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1.
Medicine (Baltimore) ; 100(16): e25646, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879746

RESUMO

ABSTRACT: To determine the association of betatrophin amounts with 25-(OH)D levels in gestational diabetes mellitus (GDM) patients, and to provide new targets for the prevention and treatment of GDM.This study included 40 GDM patients (GDM group) and 37 healthy pregnant women (control group). Betatrophin, 25-(OH)D, fasting blood glucose (FBG), HbA1c, hsCRP, and FINS levels in peripheral blood, as well as betatrophin and 25-(OH)D amounts in cord blood, were measured. Then, associations of betatrophin levels with 25-(OH)D amounts and other indexes were determined.Maternal (P = .011) and cord (P = .022) blood betatrophin levels were significantly lower in the GDM group compared with control group. Cord blood betatrophin levels were higher compared with maternal blood amounts in both the GDM and control groups (both P = .000). Serum betatrophin levels were positively associated with 25-(OH)D levels (r = 0.677, P = .000), but negatively associated with hsCRP (r = -0.335, P = .037) and HOMA-IR (r = -0.346, P = .031) levels in the GDM group. Fetal weight was higher in the GDM group compared with control group (P = .023), and negatively associated with cord blood betatrophin amounts in the GDM group (r = -0.342, P = .031). However, cord blood betatrophin levels were not significantly associated with body length, Apgar score, and cord blood 25-(OH)D levels in the GDM group (all P > .05).Serum betatrophin and 25-(OH) D levels were positively associated in women with GDM, and both significantly lower compared with control values. Fetal weight was higher in the GDM group and associated with cord blood betatrophin. These findings provide insights into developing new predictive biomarkers or therapeutic targets for GDM.


Assuntos
Proteínas Semelhantes a Angiopoietina/sangue , Diabetes Gestacional/sangue , Hormônios Peptídicos/sangue , Vitamina D/análogos & derivados , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Sangue Fetal/química , Peso Fetal , Humanos , Testes para Triagem do Soro Materno , Gravidez , Vitamina D/sangue , Adulto Jovem
2.
Medicine (Baltimore) ; 100(11): e25195, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33726012

RESUMO

ABSTRACT: The present study was conducted with an attempt to explore the correlation of serum resistin level and other metabolic hormones and immune function in neonatal umbilical cord blood.The levels of umbilical cord blood resistin, adiponectin, insulin, growth hormone, leptin, thyrotropin, thyroid hormone (T3, T4), lgM, lgA, lgG, CD4, and CD8 were measured in 180 full-term newborns delivered in hospital from October 2018 to November 2019. The delivery mode, weight, height, and gender at birth were recorded.The levels of resistin, insulin, and growth hormone in umbilical cord blood of newborns delivered vaginally were significantly higher than those born by cesarean section (P < .05), while the levels of adiponectin, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 were comparable between the 2 groups (P > .05). The levels of resistin, adiponectin, insulin, growth hormone, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 in cord blood of male and female newborns were comparable (P > .05). The newborns with birth weight ≥ 3501 g reported comparable results in the levels of resistin and growth hormone compared with those with birth weight of 3000 to 3500 g (P > .05), but were significantly higher than those with birth weight ≤ 2999 g (P < 0.05). In addition, the levels of adiponectin, insulin, leptin, TST, T3, T4, lgM, lgA, lgG, CD4, and CD8 were comparable among the 3 groups (P > .05). Based on Pearson correlation analysis, neonatal umbilical cord blood resistin was positively correlated with adiponectin, leptin, growth hormone, T3, and T4 (r = 0.281, 0.287, 0.321, 0.276, 0.269, P < .05). However, there was no significant correlation between neonatal umbilical cord blood resistin and insulin, TST, lgM, lgA, lgG, CD4, and CD8.The level of serum resistin in neonatal umbilical cord blood was associated with the delivery mode and birth weight, and positively correlated with adiponectin, leptin, growth hormone, T3, and T4. However, no correlation was observed between serum resistin in neonatal umbilical cord blood and insulin, TST, lgM, lgA, lgG, CD4, and CD8.


