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Medicine Sep 2019The universal two-child policy has now been fully implemented in China. This change requires adaptations to maternal care and childcare systems, but the features of...
The universal two-child policy has now been fully implemented in China. This change requires adaptations to maternal care and childcare systems, but the features of prenatal diagnosis before and after implementation of the policy have not been reported.We conducted a retrospective study of 6736 prenatal cytogenetic diagnoses performed on amniotic fluid cells over a 4-year period, including 2 years before and after implementation of the second child policy. Amniotic fluid cells collected through amniocentesis were cultured, harvested, and stained for chromosome analysis using standard laboratory protocols.The study included 3222 pregnant women referred before implementation of the policy, which we used as a control group, and 3514 pregnant women referred after policy implementation as an investigational study group. There were significantly fewer pregnant women aged <25 years in the investigational group than in the control group (P < .001). There were no significant between-group differences for other pregnant women aged >31 years and 27-28 years old (P > .05). A total of 358 cases with chromosomal abnormalities were diagnosed, including 129 (4%, 129/3222) in the control group which was significantly lower than the 229 (6.5%, 229/3514) in the study group (P < .001). In particular, significantly more trisomy 21 cases were observed in the study group than in the control group (120 vs 59). More pregnant women underwent non-invasive prenatal testing (NIPT) in the study group (46%) than in the control group (20%). In the study group, the average age of pregnant women who underwent NIPT was significantly higher than that of women who did not receive NIPT (P < .05). However, there were no significant between-group differences for the control group (P > .05).The number of cases with chromosomal abnormalities increased in northeastern China in the 2 years after implementation of the two-child policy. The number of pregnant women of advanced maternal age did not increase significantly, perhaps because of the widespread application of NIPT. However, the number of fetuses with Down syndrome increased significantly, suggesting that prenatal screening and diagnosis should be strengthened.
Topics: Adult; Age Factors; Amniocentesis; China; Chromosome Aberrations; Female; Humans; Population Control; Pregnancy; Prenatal Diagnosis; Public Policy; Retrospective Studies; Young Adult
PubMed: 31567968
DOI: 10.1097/MD.0000000000017200 -
British Journal of Haematology Nov 2019Sickle cell disease (SCD) and thalassaemia are genetic disorders that are caused by errors in the genes for haemoglobin and are some of the most common significant... (Review)
Review
Sickle cell disease (SCD) and thalassaemia are genetic disorders that are caused by errors in the genes for haemoglobin and are some of the most common significant genetic disorders in the world, resulting in significant morbidity and mortality. Great disparities exist in the outcome of these conditions between resource- rich and resource-poor nations. Antenatal screening for these disorders aims to provide couples with information about their reproductive risk and enable them to make informed reproductive choices; ultimately reducing the likelihood of children being born with these conditions. This review provides an overview of the current status of antenatal, pre-marital and population screening of SCD and thalassaemia in countries with both high-and low prevalence of these conditions, methods of screening in use, and discusses some of the pitfalls, ethical issues and controversies surrounding antenatal screening. It also discusses outcomes of some screening programmes and recognises the need for the establishment of antenatal screening in areas where their prevalence is highest; namely sub-Saharan Africa and India.
Topics: Anemia, Sickle Cell; Female; Hemoglobinopathies; Humans; Pregnancy; Prenatal Diagnosis; Thalassemia
PubMed: 31509241
DOI: 10.1111/bjh.16188 -
Annual Review of Genomics and Human... Aug 2022With the widespread clinical adoption of noninvasive screening for fetal chromosomal aneuploidies based on cell-free DNA analysis from maternal plasma, more researchers... (Review)
Review
With the widespread clinical adoption of noninvasive screening for fetal chromosomal aneuploidies based on cell-free DNA analysis from maternal plasma, more researchers are turning their attention to noninvasive prenatal assessment for single-gene disorders. The development of a spectrum of approaches to analyze cell-free DNA in maternal circulation, including relative mutation dosage, relative haplotype dosage, and size-based methods, has expanded the scope of noninvasive prenatal testing to sex-linked and autosomal recessive disorders. Cell-free fetal DNA analysis for several of the more prevalent single-gene disorders has recently been introduced into clinical service. This article reviews the analytical approaches currently available and discusses the extent of the clinical implementation of noninvasive prenatal testing for single-gene disorders.
Topics: Aneuploidy; Cell-Free Nucleic Acids; DNA; Female; Fetus; Humans; Pregnancy; Prenatal Diagnosis
PubMed: 35316613
DOI: 10.1146/annurev-genom-110821-113411 -
Journal of Medical Genetics Oct 2022The aim of this position statement is to provide recommendations for Canadian healthcare professionals regarding the use of genome-wide sequencing (GWS) in the context...
