Relationship of maternal grain intake and serum triglyceride levels with infant birth weight: Mothers and Children's Environmental Health (MOCEH) study.

BACKGROUND/OBJECTIVES: Maternal serum triglyceride (TG) level is known to be associated with neonatal birth weight. Although Koreans traditionally consume relatively high amounts of grain and grain products, mainly in the form of white rice, and the consumption is positively associated with serum TG levels, no study has investigated the relationship between dietary grain intake, serum TG levels and neonatal birth weight in pregnant women. This study was conducted to identify the association between infant birth weight and maternal intake of grain, as well as serum TG levels. SUBJECTS/METHODS: Subjects were 1011 pregnant women at 12-28 weeks' gestational age and their offspring. Maternal serum TG levels, dietary intake and infant birth weight were measured. RESULTS: Serum TG levels were positively related to neonatal birth weight both at mid-pregnancy (P=0.0015) and at late pregnancy (P<0.0001). Such an association only existed in subjects with the highest tertile of grain intake at mid-pregnancy (P=0.0055) but was observed in all tertiles at late pregnancy (1st P=0.0186, 2nd P=0.0146, 3rd P=0.0099). CONCLUSIONS: The relationship between maternal TG levels and infant birth weight may depend on dietary grain intake and stages of pregnancy in Korean pregnant women.

Relationship between body-mass index and serum folate concentrations in pregnant women.

The concentration of micronutrients impacts fetal development and pregnancy outcome and has been suggested to be negatively correlated with the body-mass index (BMI). We evaluated the relationship between BMI and the serum folate concentration in 802 and 660 Korean pregnant women in mid- and late pregnancy, respectively, who participated in a multicenter prospective study. There was a significant negative correlation between BMI value and the serum folate concentration at mid- and late pregnancy (P for trend 0.001 and 0.024, respectively). A general linear model confirmed this correlation at both time points after adjusting for gestational age and total folate intake. These findings are important as the serum folate concentration is a rate-limiting factor for placental folate transport to the fetus, and an inadequate folate supply may cause various malformations.

Fruit and vegetable intake influences the association between exposure to polycyclic aromatic hydrocarbons and a marker of oxidative stress in pregnant women.

BACKGROUND/OBJECTIVES: Exposure to polycyclic aromatic hydrocarbons (PAHs) during pregnancy is known to increase oxidative stress, which may influence pregnancy outcomes and health of the child. SUBJECTS/METHODS: This study investigated whether fruit and vegetable intake modifies the relationship between exposure to PAHs and oxidative stress status during pregnancy. Urinary levels of 2-naphthol and 1-hydroxypyrene (biomarkers of exposure to PAHs), and malondialdehyde (MDA; a biomarker of oxidative stress) were analyzed in 715 pregnant women at 12-28 weeks of gestation. The dietary antioxidant intake during pregnancy was estimated using the 24-h recall method. Urinary 2-naphthol, 1-hydroxypyrene and MDA levels were analyzed by high-performance liquid chromatography-fluorescence detection. RESULTS: The urinary MDA level was positively correlated with the 2-naphthol level (r=0.255, P<0.001) and 1-hydroxypyrene level (r=0.240, P<0.001). Multiple regression analysis after adjustment for covariates revealed that the urinary 1-hydroxypyrene level was positively associated with the MDA level; these positive associations only existed in pregnant women, with either the fruit and vegetable intake or the vitamin C intake in the first tertile (<390.1 g/day) or in the first and second tertiles (<141.5 mg/day), respectively. CONCLUSIONS: These results suggest that an adequate maternal intake of fruit, vegetables and vitamin C is beneficial to the defense against the oxidative stress associated with exposure to PAHs in pregnant women.

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.

Association of maternal folate nutrition and serum C-reactive protein concentrations with gestational age at delivery.

