched. The quality of studies was assessed using the revised tool for the quality assessment of diagnostic accuracy studies. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio for the predictive accuracy of ultrasound, magnetic resonance imaging and amniotic fluid analysis in detecting esophageal atresia were computed using the hierarchical summary receiver operating characteristic or DerSimonian-Laird random-effect model, according to the number of studies included in each analysis. PROSPERO registration number: CRD42017055828.
RESULTS
Twenty studies (73 246 fetuses, 1760 affected by esophageal atresia) were included. Overall, prenatal ultrasound had a sensitivity of 31.7%. Only two studies reported all data for diagnostic accuracy; based on these studies, prenatal ultrasound had a sensitivity of 41.9%, a specificity of 99.9%, a positive likelihood ratio of 88.1, a negative likelihood ratio of 0.58 and a diagnostic odds ratio of 153.7. Prenatal ultrasound correctly identified 77.9% of cases with esophageal atresia and 21.9% esophageal atresia with an associated tracheo-esophageal fistula. Polyhydramnios was present in 56.3% of cases affected by esophageal atresia, and a small or absent stomach was identified in 50.0% cases. When performed following a suspicious ultrasound, fetal magnetic resonance imaging had an good overall diagnostic accuracy for esophageal atresia, with a sensitivity of 94.7%, a specificity of 89.3%, a positive likelihood ratio of 8.8, a negative likelihood ratio of 0.06 and a diagnostic odds ratio of 149.3. Finally, amniotic fluid analysis with an esophageal atresia index ≥3 had a sensitivity of 89.9% and a specificity of 99.6% in detecting esophageal atresia.
CONCLUSIONS
Ultrasound alone is a poor diagnostic tool for identifying esophageal atresia prenatally, and has a high rate of false positive diagnoses. Magnetic resonance imaging and amniotic fluid analysis have high diagnostic accuracy for esophageal atresia. We would recommend their use following a suspicious ultrasound.
Topics: Esophageal Atresia; Humans; Prenatal Diagnosis; Reproducibility of Results
PubMed: 30659586
DOI: 10.1111/aogs.13536 -
Prenatal Diagnosis Jun 2017With a high sensitivity and specificity, non-invasive prenatal testing (NIPT) is an incomparable screening test for fetal aneuploidy. However, the method is rather newly... (Review)
Review
With a high sensitivity and specificity, non-invasive prenatal testing (NIPT) is an incomparable screening test for fetal aneuploidy. However, the method is rather newly introduced, and experiences with discordant results are few. We did a systematic review of literature reporting details of false positive and false negative NIPT results. Discordant sex chromosome results were not included. We identified 22 studies reporting case details. In total, 206 discordant cases were included, of which 88% were false positive and 12% false negative. Details on maternal age, gestational age, platform/company, Z-score, fetal fraction, results and explanation were specified. The main reasons for discordant results were confined placental mosaicism, maternal copy number variation, vanished twin, maternal cancer and true fetal mosaicism. A very high percentage of cases (67%) were reported with no obvious biological or technical explanation for the discordant result. The included cases represent only a minor part of the true number of false positive or false negative NIPT cases identified in fetal medicine clinics around the world. To ensure knowledge exchange and transparency of NIPT between laboratories, we suggest a systematic recording of discordant NIPT results, as well as a quality assurance by external quality control and accreditation. © 2017 John Wiley & Sons, Ltd.
Topics: Chromosome Aberrations; False Negative Reactions; False Positive Reactions; Female; Humans; Maternal Serum Screening Tests; Pregnancy
PubMed: 28382695
DOI: 10.1002/pd.5049 -
BMJ Open Jan 2016To measure test accuracy of non-invasive prenatal testing (NIPT) for Down, Edwards and Patau syndromes using cell-free fetal DNA and identify factors affecting accuracy. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To measure test accuracy of non-invasive prenatal testing (NIPT) for Down, Edwards and Patau syndromes using cell-free fetal DNA and identify factors affecting accuracy.
DESIGN
Systematic review and meta-analysis of published studies.
DATA SOURCES
PubMed, Ovid Medline, Ovid Embase and the Cochrane Library published from 1997 to 9 February 2015, followed by weekly autoalerts until 1 April 2015.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
English language journal articles describing case-control studies with ≥ 15 trisomy cases or cohort studies with ≥ 50 pregnant women who had been given NIPT and a reference standard.
RESULTS
41, 37 and 30 studies of 2012 publications retrieved were included in the review for Down, Edwards and Patau syndromes. Quality appraisal identified high risk of bias in included studies, funnel plots showed evidence of publication bias. Pooled sensitivity was 99.3% (95% CI 98.9% to 99.6%) for Down, 97.4% (95.8% to 98.4%) for Edwards, and 97.4% (86.1% to 99.6%) for Patau syndrome. The pooled specificity was 99.9% (99.9% to 100%) for all three trisomies. In 100,000 pregnancies in the general obstetric population we would expect 417, 89 and 40 cases of Downs, Edwards and Patau syndromes to be detected by NIPT, with 94, 154 and 42 false positive results. Sensitivity was lower in twin than singleton pregnancies, reduced by 9% for Down, 28% for Edwards and 22% for Patau syndrome. Pooled sensitivity was also lower in the first trimester of pregnancy, in studies in the general obstetric population, and in cohort studies with consecutive enrolment.
CONCLUSIONS
NIPT using cell-free fetal DNA has very high sensitivity and specificity for Down syndrome, with slightly lower sensitivity for Edwards and Patau syndrome. However, it is not 100% accurate and should not be used as a final diagnosis for positive cases.
