Usefulness of a Rapid Real-time PCR Assay in Prenatal Screening for Group B Streptococcus Colonization

BACKGROUND: Group B streptococcus (GBS) infection is a leading cause of neonatal morbidity and mortality worldwide. Here, we present the analytical and diagnostic usefulness of a new real-time PCR-based assay (Xpert GBS; Cepheid, USA) for rapid and accurate prenatal GBS screening. METHODS: We enrolled 175 pregnant women who were between 35 and 39 weeks of gestation. The analytical performance of the Xpert GBS assay was first tested using a reference GBS strain. Next, to test diagnostic performance, rectovaginal swabs were obtained from pregnant women who visited the hospital for regular antenatal screening after 34 weeks of gestation. The results of the Xpert GBS assay were compared to those of standard culture for the detection of prenatal GBS colonization. RESULTS: When any positive result from Xpert GBS or culture was considered a true positive, the sensitivity of the Xpert GBS assay and culture were 91% (20/22; 95% CI [confidence interval], 72-98) and 68% (15/22; 95% CI, 47-84), respectively. The specificity of both methods was 100% (153/153; 95% CI, 97-100). The sensitivity and specificity of the Xpert GBS assay, using the culture results as a reference, were 86.7% and 95.6%, respectively. In the Xpert GBS assay, the median threshold cycle of vaginally colonized samples was significantly lower than rectally colonized samples (P<0.01). CONCLUSIONS: The Xpert GBS assay is an accurate, rapid, easy-to-use test for the detection of maternal GBS colonization in prenatal screening that might be especially useful in clinical settings where standard culture is not feasible.

Risk Factors Associated with Group B Streptococcus Resistant to Clindamycin and Erythromycin in Pregnant Korean Women

BACKGROUND: The prevalence of group B streptococcus (GBS) among pregnant women and neonates in the Republic of Korea has increased. In addition, rates of resistance to antibiotics recommended for pregnant women allergic to penicillin, such as clindamycin and erythromycin, have increased. The aim of this study was to evaluate subject characteristics associated with GBS resistance to clindamycin and erythromycin. MATERIALS AND METHODS: A total of 418 clinical isolates from pregnant women in Korea were screened for antibiotic resistance from January 2006 to December 2011. Sociodemographic information, medical and obstetric history, and details of events during the previous 2 weeks were recorded using a standardized questionnaire. RESULTS: The resistance rates were 39.5% for clindamycin and 23.0% for erythromycin. In multiple logistic regression analysis, the subject characteristic significantly associated with resistance to both antibiotics was a history of symptomatic sore throat in the 2 weeks before obtaining the specimen (erythromycin: odds ratio [OR]: 2.13, 95% confidence interval [CI]: 1.10 to 4.13; clindamycin: OR: 2.31, 95% CI: 1.21, 4.42). Premature rupture of membranes (PROM) had an association of borderline significance. CONCLUSIONS: In the urgent treatment of GBS-colonized pregnant women, the subject's history of previous sore throat and PROM should be considered when choosing appropriate antibiotics.

Analysis of Parental Decisions Based on Sex Chromosome Abnormalities Detected Prenatally: A Ten-year update (2001-2010)

PURPOSE: The aim of this study was to analyze parental decisions regarding pregnancies in which the fetus had sex chromosome abnormalities (SCA) over a ten-year period. MATERIALS AND METHODS: We collected and reviewed records from our hospital for 2001-2010 and a genetic specialist provided-genetic counseling. RESULTS: We diagnosed 130 cases (0.71%) with SCA out of 18,376 prenatal cases from 2001 to 2010. We reviewed the records and the results of all pregnancies. We also included cases (n=84) of apparently normal anatomic fetuses to analyze the factors influencing parental decisions. We excluded 34 cases with an obvious anomaly or a presumably bad outcome and 12 cases that were not followed up. Forty-three couples (51.2%) continued their pregnancies while forty-one (48.8%) terminated them. Of 38 mosaicism cases, 21 (55.3%) were continued. Among the 20 pregnancies assisted by reproductive techniques, 15 (75%) were continued (P=0.02). More pregnancies were continued when genetic counseling was provided (61.9%) compared to cases in which it was not provided (19%) (P=0.01). CONCLUSION: Genetic counseling is important in providing appropriate information to parents. Establishing guidelines and protocols will help both obstetricians and parents to make informed decisions.

