Prenatal diagnosis and molecular cytogenetic characterization of a pure ring chromosome 21 with a 4.657-Mb 21q22.3 deletion

ObjectiveWe present diagnosis and molecular cytogenetic characterization of a pure ring chromosome [r(21)] with a 4.657-Mb 21q22.3 deletion.Case reportA 44-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype 46,XX,r(21)(p11.2q22.3). Prenatal ultrasound findings were unremarkable. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed a 4.657-Mb deletion at 21q22.3. The parental karyotypes were normal. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism and clinodactyly. Postnatal cytogenetic analysis of umbilical cord revealed a karyotype of 46,XX,r(21)(p11.2q22.3). aCGH analysis of umbilical cord revealed the result of arr 21q22.3 (43,427,188–48,084,156) × 1.0 with a 4.657-Mb 21q22.3 deletion encompassing 57 Online Mendelian Inheritance in Man (OMIM) genes including TRPM2, TSPEAR, COL18A1, COL6A1, COL6A2, LSS, PCNT, DIP2A, S100B and PRMT2. Metaphase fluorescence in situ hybridization (FISH) analysis of the umbilical cord fibroblasts confirmed a 21q22.3 deletion.ConclusionPrenatal diagnosis of an r(21) should include molecular cytogenetic characterization such as aCGH and FISH to determine the extent of the 21q22.3 deletion.     

Prenatal diagnosis of concomitant distal 5q duplication and terminal 10q deletion in a fetus with intrauterine growth restriction,congenital diaphragmatic hernia and congenital heart defects

ObjectiveWe present prenatal diagnosis of concomitant distal 5q duplication and terminal 10q deletion in a fetus with intrauterine growth restriction (IUGR), congenital diaphragmatic hernia (CDH) and congenital heart defects (CHD).Case reportA 34-year-old, gravida 4, para 2, woman was referred for amniocentesis at 21 weeks of gestation because of advanced maternal age and IUGR. There was no congenital malformation in the family. Amniocentesis revealed a derivative chromosome 10 with an additional maternal on the terminal region of 10q. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from the cultured amniocytes revealed a result of arr 5q31.3q35.5 (142, 548, 354–180,696,806) × 3.0, arr 10q26.3 (132, 932, 808–135,434,178) × 1.0 [GRCh37 (hg19)] with a 2.50-Mb deletion of 10q26.3 encompassing 19 [Online Mendelian Inheritance in Man (OMIM)] genes and a 38.15-Mb duplication of 5q31.3-q35.5 encompassing 195 OMIM genes including four CDH candidate genes of NDST1, ADAM19, NSD1 and MAML1. The mother was found to have a karyotype of 46,XX,t(5; 10) (q31.3; q26.3). Therefore, the fetal karyotype was 46,XX,der(10)t(5; 10)(q31.3; q26.3)mat. Prenatal ultrasound showed IUGR, right CDH, transposition of great artery, double outlet of right ventricle and right atrial isomerism. The pregnancy was terminated, and a malformed fetus was delivered with facial dysmorphism.ConclusionFetuses with concomitant distal 5q duplication and terminal 10q deletion may present IUGR, CDH and CHD on prenatal ultrasound.     

Prenatal diagnosis of familial submicroscopic duplication at 18q22.3 without phenotypic abnormalities

ObjectiveTo report a case of familial submicroscopic duplication at 18q22.3 without phenotypic abnormalities.Case reportHere, we reported two different cases with novel copy number variation at chromosome 18q22.3: one carried a maternally inherited 2.36 Mb microduplication, and the other carried a patrilineally inherited 1.74 Mb microduplication. The HumanCytoSNP-12 array allows for the visualization of the CNVs and maps the breakpoints. Both parents with the microduplication at 18q22.3 as well as their foetuses had normal phenotypes; the infants were regularly followed up after one year of age, and no abnormalities were found, including abnormalities related to growth, intelligence and sexual development.ConclusionOur report showed that the duplication of 18q22.3 (chr18:68,606,012-71,287,101) might represent a benign variant.     

