Prenatal Particulate Matter/Tobacco Smoke Increases Infants’ Respiratory Infections: COCOA Study

양송이,김병주,이소연,김효빈,이철민,유진호,강미진,유호성,이은,정영호,김형영,서주희,권지원,송대진,장광천,김우경,심정연,이수영,양현종,서동인,홍서아,최길용,신윤호,안강모,김경원,김은진,홍수종 대한천식알레르기학회 2015 Allergy, Asthma & Immunology Research Vol.7 No.6

Purpose: To investigate whether prenatal exposure to indoor fine particulate matter (PM2.5) and environmental tobacco smoke (ETS) affects susceptibility to respiratory tract infections (RTIs) in infancy, to compare their effects between prenatal and postnatal exposure, and to determine whether genetic factors modify these environmental effects. Methods: The study population consisted of 307 birth cohort infants. A diagnosis of RTIs was based on parental report of a physician’s diagnosis. Indoor PM2.5 and ETS levels were measured during pregnancy and infancy. TaqMan was used for genotyping of nuclear factor erythroid 2-related factor (Nrf2) (rs6726395), glutathione-S-transferase-pi (GSTP) 1 (rs1695), and glutathione-S-transferase- mu (GSTM) 1. Microarrays were used for genome-wide methylation analysis. Results: Prenatal exposure to indoor PM2.5 increased the susceptibility of lower RTIs (LRTIs) in infancy (adjusted odds ratio [aOR]=2.11). In terms of combined exposure to both indoor PM2.5 and ETS, prenatal exposure to both pollutants increased susceptibility to LRTIs (aOR=6.56); however, this association was not found for postnatal exposure. The Nrf2 GG (aOR=23.69), GSTM1 null (aOR=8.18), and GSTP1 AG or GG (aOR=7.37) genotypes increased the combined LRTIs-promoting effects of prenatal exposure to the 2 indoor pollutants. Such effects of prenatal indoor PM2.5 and ETS exposure were not found for upper RTIs. Conclusions: Prenatal exposure to both indoor PM2.5 and ETS may increase susceptibility to LRTIs. This effect can be modified by polymorphisms in reactive oxygen species- related genes.

Decreased birth weight after prenatal exposure to wildfires on the eastern coast of Korea in 2000

En-Joo Jung,Ah-Young Lim,Jong-Hun Kim 한국역학회 2022 Epidemiology and Health Vol.45 No.-

OBJECTIVES: In April 2000, a series of wildfires occurred simultaneously in five adjacent small cities located on the eastern coast of Korea. These wildfires burned approximately 23,794 hectares of forestland over several days. We investigated the effects of prenatal exposure to the by-products generated by wildfire disasters on birth weight. METHODS: Birth weight data were obtained for 1999-2001 from the birth registration database of the Korean National Statistical Office and matched with the zip code and exposed/unexposed pregnancy week for days of the wildfires. Generalized linear models were then used to assess the associations between birth weight and exposure to wildfires after adjusting for fetal sex, gestational age, parity, maternal age, maternal education, paternal education, and average exposed atmospheric temperature. RESULTS: Compared with unexposed pregnancies before and after the wildfires, mean birth weight decreased by 41.4 g (95% confidence interval [CI], -72.4 to -10.4) after wildfire exposure during the first trimester, 23.2 g (95% CI, -59.3 to 13.0) for exposure during the second trimester, and 27.0 g (95% CI, -63.8 to 9.8) during the third trimester. In the adjusted model for infants exposed in utero during any trimester, the mean birth weight decreased by 32.5 g (95% CI, -53.2 to -11.7). CONCLUSIONS: We observed a 1% reduction in birth weight after wildfire exposure. Thus, exposure to by-products generated during a wildfire disaster during pregnancy may slow fetal growth and cause developmental delays.

