Yong-Jae Kim

Influence of maternal serum levels of vitamins C and E during the second trimester on birth weight and length

Objective: It has been known that maternal oxidative stress during pregnancy plays an important role in fetal growth. However, the association between antioxidant vitamin levels and birth outcomes is not conclusive. We investigated the relationship between maternal serum levels of vitamins C and E during the second trimester and birth weight and length.Design: Prospective cohort study.Setting: Outpatient-clinic of obstetrics, Ewha Womans University Hospital, South Korea.Subjects and methods: The study subjects were 239 healthy, pregnant women who visited an obstetric clinic for antenatal care, and their singleton live births, in Seoul, Korea, between August 2001 and March 2003. We measured the levels of vitamins C and E in maternal serum during the period 24–28 gestational weeks. Each woman was interviewed for dietary intake by trained interviewers during the second trimester.Results: The serum concentration of maternal vitamin C during the second trimester was significantly associated with birth weight and length in the group of full-term deliveries. An increase of 1 μg/ml in the serum vitamin C level increased the birth weight by 27.2 g and the birth length by 0.17 cm. When we considered the levels of vitamins C and E together in the relationship with birth weight and length, we found that the heaviest birth weight and the longest birth length belonged to the group of upper vitamin C/upper vitamin E. However, dietary intake estimated by 24-h recall method was not a predictor of the levels of serum vitamins C and E.Conclusion: We found that maternal serum vitamin C levels during the second trimester were positively correlated with birth weight and length in full-term babies. We also found that birth weight and length were highest when the levels of both vitamins C and E were high. Our results indicate the importance of antioxidant nutrient balance for pregnant women who are exposed to various oxidants through food, drinking water, or inhaled air.

Relationships between pregnancy outcomes, biochemical markers and pre-pregnancy body mass index.

Objective:We examined the relationships between pre-pregnancy maternal body mass index (BMI), pregnancy outcomes and biochemical markers.Design:This study was conducted as a cross-sectional analysis.Subjects:Korean women in their second and third trimesters of pregnancy were recruited at two hospitals in the metropolitan Seoul area. Pre-pregnancy BMI was categorized in four groups according to the Asia-Pacific standard.Measurements:Fasting blood samples were obtained and analyzed for serum levels of homocysteine, folate and high-sensitivity C-reactive protein (hs-CRP). Concentrations of fetal fibronectin were assessed in the cervix and vagina, and cervical length was measured.Results:Obese subjects had a lower education level and a lower income level than subjects of normal weight. The level of maternal stress was positively associated with pre-pregnancy BMI. Normal weight subjects were more likely to eat breakfast and consume meals of appropriate size than the rest of our sample. In overweight and obese subjects, weight gain during pregnancy was significantly lower than in the underweight and normal subjects. High pre-pregnancy maternal BMI increased the risks of preterm delivery (odds ratio (OR)=2.85, confidence interval (CI)=1.20–6.74), low-birth-weight (LBW) infants (overweight subjects: OR=5.07, CI=1.76–14.63; obese subjects: OR=4.49, CI=1.54–13.13) and macrosomia. In obese subjects, the average serum folate level was significantly lower than in the underweight subjects. In obese subjects, the average serum hs-CRP level was significantly higher than in the rest of our sample.Conclusion:Pregnancy outcomes are influenced by pre-pregnancy BMI. These findings suggest that women can minimize their risks of preterm delivery, LBW and macrosomia by maintaining normal pre-pregnancy BMI.

Iron status and its association with pregnancy outcome in Korean pregnant women

Objective:The purpose of this study was to assess the prevalence of iron deficiency anemia among Korean pregnant women and to assess the association between maternal hemoglobin (Hb) level and pregnancy outcome.Design:A longitudinal study.Setting:Ewha Womans University Hospital, Seoul, Korea.Subjects:A total of 248 normal pregnant women of 24–28 weeks gestation and 190 babies born to the pregnant subjects.Methods:Maternal anthropometry, blood parameters and pregnancy outcomes were measured.Results:Mean Hb, serum iron concentration, transferrin saturation and total iron binding capacity of the subjects were 11.4 g/dl, 89.4 μg/dl, 18.7% and 484.6 μg/dl, respectively, and 30.2% of the subjects were anemic judged by Hb concentration of <10.5g/dl. When subjects were classified into tertile groups based on Hb levels, the lowest tertile (HbT1) group had significantly lower concentrations of cord serum iron and albumin than those in the highest tertile (HbT3) group. Newborn infants from the HbT1 group had significantly higher rates of preterm delivery, low birth weight and low Apgar scores than those in other groups. Logistic regression analysis showed that maternal serum albumin and Hb level were the most important predictive variables for low birth weight.Conclusions:A substantial proportion of Korean pregnant women were at risk of anemia. Infants born to women with a low Hb level showed a lower birth weight, height and Apgar scores.Sponsorship:This study was supported by a grant from the Korea Health 21 R&D project, Ministry of Health and Welfare, Republic of Korea (no. 01-PJ1-PG1-01CH15-0009).

