Fragile X carrier screening in Korean women of reproductive age.

OBJECTIVE: To estimate the distribution of the FMR1 alleles and the prevalence of the premutaion (PM) and full mutation (FM) of the FMR1 gene in Korean women of reproductive age. METHODS: Using polymerase chain reaction and Southern blot, 5829 women of reproductive age were screened (low-risk group n = 5470 and high-risk group n = 359) and 11 prenatal diagnoses were completed between September 2003 and December 2011. RESULTS: Of the 5829 women screened, normal FMR1 alleles (11,607) had a bimodal distribution with most alleles having 29 (37.87%) and 30 (31.87%) CGG repeats. Of the 5470 women in the low-risk group, 7 PM were identified, giving a PM carrier frequency of 1:781; none of the women had Fragile X syndrome. We also identified 38 intermediate alleles, with a reported incidence of 1:143. Of the 11 prenatal diagnoses, five were normal, five had a premutation, and one had a full mutation allele. CONCLUSIONS: The carrier frequency is 1/781 (0.13%) in Korean women of reproductive age. This is lower than among Caucasians, but relatively higher than in other Asian populations. Although there may be a founder effect, these results might be valuable in understanding Fragile X syndrome in Koreans and Asians as a whole.

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.

Early second trimester maternal plasma levels of thrombin-inhibitor complexes and subsequent spontaneous preterm delivery.

OBJECTIVE: Increased thrombin generation has been implicated as a mechanism for several obstetric syndromes including preterm birth preceded by preterm labor (PTL) and preterm premature rupture of membranes (PPROM). In this study, we attempted to determine whether PTL or PPROM are associated with changes in the maternal plasma thrombin level during the early second trimester. METHODS: This is a case-control study in which maternal thrombin-antithrombin (TAT) III complex concentrations at 15-21 weeks were compared between normal controls (n = 85) and women subsequently delivering preterm, due to either PTL with intact membranes (n = 21) or PPROM (n = 20). Statistical analysis was conducted using non-parametric statistics. RESULTS: PTL patients with intact membranes showed non-significant differences in median plasma TAT level (110.1 µg/L) compared with the control group (107.9 µg/L). Similarly, women destined to deliver preterm because of PPROM had non-significantly higher plasma TAT level (134.3 µg/L) than those in the control group (107.9 µg/L) (p > 0.05). Logistic regression analysis demonstrated that after controlling for confounders including vaginal bleeding, TAT levels remained not significantly associated with subsequent spontaneous preterm birth (p = 0.27). CONCLUSION: Maternal plasma TAT level is unsuitable as an early second trimester predictor of preterm birth preceded by PTL or PPROM.

Pregnancy outcomes according to increasing maternal age.

OBJECTIVES: To investigate the risks of increasing maternal age on the perinatal and obstetric outcomes. MATERIALS AND METHODS: Information about 29,760 singleton pregnancies delivered between 2005 and 2008 was extracted from our database. Patients were categorized into four groups according to age: 20-29 years, 30-34 years, 35-39 years, and ≥40 years. Multivariable logistic regression analysis was used to evaluate the adjusted odd ratios (AORs) of adverse pregnancy outcomes according to maternal age after adjusting for parity, body mass index, medical history and use of in vitro fertilization. RESULTS: The majority of adverse perinatal outcomes were associated with a maternal age ≥35 years as follows: low birth weight (AOR 1.2 and 1.6 for women aged 35-39 years and ≥40 years, respectively); Apgar score < 7 at 1 minute (AOR: 1.7 and 1.8); and chromosomal anomaly (AOR: 2.7 and 12.3). However, women aged ≥30 years also had greater risks for adverse maternal outcomes such as: gestational diabetes (AOR: 2.0, 3.6 and 5.1 for women aged 30-34 years, 35-39 years and ≥40 years, respectively); placenta previa (AOR: 1.6, 2.1 and 3.6); and cesarean delivery (AOR: 1.5, 2.3, and 4.1), as well as adverse fetal outcomes such as: preterm delivery (AOR: 1.2, 1.4 and 1.8) and neonatal intensive care unit transfer (AOR: 1.1, 1.2, and 1.6). CONCLUSION: Increasing maternal age is an independent and substantial risk factor for adverse perinatal and obstetric outcomes. These adverse outcomes become more common as increasing maternal age without a clear cutoff age.