TRIAL REGISTRATION NUMBER
CRD42014014947.
Topics: Biomarkers; Chromosome Disorders; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 18; DNA; Down Syndrome; Female; Humans; Pregnancy; Prenatal Diagnosis; Sensitivity and Specificity; Trisomy; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 26781507
DOI: 10.1136/bmjopen-2015-010002 -
The Journal of Obstetrics and... May 2023To objectively assess the quality of the published clinical practice guidelines (CPGs) on the management of pregnancies complicated by placenta accreta spectrum... (Review)
Review
OBJECTIVES
To objectively assess the quality of the published clinical practice guidelines (CPGs) on the management of pregnancies complicated by placenta accreta spectrum (PAS)disorders.
METHODS
MEDLINE, Embase, Scopus, and ISI Web of Science databases were searched. The following aspects related to the management of pregnancies with suspected PAS disorders were evaluated: risk factors for PAS, prenatal diagnosis, role of interventional radiology and ureteral stenting, and optimal surgical management. The assessment of risk of bias and quality assessment of the CPGs were performed using the (AGREE II) tool (Brouwers et al., 2010). To define a CPG as of good quality we adopted a cut-off score >60%.
RESULTS
Nine CPGs were included. Specific risk factors for referral were assessed by 44.4% (4/9) of CPGs, mainly consisting in the presence of placenta previa and a prior cesarean delivery or uterine surgery. About 55.6% of CPGs (5/9) suggested ultrasound assessment of women with risk factors for PAS in the second and third trimester of pregnancy and 33.3% (3/9) recommended magnetic resonance imaging (MRI); 88.9% (8/9) of CPGs recommended cesarean delivery at 34-37 weeks of gestation. There was not generally consensus on the use of interventional radiology and ureteral stenting before surgery for PAS. Finally, hysterectomy was the recommend surgical approach by 77.8% (7/9) of the included CPGs.
CONCLUSION
Most of the published CPGs on PAS are generally of good quality. There was general agreement among the different CPGs on PAS as a regard as risk stratification, timing at diagnosis and delivery but not on the indication for MRI, use of interventional radiology and ureteral stenting.
Topics: Pregnancy; Female; Humans; Placenta Accreta; Prenatal Diagnosis; Placenta Previa; Cesarean Section; Pregnancy Trimester, Third; Retrospective Studies; Placenta; Ultrasonography, Prenatal
PubMed: 36796351
DOI: 10.1111/jog.15544 -
American Journal of Obstetrics and... Apr 2023This study aimed to determine the incremental yield of prenatal exome sequencing over chromosomal microarray or G-banding karyotype in fetuses with: (1) intrauterine... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to determine the incremental yield of prenatal exome sequencing over chromosomal microarray or G-banding karyotype in fetuses with: (1) intrauterine growth restriction related to placental insufficiency or (2) short long bones, in isolated and nonisolated instances for both scenarios.
DATA SOURCES
Data were collected via electronic searches for relevant citations from January 2010 to April 10, 2022 in MEDLINE, Embase, Web of Science, and Cochrane, and using relevant bibliographies and data generated in-house.
STUDY ELIGIBILITY CRITERIA
Included were prospective or retrospective cohort studies and/or case series with: (1) n>5 cases of short long bones and/or intrauterine growth restriction undergoing prenatal sequencing with a clearly defined phenotype including assessment of placental function; (2) testing based on prenatal phenotype only; (3) a nondiagnostic chromosomal microarray/karyotype; and (4) known results of genetic testing.
METHODS
Incremental yield was calculated for each study and as a pooled value for the aforementioned groups using a random-effects model. Results were displayed in forest plots with 95% confidence intervals. Heterogeneity was assessed statistically using Higgins' I. Publication bias was assessed graphically using funnel plots. Quality assessment was performed using modified Standards for Reporting of Diagnostic Accuracy criteria (International Prospective Register of Systematic Reviews registration number CRD42022324680).
RESULTS
Nineteen studies were included (n=452 cases). The apparent incremental yields with prenatal sequencing were: (1) 4% (95% confidence interval, -5.0 to 12; I=0%) in isolated intrauterine growth restriction with evidence of placental insufficiency, (2) 30% (95% confidence interval, 13-47; I=1%) in intrauterine growth restriction with additional structural anomalies, (3) 48% (95% confidence interval, 26-70; I=73%) in isolated short long bones, and (4) 68% (95% confidence interval, 58-77; I=51%) in short long bones with additional skeletal anomalies. Of the 37 short long bone cases with a diagnosis, 32 had a skeletal dysplasia, with thanatophoric dysplasia and osteogenesis imperfecta being the most common (both 21.6% [n=8/37]). In fetuses with short long bones and additional skeletal features, osteogenesis imperfecta was the most common diagnosis (28% [n=57/204]). Where documented, the inheritance patterns were de novo in 75.4% (n=150) of cases.
CONCLUSION
Prenatal sequencing adds substantially to incremental yield over chromosomal microarray in fetuses with short long bones or multisystem intrauterine growth restriction. Robust studies are required to assess the utility of fetal sequencing in isolated intrauterine growth restriction with evidence of placental insufficiency, which cannot be recommended on the basis of current evidence.
Topics: Humans; Pregnancy; Female; Fetal Growth Retardation; Placental Insufficiency; Exome Sequencing; Retrospective Studies; Osteogenesis Imperfecta; Placenta; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 36209938
DOI: 10.1016/j.ajog.2022.09.045