Assuntos
Adipocinas/sangue , Peso ao Nascer , Parto Obstétrico/estatística & dados numéricos , Sangue Fetal/química , Hormônio do Crescimento Humano/sangue , Hormônios Tireóideos/sangue , Adiponectina/sangue , Feminino , Sangue Fetal/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Recém-Nascido , Insulina/sangue , Leptina/sangue , Contagem de Linfócitos , Masculino , Gravidez , Resistina/sangue , Nascimento a Termo/sangue , Tireotropina/sangue
3.
Int J Mol Sci ; 22(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33579027

RESUMO

Mothers confer natural passive immunization to their infants through the transplacental pathway during the gestation period. The objective of the present study was to establish at birth the maternal and cord plasma concentration and relationship of immunoglobulins (Igs), cytokines (CKs), and adipokines. In addition, the impact of the maternal microbiota and diet was explored. The plasma profile of these components was different between mothers and babies, with the levels of many CKs, IgM, IgG2a, IgE, IgA, and leptin significantly higher in mothers than in the cord sample. Moreover, the total Igs, all IgG subtypes, IgE, and the Th1/Th2 ratio positively correlated in the mother-infant pair. Maternal dietary components such as monounsaturated fatty acids-polyunsaturated fatty acids and fiber were positively associated with some immune factors such as IgA in cord samples. The microbiota composition clustering also influenced the plasma profile of some factors (i.e., many CKs, some Ig, and adiponectin). In conclusion, we have established the concentration of these immunomodulatory factors in the maternal-neonatal pair at birth, some positive associations, and the influence of maternal diet and the microbiota composition, suggesting that the immune status during pregnancy, in terms of CKs and Igs levels, can influence the immune status of the infant at birth.


Assuntos
Citocinas/sangue , Dieta , Sangue Fetal , Imunoglobulinas/sangue , Microbiota , Adipocinas/sangue , Adipocinas/imunologia , Citocinas/imunologia , Fezes/microbiologia , Feminino , Sangue Fetal/química , Sangue Fetal/imunologia , Humanos , Imunidade , Imunoglobulinas/imunologia , Recém-Nascido , Masculino , Estado Nutricional , Gravidez
4.
Ecotoxicol Environ Saf ; 213: 112037, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33609998

RESUMO

OBJECTIVE: Telomere length (TL) is a biomarker for biological aging, and the initial setting of TL at birth is a determinant factor of TL in later life. Newborn TL is sensitive to maternal metals concentrations, while study about the association between maternal manganese (Mn) concentrations and newborn TL was not found. Our study aimed to investigate whether newborn TL is related to maternal Mn concentrations. METHODS: Data were collected from a birth cohort study of 762 mother-newborn pairs conducted from November 2013 to March 2015 in Wuhan, China. We measured the Mn concentrations in spot urine samples collected during three trimesters by inductively coupled plasma mass spectrometry (ICP-MS) and relative cord blood TL by quantitative real-time polymerase chain reaction (qPCR). We applied multiple informant models to investigate the associations between maternal Mn concentrations and cord blood TL. RESULTS: The geometric mean of creatinine-corrected urinary Mn concentrations were 1.58 µg/g creatinine, 2.53 µg/g creatinine, and 2.62 µg/g creatinine in the first, second, and third trimester, respectively. After adjusting for potential confounders, a doubling of maternal urinary Mn concentration during the second trimester was related to a 2.10% (95% CI: 0.25%, 3.99%) increase in cord blood TL. Mothers with the highest tertile of urinary Mn concentrations during the second trimester had a 9.67% (95% CI: 2.13%, 17.78%) longer cord blood TL than those with the lowest tertile. This association was more evident in male infants. No relationship was found between maternal urinary Mn concentrations and cord blood TL during the first and third trimesters in our study. CONCLUSIONS: Our findings suggested that maternal Mn concentration during the second trimester was positively associated with newborn TL. These results might provide an epidemiology evidence on the protective role of maternal Mn for newborn TL and offer clues for the early prevention of telomere shortening related diseases.


Assuntos
Poluentes Ambientais/urina , Manganês/urina , Telômero/efeitos dos fármacos , Adulto , Envelhecimento , China , Estudos de Coortes , Feminino , Sangue Fetal/química , Humanos , Lactente , Recém-Nascido , Masculino , Manganês/análise , Exposição Materna/estatística & dados numéricos , Gravidez , Trimestres da Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Encurtamento do Telômero
5.
Nat Commun ; 12(1): 132, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420104

RESUMO

The use of pesticides to reduce mosquito vector populations is a cornerstone of global malaria control efforts, but the biological impact of most pesticides on human populations, including pregnant women and infants, is not known. Some pesticides, including carbamates, have been shown to perturb the human immune system. We measure the systemic absorption and immunologic effects of bendiocarb, a commonly used carbamate pesticide, following household spraying in a cohort of pregnant Ugandan women and their infants. We find that bendiocarb is present at high levels in maternal, umbilical cord, and infant plasma of individuals exposed during pregnancy, indicating that it is systemically absorbed and trans-placentally transferred to the fetus. Moreover, bendiocarb exposure is associated with numerous changes in fetal immune cell homeostasis and function, including a dose-dependent decrease in regulatory CD4 T cells, increased cytokine production, and inhibition of antigen-driven proliferation. Additionally, prenatal bendiocarb exposure is associated with higher post-vaccination measles titers at one year of age, suggesting that its impact on functional immunity may persist for many months after birth. These data indicate that in utero bendiocarb exposure has multiple previously unrecognized biological effects on the fetal immune system.


