Renal and extra-renal phenotypes in a fetus with a de novo pathogenic variant in the HNF1B gene.

We report a fetus with prenatal ultrasound at 21 gestational weeks showing left cystic renal dysplasia with subcapsular cysts and echogenic parenchyma, right echogenic kidney with absent corticomedullary differentiation, and left congenital diaphragmatic hernia (CDH) with bowel herniation, with intestinal atresia (IA) found on postmortem examination. Whole genome sequencing of fetal blood DNA revealed a heterozygous pathogenic variant c.344 + 2 T>G in the HNF1B gene (NM_000458). Sanger sequencing of the parental samples suggested that it arose de novo in the fetus. HNF1B-associated disorders affect multiple organs with significant phenotypic heterogeneity. In pediatric and adult patients, renal cystic disease and cystic dysplasia are the dominant phenotypes. In prenatal settings, renal anomaly is also the most common presentation, typically with bilateral hyperechogenic kidneys. Our case presented with two uncommon extra-renal phenotypes of CDH and IA besides the typical bilateral cystic renal dysplasia. This association has been reported in fetuses with 17q12 microdeletion but not with HNF1B point mutation. Our case is the first prenatal report of such an association and highlights the possible causal relationship of HNF1B defects with CDH and IA in addition to the typical renal anomalies.

Diagnostic Yield of Exome Sequencing in Fetuses with Sonographic Features of Skeletal Dysplasias but Normal Karyotype or Chromosomal Microarray Analysis: A Systematic Review.

Skeletal dysplasias are a group of diseases characterized by bone and joint abnormalities, which can be detected during prenatal ultrasound. Next-generation sequencing has rapidly revolutionized molecular diagnostic approaches in fetuses with structural anomalies. This review studies the additional diagnostic yield of prenatal exome sequencing in fetuses with prenatal sonographic features of skeletal dysplasias. This was a systematic review by searching PubMed for studies published between 2013 and July 2022 that identified the diagnostic yield of exome sequencing after normal karyotype or chromosomal microarray analysis (CMA) for cases with suspected fetal skeletal dysplasias based on prenatal ultrasound. We identified 10 out of 85 studies representing 226 fetuses. The pooled additional diagnostic yield was 69.0%. The majority of the molecular diagnoses involved de novo variants (72%), while 8.7% of cases were due to inherited variants. The incremental diagnostic yield of exome sequencing over CMA was 67.4% for isolated short long bones and 77.2% for non-isolated cases. Among phenotypic subgroup analyses, features with the highest additional diagnostic yield were an abnormal skull (83.3%) and a small chest (82.5%). Prenatal exome sequencing should be considered for cases with suspected fetal skeletal dysplasias with or without a negative karyotype or CMA results. Certain sonographic features, including an abnormal skull and small chest, may indicate a potentially higher diagnostic yield.

Genome-Wide Cell-Free DNA Test for Fetal Chromosomal Abnormalities and Variants: Unrestricted Versus Restricted Reporting.

This study aimed to compare the screening performance of genome-wide cfDNA testing for chromosomal abnormalities between two periods where additional findings were reported and not reported. Data were obtained from consecutive pregnant women with a singleton pregnancy at ≥10 weeks who requested cfDNA testing during 2015-2019. The performance of screening of the cfDNA test was determined by calculating the concordance rate, detection rate, and false-positive rate. Data from 3981 women were included. The no-result rates were similar between the two reporting periods (2.04% vs. 2.08%). Concordance rates for trisomy 21 and 18 were 100% and 100%, respectively. There were two cases tested high risk for trisomy 13, with a concordance rate of 0%. In total, 12 cases were high risk for any sex chromosome aneuploidy with an overall concordance of 75%, and 15 cases tested high risk for any rare autosomal trisomy, with a 13.3% concordance rate. The detection rates for trisomy 21 and 18 were 100% and 100%, respectively. For any SCA, the detection rate was 90%. For the two reporting periods, the combined false-positive rates were 0.93% and 0.17%, which were significantly different (p = 0.002). Restricting the reporting of additional findings from genome-wide cfDNA analysis has reduced the false-positive rate but without a reduction in the no-result rate.

