Tung-Yao Chang

The Changing Face of Early-onset Neonatal Sepsis After the Implementation of a Maternal Group B Streptococcus Screening and Intrapartum Prophylaxis Policy—A Study in One Medical Center

BACKGROUND Early-onset sepsis (EOS) is the major cause of neonatal morbidity and mortality. Maternal group B Streptococcus (GBS) screening and intrapartum antibiotic prophylaxis (IAP) were implemented in our hospital in 2004. Our aim was to evaluate the effectiveness of the program and changes in pathogens and antibiotic susceptibility. METHODS The medical charts of mothers and infants with EOS between January 2001 and November 2008 were retrospectively reviewed. EOS was defined as sepsis occurring within 72 hours of birth. Data were pooled and compared for January 2001 through September 2004 (Period 1, without GBS screening) and October 2004 through November 2008 (Period 2, with GBS screening and IAP). RESULTS The GBS screening rate increased from 10.11% in 2004 to 65% in 2008 and the IAP rate increased from 40% in 2004 to 90% in 2008. The most common EOS pathogen in Period 1 was GBS (45.4%), which decreased to 20% in Period 2 (p=0.081; trend p=0.009). The percentage of EOS because of Escherichia coli in Period 1 was 40.9% but increased to 70% in Period 2 (p=0.059). E coli EOS increased in extremely low birth weight premature babies weighing 500-1000g from Period 1 to Period 2 (p=0.031). The incidence of ampicillin-resistant E coli EOS was relatively high, but no significant change (88.9% vs. 92.9%) after implementation of GBS screening and IAP was noted. CONCLUSION GBS screening plus IAP is effective in decreasing the incidence of GBS EOS; however, an increase in EOS caused by E coli was noted. Monitoring of pathogens causing EOS is important for effective treatment.

Chromosome 17p13.3 deletion syndrome: aCGH characterization, prenatal findings and diagnosis, and literature review.

We report a molecular cytogenetic characterization of 17p13.3 deletion syndrome by array comparative genomic hybridization (aCGH), fluorescence in situ hybridization (FISH) and quantitative polymerase chain reaction (qPCR) in a fetus with lissencephaly, corpus callosum dysgenesis, ventriculomegaly, microcephaly, intrauterine growth restriction (IUGR), polyhydramnios and single umbilical artery. aCGH analysis revealed a 3.17-Mb deletion at 17p13.3, or arr [hg19] 17p13.3 (0-3,165,530)×1. The qPCR assays revealed a maternal origin of the deletion. Metaphase FISH analysis detected the absence of the LIS1 probe signal on the aberrant chromosome 17. The karyotype was 46,XX,del(17)(p13.3). We review the literature of chromosome 17p13.3 deletion syndrome with prenatal findings and diagnosis, and suggest that prenatal ultrasound detection of central nervous system anomalies such as lissencephaly, corpus callosum dysgenesis/agenesis, ventriculomegaly and microcephaly associated with IUGR, polyhydramnios, congenital heart defects, abdominal wall defects and renal abnormalities should include a differential diagnosis of chromosome 17p13.3 deletion syndrome.

Prenatal diagnosis of ring chromosome 2 with lissencephaly and 2p25.3 and 2q37.3 microdeletions detected using array comparative genomic hybridization

We present rapid aneuploidy diagnosis of ring chromosome 2 with 2p25.3 and 2q37.3 microdeletions by aCGH using uncultured amniocytes in a fetus with IUGR, microcephaly, lissencephaly and ambiguous external genitalia. Our case adds lissencephaly to the list of CNS abnormalities in ring chromosome 2 with 2p25.3 and 2q37.3 microdeletions. We discuss the consequence of haploinsufficiency of HDAC4, KIF1A, PASK, HDLBP, FRAP2 and D2HGDH on 2q37.3, and haploinsufficiency of MYT1L, SNTG2 and TPO on 2p25.3 in this case.

Third-trimester 3D Ultrasound Evaluation of Thanatophoric Dysplasia Type I

the hospital at 31 gestational weeks because of limb deformities in the fetus. The woman and her husband were healthy, and there was no family history of skeletal abnormalities. Two-dimensional (2D) ultrasound examination revealed polyhydramnios, frontal bossing, a depressed nasal bridge, a narrow chest, a protuberant abdomen, macrocephaly, shortening of the long bones, and bowing in the femurs (Figure 1). The amniotic fluid index was 300 mm. The femur length measured 2.52 cm (normal, 5.39–6.39 cm), tibia length 1.72 cm (normal, 4.82–5.98 cm), fibula length 1.89 cm (normal, 4.68–6.18 cm), humerus length 2.08 cm (normal, 4.85–6.01 cm), ulna length 2.11 cm (normal, 4.58– 5.94 cm) and radius length 1.98 cm (normal, 3.97– 5.33 cm). The long-bone measurements were below the 5th percentile of the normal biometry. The thoracic circumference (TC) was 18.79cm (normal, 20–25.5cm).