BACKGROUND/OBJECTIVES: C-reactive protein (CRP) is the most extensively studied inflammatory risk marker, and elevated serum CRP concentrations in pregnant women are known to be associated with subsequent development of preeclampsia and preterm delivery. Researchers have suggested that folate intake may help to control the inflammation process. We examined whether folate nutrition modifies the relationship between serum CRP concentration and gestational age at delivery. SUBJECTS/METHODS: Serum CRP concentrations were analyzed in 815 pregnant women between 12 and 28 weeks of gestation. Dietary intakes were assessed using a 24-h dietary recall. The serum folate and high-sensitivity CRP concentrations were analyzed by radioassay and latex agglutination tests, respectively. RESULTS: Serum CRP concentration was negatively correlated (P < 0.001) with gestational age at delivery. Serum folate concentration was negatively correlated (P < 0.01) with serum CRP concentration, and total dietary folate intake was positively correlated (P < 0.001) with serum folate concentration. Multiple regression analysis after adjustment for covariates revealed that maternal CRP concentrations were negatively associated with gestational age at delivery; these negative associations existed only when folate intake during pregnancy was below the Korean estimated average requirements (520 µg dietary folate equivalent per day), and serum folate concentrations were above the normal (6 ng/ml). CONCLUSIONS: We found that adequate maternal folate intake during pregnancy may have a beneficial role against shorter gestational age at delivery, which is associated with higher serum CRP concentrations in pregnant women.

Effect of postnatal catch-up growth on blood pressure in children at 3 years of age.

Size at birth and early postnatal growth rates appear to be important determinants of cardiovascular diseases. We examined whether intrauterine growth restriction or the subsequent catch-up postnatal weight gain leads to higher blood pressure in early life to confirm that size at birth and early postnatal growth rates appear to be important determinants of blood pressure changes in early life. Of 407 children born between December 2001 and November 2002 in hospital based-birth cohorts, 102 were followed up at 3 years of age (24.2%) at Ewha Womans University Hospital in Seoul, Korea. At 3 years of age, those who had a low birth weight still belonged in the lower-weight group than the others. The subjects' systolic blood pressure was correlated with their current weight (r=0.41) and weight gain (r=0.39), but not with their birth weight. Those with a higher current weight and higher weight gain based on birth weight (conditional weight gain) had the highest blood pressure. Systolic blood pressure increased by 0.2 mm Hg for every 100-g increase in weight at 3 years and, independently, by 1.5 mm Hg for every 100-unit increase in conditional weight gain. This study suggests that birth weight is not directly associated with blood pressure, but accelerated growth, which occurs mostly in those born with a low birth weight, seems to affect blood pressure in early life.

Reduced L-arginine level and decreased placental eNOS activity in preeclampsia.

Nitric oxide is produced enzymatically by the nitric oxide synthase (NOS), which converts L-arginine in the presence of oxygen to L-citrulline and NO. Moreover, it has been reported that asymmetric dimethylarginine (ADMA) acts as is an endogenous inhibitor of endothelial NOS (eNOS) by competing with the enzyme for L-arginine. In this study, we measured L-arginine and ADMA in normal and preeclamptic women, and also investigated the association between the Glu298Asp eNOS gene polymorphism and preeclampsia. Finally, we assessed eNOS expression levels in the placentas of both normal and preeclamptic patients, using Western blot and immunohistochemistry. L-arginine levels were found to be significantly lower in the preeclamptic women than in the normal pregnant women (p=0.02) but there were no significant differences in ADMA levels between the normal and preeclamptic women. We also determined there to be no association between the Glu298Asp eNOS gene and preeclampsia. With regard to placental eNOS expression, we detected a lower degree of eNOS expression in the preeclamptic syncytiotrophoblasts than in the normal syncytiotrophoblasts. We suggest that reduced L-arginine levels, rather than increased ADMA levels, contribute to the development of preeclampsia, and also that decreased placental eNOS expression constitutes a characteristic finding in preeclamptic placentas.

Serum cytokine profiles in patients with Plasmodium vivax malaria: a comparison between those who presented with and without thrombocytopenia.