Determining chorionicity and amnionicity in twin pregnancies: Pitfalls.

Although the accuracy of chorioamnionicity determination in multiple pregnancy is nearly 100%, some pitfalls do exist. These pitfalls may arise from some confusing sonographic appearance or because of certain rare variations of twinning going against the general principles. Pitfalls in chorionicity determination include (1) the disappearance of the twin peak sign with the regression of chorion frondosum and thinning of the intertwin membrane with advancing gestation; (2) fake twin peak sign because of other structures creeping into the intertwin membrane-placental junction; (3) intrauterine septum or synechia being mistaken as a thick intertwin membrane; (4) bipartite placenta in monochorionic twin being misinterpreted as two separate placentas of dichorionic twin; (5) erroneous fetal sex determination in sex chromosome mosaicism, monogenic disorders, and malformed genitalia in one fetus; and (6) rare twinning types such as dizygotic monochorionic twin and sesquizygotic twin. Pitfalls in amnionicity determination are (1) the lack of correlation between the number of yolk sacs and amnionicity and (2) failure to visualize the intertwin membrane because of technical issues.

The Use of Somatex Shunt for Fetal Pleural Effusion: A Cohort of 8 Procedures.

INTRODUCTION: Fetal pleural effusion may require in utero shunting which is associated with procedure-related complications. OBJECTIVE: To evaluate the efficacy and complications of the newly designed Somatex shunt in treating fetal pleural effusion. METHODS: Consecutive cases with primary fetal pleural effusion who were treated with the Somatex shunt between 2018 and 2019 were evaluated. Perinatal outcomes and complications were retrospectively analyzed. RESULTS: There were 6 cases of unilateral and 1 case of bilateral pleural effusion, and hence a total of 8 pleuroamniotic shunting procedures were performed. The median gestational age at diagnosis and shunting was 20.7 and 22.6 weeks, respectively. All 8 procedures were successful, achieving complete in utero drainage. All but one were live births (85.7%) with a median gestational age of 38 weeks. The single case of in utero death occurred 4.7 weeks after successful shunting, and no cause could be identified after autopsy. The rates of preterm birth and premature rupture of membranes were 33.3% (2/6) and 16.7% (1/6), respectively. Four of the 8 procedures (50%) had minor shunt-related complications such as dislodgement and entrapment, occurring at a median of 7.7 weeks after shunting. None of the shunts became blocked. CONCLUSIONS: The Somatex shunt is effective in relieving fetal pleural effusions with good survival rate. Overall, it was a safe instrument, though minor shunt complications occurred.

Impact of replacing or adding placental growth factor on Down syndrome screening: A prospective cohort study.

OBJECTIVES: To assess whether adding placental growth factor (PlGF) or replacing pregnancy-associated plasma protein-A (PAPP-A) improves the first trimester combined test performance for trisomy 21. METHODS: A total of 11,518 women with a singleton pregnancy who underwent the first trimester combined test between December 2016 and December 2019 were included. PlGF was measured and estimated term risk for trisomy 21 was calculated by (1) adding PlGF to the combined test and (2) replacing PAPP-A with PlGF. RESULTS: Twenty-nine pregnancies had trisomy 21. The combined tests detection rate (DR), false positive rate (FPR) and screen positive rate (SPR) were 89.7%, 5.7% and 6% respectively. DR when adding PlGF to the combined test or replacing PAPP-A remained unchanged. Replacing PAPP-A by PlGF increased FPR and SPR to 6.2% and 6.4% respectively. Adding PlGF to the combined test gave FPR and SPR rates of 5.5% and 5.7% respectively. Change in FPR and SPR was not significant (p > 0.1 for all). CONCLUSION: Adding PlGF to the combined test or replacing PAPP-A with PlGF did not improve trisomy 21 DR and resulted in a non-significant marginal change in FPR and SPR.

