• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.26 no.3
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• pp.135-145
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• 2023

Antibiotics are frequently administered during pregnancy. Although necessary to address acute infections, their use facilitates antibiotic resistance. Other associations have also been found with the use of antibiotics, such as perturbations of gut bacteria, delays in microbial maturation, and increased risks of allergic and inflammatory diseases. Little is known about how the prenatal and perinatal administration of antibiotics to mothers affects the clinical outcomes of their offspring. A literature search was conducted of the Cochrane, Embase, and PubMed engines. The retrieved articles were reviewed by two authors and verified for relevance. The primary outcome was the effect of pre- and perinatal maternal antibiotic use on clinical outcomes. Thirty-one relevant studies were included in the meta-analysis. Various aspects are discussed, including infections, allergies, obesity, and psychosocial factors. In animal studies, antibiotic intake during pregnancy has been suggested to cause long-term alterations in immune regulation. In humans, associations have been found between antibiotic intake during pregnancy and different types of infections and an increased risk of pediatric infection-related hospitalization. A dose-dependent positive association between pre- and perinatal antibiotic use and asthma severity has been reported in animal and human studies, while positive associations with atopic dermatitis and eczema were reported by human studies. Multiple associations were identified between antibiotic intake and psychological problems in animal studies; however, relevant data from human studies are limited. However, one study reported a positive association with autism spectrum disorders. Multiple animal and human studies reported a positive association between pre- and perinatal antibiotic use by mothers and diseases in their offspring. Our findings have potentially significant clinical relevance, particularly considering the implications for health during infancy and later in life as well as the related economic burden.

• Clinical and Experimental Pediatrics
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• v.56 no.9
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• pp.369-376
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• 2013

A complex interplay between genetic and environmental factors partially contributes to the development of allergic diseases by affecting development during prenatal and early life. To explain the dramatic increase in the prevalence of allergic diseases, the hygiene hypothesis proposed that early exposure to infection prevented allergic diseases. The hygiene hypothesis has changed to the microbial hypothesis, in which exposure to microbes is closely linked to the development of the early immune system and allergic diseases. The intestinal flora may contribute to allergic disease through its substantial effect on mucosal immunity. Based on findings that exposure to microbial flora early in life can change the Th1/Th2 balance, thus favoring a Th1 cell response, probiotics may be beneficial in preventing allergic diseases. However, evidence from clinical and basic research to prove the efficacy of probiotics in preventing allergy is lacking. To date, studies have yielded inconsistent findings on the usefulness of probiotics in allergic diseases. It is difficult to demonstrate an exact effect of probiotics on asthma, allergic rhinitis, and food allergy because of study limitations, such as different first supplementation period, duration, different strains, short follow-up period, and host factors. However, many studies have demonstrated a significant clinical improvement in atopic dermatitis with the use of probiotics. An accurate understanding of the development of human immunity, intestinal barrier function, intestinal microbiota, and systemic immunity is required to comprehend the effects of probiotics on allergic diseases.

• Journal of Microbiology and Biotechnology
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• v.18 no.9
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• pp.1590-1598
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• 2008

Cell proliferation and differentiation are critical processes in a developing fetal rat brain, during which programmed cell death (PCD) also plays an important role. One of the decisive factors for PCD is Bcl-2 family proteins, where Bax induces cell death, whereas Bcl-2 acts as an inhibitor of PCD. As maternal drinking is known to cause fetal alcohol syndrome (FAS) or malformation of the fetal brain during pregnancy, the objective of the present study was to investigate whether maternal ethanol exposure alters the PCD-related Bax and Bcl-2 protein expression during fetal brain development. Pregnant female rats were orally treated with 10% ethanol and the subsequent expressions of the Bax and Bcl-2 proteins examined in the fetal brain, including the forebrain, midbrain, and hindbrain, from gestational day (GD) 15.5 to GD 19.5, using Western blots, in situ hybridization, and immunohistochemistry. With regard to the ratio of Bcl-2 to Bax proteins (Bcl-2/Bax), the Bax protein was dominant in the forebrain and midbrain of the control GD 15.5 fetuses, except for the hindbrain, when compared with the respective ethanol-treated groups. Moreover, Bcl-2 became dominant in the midbrain of the control GD 17.5 fetuses when compared with the ethanol-treated group, representing an alternation of the natural PCD process by ethanol. Furthermore, a differential expression of the Bcl-2 and Bax proteins was found in the differentiating and migrating zones of the cortex, hippocampus, thalamus, and cerebellum. Thus, when taken together, the present results suggest that ethanol affects PCD in the cell differentiation and migration zones of the prenatal rat brain by modulating Bax and Bcl-2 expression in an age- and area-dependent manner. Therefore, this is the first evidence that ethanol may alter FAS-associated embryonic brain development through the alteration of Bax and Bc1-2 expression.

