Chen-Ju Lin

Outcome of Pregnancy in Patients with Systemic Lupus Erythematosus

A prospective study was performed to investigate the outcome and complications of pregnancy in patients with systemic lupus erythematosus. Twenty-nine pregnancies occurred in 22 patients. There were 12 abortions, two spontaneous and 10 induced. Fifteen women had 17 live-born neonates. Neonatal complications included nine premature deliveries, two cases of intrauterine growth retardation, and one of Treacher Collins syndrome. Obstetric complications included threatened abortion (two), placenta previa (two), and preeclampsia (three). Cesarean sections were necessary in five patients. There was no maternal or neonatal mortality. Thirteen episodes of systemic lupus erythematosus relapses were detected by incidents of increasing proteinuria (six), arthritis (four), and vasculitic rash (two). There were no statistical differences in changes in hemoglobin level, erythrocyte sedimentation rate, albumin level, antinuclear antibody titer, or C3 or C4 level between the patients who relapsed and those who did not. Pregnancy could induce a flare of systemic lupus erythematosus in previously normal patients or patients with previously inactive disease. The overall neonatal and maternal survival was good, even in patients who presented during pregnancy. Spontaneous fetal loss was low (2/29 [6.9%]); both cases occurred in mothers with inactive lupus.

The use of misoprostol in termination of second-trimester pregnancy

Misoprostol, a synthetic prostaglandin E1 analog, is initially used to prevent peptic ulcer. The initial US Food and Drug Administration-approved indication in the product labeling is the treatment and prevention of intestinal ulcer disease resulting from nonsteroidal anti-inflammatory drugs use. In recent two decades, misoprostol has approved to be an effective agent for termination of pregnancy in various gestation, cervical ripening, labor induction in term pregnancy, and possible management of postpartum hemorrhage. For the termination of second-trimester pregnancy using the combination of mifepristone and misoprostol seems to have the highest efficacy and the shortest time interval of abortion. When mifepristone is not available, misoprostol alone is a good alternative. Misoprostol, 400 μg given vaginally every 3-6 hours, is probably the optimal regimen for second-trimester abortion. More than 800 μg of misoprostol is likely to have more side effects, especially diarrhea. Although misoprostol can be used in women with scarred uterus for termination of second-trimester pregnancy, it is recommended that women with a scarred uterus should receive lower doses and do not double the dose if there is no initial response. It is also important for us to recognize the associated teratogenic effects of misoprostol and thorough consultation before prescribing this medication to patients regarding these risks, especially when failure of abortion occurs, is needed.

Impact of Second-Trimester Maternal Serum Screening on Prenatal Diagnosis of Down Syndrome and the Use of Amniocentesis in the Taiwanese Population

Summary Objective To investigate the impact of second-trimester maternal serum screening on prenatal diagnosis of Down syndrome and the use of amniocentesis in the Taiwanese population. Materials and Methods From 1990 to 2000, 166,419 amniocenteses were analyzed cytogenetically in the Taiwanese population. Among these, 58.85% were for advanced maternal age, 4.5% for abnormal ultrasound findings, 26.17% for abnormal maternal serum screening results, 1.82% for a previous child with congenital anomaly, 1.02% for a family history of chromosome aberrations, and 7.63% for other purposes. Chromosome aberrations were detected in 4,217 cases (2.53%), of which 1,277 (30.28%) were Down syndrome. Of the Down syndrome cases, 65.86% were detected by amniocentesis for advanced maternal age, 5.95% for abnormal ultrasound findings, 21.14% for abnormal maternal serum screening results, 1.25% for a previous child with congenital anomaly, 1.18% for a family history of chromosome aberrations, and 4.62% for other purposes. Results There was a prominent increase in the number of women undergoing amniocentesis in the Taiwanese population between 1990 and 2000. There was an 8.9-fold increase in the number undergoing amniocentesis for advanced maternal age, a 6.3-fold increase in that for abnormal ultrasound findings, a 46.2-fold increase in that for abnormal maternal serum screening results, a 2.9-fold increase in that for a previous child with congenital anomaly, a 5.6-fold increase in that for a family history of chromosome aberrations, and a 4.4- fold increase in that for other purposes. There was also a 35.7-fold increase in the number of prenatally detected Down syndrome cases, from seven in 1990 to 250 in 2000. The highest rates of Down syndrome were found in cases with abnormal ultrasound findings (1/99 tests). Down syndrome was 0.72-fold as common in amniocenteses performed because of positive serum screening results (1/161 tests) compared with the rate seen in the advanced maternal age group (1/116 tests). The detection rates increased from 1/449 tests in 1990, through 1/198 tests, 1/203 tests, 1/158 tests, 1/215 tests, 1/229 tests, 1/169 tests, 1/143 tests, 1/90 tests, 1/92 tests, to 1/123 tests in 2000. Conclusion Both the number of women undergoing amniocentesis and the number of detected cases of Down syndrome increased during these years. Amniocentesis in this population no longer led to a significant improvement in the detection rate of Down syndrome. In view of the effective use of amniocentesis as a diagnostic procedure for Down syndrome, efforts should be made to use more efficient prenatal screening programs and to reduce the number of unnecessary amniocenteses.