Detection of de novo del(18)(q22.2) and a familial of 15q13.2-q13.3 microduplication in a fetus with congenital heart defects

ObjectiveWe present detection of de novo del(18)(q22.2) and a familial 15q13.2-q13.3 microduplication in a fetus with congenital heart defects (CHD).Case reportA 27-year-old, primigravid woman was referred for genetic counseling because of fetal CHD. Prenatal ultrasound at 17 weeks of gestation revealed pericardial effusion, cardiomegaly and a large ventricular septal defect. The pregnancy was subsequently terminated at 18 weeks of gestation, and a 192-g female fetus was delivered with facial dysmorphism. Cytogenetic analysis of the umbilical cord revealed a karyotype of 46,XX,del(18)(q22.2). The parental karyotypes were normal. Array comparative genomic hybridization (aCGH) of the placental tissue revealed a 2.08-Mb 15q13.2-q13.3 microduplication encompassing KLF13 and CHRNA7, and a 10.74-Mb 18q22.2-q23 deletion encompassing NFATC1. The phenotypically normal father carried the same 2.08-Mb 15q13.2-q13.3 microduplication. Polymorphic DNA marker analysis confirmed a paternal origin of the distal 18q deletion.ConclusionPrenatal diagnosis of CHD should include a complete genetic study of the embryonic tissues, and the acquired information is useful for genetic counseling.     

Prenatal diagnosis and molecular cytogenetic characterization of chromosome 22q11.2 deletion syndrome associated with congenital heart defects

ObjectiveTo report prenatal diagnosis of 22q11.2 deletion syndrome in a pregnancy with congenital heart defects in the fetus.Case reportA 26-year-old, primigravid woman was referred for counseling at 24 weeks of gestation because of abnormal ultrasound findings of fetal congenital heart defects. The Level II ultrasound revealed a singleton fetus with heart defects including overriding aorta, small pulmonary artery, and ventricular septal defect. Cordocentesis was performed. The DNA extracted from the cord blood was analyzed by multiplex ligation-dependent amplification (MLPA). The MLPA showed deletion in the DiGeorge syndrome (DGS) critical region of chromosome 22 low copy number repeat (LCR) 22-A∼C. Conventional cytogenetic analysis revealed a normal male karyotype. Repeated amniocentesis and cordocentesis were performed. Whole-genome array comparative genomic hybridization (aCGH) on cord blood was performed. aCGH detected a 3.07-Mb deletion at 22q11.21. Conventional cytogenetic analysis of cultured amniocytes revealed a karyotype 46,XY. Metaphase fluorescence in situ hybridization (FISH) analysis on cultured amniocytes confirmed an interstitial 22q11.2 deletion.ConclusionPrenatal ultrasound findings of congenital heart defects indicate that the fetuses are at increased risk for chromosome abnormalities. Studies for 22q11.2 deletion syndrome should be considered adjunct to conventional karyotyping. Although FISH has become a standard procedure for diagnosis of 22q11.2 deletion syndrome, MLPA can potentially diagnose a broader spectrum of abnormalities, and aCGH analysis has the advantage of refining the 22q11.2 deletion breakpoints and detecting uncharacterized chromosome rearrangements or genomic imbalances.     