A Computerized In-Hospital Alert System for Thrombolysis in Acute Stroke

Background and Purpose— An effective stroke code system that can expedite rapid thrombolytic treatment requires effective notification/communication and an organized team approach. We developed a stroke code program based on the computerized physician order entry (CPOE) system and investigated whether implementation of this CPOE-based program is useful for reducing the time from arrival at emergency departments (ED) to evaluation steps and the initiation of thrombolytic treatment in various hospital settings. Methods— The CPOE-based program was implemented by 10 hospitals. Time intervals from arrival at the ED to blood tests, computed tomography scanning, and thrombolytic treatment during the 1-year period before and the 1-year period after the program implementation were compared. Results— Time intervals from ED arrival to evaluation steps were significantly reduced after implementation of the CPOE-based program. Times from ED arrival to CT scan, complete blood counts, and prothrombin time testing were reduced by 7.7 minutes, 5.6 minutes, and 26.8 minutes, respectively (P<0.001). The time from ED arrival to intravenous thrombolysis was reduced from 71.7±33.6 minutes to 56.6±26.9 minutes (P<0.001). The number of patients who were treated with thrombolysis increased from 3.4% (199/5798 patients) before the CPOE-based program to 5.8% (312/5405 patients) afterward (P<0.001). The CPOE implementation also improved the inverse relationship between onset-to-door time and door-to-needle time. Conclusions— The CPOE-based stroke code could be successfully implemented to reduce in-hospital time delay in thrombolytic therapy in various hospital settings. CPOE may be used as an efficient tool to facilitate in-hospital notification/communication and an organized team approach.

Effects of the interaction between the C677T 5,10-methylenetetrahydrofolate reductase polymorphism and serum B vitamins on homocysteine levels in pregnant women

Objective: The purpose of this study was to investigate the effect of the interaction between the C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes and serum levels of B vitamins on serum homocysteine levels in pregnant women.Design: A cross-sectional study.Setting: Ewha Womans University Hospital, Seoul, Korea.Subjects: A total of 177 normal pregnant women, 24.6±1.1 weeks of gestation, in a 6-month period during 2001–2002.Interventions: Serum vitamin B2, vitamin B6, and homocysteine analyses were conducted using high-performance liquid chromatography methods. Serum folate and vitamin B12 concentrations were determined using a radioimmunoassay kit. MTHFR gene mutation was investigated by the polymerase chain reaction of a genomic DNA fragment.Results: Serum homocysteine was higher in women with the T/T genotype than those with the C/T or C/C genotype of the MTHFR gene (P<0.05). Serum homocysteine was negatively correlated with serum folate in all MTHFR genotypes (P<0.001), and the correlation between the two serum levels was the strongest in the T/T genotype. Serum homocysteine was higher in the subjects with the T/T MTHFR genotype only when the serum folate was below the median level. Explanatory power of B vitamin status as predictors of serum homocysteine levels was more pronounced in the T/T genotypes (68.5%) compared with the C/T (37.9%) or C/C genotypes (20.6%).Conclusions: Serum homocysteine levels in pregnant women varied significantly with MTHFR genotype and the serum B vitamin status. Higher serum folate, vitamin B2, and vitamin B12 concentrations may lessen the MTHFR genotypic effect on serum homocysteine levels.Sponsorship: This study was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (01-PJ1-PG1-01CH15-0009).

Long-term changes in gut hormones, appetite and food intake 1 year after subtotal gastrectomy with normal body weight