Fetal Loss Rate after Mid-trimester Amniocentesis

PURPOSE: The aim of this study was to asses the fetal loss rate after mid-trimester amniocentesis. MATERIALS AND METHODS: This was a retrospective cohort study including singleton pregnant women who underwent mid-trimester amniocentesis at Cheil General Hospital from January 2008 through December 2010. The procedure-related fetal loss was defined as miscarriage within 2 weeks after amniocentesis. We evaluated the fetal loss rate within 2 weeks after amniocentesis and fetal loss rate before 24 gestational weeks. RESULTS: During the study period, a total of 4,356 singleton pregnant women underwent mid-trimester amniocentesis. A total of Five hundred ninety six women were excluded owing to follow up loss and termination of pregnancy due to abnormal karyotype or major anomaly. At our institute, the fetal loss rate within 2 weeks was 0.1% and before 24 gestational weeks was 0.3% after amniocentesis. CONCLUSION: The fetal loss rate after mid-trimester amniocentesis in our study is lower than previously reported rate. We suggest that amniocentesis is a safe procedure.

Analysis of Drug Counseling for Breastfeeding Mothers at the Korean Mothersafe Professional Counseling Center; 5 Years Experience / 대한주산의학회잡지

PURPOSE: There is a dearth of information on maternal drug exposure during lactation. The Korean Mothersafe Professional Counseling Center launched helpline to provide information and clinical consultation service on drug safety during lactation as well as in pregnancy. Here, we reviewed our 5 years' experience of counseling with drug exposed breastfeeding mothers. METHODS: The questionnaires were given to drug exposed breastfeeding mothers from January 2005 to April 2010 who contacted our helpline and follow-up survey data was collected by phone call. The questionnaires included lists of symptoms that exposed mothers experienced and that was observed in their infants, as well as demographic questions and questions about lactation. RESULTS: A total of 278 mothers completed the survey and lactational exposure was estimated. Majority of them reported that their infants and themselves never experienced serious side effects of drugs during lactation. Only 3 (1.1%) babies reported side effects and 20 (7.2%) mothers reported decreased production of breast milk. Two hundred thirty two (83.5%) mothers continued breastfeeding after counseling. Lactation was stopped temporarily in 20 (7.2%) mothers and permanently in 26 (9.3%) mothers. CONCLUSION: Most of the drugs exposed during lactation did not cause serious side effects to infants and mothers. As many drugs have inadequate data to assure safety, the clinician is left with a dilemma as to where the balance of risks and benefits lie with respect to the mother and her baby. The author expect that analyses of these counseling will contribute to provide practical answers to clinicians as well as exposed mothers and to establish correct breastfeeding practice.

Risk Factors for Group B Streptococcus Colonization Among Pregnant Women in Korea / 한국역학회지

OBJECTIVES: To identify obstetric and maternal factors related to Group B Streptococcus (GBS) colonization in pregnant women in Korea. METHODS: The study was conducted between the years 2006-2008 in four hospitals, Cheil and Eulji hospital in Seoul, and Motae and Eulji hospital in Daejeon. We recruited 2,644 pregnant women between 35 to 37 weeks of gestation who had visited for antenatal care. Participants completed a questionnaire, and urine, vaginal and rectal specimens were obtained and cultured using selective broth media. After delivery, medical records were reviewed. RESULTS: GBS colonization was significantly associated with hospital, age group, education, frequency of pregnancy, and premature rupture of membranes (PROM, more than 18 hours). After adjustment for other variables, Cheil hospital (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.20-3.52), and the first pregnancy (OR, 2.32; 95% CI, 1.12-4.81) remained significant. History of vaginitis showed marginal significance (OR, 1.50; 95% CI, 0.98-2.29). CONCLUSION: To prevent GBS infection of neonates, clinicians should be alert to the potentially higher risk of GBS colonization in pregnant women in their first pregnancy, and women with premature rupture of membranes (PROM) (18 hours+) or who have a history of vaginitis.