Molecular cytogenetic characterization of del(X)(p22.33)mat and de novo dup(4)(q34.3q35.2) in a male fetus with multiple anomalies of facial dysmorphism,ventriculomegaly, congenital heart defects,short long bones and clinodactyly

ObjectiveWe present molecular cytogenetic characterization of del(X) (p22.33)mat and de novo dup(4) (q34.3q35.2) in a male fetus with multiple anomalies of facial dysmorphism, ventriculomegaly, congenital heart defects, short long bones and clinodactyly.Case reportA 36-year-old, gravida 3, para 1, woman with short stature (152 cm) underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,Y,del(X)(p22.33)mat, dup(4)(q34.3q35.2). The mother had a karyotype of 46,X,del(X)(p22.33). Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed arr Xp22.33 × 0, 4q34.3q35.2 × 3. Prenatal ultrasound at 23 weeks of gestation revealed multiple anomalies of flat nasal bridge, ventriculomegaly, atrioventricular septal defect (AVSD) and clinodactyly. The pregnancy was subsequently terminated, and a malformed fetus was delivered with facial dysmorphism. Cytogenetic analysis of the umbilical cord revealed 46,Y,del(X)(p22.33)mat, dup(4)(q34.3q35.2)dn. aCGH analysis on the DNA extracted from the umbilical cord revealed arr [GRCh37 (hg19)] 4q34.3q35.2 (181,149,823–188,191,938) × 3.0, arr Xp22.33 (470,485–2,985,006) × 0 with a 7.042-Mb duplication of 4q34.3-q35.2 and a 2.514-Mb deletion of Xp22.33.ConclusionA male fetus with del(X)(p22.33) and dup(4)(q34.3q35.2) may present congenital heart defects and short long bones on prenatal ultrasound.     

Obstetric outcome of 6346 pregnancies with infants affected by congenital heart defects

OBJECTIVE: To evaluate whether pregnancies with infants affected by congenital heart defects are associated with adverse obstetric and perinatal outcome. STUDY DESIGN: In a prospective population-based cohort study from Sweden (1992-2001), 6346 singleton pregnancies with infants affected by congenital heart defects were, after suitable adjustments, compared to all delivered women. RESULTS: The prevalence of cardiovascular defects was 9.1 per 1000 births. Among them, mothers of 6346 infants (71%) had information on maternal smoking habits and maternal height and weight in early pregnancy that enabled the calculation of BMI. All cases with known chromosomal abnormalities and/or maternal pre-existing diabetes were excluded. Eighty-four percent (n=5338) had an isolated cardiovascular defect. Severe types occurred in 21.7% (n=1378). In the group of pregnancies with infants affected by congenital heart defects as compared to all delivered women, there was an increased risk of the following outcomes (adjusted OR (95%CI)): pre-eclampsia (1.21 (1.06-1.37)), cesarean section (1.91 (1.79-2.03)), instrumental delivery (1.21 (1.10-1.34)), pre-term delivery (2.58 (2.39-2.79)), small-for gestational age (1.96 (1.77-2.16)), meconium aspiration (1.51 (1.28-1.77)), and fetal distress (1.38 (1.17-1.63)). CONCLUSIONS: Pregnancies with infants affected by congenital heart defects are associated with several obstetric and neonatal complications.     

Prenatal diagnosis of aneuploidy and deletion 22q11.2 in fetuses with ultrasound detection of cardiac defects

OBJECTIVE: We report a prospective database evaluation of the occurrence of aneuploidy and deletion 22q11.2 after prenatal detection of cardiac abnormalities. To ensure the maximum inclusion, all cardiac defects were considered, with the exception of echogenic intracardiac foci. STUDY DESIGN: Prenatal specimens with ultrasound findings of cardiac defects were identified. Physicians were provided supplementary information that described the risk of deletion 22q11.2 syndrome if the karyotype was normal. On approval, fluorescence in situ hybridization was performed to identify the 22q11.2 microdeletion. RESULTS: Prenatal detection of cardiac abnormalities identified aneuploidy or unbalanced chromosome rearrangements in 41% of the cases that were studied. In those fetuses with normal karyotypes, 3% had the deletion 22q11.2. CONCLUSION: These results indicate that prenatal ultrasound findings of congenital heart defects identify fetuses who are at increased risk for chromosome abnormalities. Fetuses with normal karyotypes should consider having fluorescence in situ hybridization studies for the microdeletion 22q11.2 syndrome. Chromosome and fluorescence in situ hybridization studies of family members should be recommended when a fetus is identified as having the deletion 22q11.2.     