One of the peculiar features of Plasmodium vivax malaria in South Korea is the surprisingly high frequency of thrombocytopenia. The mechanism by which this malaria-related thrombocytopenia develops and its role in the pathology and progress of human infection with P. vivax have not yet been completely understood. In the present study, the serum cytokine profiles of cases of P. vivax malaria who presented with thrombocytopenia were compared with those of similar cases who did not have thrombocytopenia at presentation. The subjects were the 94 consecutive cases of P. vivax malaria who presented at five hospitals in South Korea (all near the Demilitarized Zone) between May 2000 and October 2002, 47 of whom had thrombocytopenia at presentation. When mean values and (S.E.) were compared, the thrombocytopenic patients were found not only to be generally older than the non-thrombocytopenic [25.3 (1.1) v. 21.3 (0.18) years; P < 0.001] but also to have presented with higher serum concentrations of aspartate aminotransferase [77.6 (16.6) v. 32.3 (7.4) U/litre; P < 0.0001], alanine aminotransferase [96.7 (19.0) v. 44.7 (12.0) U/litre; P = 0.0001], interleukin-1 [49.9 (7.4) v. 23.7 (5.1) pg/ml; P < 0.001], interleukin-6 [174.9 (26.4) v. 57.3 (14.6) pg/ml; P = 0.001], interleukin-10 [308.2 (39.6) v. 137.9 (23.1) pg/ml; P < 0.002] and transforming growth factor-beta [1134.3 (387.5) v. 416.6 (183.8) pg/ml; P < 0.0001], and higher levels of parasitaemia [4345.7 (966.6) v. 1443.8 (222.7) parasites/microl; P = 0.03). The non-thrombocytopenic patients, however, had relatively high total leucocyte counts [5.8 (0.24) v. 5.4 (0.66) leucocytes/nl; P = 0.03]. The thrombocytopenia associated with P. vivax malaria in South Korea therefore appears to be associated with elevated serum concentrations of both pro- and anti-inflammatory cytokines. To define the role of each cytokine in the development of thrombocytopenia during the course of acute P. vivax malaria, further prospective studies are needed.

Exposure to air pollution during different gestational phases contributes to risks of low birth weight.

BACKGROUND: Although there have been growing concerns about the adverse effects of air pollution on birth outcomes, little is known about which specific exposure times of specific pollutants contribute to low birth weight (LBW). METHODS: We evaluated the relationships between LBW and air pollution exposure levels in Seoul, Korea. Using the air pollution data, we estimated the exposure during each trimester and also during each month of pregnancy on the basis of the gestational age and birth date of each newborn. Generalized additive logistic regression analyses were conducted considering infant sex, birth order, maternal age, parental education level, time trend, and gestational age. RESULTS: The monthly analyses suggested that the risks for LBW tended to increase with carbon monoxide (CO) exposure between months 2-5 of pregnancy, with exposure to particles <10 micro m (PM(10)) in months 2 and 4, and for sulphur dioxide (SO(2)) and nitrogen dioxide (NO(2)) exposure between months 3-5. CONCLUSIONS: This study suggests that exposure to CO, PM(10,) SO(2) and NO(2) during early to mid pregnancy contribute to risks for LBW.

Is air pollution a risk factor for low birth weight in Seoul?

Environmental factors contributing to reduced birth weight are of great concern because of the well-known relation of birth weight to infant mortality and adverse effects in later life. We examined the associations between air pollution exposures during pregnancy and low birth weight among all full-term births (gestational age 37-44 weeks) for a 2-year period (January 1996 through December 1997) in Seoul, South Korea. We evaluated these associations with a generalized additive logistic regression adjusting for gestational age, maternal age, parental educational level, parity, and infant sex. We used smoothing plots with generalized additive models to analyze the exposure-response relation for each air pollutant. The adjusted relative risk of low birth weight was 1.08 [95% confidence interval (CI) = 1.04-1.12] for each interquartile increase for carbon monoxide concentrations during the first trimester of pregnancy. The relative risks were 1.07 (95% CI = 1.03-1.11) for nitrogen dioxide, 1.06 (95% CI = 1.02-1.10) for sulfur dioxide, and 1.04 (95% CI = 1.00-1.08) for total suspended particles also for interquartile increase in exposure. Carbon monoxide, nitrogen dioxide, sulfur dioxide, and total suspended particle concentrations in the first trimester of pregnancy period are risk factors for low birth weight.