Osteogenesis imperfecta type II: prenatal diagnosis and association with increased nuchal translucency and hypoechogenicity of the cranium.

Department of Medicine, Mackay Medical College, New Taipei City, Taiwan Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan Department of Biotechnology, Asia University, Taichung, Taiwan e School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan f Institute of Clinical and Community Health Nursing, National Yang-Ming University, Taipei, Taiwan Department of Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan i Taiji Fetal Medicine Center, Taipei, Taiwan Pan Chun-Heng Obs/Gyn Clinics, New Taipei City, Taiwan Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan Department of Bioengineering, Tatung University, Taipei, Taiwan

VACTERL association with hydrocephalus in a fetus conceived by in vitro fertilization and embryo transfer

OBJECTIVE We present a case of VACTERL association with hydrocephalus (VACTERL-H) in a fetus conceived by in vitro fertilization (IVF) and embryo transfer (ET) and review the literature. CASE REPORT A 35-year-old woman presented with multiple fetal anomalies at 22 weeks of gestation. She and her husband were non-consanguineous and there was no family history of congenital malformations. This was her second pregnancy conceived via IVF-ET. Two embryos had been implanted and only one survived. She underwent chorionic villus sampling at 17 weeks of gestation because of oligohydramnios and advanced maternal age. Cytogenetic analysis revealed a karyotype of 46,XY, and array comparative genomic hybridization analysis revealed no genomic imbalance. Prenatal ultrasound at 21 weeks of gestation revealed a singleton with fetal biometry equivalent to 18 weeks, ventriculomegaly, a small cerebellum, and a ventricular septal defect. Level II ultrasound showed a single umbilical artery, scoliosis, a right club hand, radial aplasia, and renal agenesis. The parents elected to terminate the pregnancy at 22 weeks of gestation, and a fetus was delivered with bilateral arthrogryposis, right radial aplasia, a club hand and thumb aplasia, hypoplasia of the left thumb, scoliosis, and an imperforate anus. The clinical findings were consistent with the diagnosis of VACTERL-H. Molecular analysis of PTEN, FANCB, and HOXD13 genes revealed no mutation. CONCLUSION Prenatal diagnosis of radial ray defects in fetuses conceived by assisted reproductive technology should include a differential diagnosis of VACTERL association with anorectal malformation. VACTERL-H may occur in pregnancy after IVF-ET.

Preliminary Descriptive Statistics of the Taiwanese Registry of Epilepsy and Pregnancy for the First 2 Years

OBJECTIVE To present the descriptive statistics of the Taiwanese Registry of Epilepsy and Pregnancy (TREP) for the first 2 years. MATERIALS AND METHODS The pregnancies were recruited from May 2004 to January 2006 with a data format compatible with the International Registry of Antiepileptic Drugs and Pregnancy (EURAP) by referral. The data were collected from either face-to-face interview, telephone interview, or chart review by a research nurse. Five questionnaires (A-E) were required for each pregnancy. The preliminary data for the first 2 years are presented with general descriptive statistics. RESULTS Until January 2006, 43 pregnancies have been registered. Questionnaire A was completed in 43 cases, questionnaire B completed in 40 cases, questionnaire C completed in 34 cases, questionnaire D completed in 27 cases, and questionnaire E in eight cases. Among the 39 pregnancies known to take antiepileptic drugs (AEDs) during pregnancy, 28 pregnancies took one AED, nine pregnancies took two AEDs, and two pregnancies took three AEDs. The most commonly used drug was carbamazepine (19/39, 48.72%). Among the 27 pregnancies, who had delivered, the cesarean section rate was 44.44% (12/27), the premature birth rate was 7.41% (2/27), and the fetal malformation rate was 3.7% (1/27). CONCLUSION The preliminary data concluded the efforts of TREP for the first 2 years. Although it is still premature to project a trend out of current data, the registry is expected to provide critical information to local prenatal counseling and contribute further to the international EURAP database.

