Prenatal detection of Xq deletion by abnormal noninvasive prenatal screening, subsequently diagnosed by amniocentesis: A case report

We experienced a case of Xq deletion -- 46,X,del(X)(q22.3) -- detected by abnormal noninvasive prenatal screening, subsequently diagnosed by amniocentesis. Genetic counseling was a challenge because there are few reports of prenatal diagnosis of Xq deletion. In each female cell, one X chromosome is inactivated at random early in development, and there may be a preferential inactivation of the abnormal X chromosome. But some proportions of genes escape inactivation. The most common manifestation in women with Xq deletion is primary or secondary ovarian failure. Critical regions for ovarian function may be located at the long arm of the X chromosome. But, the onset and the severity of ovarian failure may vary with diverse, intricate factors. We anticipate that noninvasive prenatal screening can identify the broader range of chromosomal or genetic abnormalities with the advances in technology and analytic methods. We report our case with a brief review of the literature.

Hemoperitoneum: a complication of loop electrosurgical excision procedure

Loop electrosurgical excision procedure (LEEP) is commonly performed for the management of cervical intraepithelial neoplasia. Although LEEP is considered to be a relatively simple procedure, several unexpected complications have been reported in the literature. Herein, we report a case of hemoperitoneum caused by uterine perforation following LEEP. Blood collection in pelvic cavity and two small defects of the uterus were confirmed by diagnostic laparoscopy. The defects were sutured and the patient recovered well after the operation.

Gastric type mucinous endocervical adenocarcinoma of the uterine cervix: very rare and interesting case

Gastric type mucinous endocervical adenocarcinomas of the uterine cervix (GAC) are a newly classified mucinous subtype with morphologically in 2014, WHO. They have a much more aggressiveness and show unusual metastatic patterns compared to usual type endocervical adenocarcinoma. They tend to present at higher stage and even in stage I, they have worse survival. Therefore, differential diagnosis of GAC from the usual type of endocervical adenocarcinoma is very important because they are related to a significant risk of recurrence and decreased 5-year disease-specific survival. Besides, GACs are mostly not associated with human papillomavirus (HPV) infection and p16 immunohistochemistry is also typically negative in GAC that is HPV-unassociated tumor. We report a very rare and interesting case of stage IB1 GAC with negative HPV DNA and p16.

Clinical Significance of Newborn Gastric Inflammatory Mediators

PURPOSE: We performed this study to determine (1) whether the levels of inflammatory mediators, including matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-3 (ICAM-3), in gastric fluid (GF) in premature newborns are associated with those in amniotic fluid (AF) in their mothers and (2) whether the levels of the inflammatory mediators in newborn GF are associated with the presence of intrauterine inflammation (IUI). METHODS: Sixty-two pairs of pregnant women and their premature newborns born at <35 weeks' gestation by cesarean delivery were enrolled in this study. AF and newborn GFs were obtained during cesarean section procedures. Levels of MMP-9, ICAM-3, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) were measured and compared between the AF and newborn GFs in each dyad, according to the presence or absence of chorioamnionitis (CA), preterm prelabor rupture of membranes (PPROM), and preterm labor (PTL). RESULTS: The levels of MMP-9, ICAM-3, IL-6, IL-8, and TNF-alpha in newborn GF were significantly correlated with those in AF in each dyad. The premature newborns and their mothers with CA had significantly higher GF MMP-9, IL-8, and TNF-alpha levels than those without CA. Those with PPROM or PTL showed similar findings in terms of GF MMP-9, IL-8, and TNF-alpha levels. CONCLUSION: The newborn GF immediately after birth can be a useful alternative source of information on whether a premature infant has been exposed to IUI at the time of delivery.