The utility of genome-wide cell-free DNA screening in the prenatal diagnosis of Pallister-Killian syndrome.

OBJECTIVE: To report genome-wide cell-free DNA (cfDNA) screening facilitating the diagnosis of Pallister-Killian syndrome (PKS). METHODS: This is a retrospective cohort analysis of positive genome-wide cfDNA screening results showing increased signal from chromosome 12 and the detection of PKS. The genome-wide cfDNA screening results and the subsequent investigations were reviewed. RESULTS: Three singleton pregnancies (3/29007) from 2016 to 2017 yielded positive results indicating large gains on the entire p-arm of chromosome 12. In two cases, multiple structural abnormalities were detected by prenatal ultrasound and the couples opted for termination of pregnancy. Chromosomal microarray performed on fetal skin tissues of the two abortuses detected mosaic tetrasomy 12p, consistent with PKS. In the third case, karyotype and chromosomal microarray performed on an amniotic fluid sample also showed mosaic tetrasomy 12p. In each of the three cases, genome-wide cfDNA screening revealed a large gain on chromosome 12p; subsequent prenatal or postnatal diagnostic testing confirmed the diagnosis of PKS. CONCLUSION: We report the ability of genome-wide cfDNA screening to provide early suspicion and facilitate the subsequent genetic diagnosis of PKS. As genome-wide cfDNA screening becomes increasingly available, incidental diagnosis of partial aneuploidies is expected to increase.

Objective assessment of the fetal facial profile at second and third trimester of pregnancy.

OBJECTIVE: To investigate the intraobserver and interobserver reproducibility of a novel sonographic parameter named facial maxillary angle (FMA) and to establish nomograms of FMA, inferior facial angle (IFA), frontal nasal-mental angle (FNMA), maxilla-nasion-mandible angle (MNMA), and fetal profile line (FPL) in Chinese fetuses. METHODS: In this prospective cross-sectional study, FMA, IFA, FNMA, MNMA, and FPL were measured in 592 normal fetuses between 16 and 36 gestational weeks. FMA was measured twice by the same and another operator with a blinded method on the first 50 cases. The reference interval was defined as ±2SD. The efficacy of five sonographic markers was tested in 10 fetuses with micrognathia retrieved from the database of our unit. RESULTS: The intraclass correlation coefficient (95% CI) of intraobserver and interobserver reproducibility of FMA was 0.937 (0.890-0.964) and 0.891 (0.809-0.938), respectively. FMA, FNMA, and IFA increased slightly from 16 weeks till 28-31 weeks and decreased minimally thereafter. FMA and FNMA made correct diagnosis in all affected fetuses; MNMA and IFA identified nine and eight cases respectively, and FPL only detected five cases. CONCLUSION: A fixed cutoff of 66° for FMA and 136° for FNMA may be adopted as simple screening criteria of micrognathia.

Hypoechoic liver in fetuses with trisomy 21.

The association between hypoechoic hepatomegaly in the third trimester and transient abnormal myelopoiesis (TAM) was reported previously in six fetuses with trisomy 21 (T21). We report a series of three cases of T21 in which hypoechoic liver (HL) was found in the second trimester but without evidence of TAM on both hematological and histological examination. We postulate that the hypo-echogenicity may be due to liver congestion secondary to hemodynamic disturbances seen in T21 fetuses. All three cases had negative first trimester Down syndrome screening and one case was detected solely because of the isolated finding of HL. HL per se may be associated with T21 and more positive cases are required to support this association.

Pitfalls in assessing chorioamnionicity: novel observations and literature review.

