Hyun-Mee Ryu

Increased sFlt-1 to PlGF Ratio in Women Who Subsequently Develop Preeclampsia

The purpose of this study was to determine whether the levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placenta growth factor (PlGF) are altered during the second trimester in the plasma of women who subsequently develop preeclampsia. We performed a case-control study to compare the levels of sFlt-1 and PlGF in the preeclamptic (n=46) and normal pregnant women (n=100). The maternal plasma levels of sFlt-1 and PlGF were measured by enzyme-linked immunosorbent assay. The sFlt-1 levels were significantly higher in the preeclamptic women than in normal controls (p<0.001), while the PlGF levels were significantly lower (p<0.001). In normal controls, sFlt-1 levels were positively correlated (r=0.27, p=0.008), whereas, in the preeclamptic women, those were negatively correlated with the PlGF levels (r=-0.423, p=0.005). Furthermore, the log[sFlt-1/PlGF] ratio was significantly higher in the preeclamptic women than in normal controls (p<0.001). The receiver operating characteristic curve revealed a specificity of 78% with a diagnostic sensitivity of 80.4%; the optimal cut-off value of the log[sFlt-1/PlGF] ratio was 1.4 (95% CI 0.756-0.910, p<0.001). Preeclampsia showed a strong association with increased levels of sFlt-1 and decreased levels of PlGF in the second trimester maternal plasma. Accordingly, the sFlt-1/PlGF ratio may provide early prediction of subsequent development of preeclampsia.

Rate of vertical transmission of human papillomavirus from mothers to infants: Relationship between infection rate and mode of delivery

BackgroundIn contrast to consistent epidemiologic evidence of the role of sexual transmission of human papillomavirus (HPV) in adults, various routes may be related to HPV infection in infants. We have assessed the extent of HPV infection during the perinatal period, and the relationship between mode of delivery and vertical transmission.ResultsA total of 291 pregnant women over 36 weeks of gestation were enrolled with informed consent. Exfoliative cells were collected from maternal cervix and neonatal buccal mucosa. HPV infection and genotypes were determined with an HPV DNA chip, which can recognise 24 types. The HPV-positive neonates were re-evaluated 6 months after birth to identify the presence of persistent infection. HPV DNA was detected in 18.9 % (55/291) of pregnant women and 3.4 % (10/291) of neonates. Maternal infection was associated with abnormal cytology (p = 0.007) and primiparity (p = 0.015). The infected neonates were all born to HPV-positive mothers. The rate of vertical transmission was estimated at 18.2 % (10/55) which was positively correlated with maternal multiple HPV infection (p = 0.003) and vaginal delivery (p = 0.050), but not with labour duration and premature rupture of membranes. The rate of concordance of genotype was 100 % in mother-neonate pairs with vertical transmission. The neonatal HPV DNAs found at birth were all cleared at 6 months after delivery.ConclusionsVertical transmission of HPV DNA from HPV infected mother to the neonate increased when the infant was delivered through an infected cervix. However, the absence of persistent infection in infants at 6 months after delivery may suggest temporary inoculation rather than true vertical infection.

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.

Factors associated with a positive intake of folic acid in the periconceptional period among Korean women

OBJECTIVE We aimed to investigate the factors associated with a positive intake of folic acid (FA) during the periconceptional period among Korean women. DESIGN In a cross-sectional study of demographic, obstetric and socio-economic data, history of periconceptional intake of FA and awareness of the benefits of FA supplementation in pregnancy were obtained and analysed using the chi2 test, followed by multiple logistic regression analysis. SETTING The Maternity School, Cheil General Hospital and Womens Healthcare Center, Seoul, South Korea, between October 2005 and March 2006. SUBJECTS In total 1313 pregnant women participating in a two-day training course available every month. RESULTS After excluding subjects with incomplete or inconsistent data, there were 1277 women included in the analysis. Participants were aged 29.4 (sd 2.9) years and had a mean gestational age of 27.9 (sd 7.1) weeks. Only 131 (10.3 %) women took FA during the periconceptional period. According to multiple logistic regression analyses, the adjusted OR for FA supplementation was 1.79 (95 % CI 1.10, 2.91) in women who had previous spontaneous abortions, 4.10 (95 % CI 2.43, 6.78) in women who planned their pregnancy and 6.63 (95 % CI 2.08, 21.12) in those who were aware of the protective effects of FA. CONCLUSIONS Periconceptional intake of FA was more likely among Korean women with a history of previous spontaneous abortion, who planned their pregnancy or who were aware of the protective effects of FA during pregnancy. However, the proportion of women who took FA in the periconceptional period was low.