PURPOSE AND SCOPE
The aim of this position statement is to provide recommendations for Canadian healthcare professionals regarding the use of genome-wide sequencing (GWS) in the context of diagnostic testing of the fetus during pregnancy. This statement was developed to facilitate clinical translation of GWS as a prenatal diagnostic test and the development of best practices in Canada, but the applicability of this document is broader and aims to help professionals in other healthcare systems.
METHODS OF STATEMENT DEVELOPMENT
A multidisciplinary group was assembled to review existing literature on fetal GWS for genetic diagnosis in the context of suspected monogenic diseases and to make recommendations relevant to the Canadian context. The statement was circulated for comments to the Canadian College of Medical Geneticists (CCMG) membership-at-large and, following incorporation of feedback, approved by the CCMG Board of Directors on 19 February 2021.
RESULTS AND CONCLUSIONS
The use of prenatal GWS is indicated for the investigation of multiple fetal anomalies. Its use in the context of isolated fetal anomaly should be guided by available resources and current evidence, which is continually changing. During pregnancy, GWS should be ordered by, or in collaboration with, a medical geneticist. It should be used following detailed phenotyping to interrogate known disease genes, preferably using a trio approach, following detailed fetal phenotyping. Testing should be done with an overall aim to help in the management of the pregnancy, delivery and postnatal care. It should be guided by personal utility of the test for the pregnant person and clinical utility for pregnancy and birth management, as outlined herein. Genetic counselling is crucial in making the parental decision an informed decision. Chromosomal microarray analysis should be completed in parallel or prior to GWS and should be preceded by Quantitative Fluorescent PCR (QF-PCR) for detection of common aneuploidies. In normal circumstances, only pathogenic and likely pathogenic variants with a high likelihood of being associated with the identified fetal anomalies should be reported. Reporting of secondary findings, defined as purposeful analysis of variants in a set of medically actionable genes, should not, by default, be performed in the prenatal context. Laboratories should only report incidental findings that reveal risk of a significant Mendelian condition during infancy and childhood. Should a laboratory have a policy for reporting incidental findings in medically actionable adult-onset conditions, they should only be reported with explicit opt-in consent signed by the tested individuals. Genetic counselling is crucial in disclosing the test results and the implications the results may have for the fetus. It should be emphasised that negative results do not rule out a genetic diagnosis nor guarantee a good prognosis. Postnatal phenotyping and reanalysis of existing data should be considered. Families should be given the opportunity to participate in research studies as appropriate. These recommendations will be routinely re-evaluated as knowledge of the diagnostic and clinical utility of fetal GWS during pregnancy improves.
Topics: Adult; Canada; Child; Female; Fetus; Genetic Counseling; Humans; Pregnancy; Prenatal Care; Prenatal Diagnosis
PubMed: 34544840
DOI: 10.1136/jmedgenet-2021-107897 -
Ultraschall in Der Medizin (Stuttgart,... Oct 2023To assess the spectrum of associated cardiac anomalies, the intrauterine course, and postnatal outcome of fetuses with double inlet ventricle (DIV).
PURPOSE
To assess the spectrum of associated cardiac anomalies, the intrauterine course, and postnatal outcome of fetuses with double inlet ventricle (DIV).
METHODS
Retrospective analysis of prenatal ultrasound of 35 patients with DIV diagnosed between 2003 and 2021 in two tertiary referral centers in Germany. All fetuses underwent fetal echocardiography and a detailed anomaly scan. Postnatal outcome and follow-up data were retrieved from pediatric reports.
RESULTS
33 cases of DIV were correctly diagnosed prenatally. 24 fetuses (72.7%) had a double inlet ventricle with dominant left (DILV), 7 (21.2%) with dominant right ventricular morphology (DIRV), and 2 cases (6%) with indeterminate morphology (DIIV). 4 (16.6%) were Holmes hearts. 5 of the 7 fetuses (71.4%) with DIRV had a double outlet right ventricle (DORV). Malposition of the great arteries was present in 84.8%. Chromosomal abnormalities were absent. Termination of pregnancy was performed in 8 cases (24.2%). 24 fetuses (72.7%) were live-born. 5 (20.8%) were female and 19 (79.2%) were male. The median gestational age at birth was 38+2.5 weeks. All but one child received univentricular palliation. The median follow-up time was 5.83 years with an adjusted survival rate of 91.6% (22 of 24 live-born children). There was one case of Fontan failure at 15.7 years.
CONCLUSION
DIV remains a major cardiac malformation although both prenatal diagnostics and cardiac surgery have improved over the years. The course of pregnancy is commonly uneventful. All children need univentricular palliation. The children are slightly physically limited, develop a normal intellect, and attend school regularly.