Foetal and neonatal outcomes in women reporting ingestion of low or very low alcohol intake during pregnancy.

OBJECTIVE: This study aimed to assess the pregnancy outcomes of women who reported social intake of low or very low alcohol levels during pregnancy. METHODS: Obstetric and foetal outcomes were assessed in a prospective cohort of 1667 pregnant women who reported low or very low alcohol consumption during pregnancy (cases) and 1840 alcohol-abstainer women (controls). RESULTS: Among cases, alcohol consumption occurred during the first 4.4 (median) weeks of pregnancy, with a median ingestion of 1.0 (0.01-6.0) drinks/week, equivalent to 7.6 (0.09-47.5) g/week. Cigarette smoking was reported approximately four times more often in the exposed group than in the controls (p < 0.001). Pregnancy outcomes were similar between groups. There were 37 (2.4%) babies born with malformations in the exposed group and 41 (2.4%) in the control group (p = 0.9). CONCLUSIONS: Low-to-very low levels of alcohol ingestion during pregnancy do not appear to be associated with adverse maternal or foetal outcomes.

Effective detection of fetal sex using circulating fetal DNA in first-trimester maternal plasma.

The aim of this study was to develop a simple and effective method for noninvasively detecting fetal sex using circulating fetal DNA from first-trimester maternal plasma. A study was conducted with maternal plasma collected from 203 women between 5 and 12 wk of gestation. The presence of circulating fetal DNA was confirmed by a quantitative methylation-specific polymerase chain reaction of the unmethylated-PDE9A gene (U-PDE9A). Multiplex real-time PCR was used to simultaneously quantify the amount of DYS14 and GAPDH in maternal plasma. The results were confirmed by phenotype at birth. Pregnancy outcomes and U-PDE9A concentrations were obtained in all cases, including 99 male-bearing and 104 female-bearing participants. At equivalent specificity (100%), the false-negative rate was 9.1% for DYS14 quantification cycle, 7.1% for DYS14 concentration, and 0.0% for the concentration ratio of DYS14/GAPDH, respectively. In male-bearing participants, DYS14, U-PDE9A, and GAPDH concentrations were significantly lower in the false-negative case than in correct case (P<0.001 in all). Moreover, DYS14, U-PDE9A, and GAPDH concentrations showed significantly positive associations with each other (P≤0.001 in all). The ratio of DYS14/GAPDH in maternal plasma was an effective biomarker for noninvasive fetal sex detection during the first trimester, indicating that it could be useful for clinical application.

Non-invasive epigenetic detection of fetal trisomy 21 in first trimester maternal plasma.