Ethanol toxicity affects olfactory receptor genes in forebrain of fetal mice

Chanchal Mandal,Kyoung Hwa Jung,Young Gyu Chai 대한독성 유전단백체 학회 2015 Molecular & cellular toxicology Vol.11 No.1

Toxicity of ethanol can lead to behavioral and cognitive impairments of fetus. The aim of this current study was to investigate the alteration of genes at developing fetal brain by maternal binge alcohol consumption. Genome-wide transcriptional analysis revealed a set of differentially expressed genes (20 upregulated and 21 down-regulated; 1.5-fold cut-off) on embryonic day 15 (ED15) in the developing fetal brain. The gene ontology analysis revealed the associations of these genes with sensory perception, whereas Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that they were correlated with olfactory transduction. Six olfactory receptor genes (Olfr960, Olfr1342, Olfr43, Olfr836, Olfr1262 and Olfr1419) encoding proteins involved in the olfactory transduction pathway showed reduced expression levels. The downregulation of these olfactory receptor genes may cause odor identification defects as well as abnormalities in the olfactory system. Our findings aid in the elucidation of the molecular mechanism underlying the defective olfactory processing that occurs following prenatal alcohol exposure.

The Relationship between Second-to-Fourth Digit Ratios, Attention-Deficit/Hyperactivity Disorder Symptoms, Aggression, and Intelligence Levels in Boys with Attention-Deficit/Hyperactivity Disorder

Işık Ümit,Kılıç Faruk,Aktepe Evrim,Tanrıtanır Bilal 대한신경정신의학회 2020 PSYCHIATRY INVESTIGATION Vol.17 No.6

Objective Observations of sex differences have led some scientists to doubt whether the neuroendocrine system is involved in attentiondeficit/hyperactivity disorder (ADHD) etiology. One of the interesting study subjects in this context is prenatal steroid hormone exposure. The aim of the present study was to replicate and extend previous work by addressing two research questions: 1) Are second-tofourth digit (2D:4D) ratios lower in ADHD than in controls? 2) Is there a correlation between 2D:4D ratios and symptoms of ADHD, aggression and intelligence scores in boys with ADHD?Methods The study included 100 treatment-naive male children diagnosed with ADHD and 55 healthy male children. We measured the ratios of 2D:4D and administered a Wechsler Intelligence Scale for Children-Revised to assess IQ scores, as well as behavioral rating scales, in children with ADHD and comparison individuals.Results We observed lower 2D:4D ratios in the right hand in ADHD in comparison to the control group. The left-hand ratios of 2D:4D, however, did not differ between ADHD and control groups. There were negative correlations between the left-hand 2D:4D ratios and the hyperactivity scores. However, no significant correlation was detected between right-hand 2D:4D ratios and the psychological questionnaire scores.Conclusion These results provide further evidence that fetal androgen exposure may contribute to the pathophysiology of ADHD, at least in boys.

Postnatal Growth Following Prenatal Lead Exposure and Calcium Intake

Hong, Yun-Chul,Kulkarni, Surabhi Shah,Lim, Youn-Hee,Kim, Eunjeong,Ha, Mina,Park, Hyesook,Kim, Yangho,Kim, Bung-Nyun,Chang, Namsoo,Oh, Se-Young,Kim, Young-Ju,Park, Chooghee,Ha, Eun-hee American Academy of Pediatrics 2014 Pediatrics Vol.134 No.6

<P><B>BACKGROUND:</B></P><P>The effects on postnatal growth of maternal exposure to low levels of lead during pregnancy have not been well established. In addition, information is limited regarding the protective effect of dietary calcium intake during pregnancy against the effect of lead for fetal and postnatal growth. We investigated the relationship between prenatal exposure to lead and growth at birth and 6, 12, and 24 months postnatal, and evaluated the role of calcium intake against the effect of lead.</P><P><B>METHODS:</B></P><P>A total of 1150 pregnant women, and their subsequent offspring, enrolled in a prospective birth cohort study (Mothers and Children's Environmental Health Study), were evaluated. Multivariable regression analysis was conducted to estimate the effects of prenatal maternal blood lead levels on growth at each follow-up.</P><P><B>RESULTS:</B></P><P>The blood lead levels of participating mothers were <5.0 μg/dL and mean levels were 1.25 μg/dL during the early (before 20 gestational weeks) and late (at delivery) gestational periods. Prenatal exposure to lead, particularly in late pregnancy, was significantly associated with a reduction in infantile growth at 24 months. When pregnant women had dietary calcium intake at mean or upper level, the association was not significant. In contrast, lower than mean level of calcium intake intensified the adverse effect of prenatal lead exposure on growth in children.</P><P><B>CONCLUSIONS:</B></P><P>Prenatal lead exposure <5.0 μg/dL adversely affects postnatal growth and low calcium intake aggravates the effect, indicating more stringent control of lead and sufficient intake of calcium are necessary to help children’s health.</P>