Detection of a de novo Y278C mutation in FGFR3 in a pregnancy with severe fetal hypochondroplasia: Prenatal diagnosis and literature review

OBJECTIVE We describe a prenatal molecular diagnosis of hypochondroplasia (HCH) in a pregnancy not at risk of HCH and review the literature on prenatal diagnosis of HCH. CASE REPORT A 28-year-old primigravid woman was referred for genetic counseling at 30 weeks of gestation because of short-limbed dwarfism in the fetus. The woman had a body height of 152 cm. Her husband had a body height of 180 cm. Level II ultrasound showed a normal amount of amniotic fluid and a singleton fetus with fetal biometry equivalent to 30 weeks except for short limbs. Fetal biometry measurements were as follows: biparietal diameter = 7.38 cm (30 weeks); head circumference = 28.14 cm (30 weeks); abdominal circumference (AC) = 24.64 cm (30 weeks); femur length (FL) = 3.97 cm (<5th centile); FL/AC ratio = 0.161 (normal > 0.18); humerus = 3.64 cm (<5th centile); radius = 3.49 cm (30 weeks); ulna = 3.76 cm (<5(th) centile); tibia = 3.67 cm (<5th centile); and fibula = 3.72 cm (<5th centile). The digits and craniofacial appearance were normal. A tentative diagnosis of achondroplasia (ACH) was made. DNA testing for the FGFR3 gene and whole-genome array comparative genomic hybridization (aCGH) analysis were performed using cord blood DNA obtained by cordocentesis. FGFR3 mutation analysis revealed a de novo heterozygous c.833A > G, TAC > TGC transversion in exon 7 leading to a p.Tyr278Cys (Y278C) mutation in the FGFR3 protein. aCGH analysis revealed no genomic imbalance in cord blood. After delivery, the fetus had short limbs, a narrow thorax, brachydactyly, and relative macrocephaly. Cytogenetic analysis of cultured placental cells revealed a karyotype of 46,XX. CONCLUSION Prenatal diagnosis of abnormal ultrasound findings suspicious of ACH should include a differential diagnosis of HCH by molecular analysis of FGFR3.

Second‐trimester sonographic demonstration of retrognathia and bilateral pyelectasis in a fetus with a duplication of chromosome 10q24.1→qter

within the mesenchymal tissue10. Both authors, however, agree that there is a phase during which the lymph sacs are not connected with the venous system and that the connection occurs when the embryo reaches a CRL measurement of about 30 mm. This length corresponds to 9–10 weeks of gestational age11. If there is a delay in the connection, for instance until 13–14 weeks, the lymph sacs cannot drain and lymphatic fluid accumulates within them. NT measurement would then be abnormal, as in trisomy 21. If the connection does not occur, the lymphatic sacs enlarge to form cystic structures, as in cystic hygroma.

Rapid detection of K650E mutation in FGFR3 using uncultured amniocytes in a pregnancy affected with fetal cloverleaf skull, occipital pseudoencephalocele, ventriculomegaly, straight short femurs, and thanatophoric dysplasia type II

OBJECTIVE To present the ultrasound and molecular genetic diagnosis of thanatophoric dysplasia type II (TD2). CASE REPORT A 35-year-old, primigravid woman was referred to our institution for genetic counseling and amniocentesis at 19 weeks of gestation because of advanced maternal age and sonographic abnormalities in the fetus. The prenatal ultrasound showed short straight femurs, prominent forehead, narrow chest, skin edema, short limbs, and cloverleaf skull consistent with the diagnosis of TD2. Amniocentesis revealed a karyotype of 46,XX. DNA testing for the FGFR3 gene using uncultured amniocytes revealed a heterozygous c.1948A>G, AAG>GAG transversion leading to a p.Lys650Glu(K650E) mutation in the FGFR3 gene. A prenatal ultrasound at 21 weeks of gestation showed ventriculomegaly, cloverleaf skull, straight femurs, micromelia, narrow chest, and pseudoencephalocele with a bulging occipital bone mimicking encephalocele. The pregnancy was subsequently terminated, and a 480-g malformed fetus was delivered with macrocephaly, depressed nasal bridge, short upturned nasal tip, hypoplastic midface, frontal bossing, short digits, trident-shaped hands, short limbs, cloverleaf skull, narrow chest, brachydactyly, nuchal edema, and bulging occipital bone. CONCLUSION A prenatal diagnosis of cloverleaf skull, short limbs, straight femurs, and occipital pseudoencephalocele should include a differential diagnosis of TD2. A molecular analysis of FGFR3 using uncultured amniocytes is useful for the rapid confirmation of TD2 at prenatal diagnosis.