BACKGROUND: Down syndrome (DS) is the most common known aneuploidy, caused by an extra copy of all or part of chromosome 21. Fetal-specific epigenetic markers have been investigated for non-invasive prenatal detection of fetal DS. The phosphodiesterases gene, PDE9A, located on chromosome 21q22.3, is completely methylated in blood (M-PDE9A) and unmethylated in the placenta (U-PDE9A). Therefore, we estimated the accuracy of non-invasive fetal DS detection during the first trimester of pregnancy using this tissue-specific epigenetic characteristic of PDE9A. METHODOLOGY/PRINCIPAL FINDINGS: A nested, case-control study was conducted using maternal plasma samples collected from 108 pregnant women carrying 18 DS and 90 normal fetuses (each case was matched with 5 controls according to gestational weeks at blood sampling). All pregnancies were singletons at or before 12 weeks of gestation between October 2008 and May 2009. The maternal plasma levels of M-PDE9A and U-PDE9A were measured by quantitative methylation-specific polymerase chain reaction. M-PDE9A and U-PDE9A levels were obtained in all samples and did not differ between male and female fetuses. M-PDE9A levels did not differ between the DS cases and controls (1854.3 vs 2004.5 copies/mL; P = 0.928). U-PDE9A levels were significantly elevated in women with DS fetuses compared with controls (356.8 vs 194.7 copies/mL, P<0.001). The sensitivities of U-PDE9A level and the unmethylation index of PDE9A for non-invasive fetal DS detection were 77.8% and 83.3%, respectively, with a 5% false-positive rate. In the risk assessment for fetal DS, the adjusted odds ratios of U-PDE9A level and UI were 46.2 [95% confidence interval: 7.8-151.6] and 63.7 [95% confidence interval: 23.2-206.7], respectively. CONCLUSIONS: Our findings suggest that U-PDE9A level and the unmethylation index of PDE9A may be useful biomarkers for non-invasive fetal DS detection during the first trimester of pregnancy, regardless of fetal gender.

Risk factors for group B streptococcus colonization among pregnant women in Korea.

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.

Determination of the carrier frequencies of selected GJB2 mutations in the Korean population.

OBJECTIVE: Mutations in the GJB2 gene are a major cause of hereditary hearing loss. However, only a few studies have investigated carrier frequencies of GJB2 mutations in the general population. The aim of this study was to estimate the carrier frequencies of three GJB2 mutations, including 235delC, V37I, and G45E, in the general Korean population. DESIGN: A standard questionnaire of self-reported hearing loss was used to identify and recruit subjects. Screening for three mutations was performed using an allele-specific polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and direct DNA sequencing. STUDY SAMPLE: A total of 1256 unrelated healthy individuals were analysed in the present study. RESULTS: Of the 1256 individuals, 24 had GJB2 mutations; 11 were found to be heterozygous for 235delC, 11 were heterozygous and one was homozygous for V37I, and one was heterozygous for G45E. One individual had a compound heterozygous mutation of 235delC/V37I. The allele frequencies of 235delC, V37I, and G45E mutations were 0.44%, 0.52%, and 0.04%, respectively. The carrier frequency of either the 235delC or V37I mutation was estimated to be 0.88% with 95% binomial CI, 0.44-1.56. CONCLUSIONS: These results will facilitate diagnosis of, and genetic counseling for, hearing loss in Koreans.

Melatonin receptor 1 B polymorphisms associated with the risk of gestational diabetes mellitus.

BACKGROUNDS: Two SNPs in melatonin receptor 1B gene, rs10830963 and rs1387153 showed significant associations with fasting plasma glucose levels and the risk of Type 2 Diabetes Mellitus (T2DM) in previous studies. Since T2DM and gestational diabetes mellitus (GDM) share similar characteristics, we suspected that the two genetic polymorphisms in MTNR1B may be associated with GDM, and conducted association studies between the polymorphisms and the disease. Furthermore, we also examined genetic effects of the two polymorphisms with various diabetes-related phenotypes. METHODS: A total of 1,918 subjects (928 GDM patients and 990 controls) were used for the study. Two MTNR1B polymorphisms were genotyped using TaqMan assay. The allele distributions of SNPs were evaluated by x2 models calculating odds ratios (ORs), 95% confidence intervals (CIs), and corresponding P values. Multiple regressions were used for association analyses of GDM-related traits. Finally, conditional analyses were also performed. RESULTS: We found significant associations between the two genetic variants and GDM, rs10830963, with a corrected P value of 0.0001, and rs1387153, with the corrected P value of 0.0008. In addition, we also found that the two SNPs were associated with various phenotypes such as homeostasis model assessment of beta-cell function and fasting glucose levels. Further conditional analyses results suggested that rs10830963 might be more likely functional in case/control analysis, although not clear in GDM-related phenotype analyses. CONCLUSION: There have been studies that found associations between genetic variants of other genes and GDM, this is the first study that found significant associations between SNPs of MTNR1B and GDM. The genetic effects of two SNPs identified in this study would be helpful in understanding the insight of GDM and other diabetes-related disorders.