Changing Molecular Epidemiology of Group B Streptococcus in Korea

The prevalence of group B streptococcus (GBS) among pregnant women and disease burdens in neonates and adults are increasing in Korea. Colonizing isolates, collected by screening pregnant women (n=196), and clinical isolates collected from clinical patients throughout Korea (n=234), were serotyped and screened for antibiotic resistance. Serotype III (29.8%) and V (27.7%) predominated, followed by Ia (17.0%). Antibiotic resistance was higher among clinical than colonizing isolates for erythromycin (35.1% and 26.9%; P=0.10) and for clindamycin (49.4% and 42.1%; P=0.17). erm(B) occurred in 91.9% of erythromycin resistant isolates, and 84.0% of isolates resistant to clindamycin. Only five isolates (4.2%) resistant to erythromycin were susceptible to clindamycin; by contrast, and unique to Korea, 34% of isolates resistant to clindamycin were erythromycin susceptible. Among these 60 erythromycin-susceptible & clindamycin-resistant isolates, 88% was serotype III, and lnu(B) was found in 89% of strains. Four fifths of the serotype V isolates were resistant to both erythromycin and clindamycin. Further characterization of the genetic assembly of these resistance conferring genes, erm(B) and lnu(B), will be useful to establish the clonal lineages of multiple resistance genes carrying strains.

Pregnancy Outcomes after Peri-conceptional Medication Exposure; 10 Years Experience: Study for Application of Reproductive Toxicity Information / 대한주산의학회잡지

PURPOSE: In Korea, pregnancy termination is frequently reported among women who took medications for an acute or chronic disease during pregnancy, for fear of teratogenic risk. We have previously shown that a service providing evidence-based information is helpful for women who week counseling to make a rational decision regarding their pregnancies. This study aimed to evaluate whether termination of pregnancy based on such perceptions, is justified using the 'DRug Exposure and risk Assessment in Moms' (DREAM) registry. METHODS: The study included 5,032 consenting pregnant women from the clinic and call center at the Korean Motherisk Program, from November 1999 to October 2008. The DREAM registry recorded the pregnancy outcomes (preterm birth, low birth weight, intrauterine fetal death, and congenital anomaly) of 3,328 women. RESULTS: Among women exposed to medications, time of exposure ranged from 3.5-4.6 weeks of gestation. There were 1,308 different drugs prescribed to these women. The drug most frequently prescribed was acetaminophen followed by chlorpheniramine maleate, and pseudoephedrine. There were 4.7% (n=156/3,328) women who underwent a voluntary abortion for fear of birth defects. We compared frequency of birth defects between exposed women and unexposed pregnant women in our institution during gestation. The frequency of major congenital malformations was 2.5% (n=74/2,977) in exposed group and 2.9% (n=75/2,573) in unexposed group (P=0.32). There was no statistically significant difference between exposed and control group in the rate of preterm births, intrauterine fetal death and low-birth weight babies. CONCLUSION: We did not observe increased risk of congenital malformations and adverse pregnancy outcomes in a population of pregnant women exposed to a variety of medications. Therefore these medications are not considered teratogen.

Treatment outcome of uterine compression sutures for massive postpartum hemorrhage / 대한산부인과학회지

OBJECTIVE: Uterine compression sutures such as modified B-Lynch suture or multiple square-shaped sutures of uterine body are simple methods for control of postpartum hemorrhage refractory to medical treatment. We evaluated the treatment outcome and morbidity of uterine compression sutures and analyzed clinical findings of patients undergone uterine compression sutures and postpartum hysterectomy. METHODS: From January 2005 through December 2008, we retrospectively reviewed the medical records of patients undergone uterine compression sutures or postpartum hysterectomy. We analyzed success rates of preserving uterus of uterine compression sutures according to operative indications and mode of delivery and compared maternal characteristics, operative findings, morbidities and mortality with those of postpartum hysterectomy. RESULTS: The frequency of uterine compression sutures for control of massive postpartum hemorrhage was 0.24% (73/30,677). The success rates of preserving uterus were 85.1% in uterine atony, 80.9% in placenta previa, and 40.0% in placenta accreta (P=0.051). The rates of preserving uterus of uterine compression sutures after vaginal delivery and cesarean section were 50.0% and 82.6%, respectively (P=0.164). The frequencies of postoperative morbidities such as disseminated intravascular coagulation, pulmonary edema, ileus were not different between immediate hysterectomy and hysterectomy after uterine compression sutures. There was no maternal mortality. CONCLUSION: Uterine compression suture was successful method for control of postpartum hemorrhage resulting from uterine atony and placenta previa. We suggest the use of uterine compression sutures as the first-line operation for control of postpartum hemorrhage.