Blood levels of phosphatidylethanol in pregnant women reporting positive alcohol ingestion, measured by an improved LC-MS/MS analytical method

Objective. A reliable biomarker of low alcohol exposure during pregnancy is needed to clarify the controversy on the teratogenicity of low-to-moderate alcohol levels. Methods. Blood samples were obtained from 13 pregnant women who self-reported alcohol ingestion between 2.5 and 20 drinks/week, and from 26 controls. Total lipids were extracted, and phosphatidylethanol (PEth) species 16:0/16:0, 16:0/18:1, and 16:0/18:1 were separated by high-performance liquid chromatography (HPLC) on a reverse-phase phenyl column. These PEth species were quantified by MS/MS using phosphatidylpropanol as internal standard, with electrospray ionization and MRM. Results. PEth species were not detected in women who abstained from alcohol ingestion during pregnancy, whereas PEth-16:0/18:1 was > 5 nmol/L in those with positive alcohol ingestion. PEth species were detected for up to 4 weeks after cessation of exposure. Conclusions. PEth-16:0/18:1 was detected in pregnant women at 4–6 weeks after their last low-to-moderate alcohol ingestion, and therefore appears to be a reliable biomarker of prenatal alcohol exposure to study the teratogenicity of alcohol at these exposure levels.

Characterization of phosphatidylethanol blood concentrations for screening alcohol consumption in early pregnancy

Objective. Phosphatidylethanol (PEth) is formed endogenously by the direct action of ethanol, and has a half-life long enough to make it a reliable biomarker of alcohol exposure in early pregnancy. In this study, we aimed to characterize PEth blood concentrations to differentiate different levels of alcohol exposure in pregnant women. Methods. The study consisted of 305 consecutive pregnant women who had been referred to our hospital for antenatal care. Of them, 117 self-reported alcohol ingestion in the first trimester of pregnancy and 188 were abstainers. Total PEth concentration in whole blood was quantified by liquid chromatography-mass spectrometry (LC-MS/MS). Alcohol ingestion was classified according to the United States National Institute on Alcohol Abuse and Alcoholism into light drinkers: ≤ 3 drinks/week, moderate drinkers: 3–7 drinks/week, and heavier drinkers: > 7 drinks/week (a standard drink = 14 g of ethanol). Results. Participants had quantifiable PEth blood levels 3–4 weeks after the last drink. There were 4.8% abstainers who had positive PEth concentrations; all of them reported a positive history of alcohol consumption before conception. PEth blood concentrations were significantly correlated to drinks per occasion (r = 0.44; P < 0.001) and days drinking per week (r = 0.34; P < 0.001). However, almost 74% of participants with ≤ 3 drinks/week of alcohol, and 46% with 3–7 drinks/week, had PEth blood concentrations below the lower limit of quantification (LLOQ). The area under the curve (AUC) generated by a receiver operation characteristic curve (ROC) analysis increased as the cutoff value of PEth blood concentration increased. However, the cutoff values were below or close to the LLOQ. Conclusions: Our study presents a formal characterization of PEth blood concentrations for screening alcohol ingestion in first-trimester pregnant women. However, caution is recommended for overrepresenting either negative or positive results.

Fetal and neonatal outcomes in women reporting ingestion of licorice (Glycyrrhiza uralensis) during pregnancy.