Assuntos
Poluentes Ambientais/efeitos adversos , Feto/imunologia , Exposição Materna/efeitos adversos , Sarampo/sangue , Praguicidas/efeitos adversos , Adulto , Anticorpos Antivirais/sangue , Pré-Escolar , Ensaios Clínicos Fase III como Assunto , Feminino , Sangue Fetal/química , Seguimentos , Humanos , Sistema Imunitário/efeitos dos fármacos , Imunogenicidade da Vacina , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Malária/prevenção & controle , Troca Materno-Fetal/imunologia , Sarampo/imunologia , Sarampo/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Controle de Mosquitos/métodos , Praguicidas/análise , Fenilcarbamatos/efeitos adversos , Fenilcarbamatos/análise , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Environ Sci Technol ; 55(5): 3091-3100, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33397100

RESUMO

Organophosphate tri- and diesters (tri-OPEs and di-OPEs) were quantified in 63 paired maternal and cord whole blood samples collected in Hubei, China, in which tri-o-cresyl phosphate (ToCP) was predominant. The transplacental transfer efficiencies (expressed as cord blood to maternal blood (C:M) concentration ratios) of aryl-tri-OPEs, such as ToCP (1.61) and triphenyl phosphate (TPHP) (1.06), were higher than those of alkyl-tri-OPEs (0.66-0.76). For the target tri-OPEs and some traditional organic compounds, the C:M ratios first increased with log Kow in the range of 1.63-5.23 and then decreased, showing a parabolic relationship. However, ToCP, with a log Kow of 6.34, deviated from this relationship and displayed the highest C:M ratio (1.61). Molecular docking indicated a very strong binding affinity between ToCP and transthyretin, suggesting that ToCP might be actively transported by transthyretin in the placenta. The di-OPE levels in the blood samples were significantly lower than the corresponding tri-OPE levels, and those in the cord blood were influenced not only by their transplacental behaviors but also by their low excretion rates and the metabolic characteristics of their parent compounds in the fetus. This study provides useful information for accurately assessing the health risks posed by tri-OPEs to pregnant women and fetuses.


Assuntos
Retardadores de Chama , China , Monitoramento Ambiental , Ésteres , Feminino , Sangue Fetal/química , Retardadores de Chama/análise , Humanos , Simulação de Acoplamento Molecular , Organofosfatos , Gravidez
7.
Obstet Gynecol ; 136(4): 756-764, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32925625

RESUMO

OBJECTIVE: To compare maternal and cord blood penicillin concentrations in women with and without obesity who are receiving intrapartum group B streptococcus (GBS) prophylaxis. METHODS: We performed a prospective cohort study of term women receiving intrapartum penicillin prophylaxis for GBS colonization (determined by antenatal rectovaginal culture). The following outcomes were compared between obese (body mass index [BMI] 35 or higher at delivery) and nonobese (BMI less than 30 at delivery) groups: penicillin concentration in maternal blood (after two penicillin doses) and umbilical cord blood, GBS rectovaginal colonization status on admission and after two completed doses, and neonatal GBS colonization (using a postnatal ear swab). Fifty-five women were needed to detect a 0.75 SD difference in cord blood penicillin concentrations. RESULTS: Fifty-five women were enrolled and had all specimens collected; 49 had complete data for analysis (obese n=25, nonobese n=24). There was no difference in the median maternal penicillin concentration between groups (obese 4.2 micrograms/mL vs nonobese 4.0 micrograms/mL, P=.58). There was, however, a 60% lower median cord blood penicillin concentration in the obese compared with the nonobese group (2.7 micrograms/mL vs 6.7 micrograms/mL, respectively, P<.01), with no significant difference in time from last penicillin dose to delivery (obese 2.9 hours vs nonobese 1.7 hours, P=.07). The difference in cord blood concentrations remained significant after adjustment for nulliparity, hypertensive disorders, and time from last penicillin dose to delivery. Only 59.6% of women tested positive for GBS by rectovaginal culture on admission (obese 60.9% vs nonobese 58.3%, P=.86). CONCLUSION: The median cord blood penicillin concentration was 60% lower in neonates born to women with obesity compared with those born to women without obesity. However, all concentrations exceeded the minimum inhibitory concentration. Maternal penicillin levels were not significantly different between groups. More than 40% of women who previously tested positive for GBS by antenatal culture tested negative for GBS on admission for delivery.