• Korean Journal of Biological Psychiatry
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• v.17 no.3
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• pp.136-144
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• 2010

Objectives : The $2^{nd}$ to $4^{th}$ digit length(2D : 4D) ratio reflects the amount of exposure and sensitivity to the prenatal sex hormone and it is considered to be the most convenient and useful way to understand the influence of sex hormone in the determination of human behavioral traits. This study was carried out to find the correlation between the 2D : 4D ratio and characteristics of temperament and character in Korean university students. We assumed that 2D : 4D ratio would show a strong correlation with temperament which is defined to be an inclination of an automatical emotional response to a stimulus. Methods : Participants were 104 university students who completed 2 self-report measures : Temperament and Character Inventory(TCI), Temperament Test. We examined the 2D : 4D ratio of each subject by measuring the lengths of the $2^{nd}$ and $4^{th}$ fingers using a photocopy measurement. We performed statistical analyses using correlation test and t-test to examine the relationship between 2D : 4D ratio and psychological characteristics. Results : We found out the typical sex difference in 2D : 4D ratio. Women had significantly higher 2D : 4D ratio than men. TCI-Character factor(TCI-C) didn't show any significant correlation with the 2D : 4D ratio. TCI-Tempterament factor(TCI-T) and the item of Temperament Test showed a significant correlation with the 2D : 4D ratio. In correlation analysis of the total group including all women and men, the 2D : 4D ratio showed a significant positive correlation in a subscale(shyness with stranger) of harm avoidance scales in TCI-T. In correlation analysis of women's group, the 2D : 4D ratio showed a significant positive correlation in two subscales( fear of uncertainty) and[shyness to stranger] of harm avoidance scales in TCI-T. In correlation analysis of men's group, the 2D : 4D ratio showed a significant negative correlation with a sanguine temperament item of the Temperament Test. Conclusion : The results suggest that the amount of exposure to sex hormone in the prenatal period seems to have an impact on the determination of temperament and characteristics.

• Journal of Environmental Health Sciences
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• v.34 no.1
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• pp.12-19
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• 2008

We evaluated the relationship between birth weight and mercury exposure levels in Seoul, Korea, by following a cohort of pregnant women and the outcomes of their pregnancies between 2001-2005. Eighty-five pregnant women were recruited into this study after obtaining informed consent. Samples were collected at delivery from normal pregnant women who were living in the city of Seoul, Korea. Mercury concentrations in 85 sets of maternal and cord blood samples were measured using a gold-amalgam collection method. We used multiple regression analysis to analyze the effect of mercury exposure on birth weight. The mean levels of total mercury concentrations were 5.41(ppb) in maternal blood of pregnant women and 3.58(ppb) in umbilical cord blood. The mean concentration of umbilical cord blood mercury exposures was higher than the level recommended by WHO. There was a significant correlation between maternal and cord blood mercury concentrations. Mercury concentrations of umbilical cord blood was associated with birth weight. In addition, after adjusting for potential confounding factors, we found that mercury exposure may reduce the birth weight. This study suggests that exposure to mercury concentration during pregnancy contributes to the risk of low birth weight. Therefore, prenatal and environmental education for various and possible sources of mercury exposure might be necessary for the good health of babies. The finding of this study supports the construction of national policy for environmental health management.

• Toxicological Research
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• v.17 no.2
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• pp.115-121
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• 2001

Some of endocrine disruptors with sexual hormone-like effects have been increasingly reported to be immunotoxic in many species in recent several years. Phthalate esters have possible effects on the endocrine system. Prenatal exposure to di(n-butyl) phthalate (DBP) has been reported to impair the androgen-dependent development of the male reproductive tract in rat. Therefore, the immunomodulatory effect of DBP was investigated in the developing immune system of fetal and neonatal Sprague-Dawley rats. Timed-bred pregnant SD rats were given to the doses of 0, 250, 500, and 750 mg DBP/kg$\cdot$ body weight /day by gavage once a day from gestational day (GD) 5 to 18. On GD19 or GD22/postnatal day one (PD1), the dams were euthanized, and the changes in organ weights and thymus phenotypes were examined for their offsprings. At 750 mg DBP/kg$\cdot$b.w./day in maternal exposure group, GD19 fetuses showed decreases in body weight. The spleen/body weight ratios were reduced in GD 19 fetuses from the dams exposed to 500 and 750 mg DBP/kg$\cdot$b.w./day. There were no significant changes in thymus and spleen cellularities though these cellularities showed a tendency to decrease in a dose dependent way. In the DBP-exsposed GD22/PD1 offsprings, the body weights, the relative organ weights and the cellularities did not exhibit alteration. Additionally, the percentages of CD3$^{+}$(CD4$^{+}$CD8$^{+}$, CD4$^{+}$CD8$^{-}$, CD4$^{-}$CD8$^{+}$, and CD4$^{-}$CD8$^{-}$) and CD3$^{-}$(CD4$^{+}$CD8$^{+}$, CD4$^{+}$CD8$^{-}$, CD4$^{-}$CD8$^{+}$, and CD4$^{-}$CD8$^{-}$) thymocyte subsets were not changed in any DBP-treated group. The proliferative responses of splenic T cells to Con A and B cells to LPS were decreased in all DBP-exposed GD22/PD1 offsprings.