Umbilical Cord Blood Matrix Metalloproteinase-9 Levels are associated with Funisitis / 대한주산의학회잡지

PURPOSE: Intrauterine inflammation (IUI) is a leading cause of preterm delivery. Although matrix metalloproteinase-8 (MMP-8) and intercellular adhesion molecule-1 (ICAM-1) are known to be related with IUI, it has not been fully elucidated whether MMP-9 or ICAM-3 is associated with IUI. We performed this study to determine whether the levels of tumor necrosis factor-alpha (TNF-alpha), MMP-9 and ICAM-3 in umbilical cord blood of preterm infants are associated with chorioamnionitis, funisitis or bronchopulmonary dysplasia. METHODS: Eighty-two pairs of pregnant women and their preterm newborns <35 weeks gestation were enrolled. Levels of TNF-alpha, MMP-9 and ICAM-3 in umbilical cord blood were measured using immunoassays and compared with results of histological examination of placenta and clinical data of the study participants. RESULTS: The level of MMP-9 in umbilical cord blood was significantly associated with the presence of funisitis (P =0.007). The level of TNF-alpha in umbilical cord blood was significantly associated with the development of bronchopulmonary dysplasia (P =0.030). However, presence of chorioamnionitis or funisitis was not associated with development of bronchopulmonary dysplasia. With the establishment of receiver operating characteristic (ROC) curve, the best cut-off value for umbilical blood MMP-9 was 99.42 pg/mL in identification of funisitis. The area under a constructed ROC curve for prediction of funisitis was 0.847 (standard error, 0.112; 95% confidence interval, 0.750-0.917). CONCLUSION: Measurement of MMP-9 concentration in umbilical cord blood may be an alternative way to predict whether a preterm infant has been exposed to IUI. Further study with larger numbers of subjects will be necessary to elucidate the association between the presence of IUI and neonatal adverse outcome.

Midtrimester maternal plasma concentrations of angiopoietin 1, angiopoietin 2, and placental growth factor in pregnant women who subsequently develop preeclampsia

OBJECTIVE: The aim of this study was to compare midtrimester maternal plasma concentrations of angiopoietin 1, angiopoietin 2, and placental growth factor between pregnant women who subsequently developed preeclampsia and those who did not. METHODS: Midtrimester maternal plasma was collected and stored at -70degrees C when genetic amniocentesis was performed. Cases included 37 samples of individual who subsequently developed preeclampsia, and matched controls were from individuals who did not develop preeclampsia. Angiopoietin 1, angiopoietin 2, and placental growth factor concentrations were measured by the enzyme-linked immunosorbent assay method and were compared using the Mann-Whitney U-test. A P-value <0.05 was considered significant. RESULTS: In pregnant women who subsequently developed preeclampsia, midtrimester maternal plasma concentrations of angiopoietin 1 and angiopoietin 2 were significantly higher and placental growth factor concentrations were significantly lower than in women who did not develop preeclampsia (angiopoietin 1: 10.6 [3.1-19.7] vs. 7.8 [0.9-24.4] ng/mL, P=0.031; angiopoietin 2: 31.0 [4.7-81.2] vs. 18.4 [4.2-49.7] ng/mL, P<0.001; placental growth factor: 87.1 [14.2-774.3] vs. 148.8 [57.2-425.6] pg/mL, P<0.001). Within the case group who subsequently developed preeclampsia, the placental growth factor was significantly lower in those who had fetal growth restrictions than in those who did not (placental growth factor: 72.5 [14.2-774.3] vs. 140.9 [44.2-257.5] pg/mL, P=0.003). CONCLUSION: Midtrimester maternal plasma concentrations of angiopoietin 1, angiopoietin 2, and placental growth factor may be associated with the subsequent development of preeclampsia.