Association between genetic polymorphisms in androgen receptor gene and the risk of preeclampsia in Korean women.

PURPOSE: To investigate associations between the androgen receptor (AR) polymorphisms as CAG repeats, GGC repeats and c.211G>A polymorphism and the risk of preeclampsia. METHODS: The AR polymorphisms were experienced in 184 preeclamptic patients and 190 normal pregnancies and analyzed by multiple logistic regression. RESULTS: Women with GGC repeats>16 were more frequently observed in preeclampsia, compared to those with GGC repeats≤16 [adjOR (95% CI): 3.64 (1.71-6.23)]. However, no significant differences were observed between the two groups with respect to CAG repeats. The genotypic and allelic frequencies of c.211G>A variant were significantly higher in cases than in controls (P < 0.05 for both). In the combined distribution of these polymorphisms, the highest risk of preeclampsia was found among women with the haplotype as CAG > 20/GA/GGC >16 [adjOR (95% CI): 4.26 (1.92-12.23)]. CONCLUSIONS: Our findings suggest that longer GGC repeats and c.211G>A variant in the AR gene are associated with increased susceptibility to the risk of preeclampsia.

Non-invasive prenatal detection of achondroplasia using circulating fetal DNA in maternal plasma.

PURPOSE: To perform a reliable non-invasive detection of the fetal achondroplasia using maternal plasma. METHODS: We developed a quantitative fluorescent-polymerase chain reaction (QF-PCR) method suitable for detection of the FGFR3 mutation (G1138A) causing achondroplasia. This method was applied in a non-invasive detection of the fetal achondroplasia using circulating fetal-DNA (cf-DNA) in maternal plasma. Maternal plasmas were obtained at 27 weeks of gestational age from women carrying an achondroplasia fetus or a normal fetus. RESULTS: Two percent or less achondroplasia DNA was reliably detected by QF-PCR. In a woman carrying a normal fetus, analysis of cf-DNA showed only one peak of the wild-type G allele. In a woman expected an achondroplasia fetus, analysis of cf-DNA showed the two peaks of wild-type G allele and mutant-type A allele and accurately detected the fetal achondroplasia. CONCLUSIONS: The non-invasive method using maternal plasma and QF-PCR may be useful for diagnosis of the fetal achondroplasia.

Nutritional risk factors of early development of postpartum prediabetes and diabetes in women with gestational diabetes mellitus.

OBJECTIVE: Early detection of prediabetes and diabetes after delivery helps prevent and delay the development of overt type 2 diabetes in women with gestational diabetes mellitus (GDM). We sought to identify modifiable risk factors for the early development of postpartum type 2 diabetes in women with GDM that may help establish interventions for preventing or delaying the subsequent onset of type 2 diabetes. METHODS: Three hundred eighty-one women who developed GDM during pregnancy were tested for 1) antepartum anthropometric and biochemical measurements, 2) pregnancy outcome, 3) oral glucose tolerance test at 6 to 12 wk after delivery, and 4) postpartum anthropometric, biochemical, and nutritional measurements. The subjects were divided into three groups on the basis of the postpartum oral glucose tolerance test results: normal glucose tolerance group (n=193), prediabetes (n=161), and diabetes (n=27). RESULTS: The incidences of postpartum prediabetes and diabetes at 6 to 12 wk follow-up in Korean women with GDM were 44.8% and 5.2%, respectively. Antepartum modifiable risk factors for developing type 2 diabetes at early postpartum included higher body mass index, lower ß-cell function, insulin dosage during late pregnancy, and the non-modifiable risk factor of family history of diabetes (R2=0.14). Postpartum risk factors included higher body mass index, serum triacylglycerols, hemoglobin A1c, and energy intake and lower insulin secretion capacity (R2=0.43). Animal fat intake was higher in the prediabetes and diabetes groups than in the normal glucose tolerance group, whereas breast-feeding did not alter the risk for the development of postpartum diabetes. CONCLUSION: This study strongly suggests that the development of postpartum type 2 diabetes in women with GDM can be prevented and/or delayed by lifestyle and nutritional intervention during antepartum and postpartum.