Background/Objectives:No prospective study on the long-term effects of gastric resection on gastrointestinal hormonal changes in patients with normal body weight has been reported. The aim of this study was to evaluate the 1-year effect of subtotal gastrectomy on ghrelin and peptide YY (PYY)3−36 levels.Subjects/Methods:Eighteen patients with early gastric cancer underwent subtotal gastrectomy with Billroth I reconstruction. We assessed appetite, food intake, body composition, and ghrelin and PYY3–36 levels preoperatively and 1 year after surgery.Results:There were no significant difference in the preoperative daily food intake and 1 year after subtotal gastrectomy. Weight loss occurred in all study subjects; 11.7% (n=2), 55.5% (n=10) and 33.3% (n=6) of the patients lost <5%, 5–10% and >10% of their preoperative body weight, respectively. Body mass index, waist circumference and body fat significantly decreased 1 year after subtotal gastrectomy. There were no significant differences in the appetite visual analogue scale preoperatively and 1 year after subtotal gastrectomy. The plasma ghrelin concentration decreased significantly (P=0.006), whereas PYY3−36 did not show a significant change 1 year after subtotal gastrectomy.Conclusions:Ghrelin levels and body fat decreased significantly, whereas PYY3−36 levels as well as appetite and food intake did not change significantly 1 year after subtotal gastrectomy with normal body weight. These findings suggest that decreased ghrelin might contribute directly to reduced body fat.

Coronary heart disease risk assessment and characterization of coronary artery disease using coronary CT angiography: comparison of asymptomatic and symptomatic groups

AIM To evaluate the prevalence of coronary artery disease (CAD) in relation to risk of coronary heart disease (CHD) and assess plaque characteristics from coronary computed tomography (CT) angiography in asymptomatic and symptomatic patients. MATERIALS AND METHODS Three hundred and ninety consecutive patients [asymptomatic group, n=138; symptomatic group (atypical or non-anginal chest pain), n=252] were retrospectively enrolled. They were subsequently classified into three CHD risk categories, based on the National Cholesterol Education Program guidelines, and 10 year risks of coronary events were calculated using Framingham risk score. CT was evaluated for stenosis, plaque composition, and coronary calcium scores. RESULTS CAD was observed in 42% of the asymptomatic group and 62% of the symptomatic group. In the former, the prevalence of CAD in low-, moderate- and high-risk subgroups was 21.4, 47.4 and 65%, respectively, and was 33.3, 74.4, and 72.4% in the symptomatic group. Framingham 10-year risks of coronary events were significantly higher in patients with CAD than in normal participants, and receiver operating characteristics curves showed that discriminatory power was poor in the asymptomatic group and symptomatic men, and good in symptomatic women. Of the participants in the asymptomatic group, 12% exhibited only non-calcified plaques and of the symptomatic group, 7% exhibited only non-calcified plaques. The coronary calcium score was significantly higher for significant stenosis than for non-significant stenosis in both groups. CONCLUSIONS The prevalence of CAD was not negligible even in subgroups with low-to-moderate CHD risk. Additionally, the Framingham risk score was effective for predicting CAD only in symptomatic women. Coronary calcium scores correlated with significant stenosis; however, a sizeable percentage of both groups had only non-calcified plaques.

Low Plasma Proportion of Omega 3-Polyunsaturated Fatty Acids Predicts Poor Outcome in Acute Non-Cardiogenic Ischemic Stroke Patients

Background and Purpose Alterations in blood fatty acid (FA) composition are associated with cardiovascular diseases. We investigated whether plasma FA composition was related to stroke severity and functional outcome in acute ischemic stroke patients. Methods We prospectively enrolled 156 patients with first-episode cerebral infarction, within 7 days of symptom onset. The proportion of FAs was analyzed using gas chromatography, and the summation of the omega-3 polyunsaturated fatty acids (ω3-PUFA), 18:3 ω3 α-linolenic acid, 20:3 ω3 eicosatrienoic acid, 20:5 ω3 eicosapentaenoic acid (EPA), and 22:6 ω3 docosahexaenoic acid (DHA) was reported as Σω3-PUFAs. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score on admission. Poor functional outcome was defined by modified Rankin scale (mRS) ≥3 at three months after the index stroke. Results Lower proportions of EPA (β=-0.751), DHA (β=-0.610), and Σω3-PUFAs (β=-0.462) were independently associated with higher NIHSS score, after adjusting for stroke subtype, hemoglobin, high density lipoprotein, high sensitivity C-reactive protein, fasting glucose, 16:0 palmitic acid, and Σsaturated fatty acids. Moreover, a lower proportion of DHA (odds ratio [OR]: 0.20, 95% confidence interval [CI]: 0.04-0.88), and Σω3-PUFAs (OR: 0.22, 95% CI: 0.05-0.84) showed an independent relationship with poor functional outcome after adjusting for age, sex, smoking status, NIHSS score, stroke subtype, and 16:0 palmitic acid. Conclusions Our results demonstrate that ω3-PUFAs correlated with stroke severity on admission and functional outcomes at 3 months. ω3-PUFAs are potential blood biomarkers for prognosis of acute non-cardiogenic ischemic stroke patients.