Chorionic villus sampling

Chorionic villus sampling has gained importance as a tool for early cytogenetic diagnosis with a shift toward first trimester screening. First trimester screening using nuchal translucency and biomarkers is effective for screening. Chorionic villus sampling generally is performed at 10-12 weeks by either the transcervical or transabdominal approach. There are two methods of analysis; the direct method and the culture method. While the direct method may prevent maternal cell contamination, the culture method may be more representative of the true fetal karyotype. There is a concern for mosaicism which occurs in approximately 1% of cases, and mosaic results require genetic counseling and follow-up amniocentesis or fetal blood sampling. In terms of complications, procedure-related pregnancy loss rates may be the same as those for amniocentesis when undertaken in experienced centers. When the procedure is performed after 9 weeks gestation, the risk of limb reduction is not greater than the risk in the general population. At present, chorionic villus sampling is the gold standard method for early fetal karyotyping; however, we anticipate that improvements in noninvasive prenatal testing methods, such as cell free fetal DNA testing, will reduce the need for invasive procedures in the near future.

A Case of Live Birth in a Non-communicating Rudimentary Horn Pregnancy and Rupture after Intrauterine Insemination / 대한주산의학회잡지

Rudimentary horn is a rare uterine anomaly and pregnancy in the rudimentary horn is an extremely rare condition. We report a case of live birth in a non-communicating rudimentary horn pregnancy and rupture. The pregnancy was successfully delivered by cesarean section, with neonatal and maternal survival.

A Case of Trisomy 8 Mosaicism in a Patient with Secondary Amnorreha without Abnormal Phenotype

Constitutional trisomy 8 mosaicism (CT8M) is a relatively rare aneuploidy in humans with characteristic phenotypes including typical craniofacial feature (such as deformed skull, prominent forehead, low-set and/or dysplastic ears), skeletal malformation, cardiac anomaly, renal malformation, cryptochidism, varying degree of developemental delay. Due to the extremely variable phenotypic and cytogenetic expression, CT8M has gone undiagnosed in certain patients. We report a 28-year-old women with secondary amenorreha without characteristic CT8M phenotype. Chromosomal analysis showed a CT8M (47,XX,+8[9]/46,XX[41]).

A case of microinvasive Paget's disease of the vulva: Treatment of positive resection margin with topical 5-FU cream application / 대한산부인과학회지

Extramammary Paget's disease of the vulva is a rare lesion that accounts for 1~2% of vulvar neoplasms. Paget's disease often has a microscopic extension beyond the gross lesion and shows a multifocal distribution. Positive resection margin is common. We applied 5-FU cream on the lesion who had a positive resection margin. There was no residual lesion on multiple punch biopsies after 5-FU cream treatment three months later. And there has been no evidence of disease recurrence in the 12-month follow-up period. We experienced a case of effective treatment with 5-FU cream in microinvasive Paget's disease of the vulva with positive resection margin. We present it with a brief review of literatures.

Relationship between Twin-to-twin Delivery Interval and Umbilical Artery Acid-base Status in the Second Twin

The purpose of this study was to determine the effect of twin-to-twin delivery interval on umbilical artery acid-base status of the second twin at birth. This was a retrospective cohort study of all live-born twins with measured acid-base status in umbilical arterial blood who were delivered after 34 weeks' gestation from June 2003 to February 2006. Twins with any maternal or fetal complications were excluded. Subjects were divided into two groups based on the mode of delivery of the first twin: normal cephalic vaginal deliveries (n=40) or cesarean deliveries (n=67). The inter-twin differences in umbilical arterial blood pH, PCO2, PO2, and base excess in twin newborns born vaginally were significantly greater than the corresponding differences in those born by cesarean section. A significant positive correlation was found between twin-to-twin delivery interval and inter-twin difference in umbilical arterial blood pH in twin newborns born vaginally. The umbilical arterial blood pH of the second twin was less than 7.0 in 14% (2/14) in cases delivered more than 20 min after the first twin. The umbilical arterial blood gas status of the second twin worsened with increasing twin-to-twin delivery interval, and pathologic fetal acidemia (pH<7.0) might develop in the second twin when the twin-to-twin delivery interval was greater than 20 min.