Accurate diagnosis of chorioamnionicity in multiple pregnancies is the key to appropriate clinical management of multiple gestation. Although prenatal ultrasound assessment of chorioamnionicity is well established and highly accurate if performed in early pregnancy, exceptions and artifacts arise from anatomic variations in multiple pregnancies and unusual sonographic features do exist. We have summarized our own experiences and reports from the literature on these pitfalls as follows: (1) discordant fetal sex in monochorionic pregnancies due to sex chromosome abnormalities, genital malformation in 1 fetus, or dizygotic twins forming a monochorionic placenta; (2) separate placental masses in monochorionic pregnancies due to bipartite placenta; (3) false-negative and false-positive λ sign can arise for various reasons, and in partial monochorionic/dichorionic placentas both T and λ sign may co-exist; (4) intrauterine synechia appearing as a thick and echogenic intrauterine septum may lead to erroneous diagnosis of dichorionic twins; and (5) errors in ascertaining amnionicity by the visualization of thin intertwin amniotic membranes and the number of yolk sacs. The ultrasound techniques to reduce inaccuracy in prenatal determination of chorioamnionicity and the use of single nucleotide polymorphisms based on noninvasive prenatal test to determine zygosity are also reviewed.

Uterine artery pulsatility index in the first trimester: assessment of intersonographer and intersampling site measurement differences.

OBJECTIVE: To determine intersonographer, intersampling site pulsatility index differences in the ascending branch of the uterine artery (UtA-PI) and their effect on detection rates (DR) for early onset preeclampsia (PE). METHODS: A prospective observational study was conducted including 52 women with singleton viable pregnancy at 11-13 weeks' gestation. Consecutive bilateral UtA-PI measurements were performed by two sonographers. Both sonographers hold the Fetal Medicine Foundation (FMF) uterine artery Doppler assessment competency certificates. Sonographer "A" underwent mentorship-based specialist training at the FMF; whilst sonographer "B" is a fetal maternal specialist who was deemed competent to measure UtA-PI based on completion of the FMF online course. Both sonographers were unaware of each other's UtA-PI and peak systolic velocity (PSV) measurements throughout the study. UtA-PI was measured by sonographer "A" at 1, 2 and 3 cm distally from the internal os. UtA-PI minimum ("Low-PI") and mean ("Mean-PI") were determined. Intraclass correlation (ICC), Bland-Altman analysis and Wilcoxon signed rank test were performed to determine bias, 95% limits of agreement (LOA) for intersonographer and intersampling site differences. Simulation studies were performed to determine the effect on early onset PE screening DR. RESULTS: (1) Intersite assessment indicated that UtA-PI and PSV decreased by 7-8% per centimeter relative to the measurement taken at the internal os; (2) Sonographer "B" UtA-PI measurements were significantly lower than those of sonographer "A" for "Low-PI" (p = .001), "Mean-PI" (p = .002) and PSV (p = .004) determined by Wilcoxon signed rank test. The mean reduction in "Low-PI", "Mean-PI" and PSV of sonographer "B" relative to sonographer "A" were 14.04%, 11.09% and 10.99%, respectively; (3) Measurements taken by sonographer "B" at the level of the internal os were comparable to measurements taken by sonographer "A" at 2 cm distal to the internal os (low-PI: p = .98, Mean-PI: p = .49 and PSV: p = .24); (4) Between sonographer ICC for UtA-PI was asymmetrical strong (left ICC = 0.72, 95%CI: 0.51-0.84) to fair (right ICC = 0.38, 95%CI: -0.08-0.64); and (5) The 14% mean intersonographer difference in lowest UtA-PI would have resulted in an 7% difference in PE screening performance. CONCLUSIONS: The measurement of UtA-PI is sampling site dependent with the potential for significant intersonographer differences despite the availability of a prescriptive measurement protocol. This is an important observation as it implies that sonographer "B" inadvertently measured the UtA-PI at a distal site, not at the level of internal os, compared to those measured by sonographer "A", resulting in a lower DR for early onset PE.

First Report of a Novel Deletion Due to εγδß-Thalassemia in a Chinese Family.