Moderate-to-severe obstructive sleep apnea is associated with cerebral small vessel disease

BACKGROUND Cerebral small vessel disease (SVD) is associated with increased risk of cerebral infarction and hemorrhage. Obstructive sleep apnea (OSA) is known to increase the risk of cerebrovascular disease. This study aimed to investigate the association between cerebral SVD and severity of OSA. METHODS A total of 170 patients were included from the patient registry at the present Sleep Center; these patients underwent both magnetic resonance imaging (MRI) of the brain and polysomnography (PSG) for suspected OSA. The presence and burden of white matter hyperintensities (WMHs), asymptomatic lacunar infarctions (ALIs), cerebral microbleeds (CMBs), and perivascular spaces (PVSs) were determined by MRI, and their relationships with the apnea-hypopnea index (AHI), as determined by PSG, were investigated. RESULTS Among the 170 patients, 25 (14.7%) had high-grade WMHs, 21 (12.4%) had ALIs, 21 (12.4%) had CMBs, and 34 (20.0%) had high-grade PVSs. In the multivariable analysis, after adjusting for factors including age, sex, and other variables for which p <0.1 in univariable analysis (hypertension, diabetes mellitus, previous stroke, minimal SaO2 and arousal index), moderate-to-severe OSA was associated with high-grade WMHs (odds ratio [OR] 4.72; 95% confidence interval [CI] 1.14-19.47), CMBs (OR 3.47; 95% CI 0.89-15.18), or high-grade PVSs (OR 3.64; 95% CI 1.02-13.01), but not with ALIs. The total SVD score was independently associated with increased AHI (p = 0.017), particularly in patients with moderate-to-severe OSA (β [standard error] = 0.448 (0.204), p = 0.030]. CONCLUSION Moderate-to-severe OSA is positively associated with multiple indicators of cerebral SVD, including WMHs, CMBs, and PVSs.

Rivaroxaban vs Warfarin Sodium in the Ultra-Early Period After Atrial Fibrillation–Related Mild Ischemic Stroke: A Randomized Clinical Trial

Importance In atrial fibrillation (AF)–related acute ischemic stroke, the optimal oral anticoagulation strategy remains unclear. Objective To test whether rivaroxaban or warfarin sodium is safer and more effective for preventing early recurrent stroke in patients with AF-related acute ischemic stroke. Design, Setting, and Participants A randomized, multicenter, open-label, blinded end point evaluation, comparative phase 2 trial was conducted from April 28, 2014, to December 7, 2015, at 14 academic medical centers in South Korea among patients with mild AF-related stroke within the previous 5 days who were deemed suitable for early anticoagulation. Analysis was performed on a modified intent-to-treat basis. Interventions Participants were randomized 1:1 to receive rivaroxaban, 10 mg/d for 5 days followed by 15 or 20 mg/d, or warfarin with a target international normalized ratio of 2.0-3.0, for 4 weeks. Main Outcomes and Measures The primary end point was the composite of new ischemic lesion or new intracranial hemorrhage seen on results of magnetic resonance imaging at 4 weeks. Primary analysis was performed in patients who received at least 1 dose of study medications and completed follow-up magnetic resonance imaging. Key secondary end points were individual components of the primary end point and hospitalization length. Results Of 195 patients randomized, 183 individuals (76 women and 107 men; mean [SD] age, 70.4 [10.4] years) completed magnetic resonance imaging follow-up and were included in the primary end point analysis. The rivaroxaban group (n = 95) and warfarin group (n = 88) showed no differences in the primary end point (47 [49.5%] vs 48 [54.5%]; relative risk, 0.91; 95% CI, 0.69-1.20; P = .49) or its individual components (new ischemic lesion: 28 [29.5%] vs 31 of 87 [35.6%]; relative risk, 0.83; 95% CI, 0.54-1.26; P = .38; new intracranial hemorrhage: 30 [31.6%] vs 25 of 87 [28.7%]; relative risk, 1.10; 95% CI, 0.70-1.71; P = .68). Each group had 1 clinical ischemic stroke, and all new intracranial hemorrhages were asymptomatic hemorrhagic transformations. Hospitalization length was reduced with rivaroxaban compared with warfarin (median, 4.0 days [interquartile range, 2.0-6.0 days] vs 6.0 days [interquartile range, 4.0-8.0]; P < .001). Conclusions and Relevance In mild AF-related acute ischemic stroke, rivaroxaban and warfarin had comparable safety and efficacy. Trial Registration clinicaltrials.gov Identifier: NCT02042534