• Korean Journal of Biological Psychiatry
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• v.22 no.4
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• pp.205-215
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• 2015

Objectives Sex hormones exposure during the prenatal period has an effect on cerebral lateralization. Male brains are thought to be more lateralized than female brains. Bipolar disorder was known to show abnormalities in cerebral laterality whose characteristics could be estimated by electroencephalography (EEG) coherences. We studied sex-related differences of EEG coherences between healthy controls and patients with bipolar disorder to examine the sex effects in the genesis of bipolar disorder. Methods Participants were 25 patients with bipolar disorder (11 male, 14 female) and 46 healthy controls (23 male, 23 female). EEG was recorded in the eyes closed resting state. To examine dominant EEG coherence associated with sex differences in both groups within five frequency bands (delta, theta, alpha, beta, and gamma) across several brain regions, statistical analyses were performed using analysis of covariance. Results Though statistically meaningful results were not found, some remarkable findings were noted. Healthy control females showed more increased interhemispheric coherences than control males in gamma frequency band. There were no differences in the intrahemispheric coherences between the healthy control males and females. In patients with bipolar disorder, female dominant pattern in interhemispheric coherences was attenuated compared with healthy control. Conclusions Sex differences of EEG coherences, which could be a marker for cerebral laterality, were attenuated in patients with bipolar disorder compared with healthy controls. These results imply that abnormal sex hormone exposure during early development might play some role in the pathogenesis of bipolar disorder.

• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.67-74
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• 2009

Exposures to environmental chemicals that mimic endogenous hormones are proposed for a number of adverse health effects, including infertility, abnormal prenatal and childhood development and above all cancers. In addition, recently miRNA (micro RNA) has been recognized to play an important role in various diseases and in cellular and molecular responses to toxicants. In this study, endocrine disrupting environmental toxicant, nonylphenol (NP) was treated to MCF-7 (Human breast cancer cell) and HepG2 (Human hepatocellular liver carcinoma) cell line at 3 hrs and 48 hrs time point and miRNA analysis using $mirVana^{TM}$ miRNA bioarray was performed and compared with total mRNA microarray data for the same cell line and treatment. Robust data quality was achieved through the use of dye-swap. Analysis of microarray data identifies a total of 20 and 11 miRNA expressions at 3 hrs and 48 hrs exposure to NP in MCF-7 cell line and a total of 14 and 47 miRNA expression at 3 hrs and 48 hrs exposure respectively to NP in HepG2 cell line. Expression profiling of the selected miRNA (let-7c, miR-16, miR-195, miR-200b, miR200c, miR-205, and miR-589) reveals changes in the expression of target genes related to metabolism, immune response, apoptosis, and cell differentiation. The present study can be informative and helpful to understand the role of miRNA in molecular mechanism of chemical toxicity and their influence on hormone dependent disease. Also this study may prove to be a valuable tool for screening potential estrogen mimicking pollutants in the environment.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.3
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• pp.79-93
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• 2014

Objectives: This study was to establish safety and efficacy of using herbal medicine during pregnancy and to investigate patient's satisfaction. Methods: We investigated general pregnancy outcome, birth history, newborn infant's physical condition and patient's satisfaction. Survey respondents were 54 gynecological outpatients who visited Daejeon University Dunsan Oriental hospital from January 1, 2011 through February 28, 2013. Results: A total of fifty one cases maintained pregnancy and 3 cases had miscarriages. Forty seven cases delivered normally, 4 cases gave birth prematurely. There was no congenital malformation due to using herbal medicine and most of newborn babies had on the average weight and height and were healthy condition. The average score of patient's satisfaction was 3.44 point (Excellent=5). Conclusions: This study presents safety and efficacy of using herbal medicine during pregnancy.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.34 no.1
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• pp.37-44
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• 2023

Objectives: Tic disorders are highly heritable; however, growing evidence suggests that environmental factors play a significant role in their pathogenesis. Studies on these factors have been inconsistent, with conflicting results. Therefore, this study aimed to examine the associations of pre- and perinatal exposure to Tourette syndrome (TS) or chronic tic disorders (CTD) in Korean school-aged children. Methods: This case-control study used data from a large prospective cohort study. The primary outcome was TS/CTD diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria and Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version-Korean Version. Demographic, pre-, and perinatal information was obtained from the maternal questionnaires. Data between the TS/CTD and control groups were compared using the chi-squared or Student's t-test, as appropriate. Two-step logistic regression analyses were used to test the association between TS/CTD and pre- and perinatal risk factors. Results: We included of 223 children (78 with TS/CTD and 145 controls). Significant differences in the demographic data between the two groups were observed. The male sex ratio, mean parental age, parental final education level, and family history of tics were included as confounders. In the final adjusted multivariable model, TS/CTD was significantly associated with antiemetic exposure during pregnancy (odds ratio [OR]=16.61, 95% confidence interval [CI] 1.49-185.22, p=0.02) and medically assisted reproduction (OR=7.89, 95% CI 2.28-27.28, p=0.01). Conclusion: Antiemetic exposure and medically assisted reproduction are significantly associated with the risk of TS/CTD. These results should be replicated in future prospective and gene-by-environment studies.