A fetus of Chinese descent presented with ultrasound features of anemia at 20 weeks' gestation. Father had low a mean corpuscular volume (MCV) level. Multiplex gap-polymerase chain reaction (gap-PCR) excluded common α-thalassemia (α-thal) deletions and mutations and PCR sequencing of the α1- and α2-globin genes were negative. The fetus had a normal karyotype. Array comparative genomic hybridization (aCGH) showed a single copy loss of 189.87 kb in chromosome 11p15.4, involving the whole ß-globin gene cluster, inherited from the father. Multiplex ligation-dependent probe amplification (MLPA) confirmed the deletion included the ε-globin gene, confirming the diagnosis of heterozygous (εγδß)0-thalassemia [(εγδß)0-thal], also inherited from the father. The fetus had a worsening anemic condition in utero and required a transfusion at 26 weeks' gestation, raising the hemoglobin (Hb) level from 5.3 to 12.6g/dL. A cesarean-section was subsequently performed at 32 weeks' gestation because of reduced fetal movements, and a 1650g baby girl with good Apgar scores was delivered. Hemoglobin at birth was 12.8g/dL, gradually dropping to 6.8 g/dL, requiring three neonatal transfusions. Her condition gradually stabilized after 2 months with Hb stable at 8.0 g/dL. Family screening by MLPA showed that the paternal grandmother carried the same deletion. The deletion in this case is distinct and is the reported first case. The deletion transmitted across three successive generations with great phenotypic variation. The final adult phenotype of (εγδß)0-thal is usually mild, therefore, with accurate prenatal diagnosis this condition is salvageable by in utero and early neonatal transfusions, preventing adverse pregnancy and neonatal outcomes.

Pseudoamniotic Band Syndrome after In Utero Intervention for Twin-to-Twin Transfusion Syndrome: Case Reports and Literature Review.

Pseudoamniotic band syndrome (PABS) is a rare iatrogenic complication that arises after invasive procedures in monochorionic twins. We report 3 cases of PABS, 2 after fetoscopic laser photocoagulation and 1 after bipolar cord coagulation. Two cases were detected antenatally by ultrasound; out of the two, one underwent successful fetoscopic release of amniotic band, which is the first report in twin pregnancy to our knowledge. In our centre, the incidence of PABS was found to be 2%. There were 25 cases of PABS reported previously, of which 12 cases with clinical details were reviewed together with our 3 cases. The fetal limbs were involved in all 15 cases, leading to constriction or amputation. The umbilical cord was involved in 2 cases, resulting in fetal death in one and pregnancy termination in the other. Antenatal detection of PABS is rare (27%; 4/15) as this requires a high index of suspicion. Serial postoperative targeted ultrasound surveillance of the fetal limbs and umbilical cord is necessary, particularly when features of septostomy or chorioamniotic membrane separation are found. Colour Doppler examination for the perfusion of the affected limb should be performed when PABS is detected. Fetoscopic release of amniotic band could salvage the fetal limb from amputation when impaired blood flow is detected.

Seasonality of fetal trisomy 21--have ambient air pollutants played a role?

OBJECTIVE: To examine the seasonality of fetal trisomy 21 and its relationship with ambient air pollutants. METHODS: The averaged incidence by month-of-conception of the 113 cases (2002-2009) in our registry was correlated with month of conception and monthly ambient levels of nitrogen oxides (NOx, NO and NO2), sulfur dioxide, carbon monoxide, and ozone as reported by the Hong Kong Environmental Protection Department at the month of, and four-week after, conception. RESULTS: The incidence was highest in February (3.45/1000 births) and lowest in October (1.28/1000 births), and showed a significant difference (p = 0.003) and positive correlation (p = 0.003) from winter to autumn. It was also correlated with NO (p = 0.017) and inversely with ozone (p = 0.014) at conception. CONCLUSIONS: Seasonal variation in incidence of fetal trisomy 21 was correlated with ambient levels of nitric oxides and ozone. The role of environmental pollutants on fetal aneuploidy warrants further investigation.