Gender difference in the effects of lead exposure at different time windows on neurobehavioral development in 5-year-old children

Joo, Hyunjoo,Choi, Jong Hyuk,Burm, Eunae,Park, Hyesook,Hong, Yun-Chul,Kim, Yangho,Ha, Eun-Hee,Kim, Yeni,Kim, Bung-Nyun,Ha, Mina Elsevier 2018 The Science of the total environment Vol.615 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Although the association between lead exposure and children's neurodevelopment has been studied, gender differences remain to be investigated. We examined the effects of lead exposure on the neurobehavioral development of 5-year-old children to identify the vulnerable time window of exposure and potential gender difference.</P> <P><B>Method</B></P> <P>A total of 1751 pregnant women and children participated in the prospective birth cohort study, Mothers and Children's Environmental Health study, since 2006. Lead levels were measured in the maternal blood in early and late pregnancies, in cord blood at birth, and in 2-, 3-, and 5-year-old children's blood. The behavior of 575 children aged 5years were assessed using the Korean Child Behavior Checklist. The association between the blood lead level at each time window and behavior was examined using a generalized linear model adjusted for potential confounders and covariates.</P> <P><B>Results</B></P> <P>Lead levels at late pregnancy were significantly associated with increased risk of behavioral problems in males. Lead levels in 2- and 5-year-old children's blood significantly increased behavioral risks in females: for a 1-μg/dL increase in blood lead levels, the score for total behavioral problems increased by 3.00 (95% confidence interval [CI]: 0.56–5.45) during the late pregnancy in males, whereas it increased by 3.82 (95% CI: 1.25–6.39) at 2years and by 5.72 (95% CI: 0.44–10.99) at 5years in females with a stronger effect in attention and sleep problems.</P> <P><B>Conclusion</B></P> <P>Effects of lead toxicity on children's neurobehavioral development showed gender differences. Males were more susceptible to prenatal exposure, while females were more susceptible to postnatal exposure with stronger effects in attention and sleep problems.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Appreciation on gender differences is useful for understanding the mechanism underlying neurodevelopmental toxicity. </LI> <LI> Behavioral problems in 5-years’ children were examined in association with blood lead levels from prenatal to 5years. </LI> <LI> Behavioral problems significantly increased by increase of lead exposure at prenatal in male while at postnatal in female. </LI> <LI> Females with postnatal lead exposure showed a stronger association in attention and sleep problems than males. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

태아기 Topiramate 노출과 신경발달 장애 위험에 관한 체계적 문헌고찰

이주연,임다정,정종현,이정민,이모세 대한약물역학위해관리학회 2023 약물역학위해관리학회지 Vol.15 No.2

This systematic review aimed to investigate the potential risk of neurodevelopmental disorders resulting from fetal exposure to topiramate. Methods: A comprehensive search was conducted in major foreign databases, including PubMed and EMBASE, up to November 6, 2022. Studies that reported the risk of neurodevelopmental disorders in children exposed to topiramate during prenatal life were included in this review. Two reviewers independently screened the titles, abstracts, and full-text articles, and data were extracted using a standardized form. Results: Three studies that met the inclusion criteria were selected for analysis. Even though a recent large cohort study based on Nordic data showed that prenatal topiramate exposure significantly increases the risk of neurogenerative disorders including intellectual disability or autism spectrum disorder, other two studies did not show the significant results. Conclusion: While a recent study suggested that topiramate increases the risk of neurodevelopment disorders, previous two studies did not show the consistent results. Further studies with larger sample sizes, longer follow-up periods are needed.

