• Toxicological Research
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• v.29 no.1
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• pp.27-34
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• 2013

This study was conducted to investigate the potential embryo-fetal toxicity and toxicokinetics of the antimalarial agent artesunate (ARTS) in Sprague-Dawley rats. Pregnant rats were administered ARTS daily from gestational day 6~15 via oral gavage, at test doses of 0, 2, 4, or 8 mg/kg (22 females per group). The fetuses were examined for external, visceral, and skeletal abnormalities on gestational day 20. With regard to the dams, there were no deaths, treatment-related clinical signs, changes in body weight, or food intake in any of the treatment groups. There were no treatment-related gross findings at necropsy in any treatment group. In the 8 mg/kg group, there was a decrease in gravid uterine weight and in the weight of female fetuses. There was also an increase in fetal deaths (primarily late resorptions) and an increase in post-implantation losses (37%) at 8 mg/kg. An increase in the incidence of visceral and skeletal variations at 4 and 8 mg/kg was observed. These defects included minor changes in the appearance of the kidney and thymus, as well as absent ribs or thoracic vertebrae. Toxicokinetics were assessed in a parallel study, using 4 mated females per group. Using liquid chromatography-mass spectrometry (LC-MS) analysis, the concentration of ARTS and its metabolite dihydroartemisinin (DHA) were quantified in plasma from rats on gestational days 5, 6, 10, and 15. Amniotic fluid was assayed for ARTS and DHA on gestational day 15. There was evidence of rapid conversion of ARTS to the metabolite DHA in maternal plasma, since ARTS could not be consistently detected in plasma at the three doses tested. ARTS and DHA were not detected in amniotic fluid at gestational day 15, indicating limited placental transfer of the two agents. The embryo-fetal no-observable-adverse-effect level (NOAEL) of the test item was considered to be 8 mg/kg/day for dams, and 2 mg/kg/day for embryo-fetal development.

• YAKHAK HOEJI
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• v.42 no.5
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• pp.534-539
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• 1998

Effect of recombinant human epidermal growth factor (rhEGF, DWP401) on fetal external, visceral and skeletal malformation during organogenesis was examined. Pregnant Sprauge-Daw ley rats were administered with 0.2, 1 and 5mg/kg/day subcutaneously on gestation day 6 through 16. Dams were sacrified at 20th day of gestation. Materal body weight, food consumption and clinical observation were not changed. Significant dose-dependent increase of relative and absolute liver weight were observed in the treatment group, whereas other organ weights were not changed. Placental weight of 1 and 5mg/kg/day group and number of resorption in 5mg/kg/day treatment group were significantly increased. External and visceral malformation of fetuses were not observed with treatment. However, skeletal variations(increase of asymmetry sternebrae, decrease of dumb-bell and asymmetry sternbrae at 5mg/kg/day, and fused stemebrae at 5mg/kg/day) were observed. These results showed that rhEGF (DWP401) may not have embryo and/or fetal developmental toxicity effect in rats.

• Journal of Korean Medical Science
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• v.33 no.50
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• pp.318.1-318.10
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• 2018

Background: In this prospective cohort study, we investigated the association between fatty acid ethyl esters (FAEEs) in meconium as biomarkers of prenatal ethanol exposure and growth deficits, as birth outcomes, that constitute several of the key cardinal features of fetal alcohol syndrome. Methods: A total of 157 meconium samples were collected from enrolled infants within 24 hours of birth, and nine FAEEs were quantified using liquid chromatography/tandem mass spectrometry. The relationships between cumulative concentrations of nine species of FAEEs in meconium and birth parameters of growth (age-sex-specific centiles of head circumference [HC], weight, and length) and respective and combined birth outcomes of growth deficits (HC ${\leq}10th$ centile, weight ${\leq}10th$ centile, and length ${\leq}10th$ centile) were determined. Results: Multivariate logistic regression analysis demonstrated that higher cumulative concentrations of meconium FAEEs correlated with elevated risks for HC and length, both, 10th percentile or less (adjusted odds ratio [aOR], 2.94; 95% confidence interval [CI], 1.12-7.74; P = 0.029) and HC and weight and length, all of them, 10th percentile or less (aOR, 3.27; 95% CI, 1.12-9.59; P = 0.031). Conclusion: The elevated cumulative FAEEs in meconium were associated with combined growth deficits at birth, specifically HC and length, both, 10th percentile or less, which might be correlated with detrimental alcohol effects on fetal brain and bone development, suggesting a plausible alcohol-specific pattern of intrauterine growth restriction.