Radiofrequency ablation for selective reduction in complicated monochorionic multiple pregnancies.

OBJECTIVE: To evaluate the perinatal outcome of monochorionic (MC) multiple pregnancies after selective reduction by radiofrequency ablation (RFA). METHODS: A case series of all MC multiple pregnancies with selective reduction by RFA in one single institution was reviewed. RESULTS: Ten consecutive patients with an MC pregnancy (9 pairs of twins and 1 set of triplets) underwent RFA. The median gestational age at the time of the procedure was 15.6 weeks (range, 12.3-19.6). The indications for selective reduction included discordance for fetal anomalies (4 cases), twin reversed arterial perfusion sequence (3 cases), selective intrauterine growth restriction (2 cases) and severe twin-twin transfusion syndrome (1 case). All procedures were technically successful in achieving selective reduction. The overall survival rate of the co-twin was 81.8% (9/11), and the median gestational age at delivery was 35.9 weeks (range, 32.4-38.6). There was one preterm delivery before 34 weeks of gestation (11.1%). Preterm premature rupture of the membranes occurred in 2 patients (20%); however, this was not observed within 4 weeks postoperatively, nor did they deliver before 32 weeks. CONCLUSIONS: RFA is a promising technique for selective reduction in complicated MC multiple pregnancies with a high survival rate and low complication rate.

The influence of image setting on intracranial translucency measurement by manual and semi-automated system.

OBJECTIVE: To investigate the agreement between manual and semi-automated system and the effect of different image settings on intracranial translucency (IT) measurement. METHODS: A prospective study was conducted on 55 women carrying singleton pregnancy who attended first trimester Down syndrome screening. IT was measured both manually and by semi-automated system at the same default image setting. The IT measurements were then repeated with the post-processing changes in the image setting one at a time. The difference in IT measurements between the altered and the original images were assessed. RESULTS: Intracranial translucency was successfully measured on 55 images both manually and by semi-automated method. There was strong agreement in IT measurements between the two methods with a mean difference (manual minus semi-automated) of 0.011 mm (95% confidence interval--0.052 mm-0.094 mm). There were statistically significant variations in both manual and semi-automated IT measurement after changing the Gain and the Contrast. The greatest changes occurred when the Contrast was reduced to 1 (IT reduced by 0.591 mm in semi-automated; 0.565 mm in manual), followed by when the Gain was increased to 15 (IT reduced by 0.424 mm in semi-automated; 0.524 mm in manual). CONCLUSIONS: The image settings may affect IT identification and measurement. Increased Gain and reduced Contrast are the most influential factors and may cause under-measurement of IT.

Carbimazole embryopathy in a Chinese population: case series and literature review.

BACKGROUND: The data in the literature suggests that Methimazole (MMI)/Carbimazole (CMZ) embryopathy is rare. This study examined the incidence of CMZ embryopathy in the Hong Kong Chinese population and the factors associated with its development. METHODS: Of the 145 pregnant women with hyperthyroidism managed from 2008 to 2010, 29 (20%) had taken CMZ during pregnancy. The presence and details of birth defects, the dosage of CMZ, and the period of exposure during pregnancy were examined in these 29 pregnancies. All cases of CMZ embryopathy in the English literature were reviewed in the same way. RESULTS: Of the 27 babies (93.1%) with known outcome, 3 had aplasia cutis and 1 had an omphalocele in addition, and 1 affected baby had a sibling with aplasia cutis and patent vitellointestinal duct. The incidence of CMZ embryopathy in our study group is 11.1%. Amongst the 21 cases of CMZ embryopathy in the literature, 85% were exposed to a CMZ dosage of ≥20 mg/day, and the minimum duration of exposure being 7 weeks from last menstrual period. The most common abnormality is ectodermal anomaly (62%), followed by oro-nasal anomaly (48%), facial dysmorphism (38%), gastrointestinal anomaly (33%) and abdominal wall defect (19%). There was no relationship between the type of abnormality and the dosage or duration of exposure to CMZ. CONCLUSIONS: The incidence of CMZ embryopathy in our study group is 11.1%. Critical factors for its development are exposure to a CMZ dosage of ≥20 mg/day before 7 weeks of gestation. Genetic susceptibility may also play a role.