Perinatal Outcomes of Triplet Pregnancies / 대한산부인과학회지

OBJECTIVE: To evaluate the perinatal outcomes and maternal complications associated with triplet pregnancies. METHODS: Medical records of consecutive triplet pregnancies delivered in ( )( )Hospital from 1997 to 2005 were reviewed for maternal and neonatal outcomes. Pregnancies associated with lethal congenital anomalies or the case that being delivered before 20 weeks of gestation were excluded. Neonatal outcomes included respiratory distress syndrome, retinopathy of prematurity, necrotizing enterocolitis, intraventricular hemorrhage and low Apgar scores, congenital anomaly and so on. Maternal outcomes included preeclampsia, preterm delivery, anemia and blood transfusion and so on. RESULTS: The mean gestational age at delivery was 31.5+/-4.1 weeks, and the mean birth weight for triplets was 1,654.4+/-578.1 g. 31 of total 39 neonates (79.5%) were admitted to the neonatal intensive care unit, and 9 neonates (23.1%) received mechanical ventilator care as well. Neonatal death occurred in 6 of 39 neonates (15.4%). Congenital anomaly was seen in 3 of 39 neonates (7.7%). Hyperbilirubinemia developed in 16 of 39 neonates (44.4%). Respiratory distress syndrome developed in 3 of 39 neonates (7.7%). The most common maternal complication was preterm labor (76.9%), followed by anemia (46.1%), preterm premature rupture of membrane (30.8%) and blood transfusion (7.7%). Five patients (5/13, 38.5%) received tocolytic therapy. CONCLUSION: The main cause of neonatal death in triplet pregnancies is the respiratory distress syndrome in extreme preterm delivery. The most common neonatal morbidities are hyperbilirubinemia and apnea of prematurity. There is no difference in neonatal outcomes according to birth order. The most common maternal complications are preterm delivery and anemia. The adverse outcomes of triplet pregnancies are mainly due to preterm delivery.

Perinatal Outcomes of Triplet Pregnancies / 대한산부인과학회지

OBJECTIVE: To evaluate the perinatal outcomes and maternal complications associated with triplet pregnancies. METHODS: Medical records of consecutive triplet pregnancies delivered in ( )( )Hospital from 1997 to 2005 were reviewed for maternal and neonatal outcomes. Pregnancies associated with lethal congenital anomalies or the case that being delivered before 20 weeks of gestation were excluded. Neonatal outcomes included respiratory distress syndrome, retinopathy of prematurity, necrotizing enterocolitis, intraventricular hemorrhage and low Apgar scores, congenital anomaly and so on. Maternal outcomes included preeclampsia, preterm delivery, anemia and blood transfusion and so on. RESULTS: The mean gestational age at delivery was 31.5+/-4.1 weeks, and the mean birth weight for triplets was 1,654.4+/-578.1 g. 31 of total 39 neonates (79.5%) were admitted to the neonatal intensive care unit, and 9 neonates (23.1%) received mechanical ventilator care as well. Neonatal death occurred in 6 of 39 neonates (15.4%). Congenital anomaly was seen in 3 of 39 neonates (7.7%). Hyperbilirubinemia developed in 16 of 39 neonates (44.4%). Respiratory distress syndrome developed in 3 of 39 neonates (7.7%). The most common maternal complication was preterm labor (76.9%), followed by anemia (46.1%), preterm premature rupture of membrane (30.8%) and blood transfusion (7.7%). Five patients (5/13, 38.5%) received tocolytic therapy. CONCLUSION: The main cause of neonatal death in triplet pregnancies is the respiratory distress syndrome in extreme preterm delivery. The most common neonatal morbidities are hyperbilirubinemia and apnea of prematurity. There is no difference in neonatal outcomes according to birth order. The most common maternal complications are preterm delivery and anemia. The adverse outcomes of triplet pregnancies are mainly due to preterm delivery.