Genetic polymorphism of catechol-O-methyltransferase and cytochrome P450c17α in preeclampsia.

OBJECTIVE: Catechol-O-methyltransferase (COMT) and cytochrome P450c17α (CYP17A1) are key enzymes involved in the metabolism of steroid hormones; genetic polymorphisms in these genes affect enzyme activity. Recently, functional polymorphisms in the COMT and CYP17A1 genes have been suggested as a susceptible marker for intrauterine fetal growth restriction, a typical complication of preeclampsia. Moreover, a close association between COMT and preeclampsia was reported. We therefore investigated the relationships between COMT and CYP17A1 polymorphisms and the risk of preeclampsia. METHODS: A total of 164 preeclamptic women and 182 normotensive women were enrolled. COMT (Val158Met) and CYP17A1 (-34T/C) polymorphisms were genotyped by quantitative fluorescent-polymerase chain reaction. Multiple logistic regression analysis was used to estimate the risks of preeclampsia according to genotypes. RESULTS: The adjusted odds ratios (adjOR) for the risks of preeclampsia, severe preeclampsia and preeclampsia for small-for-gestational-age (SGA) infants were 1.97 [95% confidence interval (CI): 1.02-3.83], 3.29 (95% CI: 1.60-6.77), and 4.05 (95% CI: 1.78-9.22), respectively, in women homozygous for the variant COMT allele. No significant differences were observed between the two groups with respect to CYP17A1 polymorphisms, indicating that variants of this gene have no effects on preeclampsia. The highest risks of preeclampsia were found among women with homozygous variant genotypes of both genes [adjOR (95% CI): 4.58 (1.92-22.81)]. Moreover, the adjOR for preeclamptic complications in those women was 5.09 (95% CI: 1.93-27.88) for severe preeclampsia and 15.65 (95% CI: 3.19-76.82) for SGA preeclampsia. CONCLUSION: These findings suggest that homozygosity for the variant allele of the maternal COMT gene may increase susceptibility to preeclampsia.

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.

Transforming growth factor-beta 1 gene polymorphisms in Korean patients with pre-eclampsia.

PROBLEM: The aim of this study was to investigate whether c.869T>C (Leu10Pro) and c.915G>C (Arg25Pro) polymorphisms in exon1 of the transforming growth factor-beta1 (TGF-beta1) gene are associated with development of pre-eclampsia (PE) in Korean women. METHOD OF STUDY: We analyzed blood samples from 164 patients with PE and 182 healthy pregnant women using the polymerase chain reaction and DNA sequencing. RESULTS: The frequencies of the 869CC and combined TC/CC genotypes were higher in patients with PE than in healthy controls. In the PE with intrauterine growth restriction (IUGR), the frequencies of these genotypes were also higher than that in controls. Furthermore, the 869C allele frequency was significantly higher in both PE and IUGR-complicated PE than in controls. Multivariate analysis showed that the 869TC, CC, and combined TC/CC genotypes were associated with an increased risk of PE compared with the 869TT genotype. In addition, the 869TC, CC, and combined TC/CC genotypes were significantly associated with an increased risk of IUGR-complicated PE compared with the 869TT genotype. The TGF-beta1 c.915G>C polymorphism was not detected in our population. CONCLUSION: Our findings indicate that the TGF-beta1 c.869T>C polymorphism may be a genetic risk factor for PE and IUGR-complicated PE.

Clinical findings of multiple pregnancy with a complete hydatidiform mole and coexisting fetus.