Prenatal features of 17q12 microdeletion and microduplication syndromes: A retrospective case series

ObjectiveTo present the experience on prenatal features of 17q12 microdeletion and microduplication syndromes.Materials and methodsPrenatal chromosomal microarray analysis (CMA) were conducted between January 2015 and December 2018 at a single Chinese tertiary medical centre. Information of cases identified with 17q12 microdeletion or microduplication syndromes were retrospectively collected. Foetal ultrasonographic findings were reviewed, and other information about the gestation week at diagnosis, inheritance and pregnancy outcomes were also included.ResultsTen pregnancies with 17q12 microdeletion and 4 with 17q12 microduplication were identified. The copy number variation (CNV) sizes were 1.39–1.94 Mb in the deleted cases and 1.42–1.48 Mb in the duplicated cases, respectively. All the duplicated and deleted regions included HNF1B and LHX1 genes. Most individuals with 17q12 deletion presented kidney anomalies (9/10), with renal hyperechogenicity being the most common finding (7/10). Fetuses with 17q12 duplication presented a wide phenotypic spectrum, including “double bubble” sign, structural anomalies of the heart and growth anomalies.ConclusionsOur experience further demonstrated the high correlation between 17q12 microdeletion and renal anomalies especially hyperechogenic kidneys. Structural anomalies of the heart were newly identified phenotypes of 17q12 duplication during prenatal period. Besides, growth anomalies and duodenal atresia might be associated with the duplication.     

Prenatal diagnosis of a familial 1q21.1-q21.2 microdeletion in a fetus with polydactyly of left foot on prenatal ultrasound

Objective

We present prenatal diagnosis of a familial 1q21.1-q21.2 microdeletion in a fetus with polydactyly of left foot on prenatal ultrasound.

Routine screening with fetal echocardiography for prenatal diagnosis of congenital heart disease

Congenital cardiac anomalies are the most common congenital anomalies, occurring in approximately eight of 1000 live births. Proper perinatal and neonatal management is dependent upon accurate prenatal diagnosis. Approximately 10% of fetuses with cardiac abnormalities have identified risk factors; hence, most of the anomalies occur in pregnancies without prenatal risk factors. The application of detailed fetal echocardiography for prenatal screening, at present reserved mainly for high-risk cases, requires further evaluation before being recommended for the general population.

This article presents our experience of evaluating the accuracy of fetal echocardiography as a screening method in detecting cardiac anomalies in the general population of Singapore. We reviewed data from 39 808 pregnant women who received antenatal care at the National University Hospital, Singapore, between January 1986 and December 1994, and who underwent routine fetal echocardiography at 21-22 weeks of gestation. We identified 294 cases of congenital heart defects by fetal echocardiography. We obtained a sensitivity of 85.4% for the detection of congenital heart disease, and a specificity of 99.9% to rule out such anomalies. Our positive and negative predictive rates were 87.7% and 99.9%, respectively.

We recommend routine screening by echocardiography of all pregnancies at 21-22 weeks of gestation, irrespective of risk stratifcation, for the prenatal detection of cardiac anomalies, in order to improve perinatal management.     

Prenatal diagnosis of a familial 5p14.3-p14.1 deletion encompassing CDH18, CDH12, PMCHL1, PRDM9 and CDH10 in a fetus with congenital heart disease on prenatal ultrasound

Objective

We present prenatal diagnosis of a familial 5p14.3-p14.1 deletion in a fetus with congenital heart disease on prenatal ultrasound.