Maternal intake of licorice from dietary sources has been associated with adverse maternal and fetal outcomes. We prospectively studied the outcome of 185 singleton pregnancies who took over-the-counter or naturopathic formulations containing licorice during their pregnancy, and 370 age-matched singleton pregnant controls that were not exposed to any potential teratogen. The indication in 56.8% of the women taking licorice was for cough and cold control, with the maximum dose of 2104 mg/day and exposure occurring between the 4th day and 25th week of gestation. The rate of stillbirths was marginally higher among women who took licorice than those who did not (OR = 7.9; 95% CI 0.9-71.5; p = 0.048), and significantly higher when compared to the general population in the Republic of Korea (OR = 13.3; 95% CI 4.9-35.8; p < 0.001). Other fetal outcomes assessed in the study were similar between the two study groups, e.g., the OR of major malformations was 3.9 (95% CI 0.4-43.5; p = 0.27). In conclusion, the present study suggests that licorice is not a major teratogen. However, whether licorice may increase the risk of stillbirths requires careful consideration in further studies with a larger sample size.

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.

Prenatal diagnosis of Pallister–Killian syndrome in two fetuses with increased nuchal translucency

Pallister–Killian syndrome (PKS), or mosaic tetrasomy 12p, is a rare, sporadically occurring disorder described first by Pallister (Pallister et al., 1977) in two adult patients, and later by Killian (Teschler-Nicola and Killian, 1981). Individuals with PKS generally show a ‘coarse’ face, sparse hair or temporal alopecia, pigmentary dysplasia, short and broad hands, mental retardation, and seizures. PKS is cytogenetically characterized by a tissue-limited mosaicism. Most fibroblasts have 47 chromosomes with an extra-small metacentric chromosome, whereas the karyotype of lymphocytes is usually normal. The extra metacentric chromosome is an isochromosome of the short arm of chromosome 12 (Peltomaki et al., 1987; Warburton et al., 1987). Prenatal diagnosis of the syndrome has been reported in 60 cases since the first description by Gilgenkrantz et al. (1985). Measurements of fetal nuchal translucency in the first trimester have been used as a screening test for trisomy 21, also known as Down syndrome. It is recognized that other chromosomal abnormalities may also present with increased nuchal translucency (INT). We present two cases of early prenatal diagnosis of PKS after detection of INT during routine first-trimester screening for trisomy 21. A 33-year-old woman (G3P0) presented for a nuchal translucency screening for trisomy 21. The pregnancy had been uncomplicated, and there was no significant medical or family history. The initial screening scan was performed at 11 + 5 weeks’ gestation, and a nuchal translucency measurement of 3.2 mm was obtained. The couple was counseled concerning the options of different invasive tests to obtain cells for karyotyping, and eventually requested amniocentesis at 16 weeks’ gestation. At the time of amniocentesis, a hygroma coli was noted on ultrasound. Other internal abnormalities were not detected. The amniotic fluid volume was in the normal range. The conventional G bands produced with trypsin and Giemsa (GTG) of cultures of the amniocytes

Pregnancy outcome after exposure to oral contraceptives during the periconceptional period

To evaluate whether periconceptional exposure to oral contraceptives (OCs) increased adverse pregnancy outcomes, 136 pregnant women taking OCs within the periconceptional period were identified at the Korean Motherisk Program. Of them, 120 pregnant women accepted to participate in their study and were followed up until completion of the pregnancy. A control group of 240 age- and gravidity-matched pregnant women exposed to non-teratogen drugs for at least 1 month before pregnancy was also included. The median gestational age at delivery was 39.1 (27.0–41.0) weeks in the exposed group and 39.3 (27.4–42.0) weeks in the control group (P = 0.19). In the exposed group, 7.1% of babies were born with low birth weight versus 2.6% in the control group (P = 0.068). The number of preterm deliveries or babies born large for gestational age did not differ between the two groups. In the exposed group, the rate of birth defects was 3.2% (n = 3/99) versus 3.6% (n = 7/193) in the control group (P = 1.0). There were 15 women who took high doses of progesterone (emergency contraception) and no adverse fetal outcomes were observed. In conclusion, periconceptional exposure to OCs does not appear to increase the risk for adverse pregnancy outcomes.