임신 중 약물 노출과 자녀의 알레르기 질환

이희철 한국모자보건학회 2017 한국모자보건학회지 Vol.21 No.1

Recent studies reported increased risks for the development of allergic diseases in children after prenatal exposure to drugs. The mechanisms by which drug exposure may actually cause allergic diseases are not known. It has been suggested that these drugs promote transplacental allergen transfer to the fetus, resulting in the preservation of allergens. If transferred to the fetus, these allergens could induce a Th2-dominant immune response and allergic sensitization of the fetus. The development of the fetal immune system is influenced by the allergic state of the mother. Maternal IgE can cross fetal membranes, and a Th2-dominant phenotype in the mother can promote an allergy-prone phenotype in the fetus. The fetal immune system starts early in development but mainly matures in later trimesters. Maternal use of antibiotics during pregnancy may prove to be a risk factor for persistent wheezing and allergy development in early infancy. Paracetamol exposure during pregnancy was associated with allergic rhinitis, its use until 6 months of age was associated with allergic sensitization and a history of asthma in girls. Exposure to proton pump inhibitors (PPIs) and Histamine 2-antagonists (H2As) has been associated with an increased risk for the development of atopic dermatitis, asthma, allergic rhinitis, and especially with the development of multiple allergic diseases. Our reviews showed it is necessary to prescribe such drugs under the consultation of an expert physician and to try and reduce exposure as much as possible to prevent offspring allergies in the case of mothers with a history of allergic diseases.

Long-term prenatal stress increases susceptibility of N-methyl-D-aspartic acid-induced spasms in infant rats

권혁희,이태관,홍진표,김동운,강준원 대한소아청소년과학회 2018 Clinical and Experimental Pediatrics (CEP) Vol.61 No.5

Purpose: Infantile spasms, also known as West syndrome, is an age-specific epileptic seizure. Most patients with this condition also exhibit delayed development. This study aimed to determine the effect of long-term prenatal stress on susceptibility to infantile spasms. Methods: We subjected pregnant rats to acute or chronic immobilization stress. Resulting offspring received N-methyl-D-aspartic acid (15 mg/kg, intraperitoneally) on postnatal day 15, and their behaviors were observed 75 minutes after injection. The expression of KCC2 and GAD67 was also determined using immunohistochemistry. Results: Exposure to long-term prenatal stress increased the frequency of spasms and decreased the latency to onset of spasms compared with offspring exposed to short-term prenatal stress. Expression of KCC2 and GAD67 also decreased in the group exposed to long-term prenatal stress compared with the group exposed to short-term prenatal stress. Conclusion: Our study suggests that exposure to long-term prenatal stress results in increased susceptibility to seizures.

Path analysis of prenatal mercury levels and birth weights in Korean and Taiwanese birth cohorts

Kim, Byung-Mi,Chen, Mei-Huei,Chen, Pau-Chung,Park, Hyesook,Ha, Mina,Kim, Yangho,Hong, Yun-Chul,Kim, Young Ju,Ha, Eun-Hee Elsevier 2017 Science of the Total Environment Vol.605 No.-

<P><B>Abstract</B></P> <P>Prospective cohort studies of the effect of mercury (Hg) exposure on birth weight have shown conflicting results. We combined data from Taiwanese and Korean birth cohorts, and assessed the effects of Hg exposure on birth weight. The first cohort was drawn from the Mothers and Children's Environmental Health (MOCEH) study performed in Korea from 2006 to 2010. The second cohort was enrolled from 2004 to 2005 and included singleton term births from the Taiwan Birth Panel Study (TBPS). In total, 1147 pregnant women were included in this study. A pooled analysis was performed to obtain combined estimates of the association between prenatal total Hg exposure and birth weight. A significant negative association between maternal and cord blood Hg and birth weight in the high-Hg group (Hg level>25th percentile) was detected (maternal blood: β=−0.056; 95% CI, −0.100 to −0.013, cord blood: β=−0.075; 95% CI, −0.121 to −0.028). Hg level showed a negative coefficient in the path analysis, indicating an adverse effect on birth weight (total effects: β=−0.177, <I>P</I> =0.01 in MOCEH, β=−0.204, <I>P</I> =0.03 in TBPS), but fish consumption exhibited a strong positive coefficient. In addition, fish consumption exerted a significant indirect effect on birth weight through exposure to cord blood Hg. Exposure to hazardous contaminants and beneficial nutrients may be highly correlated in those who frequently consume fish. Moreover, Hg in cord blood may adversely affect birth weight.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The association between Hg from fish consumption and birth weight is unclear. </LI> <LI> Path analysis showed a direct path from fish consumption to cord blood Hg. </LI> <LI> Cord blood Hg level was directly related to lower birth weight. </LI> <LI> Decreased between birth weight was indirectly related to fish consumption. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>