二维超声四切面法在胎儿先天性心脏病产前筛查中的价值

目的 评价二维超声四切面法,即四腔心切面、左室流出道切面、右室流出道切面和三血管平面在胎儿先天性心脏病(congenital heart disease,CHD)筛查中的价值. 方法 应用二维超声四切面法对孕21～25周的2419例胎儿进行CHD筛查,并对所有2382例活产新生儿行超声心动图检查.统计学分析采用x2检验,并计算敏感性、特异性、阳性预测值和阴性预测值. 结果 2419例胎儿中产前筛查出CHD共281例(11.62％),其中简单型CHD 245例(87.18％)、复杂型CHD 36例(12.82％).高危因素组和非高危因素组阳性率分别为13.60％(34/250)和11.39％(247/2169),差异无统计学意义(x2=1.069,P=0.301).产前四切面法筛查阳性且新生儿期超声心动图检查诊断CHD 36例,总体敏感性、特异性、阳性预测值、阴性预测值分别为12.8％、99.8％、90.0％和89.7％;诊断简单型CHD 7例,敏感性2.9％;复杂型CHD 29例,敏感性80.6％.产后新生儿诊断CHD252例,占活产新生儿总数的10.58％(252/2382),其中简单型241例,复杂型11例. 结论 二维超声产前四切面法对简单型CHD诊断敏感性较低,对复杂型CHD诊断的敏感性较高.在常规产前超声检查中加入心脏四切面法可筛查出大部分的胎儿复杂型CHD,而简单型CHD漏诊率仍较高,新生儿超声心动图普查可弥补产前CHD筛查的不足.     

Detection of paternal origin of fetal de novo rea(21q;21q) down syndrome in a pregnancy of a young woman associated with an abnormal first-trimester maternal serum screening result

ObjectiveWe present detection of paternal origin of fetal de novo rea(21q;21q) Down syndrome in a pregnancy of a young woman associated with an abnormal first-trimester maternal serum screening result.Case reportA 26-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of an abnormal first-trimester screening result of 1/139 risk of Down syndrome calculated by 3.109 multiples of the median (MoM) of maternal serum free β-hCG and 0.454 MoM of pregnancy associated plasma protein-A (PAPP-A). Her husband was 29 years old, and the couple had a 1-year-old healthy daughter. Amniocentesis revealed a karyotype of 46,XX,+21,der(21;21)(q10;q10). The pregnancy was terminated at 19 weeks of gestation, and a malformed fetus was delivered. The parental karyotypes were normal. Postnatal analysis of the umbilical cord showed a karyotype of 46,XX,+21,der(21;21) (q10;q10). Polymorphic DNA marker analysis on the DNA extracted from parental bloods and umbilical cord confirmed a paternal origin of the de novo rea(21q;21q) Down syndrome.ConclusionPrenatal diagnosis of de novo rea(21q;21q) Down syndrome should include a polymorphic DNA marker analysis of the parental origin, and the acquired information is useful for genetic counseling of the recurrence of unbalanced rea(21q;21q) offspring and the determination of low-level tissue mosaicism or gonadal mosaicism in one of the parents.     

Prenatal diagnosis of a familial normal euchromatic variant of dup(15)(q11.2q11.2) in a pregnancy with a favorable outcome

ObjectiveWe present prenatal diagnosis of a familial normal euchromatic variant of dup(15)(q11.2q11.2) in a pregnancy with a favorable outcome.Case reportA 32-year-old woman underwent elective amniocentesis at 17 weeks of gestation because of anxiety. Amniocentesis revealed a karyotype of 46,XX,dup(15)(q11.2q11.2). Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1–22, X) × 2 with no genomic imbalance. Cytogenetic analysis of the parental bloods showed that the mother had a karyotype of 46,XX,dup(15)(q11.2q11.2), and the father had a karyotype of 46,XY. Prenatal ultrasound findings were unremarkable. A healthy 2948 g female baby was delivered at 39 weeks of gestation without any phenotypic abnormality. Cytogenetic analysis of the cord blood revealed a karyotype of 46,XX,dup(15)(q11.2q11.2).ConclusionPrenatal diagnosis of dup(15)(q11.2q11.2) should include a differential diagnosis of a 15q11.2 (BP1-BP2) microduplication encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1, and aCGH analysis is useful for the differential diagnosis under such a circumstance.     