OBJECTIVE: The aim of this series was to evaluate the clinical features, management, and outcomes of multiple pregnancy with a complete hydatidiform mole and coexisting fetus (CHMCF). METHODS: Between 1998 and 2008, we investigated 6 women with a diagnosis of a CHMCF. The gestational age at diagnosis, symptoms, serum b-human chorionic gonadotropin levels, cytogenetic and molecular analysis findings, complications, routes of delivery, and pregnancy outcomes were assessed. RESULTS: All cases were diagnosed before 14 weeks' gestation by sonography. Only 1 ended with the delivery of a live-born neonate, whereas the other 5 cases required termination of pregnancy (TOP) before 21 weeks' gestation because of severe maternal complications (eg, preeclampsia, thyrotoxicosis, lung metastasis, and heavy bleeding) or intrauterine fetal death. The pathologic diagnosis of a complete hydatidiform mole was confirmed in all cases. Two patients required methotrexate for treatment of persistent trophoblastic disease (PTD). CONCLUSIONS: On the basis of our experience, in cases with a normal karyotype and no gross fetal abnormalities on sonography, we carefully recommend continuation of pregnancy as long as maternal complications are absent or controllable. However, updated treatment criteria are still needed, and intensive maternal follow-up is necessary in the postpartum period because maternal complications during pregnancy and PTD after TOP are not uncommon.

Soluble endoglin and transforming growth factor-beta1 in women who subsequently developed preeclampsia.

OBJECTIVE: This study aimed to analyze the differences of soluble endoglin (sEng) and transforming growth factor-beta1 (TGF-beta1) according to preeclamptic complications and to investigate the correlation between these factors and the clinical symptoms of preeclampsia. METHOD: We estimated the levels of sEng and TGF-beta1 in plasma collected in the second trimester at the time of genetic amniocentesis from 60 women who subsequently developed preeclampsia and 124 contemporaneous normotensive women. RESULTS: sEng levels were higher in cases than in controls, whereas TGF-beta1 levels were lower (P < 0.001). sEng levels, but not TGF-beta1 levels, were higher in cases with severe or preterm delivery than in cases with mild preeclampsia or term delivery (P < 0.001) and were increased in cases destined to deliver a small gestational age neonate (P < 0.001). Moreover, sEng levels, but not TGF-beta1 levels, showed a positive correlation with maximum diastolic and systolic blood pressure (r = 0.57, P < 0.001; and r = 0.33, P < 0.001, respectively) and proteinuria (r = 0.42, P < 0.001). CONCLUSION: Early midtrimester plasma levels of sEng are predictive of subsequence occurrence and severity of preeclampsia, in terms of severity of hypertension and proteinuria, prematurity, and association with small for gestational age neonates.

Pregnancy outcome of women inadvertently exposed to ribostamycin during early pregnancy: a prospective cohort study.

No information is currently available on the safety of the aminoglycoside ribostamycin in pregnancy. We aimed to study the pregnancy outcome of women inadvertently exposed to ribostamycin during the first trimester of pregnancy. In a prospective cohort study, 102 women inadvertently exposed to ribostamycin during the first trimester of pregnancy and an age- and gravidity-matched control group, were enrolled. Study outcomes were gestational age at birth, major and minor malformations, and birth weight. Fetal outcomes were evaluated in 85 women inadvertently exposed to ribostamycin during the first-trimester of pregnancy and in 170 control subjects. Newborns were clinically examined at birth by a neonatologist and by imaging studies if any suspicious abnormalities were noted. There were 4/85 (4.9%) babies born with major malformations in the exposed group and 3/170 (1.8%) in the control group (P=0.7). Gestational age at delivery, rate of minor anomalies, rate of preterm births, and birth weight were not different between groups. In conclusion, similar to what is reported for other aminoglycoside, exposure to ribostamycin during the first-trimester of pregnancy does not appear to increase the risk of adverse fetal outcomes.