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.

3q26.31-q29 duplication and 9q34.3 microdeletion associated with omphalocele, ventricular septal defect, abnormal first-trimester maternal serum screening and increased nuchal translucency: prenatal diagnosis and aCGH characterization.

We present prenatal diagnosis and array comparative genomic hybridization characterization of 3q26.31-q29 duplication and 9q34.3 microdeletion in a fetus with omphalocele, ventricular septal defect, increased nuchal translucency, abnormal first-trimester maternal screening and facial dysmorphism with distinct features of the 3q duplication syndrome and Kleefstra syndrome. The 26.61-Mb duplication of 3q26.31-q29 encompasses EPHB3, CLDN1 and CLDN16, and the 972-kb deletion of 9q34.3 encompasses EHMT1. We review the literature of partial trisomy 3q associated with omphalocele and discuss the genotype-phenotype correlation in this case.

Prenatal diagnosis and molecular cytogenetic characterization of a 1.07-Mb microdeletion at 5q35.2–q35.3 associated with NSD1 haploinsufficiency and Sotos syndrome

OBJECTIVE To present prenatal diagnosis and molecular cytogenetic characterization of a de novo 5q35 microdeletion associated with Sotos syndrome. METHODS This was the first pregnancy of a 29-year-old woman. The pregnancy was uneventful until 27 weeks of gestation when left ventriculomegaly was first noted. At 31 weeks of gestation, polyhydramnios, macrocephaly, and ventriculomegaly were prominent on ultrasound, and left pyelectasis and bilateral ventriculomegaly were diagnosed on magnetic resonance imaging. The woman underwent amniocentesis and cordocentesis at 32 weeks of gestation. Conventional cytogenetic analysis was performed using cultured amniocytes and cord blood lymphocytes. Array comparative genomic hybridization (aCGH) was performed on uncultured amniocytes and parental blood. Metaphase fluorescence in situ hybridization (FISH) was performed on cultured lymphocytes. RESULTS Conventional cytogenetics revealed a karyotype of 46,XX. aCGH on uncultured amniocytes revealed a de novo 1.07-Mb microdeletion at 5q35.2-q35.3 encompassing NSD1. Metaphase FISH analysis on the cord blood lymphocytes confirmed the deletion at 5q35.2. The postnatal phenotype was consistent with Sotos syndrome. CONCLUSION Fetuses with Sotos syndrome may present macrocephaly, polyhydramnios, ventriculomegaly, and pyelectasis in the third trimester. aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome.