Influence of genetic susceptibility on the urinary excretion of 8-hydroxydeoxyguanosine of firefighters.

OBJECTIVES: Oxidative DNA damage has been implicated in carcinogenesis. The DNA damage can be assessed from the urinary excretion of the DNA-repair product 8-hydroxydeoxyguanosine (8-OH-dG). The factors were investigated that influenced the excretion of urinary 8-OH-dG in 78 firefighters. METHODS: 53 Out of 78 firefighters were exposed to fire within 5 days of the study and 25 were not. 8-OH-dG was measured by ELISA and the distribution of the genotypes of CYP1A1, CYP2E1, GSTM1, and GSTT1 was measured by polymerase chain reaction. RESULTS: The homozygous wild type frequencies of CYP1A1 MspI, CYP1A1 ile-val, CYP2E1, GSTM1, and GSTT1 were 31.5%, 56.2%, 60.3%, 50.7%, and 53.4%, respectively. The geometric mean of urinary 8-OH-dG was 14.1 ng/mg creatinine in more active firefighters and 12.3 ng/mg creatinine in non-exposed and less active subjects. Significantly increased concentrations of urinary 8-OH-dG were found to be associated with cigarette smoking, and 14% of the variation of 8-OH-dG was explained by cigarettes smoked per day. The CYP1A1 MspI, CYP1A1 ile-val, GSTM1, and GSTT1 genetic polymorphisms were not found to be significantly associated with the urinary excretion of 8-OH-dG. However, the subjects carrying the CYP2E1 mutant type excreted higher concentrations of 8-OH-dG and there was a marginally significant interaction of GSTT1 with firefighting activity. Multiple regression analysis confirmed that smoking was the strongest predictor of excretion of 8-OH-dG. Age, body mass index, and firefighting activity were not significant predictive factors for urinary 8-OH-dG. CONCLUSION: Smoking and CYP2E1 gene polymorphism may be important factors in carcinogenesis and the GSTT1 positive genotype may be a genetic susceptibility factor in firefighters who are exposed regularly to various chemical carcinogens.

PM(10) exposure, gaseous pollutants, and daily mortality in Inchon, South Korea.

To evaluate the relative importance of various measures of particulate and gaseous air pollution as predictors of daily mortality in Inchon, South Korea, the association between total daily mortality and air pollution was investigated for a 20-month period (January 1995 through August 1996). Poisson regression was used to regress daily death counts on each air pollutant, controlling for time trends, season, and meteorologic influences such as temperature and relative humidity. Regression coefficients of a 5-day moving average of particulate matter less than or = to 10 microm in aerodynamic diameter (PM(10)) on total mortality were positively significant when considered separately and simultaneously with other pollutants in the model. PM(10) remained significant when the models were confined to cardiovascular or respiratory mortality. Sulfur dioxide (SO(2)) and carbon monoxide (CO) were significantly related to respiratory mortality in the single-pollutant model. Ozone exposure was not statistically significant with regard to mortality in the above models, and graphic analysis showed that the relationship was nonlinear. A combined index of PM(10), nitrogen dioxide, SO(2), and CO seemed to better explain the exposure-response relationship with total mortality than an individual air pollutant. Pollutants should be considered together in the risk assessment of air pollution, as opposed to measuring the risk of individual pollutants.

Air pollution and daily mortality in Inchon, Korea.