• Journal of Nutrition and Health
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• v.31 no.8
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• pp.1263-1269
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• 1998

The maintenance of adequate folate levels in the umbilical cord blood is esential for supplying tissue requirements of fetal growth. However, there is data on folate levels in the cord blood of Korean infant. The present investigation was undertaken to determine folate levels in cord blood and aassess relationships between folate levels and pregnancy outcomes. Dietary and supplementary folate intake was obtained from thirty subjects who were in the third trimester fo pregancy . The umbilical cord blood was drawn at delivery and pregnancy outcomes for the subjects were collected from their medical records. Erythrocyte and plasma folate levels in the cord blood were analyzed. The subjects were divided into two groups ; high folate (HF, $\geq$654ng/ml) and low folate (LF, <654ng/ml) groups according to erythrocyte folate levels in cord blood. Dietary folate intake and the amount of supplemental folates were not significantly different between the two experimental groups. However, infant birth weight (3540$\pm$295g) and placental weight(910$\pm$85g) for the HF group were significantly higher(p=0.0041 and p=0.109, respectively) than those for the LF group, which were 3127 $\pm$419g and 823$\pm$80g , respectively. Although it was not significant, the gestational weight gain for the HF group was 2.8kg higher than that for the LF group. Thus, the erythrocyte folate level in the cord blood was significantly related to infant birth weight and placental weight. These results confirm that a high erythrocyte folate level in the umbilical cord blood promotes both fetal and placental growth and improves gestational weight gain as well.

• Journal of Yeungnam Medical Science
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• v.15 no.1
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• pp.135-142
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• 1998

Maternal weight gain during pregnancy has been consistently associated with infant birth weight and pregnancy outcome. Our purpose was to determine the relationship between maternal weight gain pattern and birth weight. Consequently, maternal weight gain is monitored carefully and is encouraged during prenatal care in order to improve pregnancy outcome. Our study group included both 424 uncomplicated women and infant delivered at the Yeungnam University Hospital between 1993-1996. All recorded prenatal weight gain measurements were used to estimate maternal trimester weight gain, pattern of gain (based on low versus not-low gain at each trimester), and total gain at delivery. Multiple linear regression analysis was used to assess the relationship between these weight gain measurements and fetal birth weight. Each kilogram of maternal gain in the first, second, and third trimesters was associated with statistically related to the increase in fetal birth weight by 31.3, 19.0, and 24.5g, respectively. When compaired with the pattern of gain that was not low in any trimester, patterns with low gain in the first trimesters were associated with significant decreases in birth weight, but no important change in birth weight was seen for the group whose gains were not low in the first trimester. The results suggest that specific patterns of maternal weight gain, particularly weight gain during the first trimester, are related to fetal birth weight.

• Journal of Cardiovascular Imaging
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• v.30 no.2
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• pp.125-134
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• 2022

BACKGROUND: To assess the interventricular septum (IVS) volume of fetuses from pre-gestational diabetes mellitus (DM) pregnant women by 3-dimensional ultrasound using spatiotemporal image correlation (STIC) and virtual organ computer-aided analysis (VOCAL) methods. METHODS: This was a prospective cross-sectional study of 45 fetuses from pre-gestational DM and 45 fetuses from healthy pregnant women (controls). Only singleton pregnancies between 20 and 34 + 6 weeks of gestation were included. The fetal IVS volumes were obtained off-line using STIC and VOCAL methods. To analyze differences among variables, the Student's t-test and Mann-Whitney U test were used. The correlation among continuous variables was determine using Spearman's correlation test (r). RESULTS: The median of fetal IVS volume was significantly higher in pre-gestational DM than in healthy pregnant women (0.3 cm³ vs. 0.2 cm³, p = 0.032). A strong positive correlation was observed between fetal IVS volume and gestational age at the time of ultrasound examination (r = 0.75, R² = 0.48, p < 0.0001) and between fetal IVS volume and estimated fetal weight (r = 0.63, R² = 0.37, p < 0.0001). No significant correlation was noted between fetal IVS volume and glycated hemoglobin levels (r = -0.16, R² = 0.01, p = 0.540) in the pre-gestational DM pregnant women. CONCLUSIONS: Significant differences were observed in fetal IVS volumes between pre-gestational and healthy mothers, with higher values in the fetuses of pre-gestational DM pregnant women.

• Journal of Preventive Medicine and Public Health
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• v.17 no.1
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• pp.251-257
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• 1984