Mosaicism for a 15q11.2 microduplication with a normal euploid cell line at amniocentesis in a pregnancy with a favorable fetal outcome and postnatal decrease of the aneuploid cell line with the microduplication

ObjectiveWe present mosaicism for a 15q11.2 microduplication with a normal euploid cell line at amniocentesis in a pregnancy with a favorable fetal outcome and postnatal decrease of the aneuploid cell line with the microduplication.Case reportA 35-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed 33.76% mosaicism for a 15q11.2 microduplication. She was referred for genetic counseling. Repeat amniocentesis was performed at 23 weeks of gestation, and the karyotype was 46,XY. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed the result of arr [GRCh37 (hg19)] 15q11.2 (23, 889, 686–25,514,125) × 2.45, consistent with a mosaic 1.624-Mb microduplication with the mosaic level of 40%–45% (log₂ ratio = 0.28) encompassing nine OMIM genes of MAGEL2, NDN, PWRN2, PWRN1, NPAP1, SNRPN, SNHG14, SNORD116-1 and SNORD115-1. Interphase fluorescence in situ hybridization (FISH) analysis on 100 uncultured amniocytes detected a 15q11.2 duplication in 19 cells, consistent with 19% (19/100 cells) mosaic15q11.2 duplication. Polymorphic DNA marker analysis excluded uniparental disomy (UPD) 15. Prenatal ultrasound findings were unremarkable. She was advised to continue the pregnancy, and a 3865-g phenotypically normal male baby was delivered. aCGH analysis on the DNA extracted from cord blood at birth and buccal mucosal cells at age four months revealed arr (1–22) × 2, X × 1, Y × 1 and detected no genomic imbalance in all samples. Interphase FISH analysis on 104 buccal mucosal cells at age four months detected four cells (4/104 = 4%) with a 15q11.2 duplication, compared with 0% (0/102 cells) in the normal control. The neonate was normal in the development.ConclusionMosaicism for a 15q11.2 microduplication at amniocentesis with a normal euploid cell line can be a benign condition and associated with a favorable fetal outcome and postnatal decrease of the aneuploid cell line with the microduplication.     

Successful prenatal treatment of congenital heart block with ritodrine administered transplacentally

Congenital heart block (CHB) is rather rare, and a poorer prognosis has been documented in fetuses with a ventricular rate <55 beats per minutes (bpm), in which therapeutic interventions during pregnancy have been warranted. We present a case of CHB associated with maternal anti-SSA/Ro antibody, diagnosed at 28 weeks’ gestation. Fetal echocardiography revealed atrioventricular dissociation, with an atrial rate of 170 bpm and a ventricular rate of 54 bpm. To increase the fetal heart rate, maternal intravenous ritodrine infusion was undertaken, fetal ventricular rate was rapidly increased to 65 bpm. The pregnancy successfully continued until term, and a female infant weighing 2919 g was delivered by cesarean section with Apgar scores of 8 and 8 and 1 and 5 min. The infant is now 12 months of age and growing normally on oral terbutaline without pacing. In a case of fetal heart block, maternal administration of ritodrine may be a therapeutic intervention to improve the fetal and neonatal prognosis. Received: 27 May 2001 / Accepted: 20 August 2001 Correspondence to H. Matsushita     

Prenatal diagnosis and molecular cytogenetic characterization of a chromosome 1q42.3-q44 deletion in a fetus associated with ventriculomegaly on prenatal ultrasound

