• Reproductive and Developmental Biology
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• 제30권4호
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• pp.235-245
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• 2006

Di-n-butyl phthalate (DBP), diisononyl phthalate (DINP) and di-(2-ethylhexyl) adipate (DEHA) are ubiquitously distributed chemicals that are widely used as plasticizers and also found at low levels in foods. The aims of this study were to determine whether perinatal exposure to DBP, DINP and DEHA could alter normal patterns of neonatal development. Dams were provided with pulverized soy-free diet containing 20, 200, 2,000 and 10,000 ppm of DBP, 40, 400, 4.000 and 20,000 ppm of DINP, or 480, 2,400 and 12,000 ppm of DEHA from gestational day 15 to postnatal day 21. Exposure to the high doses of DBP, DINP and DEHA during gestational period significantly decreased food consumption and body weight gain of dams. These chemicals reduced neonatal body weight as well as that of the after maturation. Also, exposure to DINP of all the doses used and the higher doses (2,400 and 12,000 ppm) of DEHA decreased AGD at PND 1 in male neonates, though that to DBP did not affect AGD in males. In female neonates, an increase in AGD was observed in DBP- and DINP-exposed animals at the highest doses. Moreover, these chemicals affected survival rate of pups at PND 5, and delayed onset of eye opening in all chemica1-exposed groups at PND 17. These results suggest that perinatal exposure to these chemicals may affect the normal development and/or growth of offspring.

• Clinical and Experimental Pediatrics
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• 제59권8호
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• pp.319-327
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• 2016

Allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergy, are most common chronic, noncommunicable diseases in childhood. In the past few decades, the prevalence has increased abruptly worldwide. There are 2 possible explanations for the rising prevalence of allergic diseases worldwide, that an increased disease-awareness of physician, patient, or caregivers, and an abrupt exposure to unknown hazards. Unfortunately, the underlying mechanisms remain largely unknown. Despite the continuing efforts worldwide, the etiologies and rising prevalence remain unclear. Thus, it is important to identify and control risk factors in the susceptible individual for the best prevention and management. Genetic susceptibility or environments may be a potential background for the development of allergic disease, however they alone cannot explain the rising prevalence worldwide. There is growing evidence that epigenetic change depends on the gene, environment, and their interactions, may induce a long-lasting altered gene expression and the consequent development of allergic diseases. In epigenetic mechanisms, environmental tobacco smoke (ETS) exposure during critical period (i.e., during pregnancy and early life) are considered as a potential cause of the development of childhood allergic diseases. However, the causal relationship is still unclear. This review aimed to highlight the impact of ETS exposure during the perinatal period on the development of childhood allergic diseases and to propose a future research direction.

• Reproductive and Developmental Biology
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• 제30권4호
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• pp.247-253
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• 2006

Our previous research has identified granulin (grn) and p130 genes as sex steroid-inducible genes in the rat hypothalamus, which might be involved in sexual differentiation of the brain. Phthalate esters that are used as plasticizers and also found at low levels in foods such as dairy products are often mentioned as suspected endocrine disrupters. The purpose of the present study is to elucidate whether perinatal exposure to di-n-butyl phthalate (DBP), diisononyl phthalate (DINP) and di-2-ethylhexyl adipate (DEHA) affects hypothalamic sex steroid-inducible genes. The present study assessed the effects of perinatal exposure to DBP, DINP and DEHA on sex steroid hormones levels and hypothalamic gm and p130 mRNA expressions at postnatal day (PND) 3 and 7. Pregnant rats were fed a soy-free diet containing 20, 200, 2,000 and 10,000 ppm of DBP, 40, 400, 4,000 and 20,000 ppm of DINP, or 480, 2,400 and 12,000 ppm of DEHA from gestational day (GD) 15 to GD 3 or 7. At PND 3 and 7, perinatal exposure to these chemicals did not substantially affect serum concentrations of testosterone and estradiol. At PND 3, the expression of grn mRNA levels in males was decreased by DEHA, and that of p130 was decreased by DBP, DINP and DEHA, though the effects were not dose-dependent. At PND 7, the expression of gm gene in female pups was increased by higher doses of DBP and all the doses, except for 4,000 ppm, of DINP, while that in male pups decreased by 480 and 12,000 ppm of DEHA. Hypothalamic expression of p130 mRNA in males was increased by lower doses of DBP and all the doses of DINP, whereas that of females was decreased by 480 and 2,400 ppm of DEHA. These results suggest that these chemicals may affect the expression of gm and p130 genes by directly acting on the hypothalamus, thus leading to inappropriate expression of these genes.