Detection of the fetal conotruncal anomalies using real-time three-dimensional echocardiography with live xPlane imaging of the fetal ductal arch view.

OBJECTIVE: To evaluate the role of live xPlane imaging of ductal arch view in detection of fetal conotruncal anomalies. METHODS: Two hundred selected singleton pregnancies, including 152 normal cases, 27 conotruncal anomalies and 21 other types of fetal heart abnormalities were enrolled in this observational study. All the cases were scanned to visualize the ductal arch view with live xPlane imaging by a single observer. The detection rate of conotruncal and non-conotruncal anomalies with live xPlane imaging was compared. RESULTS: In using this new method of live xPlane imaging, an abnormal ductal arch view was visualized in 92.6% of fetal conotruncal anomalies, compared with that of non-conotruncal anomalies (23.8%, p < 0.001). CONCLUSION: The ductal arch view can be obtained by live xPlane imaging. This method is relatively simple and feasible, hence may be a useful tool to detect fetal conotruncal anomalies.

Can live xPlane imaging of the in-plane view of interventricular septum be used to detect fetal conotruncal anomalies?

OBJECTIVE: To evaluate the feasibility of live xPlane imaging visualizing the in-plane view of IVS in the screening of the fetal conotruncal anomalies. METHOD: One hundred and fifty-two consecutive normal singleton fetuses and forty-eight fetal cardiac defects (27 conotruncal and 21 non-conotruncal cases), were enrolled in this study. The in-plane view of IVS was firstly acquired with live xPlane imaging and then judged whether it is normal or not by one operator. The focus was put on observing the relationship of pulmonary artery and aorta. The comparison between conotruncal and non-conotruncal anomalies in demonstrating the relationship of pulmonary artery and aorta was performed. RESULT: There were 27 cases of conotruncal anomalies enrolled in this study and 19 cases (70.4%) had the abnormal relationship of aorta and pulmonary artery in the in-plane view of IVS. In 21 cases of non-conotruncal CHDs, however, there were only 5 cases (23.8%) had the abnormal relationship in the in-plane view of IVS (p < 0.001). CONCLUSION: Live xPlane imaging of the in-plane view of IVS is feasible to detect the fetal conotruncal anomalies, which may potentially be a useful tool for the non-experienced operators to screen the fetal conotruncal anomalies.

Environmental factors in the first trimester and risk of oral-facial clefts in the offspring.

The averaged incidences of nonsyndromal/isolated cleft lip (CL), cleft palate (CP), and cleft lip with cleft palate (CLCP) by each month-of-conception, and managed in our hospital in from 2002 to 2009 were correlated with the reported levels of sunshine, ultraviolet radiation, and ambient nitrogen oxides (nitrogen oxide, nitrogen monoxide, and nitrogen dioxide), sulfur dioxide, and ozone, at the month of, and then at 4 and 8 weeks after, conception. There were 25, 12, and 22 cases each of CL, CP, and CLCP, respectively, totaling 59 cases (1.21 of 1000 births). On regression analysis, sunshine correlated inversely with the isolated CL at (P = .009) 4 weeks (P = .005) and 8 weeks (P = .008) postconception, and with CP (P = .009) and CLCP (P < .001) at 8 weeks postconception, while NOx correlated inversely with CL (P = .018) and NO with CLCP (P = .031), at 8 weeks postconception. Our results suggested that the interaction between sunshine and nitrogen oxides with other factors results in the reported seasonal variation in the incidence of isolated oral-facial clefts.