Low birth weight baby, defined as the baby born with less than or equal to 2,500g of body weight by WHO has been a great concern in the fold of maternal and child health since the low birth weight is a major cause of high perinatal mortality. Any measure to prevent the low birth weight baby is most desirable not only for saving the life of a baby but also for levelling up the health of the whole society. The authors attempted to figure out how some known maternal risk factors are related to the low birth weight and to measure their strengh of associations in terms of relative risk using hospital birth records. For this study, hospital birth records of 66 low birth weight cases and sex-parity matched 198 normal controls were chosen from Kangnam St. Mary's Hospital, Catholic Medical Center, and the data were analyzed in regards to several maternal factors. The risk factors studied were mother's age, mother's ABO blood type, previous histories of abortion, low birth weight baby, fetal wastage, and maternal diseases represented by anemia, hypertension, proteinuria, and glucosuria. The results obtained in this study were as follows: 1. The mean body weight of the cases and controls were 1,955g and 3,251g, respectively, and the heights were 41cm for cases and 50cm for controls. Mean gestation periods of cases and controls were 34 weeks and 39 weeks, respectively. 2. Young mother(less than or equal to 20 years of age) or old mother(more than or equal to 30 years of age) experienced more frequently the delivery of low birth weight babies than mothers in between 21 and 29 years of age. But the difference was not statistically significant. 3. Mothers whose blood type was O tended to have slighty higher frequency of low birth weight babies while B mothers have lower frequency. But the difference was not statistically significant too. 4. Those mothers who had experienced low birth weight baby in the past tended to give more births of low birth weight babies. This factor is even statistically significant and the relative risk of the prior experience of low birth weight was 6.7. 5. Mothers with experience of fetal losses and mothers of more than two pregnancies had higher frequency of low birth weight than the mothers with no fatal losses and of first pregnancy, but the difference was not statistically significant. 6. Statistically significant higher frequency of low birth weight were found in mothers with hypertension(odds ratio=4.07), anemia(odds ratio=22,33), and proteinuria(odds ratio=2.79). In summary, these study results strongly suggest that in order to prevent the low birth weight, special care should be made when the mother is too young or too old, and when the mother has experienced deliveries of low birth weight and fetal deaths. Medical control for the maternal diseases such as anemia and hypertension is also needed before or during the pregnency.

• Nutrition Research and Practice
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• v.5 no.2
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• pp.112-116
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• 2011

We investigated the effect of paternal folate status on folate content and expression of the folate transporter folate receptor ${\alpha}$ ($FR{\alpha}$) in rat placental tissues. Rats were mated after males were fed a diet containing 0 mg of folic acid/kg of diet (paternal folate-deficient, PD) or 8 mg folic acid/kg of diet (paternal folate-supplemented, PS) for 4 weeks. At 20 days of gestation, the litter size, placental weight, and fetal weight were measured, and placental folate content (n=8/group) and expression of $FR{\alpha}$ (n=10/group) were analyzed by microbiological assay and Western blot analysis, respectively. Although there was no difference observed in litter size or fetal weight, but significant reduction (10%) in the weight of the placenta was observed in the PD group compared to that in the PS group. In the PD group, placental folate content was significantly lower (by 35%), whereas $FR{\alpha}$ expression was higher (by 130%) compared to the PS group. Our results suggest that paternal folate status plays a critical role in regulating placental folate metabolism and transport.

• Toxicological Research
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• v.17 no.1
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• pp.27-32
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• 2001

Korean ginseng products have been fumigated with ethylene oxide (EO) for sterilization and prolongation of storage periods. However, there had been controversies indicating that consumption of EO treated foods might cause harmful effects in human. In Korea, the use EO gas for food treatment was banned in 1991. Since then, irradiation technique has been developed as an alternative. This study was carried out to evaluate the safety of irradiated ginseng on embryo and fetal developmental toxicity effects in rats. Either EO gas fumigated or $\gamma$-irradiated ginseng was administered to pregnant Wistar rats by oral gavage from gestational day 7 to 17. The amount of irradiation used in this study was 5, 10 and 30 kGy, respectively. There were no treatment related changes of dams in deaths, clinical signs, food consumption and body/organ weight. No treatment related changes in implantation ratio, litter size, sex ratio and body/organ weight of fetuses were observed. Also, no F1fetuses with external, visceral, head and skeletal mal-formation were observed. The results of this study showed that $\gamma$-irradiated ginseng, up to 30 kGy, has no adverse effects on fetal development of rats.

• Biomedical Science Letters
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• v.20 no.1
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• pp.43-47
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• 2014

To understand the effect of prenatal stress on sex-specific changes in embryonic and placental growth, a synthetic glucocorticoid (dexamethasone) was administered intraperitoneally at a dosage of 1 mg/kg body weight (BW) (Dex1) or 10 mg/kg BW (Dex10) to pregnant ICR mice at the gestational days 7.5, 8.5 and 9.5 post coitum (p.c.). Embryos and placentas were then harvested at days 11.5 and 18.5 p.c., and their body weight and size were measured following the determination of sex through PCR using Sry specific primers in tail tissues. As a result, female embryos presented reduced fetal body weight and size in Dex1- and Dex10-treated groups than those of control group at the embryonic day 11.5 p.c. Interestingly, the growth seems to be recovered at day 18.5 as there was no difference in growth between control and dexamethasone treated groups. In the case of males, Dex1 induced a decrease in fetal weight in day 11.5 and this pattern was maintained until day 18.5, whereas their growth was not affected by Dex10 treatment. Placental growth showed similar patterns to fetal growth in both sexes but the extent of reduction was not statistically significant in most cases. Placental weights in Dex1- and Dex10-treated group were decreased significantly in male only. The results imply that the effect of prenatal stress is largely sex dependent due to different strategies for growth and survival in a stressful environment.