Pregnancy Outcomes after Conservative Treatment of Cervical Intraepithelial Lesions: Cold Knife Conization and Loop Electrosurgical Procedure / 대한주산의학회잡지

OBJECTIVE: In this study, we evaluated whether different methods of conization of the cervix were associated with an increased risk of adverse pregnancy outcomes in subsequent pregnancy. METHODS: A retrospective case-control study was conducted. The study group included women who had undergone cold knife conization (n=170) or a loop electrosurgical excision procedure (LEEP) (n=86) and then had subsequent singleton pregnancies. The control group (n=497) included women with no history of cervical surgery. The outcomes were spontaneous preterm delivery and various neonatal outcomes such as low birth weight (LBW) and perinatal mortality. RESULTS: Cold knife conization was associated with a significantly increased risk of preterm delivery less than 34 weeks (relative risk 4.9, 95% confidence interval 1.6-15.1), preterm delivery less than 28 weeks (7.6, 15-39.6), LBW (2.6, 1.2-5.8), and perinatal mortality (11.9, 1.3-107.6). LEEP was not associated with a increased risk of adverse pregnancy outcomes. CONCLUSION: Cold knife cone biopsy, but not LEEP of the cervix, is associated with an increased risk of preterm delivery less than 34 weeks of gestation and adverse neonatal outcomes. Clinicians counsel women appropriately before conservative treatment of cervical intraepithelial lesions.

Effective Method for Extraction of Cell-Free DNA from Maternal Plasma for Non-Invasive First-Trimester Fetal Gender Determination: A Preliminary Study

PURPOSE: To find the most effective method for extraction of cell-free DNA (cf-DNA) from maternal plasma, we compared a blood DNA extraction system (blood kit) and a viral DNA extraction system (viral kit) for non-invasive first-trimester fetal gender determination. MATERIALS AND METHODS: A prospective cohort study was conducted with maternal plasma collected from 44 women in the first-trimester of pregnancy. The cf-DNA was extracted from maternal plasma using a blood kit and a viral kit. Quantitative fluorescent-polymerase chain reaction (QF-PCR) was used to detect the SRY gene and AMEL gene. The diagnostic accuracy of the QF-PCR results was determined based on comparison with the final delivery records. RESULTS: A total of 44 women were tested, but the final delivery record was only obtained in 36 cases which included 16 male-bearing and 20 female-bearing pregnancies. For the blood kit and viral kit, the diagnostic accuracies for fetal gender determination were 63.9% (23/36) and 97.2% (35/36), respectively. CONCLUSION: In non-invasive first-trimester fetal gender determination by QF-PCR, using a viral kit for extraction of cf-DNA may result in a higher diagnostic accuracy.

Changes in biochemical markers of bone turnover and bone mineral density during pregnancy and postpartum in korean women / 대한산부인과학회지

OBJECTIVE: To show the patterns of changes in biochemical markers of bone turnover and ultrasound bone mineral density (BMD) during pregnancy and postpartum in Korean women. METHODS: We conducted a prospective study between February 2004 and February 2005. Forty-one healthy singleton pregnant women were included. We used quantitative ultrasonography for BMD measurement which is advantageous to pregnant women because it is radiation-free and it provides very accurate BMD that correlates highly with BMD measured by conventional dual energy x-ray absorptiometry. We measured marker of bone resorption (beta-Crosslaps), bone formation [total alkaline phosphatase (ALP), osteocalcin (OC)], total calcium, phosphorus and parathyroid hormone (PTH) during and after pregnancy. RESULTS: During pregnancy, BMD slightly decreased in the third trimester. Bone resorption marker (beta-Crosslaps) increased steadily during pregnancy and immediate postpartum. Markers of bone formation (ALP, osteocalcin) increased from late pregnancy. Total calcium decreased slightly as bone resorption peaks in second trimester. PTH and phosphorus increased steadily throughout pregnancy and postpartum. CONCLUSION: Pregnancy is characterized by high bone turnover in Korean women with resorption preceding formation.

