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.

[Perinatal outcome of monochorionic twin pregnancies].

OBJECTIVE: To study the perinatal outcome of monochorionic (MC) twin pregnancies. METHODS: The 197 cases of MC twin pregnancies delivered in obstetric unit of Prince of Wales Hospital from Jan. 2005 to Dec. 2010 were enrolled in this retrospective study,which were divided into 3 groups:uncomplicated MC pregnancy (136 cases), twin to twin transfusion syndrome (TTTS, 32 cases), selective intrauterine growth restriction (sIUGR, 29 cases). RESULTS: (1) The gestational age at delivery in TTTS (30 weeks vs.37 weeks, P<0.01) or sIUGR (34 weeks vs.37 weeks, P<0.01) group were significantly lower than those in uncomplicated MC pregnancy. The number of live-born in TTTS (36 cases) or sIUGR (47 cases) group were significantly lower than those in uncomplicated MC pregnancy (261 cases, P<0.01). (2) The incidence of fetal death (IUFD) in TTTS [34% (11/32) vs. 4% (6/136), P<0.01] or sIUGR group [28% (8/29) vs. 4% (6/136), P<0.01] were significantly higher than those in uncomplicated MC pregnancy group. (3) The incidence of birth weight (BW) discordance>25% in TTTS [5/15 vs.7.7% (10/130), P<0.05] or sIUGR [33% (7/21) vs. 7.7% (10/130), P<0.05] group were significantly higher than those in uncomplicated MC pregnancy group. (4) The incidence of preterm delivery before 37 weeks was 49% (66/136) and 69% (20/29) respectively in uncomplicated MC pregnancy and sIUGR. The incidence of preterm delivery in sIUGR group were significantly higher than that in uncomplicated MC pregnancy group (P<0.05). (5) The incidence of perinatal mortality in TTTS[12%(5/41) vs.0.4% (1/262), P<0.01] or sIUGR [10%(5/52) vs. 0.4% (1/262), P<0.01] group were significantly higher than those in uncomplicated MC pregnancy group. (6) The incidence of estimated fetal weight (EFW) discordance>25% was 17% (23/136) in uncomplicated MC pregnancy, 52% (15/29) in sIUGR, 63% (20/32) in TTTS. In uncomplicated MC pregnancy or sIUGR, pregnancies with EFW discordance>25% was associated with lower gestational age at delivery, higher incidence of preterm delivery and admission to NICU than those with EFW discordance≤25% (P<0.05). In uncomplicated MC pregnancy, pregnancies with EFW discordance>25% was associated with higher incidence of neonatal asphyxia (Apgar score 1 minute≤7) than those with EFW discordance≤25% (P<0.05). (7) Compared to uncomplicated MC pregnancy, the incidence of umbilical artery (UmA) flow abnormality was higher in TTTS[38% (12/32) vs. 9.6% (13/136), P<0.01] or sIUGR [41% (12/29) vs. 9.6% (13/136), P<0.01]. The incidence of IUFD in pregnacies with UmA flow abnormality was 2/13, 6/12 and 5/12 respectively in uncomplicated MC pregnancy, TTTS and sIUGR. CONCLUSIONS: MC pregnancies complicated by either TTTS or sIUGR have poorer perinatal outcome as compared with uncomplicated MC pregnancies. MC pregnancies with EFW discordance>25% and UmA flow abnormality are associated with even worse perinatal outcome. Close fetal monitoring is needed in MC pregnancies in order to reduce perinatal mortality.

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.

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.

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.