• Journal of Animal Science and Technology
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• 제48권5호
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• pp.651-662
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• 2006

프탈레이트 에스테르는 플라스틱 가소제로서 이용되며 또한 유제품과 같은 음식에서 미량으로 발견되고, 종종 내분비 교란물질로 의심되고 있다. 본 연구의 목적은 DBP, DINP 또는 DEHA의 주산기 노출이 랫트에 있어 성 성숙 후, 번식기능 특히 뇌의 성분화에 어떤 영향을 끼치는 지에 대해 조사하였다. 이를 수행하기 위해서, 어미에게 식물성 에스트로겐의 함유가 낮은 분말 사료에 다음과 같은 단계적 농도의 DBP (20, 200, 2000, 10000 ppm), DINP (40, 400, 4000, 20000 ppm), DEHA (480, 2400, 12000 ppm)를 혼합한 후, 임신 15일째부터 출생 후, 21일째 (이유기)까지 섭취 시켰고, 성 성숙 후, 혈청 성호르몬 및 성선자극호르몬의 레벨과 교배행동 및 성주기 회귀를 분석하였다. 그 결과, DBP, DINP 또는 DEHA의 주산기 노출에 의한 생후 20~21주째의 암수 랫트에 있어, 성호르몬 및 성선자극호르몬의 레벨뿐만 아니라 암컷의 성주기의 회귀에 대해 어떠한 영향을 주지 않았다. 이것은 시상하부－하수체－성선축의 내분비계를 제어하는 뇌의 성분화에는 이들 화학물질이 영향을 주지 않았다는 사실을 시사한다. 하지만, 수컷의 성행동 특히, 사정 (ejaculation)과 암컷의 로도시스 반응이 억제되는 것이 관찰되었다. 이러한 결과로부터 DBP, DINP 또는 DEHA의 주산기 노출은 성선자극 호르몬의 분비에는 영향을 주지 않지만, 성행동을 제어하는 시상하부의 어떤 영역에 직접적으로 작용할 가능성 즉, 뇌의 성분화에 영향을 끼쳐 성 성숙 후, 성 특이적 행동을 억제시킬 가능성을 시사한다.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제34권1호
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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.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제26권3호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-1
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• pp.104-105
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• 2003

Hypoxic-ischemic (H-I) encephalopathy in the prenatal and perinatal period is a major cause of morbidity and mortality and often results in cognitive impairment, seizures, and motor impairment (cerebral palsy). Many studies of neonatal H-I brain injury have utilized the well characterized Levine model in which unilateral carotid ligation is followed by exposure to hypoxia. (omitted)

• Clinical and Experimental Pediatrics
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• 제57권3호
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• pp.101-109
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• 2014

The use of glucocorticoids (GCs) in the perinatal period is suspected of being associated with adverse effects on long-term neurodevelopmental outcomes for preterm infants. Repeated administration of antenatal GCs to mothers at risk of preterm birth may adversely affect fetal growth and head circumference. Fetal exposure to excess GCs during critical periods of brain development may profoundly modify the limbic system (primarily the hippocampus), resulting in long-term effects on cognition, behavior, memory, co-ordination of the autonomic nervous system, and regulation of the endocrine system later in adult life. Postnatal GC treatment for chronic lung disease in premature infants, particularly involving the use of dexamethasone, has been shown to induce neurodevelopmental impairment and increases the risk of cerebral palsy. In contrast to studies involving postnatal dexamethasone, long-term follow-up studies for hydrocortisone therapy have not revealed adverse effects on neurodevelopmental outcomes. In experimental studies on animals, GCs has been shown to impair neurogenesis, and induce neuronal apoptosis in the immature brains of newborn animals. A recent study has demonstrated that dexamethasone-induced hypomyelination may result from the apoptotic degeneration of oligodendrocyte progenitors in the immature brain. Thus, based on clinical and experimental studies, there is enough evidence to advice caution regarding the use of GCs in the perinatal period; and moreover, the potential long-term effects of GCs on brain development need to be determined.

• Clinical and Experimental Pediatrics
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• 제46권10호
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• pp.1047-1050
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• 2003

저자들은 분만 10일 전 herpes zoster 진단받은 산모에서 출생한 환아에서 피부 병변 없이 신경학적 이상 증세만을 보이는 perinatal varicella infection 1례를 경험하였기에 보고하는 바이다.

• Clinical and Experimental Pediatrics
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• 제55권2호
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• pp.35-41
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• 2012

Passive exposure to tobacco smoke significantly contributes to morbidity and mortality in children. Children, in particular, seem to be the most susceptible population to the harmful effects of environmental tobacco smoke (ETS). Paternal smoking inside the home leads to significant maternal and fetal exposure to ETS and may subsequently affect fetal health. ETS has been associated with adverse effects on pediatric health, including preterm birth, intrauterine growth retardation, perinatal mortality, respiratory illness, neurobehavioral problems, and decreased performance in school. A valid estimation of the risks associated with tobacco exposure depends on accurate measurement. Nicotine and its major metabolite, cotinine, are commonly used as smoking biomarkers, and their levels can be determined in various biological specimens such as blood, saliva, and urine. Recently, hair analysis was found to be a convenient, noninvasive technique for detecting the presence of nicotine exposure. Because nicotine/cotinine accumulates in hair during hair growth, it is a unique measure of longterm, cumulative exposure to tobacco smoke. Although smoking ban policies result in considerable reductions in ETS exposure, children are still exposed significantly to tobacco smoke not only in their homes but also in schools, restaurants, child-care settings, cars, buses, and other public places. Therefore, more effective strategies and public policies to protect preschool children from ETS should be consolidated.