The Y153H Variant of the STOX1 Gene in Korean Patients with Preeclampsia

PURPOSE: Preeclampsia is a multifactorial disorder with genetic and environmental components. Recently, the STOX1 gene, identified as a candidate gene for preeclampsia in Dutch women, has been shown to be placentally expressed and subject to imprinting with preferential transmission of the maternal allele. The purpose of this study is to investigate whether there is an association between the STOX1 Y153H variation and preeclampsia in Korean pregnant women. MATERIALS AND METHODS: This study involved 202 preeclamptic and 204 healthy pregnant women who were genotyped for the Y153H variant of the STOX1 gene using a commercially available SNapShot assay kit and an ABI Prism 3730 DNA Analyzer. RESULTS: There were no significant differences in genotype frequencies of the Y153H variant of the STOX1 gene between preeclamptic patients and normal controls (P>0.05). The H allele frequency of the STOX1 Y153H variation was similar in patients with preeclampsia (87.1%) and in normal controls (86.5%). In addition, multiple logistic regression analysis showed that the YH, HH, and YH/HH genotypes were not associated with an increased risk of preeclampsia when compared to the YY genotype. CONCLUSION: This is the first study to characterize the Y153H variant of the STOX1 gene in Korean patients with preeclampsia. We found no differences in the genotype and allele frequencies between preeclamptic and normal pregnancies. Although limited by a relatively small sample size, our study suggests that the STOX1 Y153H variation is not associated with the development of preeclampsia in Korean pregnant women.

Tumor Necrosis Factor-alpha Gene Polymorphism (C-850T) in Korean Patients with Preeclampsia

PURPOSE: Preeclampsia is a multisystem human pregnancy-specific disorder. The pathophysiology of preeclampsia is linked with over-stimulation of inflammatory cytokines by placental ischemia via reduced uterine perfusion pressure during pregnancy. Although an increase in tumor necrosis factor (TNF)-alpha has been reported in preeclamptic women, there is little evidence of a relationship between TNF-alpha gene variations and preeclampsia. In this study, we identified a single-nucleotide polymorphism (SNP), C-850T, in the TNF-alpha gene promoter region in Korean preeclamptic women and investigated the association between this SNP and the development of preeclampsia. MATERIALS AND METHODS: This polymorphism was analyzed in peripheral blood samples from 198 preeclamptic pregnancies and 194 normotensive pregnancies using a SNapShot kit and an ABI Prism 3100 Genetic analyzer. RESULTS: Genotypes and allele frequencies for C-850T did not differ between preeclamptic and normotensive pregnancies. The distributions of genotypes (CC, CT and TT) were 74.3%, 22.2% and 3.5%, respectively, in preeclamptic pregnancies, and 71.6%, 25.8% and 2.6%, respectively, in normotensive pregnancies. The frequencies of the C and T alleles were 0.85 and 0.15 in preeclamptic pregnancies and 0.84 and 0.16 in normotensive pregnancies, respectively. There was no increased risk of preeclampsia in subjects with the CT (OR, 0.83; P=0.44) or TT genotypes (OR, 1.32; P=0.64). CONCLUSION: We found no differences in the genotypes or allele frequencies of the TNF-alpha gene polymorphism between preeclamptic and normotensive pregnancies. This study suggests that the TNF-alpha gene polymorphism may be not associated with the development of preeclampsia in pregnant Korean women.

Prenatal Diagnosis of the 22q11.2 Duplication Syndrome

The 22q11.2 duplication syndrome is an extremely variable disorder with a phenotype ranging from normal to congenital defects and learning disabilities. Recently, the detection rate of 22q11.2 duplication has been increased by molecular techniques, such as array CGH. In this study, we report a familial case of 22q11.2 duplication detected prenatally. Her first pregnancy was terminated because of 22q11.2 duplication detected incidentally by BAC array CGH. The case was referred due to second pregnancy with same 22q11.2 duplication. We perfomed repeat amniocentesis for karyotype and FISH analysis. Karyotype analysis from amniocytes and parental lymphocytes were normal, while FISH analysis of interphase cells presented a duplication of 22q11.2 in the fetus and phenotypically normal mother. The fetal ultrasound showed grossly normal finding. After genetic counseling about variable phenotype with intrafamilial variability with 50% recurrence rate, the couple decided to continue the pregnancy. The newborn had no apparent congenital abnormalities until 2 weeks after birth. We recommend that family members of patients with a 22q11.2 duplication be tested by the interphase FISH analysis. Also, we point out the importance of genetic counseling and an evaluation of the clinical relevance of diagnostic test results.