Assuntos
Sangue Fetal/química , Triagem Neonatal/métodos , Obesidade , Penicilinas , Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , Streptococcus agalactiae/isolamento & purificação , Adulto , Antibacterianos/sangue , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Índice de Massa Corporal , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Obesidade/sangue , Obesidade/complicações , Obesidade/diagnóstico , Avaliação de Processos e Resultados em Cuidados de Saúde , Penicilinas/sangue , Penicilinas/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/tratamento farmacológico , Reto/microbiologia , Infecções Estreptocócicas/sangue , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/tratamento farmacológico , Vagina/microbiologia
8.
PLoS One ; 15(8): e0236708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790684

RESUMO

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are a kind of endocrine disruptors, which can enter human body by the inhalation of PAH-containing matter and the ingestion of PAH-containing foodstuffs. Studies showed that PAHs can cross the placental barrier and might cause adverse effects on the fetus. OBJECTIVES: This meta-analysis aimed to estimate the associations between prenatal exposure to PAHs and birth weight. METHODS: Articles published in English until May 8, 2020 and reported the effects of prenatal exposure to PAHs on birth weight were searched in multiple electronic databases including PubMed, the Web of Science, EMBASE and the Cochrane Library. The included studies were divided into three groups in accordance with the measurement of PAHs exposure. Then coefficient was extracted, conversed and synthesized by random-effects meta-analysis. And risk of bias was assessed for each study. RESULTS: A total of 3488 citations were searched and only 11 studies were included finally after double assessment. We found that there were no association between PAH-DNA adducts in cord blood (low/high) (OR: 1.0, 95%CI: 0.97, 1.03), 1-hydroxy pyrene (1-HP) concentration in maternal urine (OR: 1.0, 95%CI: 0.97, 1.03) and prenatal maternal airborne PAHs exposure (OR: 0.97, 95%CI: 0.93, 1.01) and birth weight. However, we observed ethnicity may change the effects of PAHs exposure on birth weight. CONCLUSIONS: There is no significant relationship between prenatal exposure to PAHs and birth weight in our meta-analysis. Further studies are still needed for determining the effects of prenatal PAHs exposure on birth weight.


Assuntos
Peso ao Nascer/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Exposição Materna , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Atmosféricos/química , Poluentes Atmosféricos/toxicidade , Adutos de DNA/química , Bases de Dados Factuais , Disruptores Endócrinos/química , Feminino , Sangue Fetal/química , Humanos , Razão de Chances , Hidrocarbonetos Policíclicos Aromáticos/química , Gravidez , Pirenos/urina
9.
Artigo em Inglês | MEDLINE | ID: mdl-32752242

RESUMO

PURPOSE: Comparison of the activity of 11beta-hydroxysteroid dehydrogenase type 2 in the placenta and the umbilical cord blood cortisol level between caesarean sections with or without uterine contraction and vaginal delivery groups. Cortisol is the main stress hormone responsible for the normal adaptation of the neonate to extrauterine life. The disorders resulting from a dysfunction of the 11ß-HSD 2-cortisol system can explain the higher risk of developing diseases in children born by caesarean section. METHODS: 111 healthy, pregnant women in singular pregnancy at term of delivery were included into the study. The study comprised 11ß-HSD 2 in placental tissue from 49 pregnant women delivering by elective caesarean section and 46 pregnant women delivering by vagina. In 16 cases of the elective caesarean section, regular uterine contractions were declared. Cortisol level was estimated in umbilical cord blood directly after delivery. RESULTS: We found no statistically significant differences in the activity of 11ß-HSD 2 in placentas delivered via caesarean sections (29.61 on average in elective caesarean sections and 26.65 on average in intrapartum caesarean sections) compared to vaginal deliveries (31.94 on average, p = 0.381), while umbilical cord blood cortisol in the elective caesarean sections group was significantly lower (29.86 on average) compared to the vaginal deliveries (55.50 on average, p < 0.001) and intrapartum caesarean sections (52.27 on average, p < 0.001). CONCLUSIONS: The model of placental 11ß-HSD 2 activity and umbilical cord blood cortisol concentration seems to be significant in conditions of stress associated with natural uterine contractions in labour.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 2 , Cesárea , Hidrocortisona , Trabalho de Parto , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Criança , Feminino , Sangue Fetal/química , Humanos , Hidrocortisona/análise , Recém-Nascido , Placenta/metabolismo , Gravidez , Estresse Fisiológico , Contração Uterina
10.
Ecotoxicol Environ Saf ; 203: 111009, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32684521