The association between total daily mortality and air pollution was investigated for a 1-year period (January 1995 to December 1995) in Inchon, Korea. The purpose of this study was to evaluate the relative importance of particulate and gaseous air pollution as predictors of daily mortality. Concentration of total suspended particulates (TSP), inhalable particles (PM10), and gaseous pollutants, such as sulfur dioxide, nitrogen dioxide, ozone, carbon monoxide, were measured daily during the study period. A generalized additive model was used to regress daily death counts on each air pollutant, controlling for time trend and meteorologic influences such as temperature or relative humidity. Total mortality was found to increase 1.2% (95% CI: 0.2 to 2.2%) for each 10 microg/m3 increase in 6-day moving average of TSP, and 1.2% (95% CI 0.2 to 2.1%) for each 10 microg/m3 increase in 5-day moving average of PM10. The association is similar in magnitude to associations between particulate air pollution and mortality found in several other communities in America and Europe. Associations with gaseous pollutants were all statistically insignificant in the generalized additive model. The relative risk of death increased at particulate levels that were well below the current Korean Ambient Air Quality Standard.

Determinants of pharmacologic treatment failure in panic disorder.

BACKGROUND: We systematically assessed reasons for failure of pharmacologic treatment for panic disorder in patients referred to a specialty anxiety and mood disorders clinic and examined possible determinants of treatment-resistant panic disorder. METHOD: Interview data were obtained from 106 patients with DSM-III-R panic disorder seen in consultation. Data for each of 252 past medication trials included dose, duration of treatment, side effects, outcome, and reason for discontinuation. T tests and chi-square analyses were used to compare demographic and clinical characteristics of patients failing versus responding to adequate trials and those with and without intolerable medication side effects. RESULTS: Of 252 medication trials, 190 used effective antipanic medications, and only 59 (23%) were adequate in dose and duration. The most common reason for treatment failure was intolerable side effects, occurring in 51 (27%) of 190 trials using effective antipanic medications. Patients discontinuing treatment due to adverse effects had higher Hamilton Rating Scale for Anxiety scores and were less likely to have a history of substance abuse. Discontinuation due to side effects was significantly more common with tricyclic antidepressants than with benzodiazepines. True treatment resistance was reported in 14 (24%) of 59 adequate medication trials. Treatment-resistant patients were younger and had a higher lifetime rate of major depression. CONCLUSION: Although use of ineffective medications or inadequate trials were important factors, the most common reason for treatment failure was side effects, especially with tricyclic antidepressants. True treatment resistance was less common, since few medication trials were adequate in dose and duration, and may be associated with comorbidity.

Application of PCR from the fine needle aspirates for the diagnosis of cervical tuberculous lymphadenitis.

Tuberculosis remains a major public health problem worldwide. A definitive and accurate diagnosis of tuberculosis in cervical lymphadenopathy is important because satisfactory results can be achieved with chemotherapy alone, obviating surgery. Recently, fine needle aspiration cytology (FNAC) has provided an alternative and easy procedure for collection of material for cytomorphologic and bacteriologic examination. But the detection rate for M. tuberculosis from the aspirate material is still low with Ziehl-Neelson stain and even with culture. The authors therefore performed polymerase chain reaction (PCR) for mycobacterial DNA sequences in 31 cases of cytodiagnosis of tuberculous lymphadenitis and compared conventional bacteriologic methods. Ziehl-Neelson staining for acid-fast bacilli (AFB) was positive in 3 cases (10%) in direct smears, and the cultures for M. tuberculosis were positive in 6 cases (19%). In 19 (61%) among 31 samples, mycobacterial DNA fragments were detected, using the PCR method. With combined conventional and PCR method, the rate of detection was increased to 68 percent high. In conclusion, PCR is the most sensitive technique in the demonstration of M. tuberculosis in patient with clinically suspected as tuberculosis, who have AFB stain or culture negative cytology. Combined conventional and PCR methods as well as cytologic findings are of further help in the detection and characterization of M. tuberculosis.