Fetal Anomaly and Pregnancy Outcomes after Exposure to Ibuprofen in First Trimester of Pregnancy / 대한주산의학회잡지

PURPOSE: Ibuprofen is a non steroidal anti-inflammatory drug used for treating fever and pain including headache, arthralgia, and back pain. There is scarce information on the safety of ibuprofen associated with fetal anomaly when used early in pregnancy. Epidemiology studies have suggested that use of NSAIDs, including ibuprofen, during pregnancy may increase the risk of cardiac defects and gastroschisis. The aim of the study was to evaluate fetal outcomes among pregnant women who were unintentionally exposed to ibuprofen in early pregnancy. METHODS: Total 381 pregnant women who were unintentionally exposed to ibuprofen during early pregnancy were prospectively followed up. In addition, 643 age and gravity matched pregnant women not exposed to any potential teratogenic agent during pregnancy were recruited as controls. Patients were followed-up until delivery or loss to follow-up. Newborns were examined in order to identify any major congenital malformation. RESULTS: Mean age of exposed women was 31.2+/-3.4 years, with a mean number of previous pregnancies of 2.3+/-1.2 and mean gestational weeks at exposure of 4.4+/-2.2. All gestations were confirmed by ultrasonography. Of exposed women, 17 (5.6%) had spontaneous abortions, 16 were on- going pregnancies, 1 had an intra-uterine fetal death, 21 artificial abortion and 55 cases were lost to follow-up. Therefore, 271 pregnancies unintentionally exposed to ibuprofen were evaluated, each delivering a singleton baby. Three babies had congenital anomalies: one had unilateral hydronephrosis, another baby was born with a unilateral inguinal hernia. The last baby was born with unilateral kidney dysplasia with megaureter. In the control group, 6 babies were born with major malformations [1.11% vs. 1.31% (P=0.552, OR: 0.841, 95% CI: 0.2 to 3.4)]. CONCLUSION: These preliminary results suggest that the ibuprofen may not be a major human teratogen.

No association between endothelin-1 gene polymorphisms and preeclampsia in Korean population

PURPOSE: Preeclampsia is a major cause of maternal and perinatal mortality and morbidity and is considered to be a multifactorial disorder involving a genetic predisposition and environmental factors. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, and alterations in the ET-1 system are thought to play a role in triggering the vasoconstriction seen with preeclampsia. The aim of this study was to examine the frequency of the 4 common single-nucleotide polymorphisms (SNPs) (c.1370T>G, c.137_139delinsA, c.3539+2T>C, and c.5665G>T) of the ET-1 gene in normotensive and preeclamptic pregnancies and to investigate whether these SNPs are associated with preeclampsia in pregnant Korean women. METHODS: We analyzed blood samples from 206 preeclamptic and 216 normotensive pregnancies using a commercially available SNapShot kit and an ABI Prism 3100 Genetic analyzer. RESULTS: There were no significant differences in genotype or allele frequencies of the 4 SNPs in the ET-1 gene between preeclamptic and normotensive pregnancies. The respective frequencies of the 3 haplotypes (TDTG, GDCT, and TICT; >10% haplotype frequency) were 61%, 13% and 13%, respectively, in preeclampsic pregnancies and 62%, 14% and 12%, respectively, in normotensive pregnancies. The frequencies of these haplotypes were similar for both groups. Using multiple logistic regression analysis, we did not observe an increase in the risk of preeclampsia for the 4 SNPs of the ET-1 gene under either a recessive or dominant model. CONCLUSION: This study suggests that the 4 SNPs of the ET-1 gene are not associated with an increased risk for preeclampsia in pregnant Korean women.

Association study of LEP and LEPR gene polymorphisms and the development of type 2 diabetes mellitus in Korean women with a history of gestational diabetes / 대한산부인과학회지