ObjectiveWe present prenatal diagnosis and molecular cytogenetic characterization of a chromosome 1q42.3-q44 deletion in a fetus associated with ventriculomegaly on prenatal ultrasound, and we discuss the genotype–phenotype correlation.Case reportA 36-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XX,del(1) (q42.3q44). Simultaneous array comparative genomic hybridization analysis on uncultured amniocytes revealed arr 1q42.3q44 (234,747,397–246,081,267) × 1 [GRCh37 (hg19)] with an 11.33-Mb 1q42.3-q44 deletion encompassing RGS7, FH, CEP170, AKT3, ZBTB18 and HNRNPU. The parental karyotypes were normal. Prenatal ultrasound at 20 weeks of gestation revealed bilateral ventriculomegaly and dilation of the third ventricle. The pregnancy was subsequently terminated, and a malformed female fetus was delivered with characteristic facial dysmorphism. Postnatal conventional and molecular cytogenetic analyses confirmed the prenatal diagnosis. Polymorphic DNA marker analysis showed a paternal origin of the distal 1q deletion in the fetus.ConclusionFetuses with a chromosome 1q42.3-q44 deletion may present ventriculomegaly on prenatal ultrasound. Prenatal diagnosis of ventriculomegaly should include a differential diagnosis of chromosome 1q distal deletions, and aCGH is useful under such a circumstance.     

Detection of congenital heart defects throughout pregnancy; impact of first trimester ultrasound screening for cardiac abnormalities

Objective: To evaluate prospectively the efficacy to screen for congenital heart defects (CHD) during the first trimester nuchal translucency (NT) ultrasound examination by assessing the four chambers’ view of fetal heart. Methods: Pregnancies that were examined prospectively by ultrasound in the first trimester (11th–14th week), the second (19th–24th week) and third trimester were included in the study. 3774 fetuses were examined and fetal heart was assessed during the NT scan by examining the four chambers view. Detailed echocardiography was performed during the anomaly and growth scans. Diagnosis of congenital heart defects (CHD) was further confirmed by a fetal cardiologist. Results: The four chambers view was obtained in 99.52% of the cases. CHD were diagnosed in 29 fetuses (0.77%). Thirteen cases (44.8%) were detected during the 11–13 weeks’ scan, 14 cases (48.3%) during the anomaly scan, 1 CHD (3.5%) during the third trimester scan and 1 case (3.5%) postpartum. Conclusion: Assessment of the four chambers of fetal heart early in pregnancy was feasible and allowed the detection of 45% of CHD. Additional parameters of fetal cardiac anatomy during the NT scan may further improve the detection rate providing pregnancy management information early in the first trimester.     

Placenta-related complications in women carrying a foetus with congenital heart disease

Introduction: Recent studies pointed to an intrinsically angiogenic imbalance in CHD in the maternal and foetal circulation suggestive of impaired placentation.

Objectives: To assess whether pregnant women with a CHD foetus are at greater risk of placenta-related complications.

Methods: Perinatal results of women with a CDH foetus were compared with those of a non-selected population followed up at our centre. Multiple pregnancies and chromosomal abnormalities were excluded from the analysis.

Results: About 279 pregnancies with CHD foetuses were included. Mothers were classified in three groups according to the foetal cardiac defect: 104 (37.3%) atrioventricular defect, 102 (36.5%) conotruncal anomalies and 73 (26.2%) left-ventricular outflow tract obstruction. A significantly higher incidence of pre-eclampsia was observed in the CHD group compared with the normal population (5.7% versus 1.2% p?<?0.0001) [OR 5.96 (95% CI – 3.19–10.54)]. About 9.7% of foetuses with CHD had?<?3rd birth weight percentile compared with 3% for the normal population [OR 3.32 (95% CI – 2.39–4.56)]. A higher incidence of stillbirth was also observed in the CHD group compared with the normal population (2.5% versus 0.4%) [OR 9.45 (95% CI – 3.35–23.3)].

Conclusions: Women carrying a foetus with CHD have a high risk of pre-eclampsia and intrauterine growth restriction. The relationship between CHD and placenta-related complications could be an encouraging topic for future research.