Topics: Pregnancy; Infant, Newborn; Humans; Male; Female; Child; Infant; Retrospective Studies; Bays; Ultrasonography, Prenatal; Prenatal Diagnosis; Heart Defects, Congenital; Fetus
PubMed: 35777369
DOI: 10.1055/a-1866-4538 -
Journal of the American Heart... Aug 2021Background Placental derived cell-free DNA (cfDNA), widely utilized for prenatal screening, may serve as a biomarker for preeclampsia. To determine whether cfDNA...
Background Placental derived cell-free DNA (cfDNA), widely utilized for prenatal screening, may serve as a biomarker for preeclampsia. To determine whether cfDNA parameters are altered in preeclampsia, we conducted a case-control study using prospectively collected maternal plasma (n=20 preeclampsia, n=22 normal) using our in-house validated prenatal screening assay. Methods and Results Isolated cfDNA was quantified, sequenced using Illumina NextSeq 500, and the placental-derived fraction was determined. Clinical and test characteristics were compared between preeclampsia and controls, followed by comparisons within the preeclampsia cohort dichotomized by cfDNA concentration. Lastly, cfDNA parameters in preeclampsia were correlated with markers of disease severity. Maternal age, body mass index, gestational age at delivery, cesarean rate, and neonatal birthweight were expectedly different between groups (≤0.05). The placental-derived cfDNA fraction did not differ between groups (21.4% versus 16.9%, =0.06); however, total cfDNA was more than 10 times higher in preeclampsia (1235 versus 106.5 pg/µL, <0.001). This relationship persisted when controlling for important confounders (OR 1.22, 95% CI 1.04-1.43, =0.01). The dichotomized preeclampsia group with the highest cfDNA concentration delivered earlier (33.2 versus 36.6 weeks, =0.02) and had lower placental-derived fractions (9.1% versus 21.4%, =0.04). Among preeclampsia cases, higher total cfDNA correlated with earlier gestational age at delivery (=0.01) and higher maximum systolic blood pressure (=0.04). Conclusions At diagnosis, total cfDNA is notably higher in preeclampsia, whereas the placental derived fraction remains similar to healthy pregnancies. In preeclampsia, higher total cfDNA correlates with earlier gestational age at delivery and higher systolic blood pressure. These findings may indicate increased release of cfDNA from maternal tissue injury.
Topics: Adult; Biomarkers; Blood Pressure; Body Mass Index; Case-Control Studies; Cell-Free Nucleic Acids; Correlation of Data; Female; Gestational Age; Humans; Maternal Age; Placenta; Pre-Eclampsia; Pregnancy; Prenatal Diagnosis; Reproductive History; Severity of Illness Index
PubMed: 34310191
DOI: 10.1161/JAHA.121.021477 -
Prenatal Diagnosis Feb 2021The study was designed to assess the impact of socioeconomic barriers on the rate of prenatal diagnosis of critical congenital heart disease (CCHD).
OBJECTIVE
The study was designed to assess the impact of socioeconomic barriers on the rate of prenatal diagnosis of critical congenital heart disease (CCHD).
METHODS
This was a retrospective review of the Medicaid analytic extract (MAX) dataset, a national Medicaid administrative claims database with linked maternal-infant claims, from 2007 to 2012. Infants with CCHD were identified by searching for International Classification of Diseases (ICD) 9 codes and Procedural Coding System (PCS) codes for CCHD within the first 6 months after the delivery date. Multivariate logistic regression was used to evaluate the effect of maternal and socioeconomic factors on the prenatal diagnosis rate.
RESULTS
There were 4702 mother-infant dyads included in the analysis. The prenatal diagnosis rate of CCHD was 27.9%. Factors independently associated with odds of prenatal diagnosis of CCHD were presence of maternal diabetes (OR, 2.055; P < .001), ZIP code level median household income (OR, 1.005; P = .015), sonographer labor quotient (OR, 1.804; P = .047), the year of the delivery (OR, 1.155; P < .001), and needing a view other than a 4 chamber or outflow tract view to obtain the diagnosis (OR, 0.383; P < .001).
CONCLUSION
Maternal health, diabetes, socioeconomic factors, and access to sonographers impacts prenatal diagnosis of CCHD.
Topics: Adult; Female; Health Services Accessibility; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Logistic Models; Male; Pregnancy; Prenatal Diagnosis; Retrospective Studies; Risk Factors; Socioeconomic Factors; United States
PubMed: 33169368
DOI: 10.1002/pd.5864 -
BMC Pregnancy and Childbirth Nov 2023Although the traditional contingent screening strategy is effective, there are still undetected low-risk trisomy 21. This study aims to define appropriate cut-off values...