Two Cases of Pregnancies Complicated with Central Diabetes Insipidus / 대한산부인과학회지

Diabetes insipidus is an unusual cause of urinary frequency during pregnancy. It occurs in 2 to 6 per 100,000 pregnancies. It is a disorder in which the abnormal secretion, degradation, or activity of vasopressin cause hypotonic polyuria, polydipsia, and dehydration. And this syndrome appears to be associated with multiple gestations, preeclampsia, and abnormal liver function. We report two cases of pregnancies complicated with diabetes insipidus. One patient was diagnosed during pregnancy and DDAVP (L-deamino-8-d-arginine vasopressin) was used to manage diabetes insipidus. The other patient was diagnosed before pregnancy and DDAVP was not used.

A case of chorioangioma of placenta complicated by fetal anemia and fetal hydrops / 대한산부인과학회지

Benign chorioangioma of the placenta is the most common primary tumor of the placenta similar to hamartoma. Most small-sized tumors do not make any clinical problem, but uncommon large tumors (>5 cm in diameter) may produce both maternal and fetal complications, such as polyhydramnios, preterm labor, fetal hydrops, microangiopathic hemolytic anemia, disseminated intravascular coagulation, intrauterine growth restriction, preeclampsia and placental abruption. In this respect, the diagnosis and management of chorioangioma and its complication should be done appropriately. We report a case of chorioangioma presenting with polyhydramnios, preterm labor, fetal anemia and fetal hydrops, diagnosed by antenatal ultrasonography and postnatal placental histologic examination, and live born baby with the brief review of the literature related to this type of tumor.

Prognostic Implication of Associated Cleft Palate in Patients with Cleft Lip / 대한주산의학회잡지

OBJECTIVE: The objective of this study is to compare the pregnancy outcomes and postnatal developmental problems according to the types of cleft lip and/or palate, and to evaluate the increase of the risk of the presence of cleft palate. METHODS: Retrospective analysis was performed in 96 cases of cleft lip and/or palate that were delivered, aborted, or terminated at Seoul National University Hospital from January 1990 to July 2004. The cases of cleft lip and/or palate were categorized based on the Nyberg's classification, and cleft palate alone was added to it. According to the types, the frequencies of associated anomaly and chromosomal anomaly were assessed, and the frequencies of termination, spontaneous abortion, fetal death in utero, and infant death were compared. When long-term follow-up was possible among the surviving infants, we compared the frequencies of ventilatory tube insertion into the middle ear, hearing problem, and speech-language problem. We evaluated the increase of the risk in the presence of cleft palate. RESULTS: Associated anomalies were present in 23.7% (9/38) of cases with cleft lip alone and in 55.1% (32/58) of those with cleft palate. The most common associated anomaly was cardiac anomaly. The surviving infants with cleft palate showed significantly higher rates of ventilatory tube insertion (70.0% [14/20] vs 3.1% [1/32]) and speech-language problem (42.1% [8/19] vs 10.7 % [3/28]) than those with cleft lip alone. The presence of cleft palate increased the risk of occurrence of associated anomaly (OR 3.97), termination (OR 5.20), infant death (OR 12.96), ventilatory tube insertion (OR 72.33), and speech-language problem (OR 6.06). CONCLUSION: Associated cleft palate in patients with cleft lip has a poor impact on pregnancy outcomes, middle ear disease, and speech-language problem. Therefore, during the prenatal screening ultraso-nography, the careful examination should be directed for the detection of cleft palate in cases with cleft lip.