OBJECTIVE: The history of gestational diabetes (GDM) is a high risk for the development of type 2 diabetes mellitus (T2DM). The purpose of this study is to investigate the genetic association of LEP and LEPR gene polymorphisms and the development of T2DM in Korean women of history of GDM. METHODS: Women diagnosed as GDM during pregnancy from January 1992 to December 2002 were recruited. Those women with a T2DM at the time of study were classified as T2DM positive group, and without T2DM, as T2DM negative group. 2 genes (LEP and LEPR genes) and 8 SNPs (LEP-632G>A, +4950G>A, +4998A>C, and LEPR-141013T>C, -186A>G, +5193G>A, +7187A>C, +27265A>G) were selected. The TaqMan assay for genotyping and the statistical analysis for phenotypic and genetic factors between 2 groups were analyzed. RESULTS: A total of 54 women, T2DM positive (n=20) and T2DM negative (n=34) were enrolled. At the time of diagnosis of GDM, HbA1c, 50 g and 100 g oral glucose tolerance test, and insulin level were significantly associated between T2DM positive and negative groups (P<.05). In analysis of genetic risk to T2DM, the significant association related with any SNPs was not shown between T2DM positive and negative groups. CONCLUSION: In Korean women having past history of GDM, there was no relationship between 2 genes and the development to T2DM. To clarify a effect of candidate genes related with development of T2DM, there will need more samples and genes.

Intercellular Adhesion Molecule-1 Gene Polymorphism (K469E) in Korean Preeclamptic Women

PURPOSE: Preecalmpsia is a pregnancy-specific disorder that reflects widespread endothelial dysfunction resulting from increases of adhesion molecule expression. Intercellular adhesion molecule-1 (ICAM-1) is involved in the pathogenetic mechanisms responsible for preeclampsia, and ICAM-1 plasma levels and/or function is genetically influenced. Therefore, we evaluated the distribution of ICAM-1 gene K469E polymorphism in pregnant Korean women with preeclampsia and evaluated the association between this polymorphism and preeclampsia. METHODS: The K469E polymorphism was analyzed in peripheral blood samples from 197 preeclamptic pregnancies and 193 normotensive pregnancies by a SNapShot kit and an ABI Prism 3100 Genetic analyzer. RESULTS: Genotypic and allelic frequencies of ICAM-1 gene polymorphism (K469E) did not differ between preeclamptic and normotensive pregnancies. The distributions of the KK, KE, and EE genotypes were 40.6%, 43.7%, and 15.7%, respectively, in preeclamptic pregnancies and 38.9%, 45.1%, and 16.1%, respectively, in normotensive pregnancies. The frequencies of K and E alleles were 0.62 and 0.38, respectively, in preeclamptic pregnancies and 0.61 and 0.39, respectively, in normotensive pregnancies. By multiple logistic regression analysis, there was no increased risk of preeclampsia in subjects with ICAM-1 KE (OR, 1.08; P=0.74) or EE (OR, 1.07; P=0.88) genotypes. CONCLUSION: This study suggests that the ICAM-1 gene K469E polymorphism does not associate with an increased risk of preeclampsia in pregnant Korean women.

Polymorphisms of 5, 10-Methylentetrahydrofolate Reductase (MTHFR C677T) and Methionine Synthase Reductase (MTRR A66G) as Maternal Risk Factors for Fetal Aneuploidy

PURPOSE: Aneuploidy is the cause of diseases such as Down syndrome or Edward syndrome and, more generally, is a major cause of mental retardation and fetal loss. The purpose of this study was to evaluate the association between MTHFR (C677T) or MTRR (A66G) polymorphisms and fetal aneuploidy. MATERIALS AND METHODS: Data was collected from 37 women who had a fetus with aneuploidy (cases) and 78 women who had previously delivered at least two healthy children without aneuploidy and did not have a history of miscarriage or abnormal pregnancy (controls). The MTHFR (C677T) or MTRR (A66G) polymorphisms were analyzed by PCR-restriction fragment length polymorphism assay. RESULTS: The frequencies of the MTHFR 677 CC, CT, and TT genotypes were 30.7%, 48.7%, and 20.6% in the control group and 37.8%, 48.6%, and 13.5% in the case group, respectively. There were no significant differences in genotype frequencies between the two groups. For the MTRR A66G polymorphism, the frequencies of the AA, AG and GG genotypes were 50%, 46.1%, and 3.9% in the control group and 13.5%, 81.1%, and 5.4% in case group, respectively. The frequency of the MTRR AG mutant was significantly increased in the case group, with an odds ratio of 6.5 (95% CI: 2.3-18.6, P<0.05). CONCLUSION: The results of this study suggest that mother carriers with the MTRR G allele have an increased risk of fetal aneuploidy, while the MTHFR T allele is not associated with increased risk of fetal aneuploidy. The MTRR A66G polymorphism may be a risk factor for producing a child with chromosomal aneuploidy.