Maternal transmission of interstitial microdeletion in 5q13.2 detected during prenatal diagnosis of coarctation of the aorta

Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan Department of Medicine, Mackay Medical College, New Taipei City, 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 Gene Biodesign Co. Ltd, Taipei, Taiwan Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan Department of Bioengineering, Tatung University, Taipei, Taiwan

HUGE PRIMARY VAGINAL STONE IN A RECUMBENT WOMAN

Summary Objective Vaginal stones are rare and primary vaginal stones are extremely rare. A primary vaginal stone originating from urinary stasis in the vagina may be due to anatomic abnormalities, vaginal outlet obstruction, infection, or vesicovaginal fistulae, while secondary vaginal stones result from crystallization of urinary constituents around a foreign body in the vagina. Case Report This 43-year-old female had cerebral palsy due to tuberculosis meningitis when she was 3 years old. She had been bedridden with urinary and fecal incontinence since then. She was admitted to our medical ward due to acute abdominal distension with poor appetite and weight loss. On arrival, leukocytosis with dehydration was noted and medical treatment was given initially. Imaging studies showed stool impaction with abdominal ileus and a huge calcified density measuring 10 cm in diameter in the pelvis. Exploratory laparotomy showed that the mass was in the vagina. A laminated and pear-shaped mass was removed through an incision in the anterior vaginal cuff. Pathologic examination showed lithiasis composed of calcification mixed with fibrinous exudates and fragments of reactive squamous epithelium. The postoperative course was smooth with uneventful convalescence and she was discharged and doing well at the time of writing. Conclusion Although vaginal stones are very rare, they may be formed in recumbent women due to urinary stasis, and the calculi may cause obstruction of the bowel or urinary tract.

Late-onset fetal bilateral pleural effusions associated with Down syndrome

OBJECTIVE We present two cases of late-onset bilateral fetal pleural effusions associated with fetal Down syndrome. CASE REPORTS Case 1. A 33-year-old Vietnamese woman had undergone regular sonographic examinations since 23 weeks of gestation and no abnormality had been noted. However, bilateral moderate pleural effusions were found at 33 weeks of gestation, and massive pleural effusion, ascites and polyhydramnios developed at 34 weeks of gestation. Aspiration of the pleural effusion was subsequently performed. Clinical laboratory surveys of the aspiration fluid excluded toxoplasmosis and cytomegalovirus infection. Cytogenetic analysis of cultured lymphocytes derived from pleural effusion revealed a karyotype of 47,XX,+21. The parents elected to continue the pregnancy. Intrauterine fetal demise occurred at 37 weeks of gestation, and a macerated female baby was delivered. Postnatal cytogenetic analysis of the umbilical cord confirmed the prenatal diagnosis. Case 2. A 41-year-old Pakistani woman had undergone regular sonographic examinations and no abnormality had been noted. However, isolated bilateral mild pleural effusions were noted at 27 weeks of gestation. Amniocentesis revealed a karyotype of 47,XY,+21 and simultaneous array comparative genomic hybridization analysis of uncultured amniocytes confirmed the diagnosis of Down syndrome. The pregnancy was subsequently terminated. CONCLUSION Fetuses with Down syndrome may present late-onset bilateral pleural effusions. Prenatal diagnosis of late-onset bilateral pleural effusions should raise the possibility of fetal Down syndrome and cytogenetic investigation is warranted.

Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 21q11.2-q21.1 and a literature review

OBJECTIVE We present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from chromosome 21q11.2-q21.1, and we review the literature of an sSMC(21) with a duplication of 21q11.2-q21.1. CASE REPORT A 40-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+mar [18]/46,XX [4]. The parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. aCGH analysis of cultured amniocytes revealed a 2.855-Mb duplication of 21q11.2-q21.1 encompassing the genes of LIPI, ABCC13 and NRIP1. Metaphase fluorescence in situ hybridization analysis on cultured amniocytes revealed a result of 47,XX,+mar .ish der(13/21) (D13/21Z1+) [10]. Spectral karyotyping analysis determined the origin of chromosome 21 in the sSMC. A female fetus was delivered with no phenotypic features of Down syndrome and no structural abnormalities. We discuss the genotype-phenotype correlation of LIPI, ABCC13 and NRIP1, and review the literature of an sSMC(21) associated with dup(21)(q11.2q21.1). CONCLUSION aCGH is useful for identification of the nature and genetic component of a prenatally detected sSMC.