BACKGROUND
Although the traditional contingent screening strategy is effective, there are still undetected low-risk trisomy 21. This study aims to define appropriate cut-off values of serum biochemical markers at low-risk and develop a strategy for sequential prenatal testing associated with first-trimester screening to increase the detection rate of trisomy 21.
METHODS
This was a 9-year retrospective analysis of singleton pregnant women who underwent serum biochemical screening or combined first-trimester screening (CFTS) in the first trimester. For the low-risk group, the cut-off values of the serum biochemical markers were adjusted to determine the appropriate detection efficiency. Gravidas with abnormal serum biochemical markers at low-risk were advised to undergo further non-invasive prenatal screening (NIPS), whereas others continued with routine prenatal care.
RESULTS
When cut-off values of free beta subunit of human chorionic gonadotropin (free β-hCG) multiples of the median (MoM) or pregnancy-associated plasma protein A (PAPP-A) MoM were defined with ≥ 2.75 or ≤ 0.5, 7.72% (2,194/28,405) in the serum biochemical screening group and 12.36% (4,005/32,403) in CFTS group could be detected as abnormal results for further NIPS. Finally, 55.56% (5/9) and 85.71% (6/7) of trisomy 21 cases with false-negative results were detected, and the overall detection rate for trisomy 21 was improved by 10.64% (5/47) and 12.77% (6/47), respectively.
CONCLUSIONS
The new contingent screening strategy can increase the detection rate of trisomy 21 compared with the traditional contingent screening strategy.
Topics: Pregnancy; Humans; Female; Down Syndrome; Pregnancy Trimester, First; Chorionic Gonadotropin, beta Subunit, Human; Prenatal Diagnosis; Retrospective Studies; Nuchal Translucency Measurement; Biomarkers; Pregnancy-Associated Plasma Protein-A; Trisomy
PubMed: 37964244
DOI: 10.1186/s12884-023-06115-1 -
Turkish Journal of Ophthalmology Aug 2020In this article, we report a 21-gestational-week fetus diagnosed with congenital cataract by ultrasonography. The parents decided to terminate the pregnancy and asked...
In this article, we report a 21-gestational-week fetus diagnosed with congenital cataract by ultrasonography. The parents decided to terminate the pregnancy and asked for examination of the fetus. An amniocentesis was performed for fetal karyotyping. After termination of the pregnancy, fetal autopsy was conducted. Whole exome sequencing (Trio-WES) analysis of the mother and father was done from peripheral blood samples. In the pathologic autopsy report, bilateral anterior and posterior subcapsular cataracts were confirmed. Whole exome sequencing analysis revealed a previously unreported class 3 variant of uncertain significance (c755A>G [P.Lys252Arg]) of the gene, which is associated with congenital cataract, that was homozygous in the fetus and heterozygous in the parents. The obtained result is consistent with a genetic diagnosis of isolated autosomal recessive cataract.
Topics: Adult; Cataract; Female; Fetus; Follow-Up Studies; Gestational Age; Humans; Pregnancy; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 32854469
DOI: 10.4274/tjo.galenos.2020.05014 -
BMC Pregnancy and Childbirth Jan 2022The purpose of this study is to evaluate the impact of prenatal screening tests on prenatal diagnosis in Taiwan's 14 years from 2006 to 2019.
BACKGROUND
The purpose of this study is to evaluate the impact of prenatal screening tests on prenatal diagnosis in Taiwan's 14 years from 2006 to 2019.
METHODS
The prenatal screening methods evolved from the second-trimester serum screening to combined first-trimester screening (cFTS) and then followed by the non-invasive cell-free DNA prenatal test (NIPT). The data used by the Department of Statistics, the Ministry of Health and Welfare and Department of Household Registration, Ministry of the Interior public website.
RESULTS
This regional registry-based cohort retrospective study examined a total of 2,775,792 births from January 2006 to December 2019. The proportion of advanced maternal age (AMA) pregnancies increased from 11.63% in 2006 to 30.94% in 2019. Overall, invasive diagnostic testing was used in 87.22% of AMA pregnancies. The prenatal detection rate of trisomy 21 and 18 increased from 74.1% and 83.3% in 2006 to 96.9% and 98.8% in 2019, respectively.
CONCLUSION
During the second-trimester and cFTS periods, the percentage of AMA pregnancies increased every year and the number of invasive procedures also accompany with increased percentage of AMA. However, during the period that NIPT were implemented, the percentage of invasive procedures decreased.
Topics: Cohort Studies; Cytodiagnosis; Down Syndrome; Female; Humans; Maternal Age; Maternal Serum Screening Tests; Noninvasive Prenatal Testing; Pregnancy; Pregnancy Trimesters; Prenatal Diagnosis; Registries; Retrospective Studies; Taiwan; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 35012459
DOI: 10.1186/s12884-021-04360-w