Eisenmenger syndrome in pregnancy at second and third trimester / 대한산부인과학회지

OBJECTIVE: Because women with Eisenmenger syndrome are counseled strongly not to conceive, pregnancy cases with Eisenmenger syndrome are rare in clinical situation. We performed this study to analyze pregnancies at second and third trimester complicated by Eisenmenger syndrome and to evaluate changes during pregnancy and their outcomes. METHODS: Medical records were reviewed retrospectively for Eisenmenger syndrome patients who delivered at second and third trimester at Seoul National University Hospital from January 1989 to October 2005. RESULTS: Among the total of 6 pregnant women, 4 women delivered after 34 weeks and 2 women had therapeutic termination during second trimester. All 4 women who delivered after 34 weeks were categorized as class III by New York Heart Association classification. Maternal mortality rate was 33% (2 of 6 cases). All mortality cases were patients who delivered after 34 weeks. All neonates were small for gestational age with no neonatal death. There was no neonatal morbidity except one case of congenital atrial septal defect. CONCLUSION: Maternal mortality occurred in half of the women who continued their pregnancy beyond second trimester. We think that pregnancy should be still discouraged in patients with Eisenmenger syndrome and that therapeutic abortion should be offered in early pregnancy period.

A Case of Intracranial Cavernous Hemangioma Diagnosed in Pregnancy / 대한산부인과학회지

The cavernous hamangioma is a relatively rare intracranial vascular malformation and generally asymptomatic, Seizure is the most common clinical presentation and the hemorrhage is the second. Because reproductive females have the hormonal and hemodynamic changes, the first symptoms might develope in the gestational period. As we experienced a case of intracranial cavernous hemangioma initially diagnosed in pregnancy with new-onset seizures, we report this case with a brief review of literature.

Delayed-Interval Delivery after Cerclage Operation in a Case of Twin Pregnancy with One Fetal Delivery / 대한산부인과학회지

With delayed childbearing and increased use of ovulation-stimulating drugs and assisted reproductive technologies (ART), the incidence of multiple pregnancies has increased dramatically in the past 20 years. One of the most common and serious complications of multiple pregnancies is preterm delivery. The delivery of the initial fetus in a multiple gestation usually is followed by the delivery of the subsequent fetus or fetuses shortly there after. However, a few successful delayed-interval deliveries have been reported since the first case in 1880 by Carson. Since that time, an interest in delayed-interval delivery has been developed and spurred by the increased prevalence of multiple gestations and preterm deliveries associated with these pregnancies. We report a case of a delayed-interval delivery in a twin pregnancy with an interval of 71 days. This case is the longest interval case and the fisrt delayed-interval delivery in monochorionic twin in Korea.

Ultrasonographic indicators in predicting postnatal outcomes of antenatally detected ventriculomegaly / 대한산부인과학회지

OBJECTIVE: The aim of this study was to find out the prognostic indicators of antenatally detected ventriculomegaly. METHODS: During the study period (Nov. 1995 through Jan. 2003), we identified 96 cases of fetal ventriculomegaly and reviewed their antenatal and postnatal follow-up records retrospectively. Excluding cases of termination before viable stage and incomplete follow-up, 68 cases were evaluated. Severe ventriculomegaly (fetal hydrocephalus; n=30) was defined as lateral ventricular atrial width (LVAW) greater than 15 mm, and mild ventriculomegaly (n=38) was defined as LVAW between 10 and 15 mm. Subgroup of LVAW <12 mm (n=23) was also analyzed. Antenatal workup included detailed ultrasonography, TORCH test and karyotyping. Outcome parameters were the presence of progressive lesion, NICU admission, shunt operation and critical damage that included delayed development, cerebral palsy and death after live birth. RESULTS: Overall survival rate was 89.7% (61/68) and the median postnatal follow-up duration was 17.0 (0.0-69.3) months. Severe ventriculomegaly group showed higher incidence of progressive lesion, NICU admission and shunt operation than did mild group. Within mild ventriculomegaly group, critical damage was more common in cases with associated anomalies, and this difference was present even in the subgroup of LVAW <12 mm (2/16 vs. 4/7, p<0.05). CONCLUSION: In mild ventriculomegaly group, comprehensive antenatal workup including detailed ultrasonography is important because associated anomaly is a poor prognostic factor, even in cases of LVAW <12 mm. In terms of critical damage such as developmental delay, cerebral palsy and postnatal death, the prognosis of cases with mild ventriculomegaly is also guarded.