RESUMO

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) exist extensively in the environment. Toxicological studies suggested PBDEs may interfere with adipogenic pathways. However, few human evidence addressed PBDE exposures in utero related to childhood adiposity. OBJECTIVE: We assessed associations between PBDEs concentrations in cord serum and childhood adiposity measures at 7 years. METHODS: Among 318 mother-child pairs from Sheyang Mini Birth Cohort Study (SMBCS) in China, nine PBDE congener concentrations were quantified in umbilical cord serum using gas chromatography-negative chemical ionization mass spectrometry (GC-NCI-MS). Anthropometric indicators of children aged 7 years were measured, including weight, height and waist circumference. Age and sex-specific body mass index (BMI) z scores were calculated based on World Health Organization (WHO)'s child growth standards. Multivariate linear and logistic regression models adjusted for putative confounders were performed to examine associations between PBDE congeners and adiposity parameters. RESULTS: BDE-209 was the most abundant congener of PBDEs with a median value of 19.5 ng/g lipid. The geometric mean values of nine PBDE congeners ranged from below limit of detection (LOD) to 18.1 ng/g lipid, and the detection rates were 46.5%~96.5%. Cord serum BDE-153 and BDE-154 concentrations were associated with lower childhood BMI z score (regression coefficient, ß=-0.15, 95% confidence interval: -0.29, -0.02; p=0.02; ß=-0.23, 95%CI: -0.43, -0.03; p=0.03, respectively) and lower waist circumference (ß=-0.75 cm, 95%CI: -1.43, -0.06; p=0.03; ß=-1.22 cm, 95%CI: -2.23, -0.21; p=0.02, respectively), after controlling for potential confounders. Moreover, prenatal BDE-154 exposure was related to a decreased obesity risk of children aged 7 years (odds ratio, OR=0.46, 95%CI: 0.22, 0.94; p=0.03). These effects were only observed among boys in sex-straitified analyses. CONCLUSIONS: Cord serum BDE-153 and BDE-154 concentrations were related to reduced adiposity measures at 7 years of age. Further evidence regarding the impacts of prenatal PBDE exposures on childhood development is warranted.


Assuntos
Adiposidade , Poluentes Ambientais/sangue , Sangue Fetal/química , Éteres Difenil Halogenados/sangue , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Índice de Massa Corporal , Criança , China/epidemiologia , Estudos de Coortes , Poluentes Ambientais/química , Feminino , Éteres Difenil Halogenados/química , Humanos , Masculino , Gravidez , Circunferência da Cintura
11.
Toxicol Lett ; 332: 82-87, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32569803

RESUMO

BACKGROUND: Glycidol, a probable human carcinogen, is a reactive chemical released in the gastrointestinal tract from glycidyl fatty acid esters, which are heat-induced dietary contaminants. OBJECTIVES: To investigate the prenatal transfer of glycidol, a specific hemoglobin adduct was measured as a biomarker for internal glycidol exposure in paired cord and maternal blood samples. METHODS: In 100 mother-newborn pairs from the Belgian ENVIRONAGE (ENVIRonmental influence ON AGEing in early life) birth cohort, we studied the correlation between levels of the glycidol-derived hemoglobin adduct N-(2,3-dihydroxypropyl)-valine (2,3-diHOPr-Val) in paired cord and maternal blood samples. The adduct levels were determined after cleavage with a modified Edman degradation by using ultra-high performance liquid chromatography-tandem mass spectrometry and an isotope-labeled reference standard. RESULTS: 2,3-DiHOPr-Val was detectable in all 100 maternal blood samples and in 96 cord blood samples (LOD =0.5 pmol 2,3-diHOPr-Val/g hemoglobin), with medians of 5.4 (range: 2.3-29.2) and 1.6 (range: LOD - 8.9) pmol/g hemoglobin), respectively. In blood samples of mothers who smoked during pregnancy and in the cord blood samples of their newborns (n = 6), the median 2,3-diHOPr-Val levels were 16.7 (range: 6.4-29.2) and 6.2 (range: LOD - 8.6) pmol/g hemoglobin, respectively. The median ratio of 2,3-diHOPr-Val levels of cord to maternal blood was 0.35 (range: 0.19-1.14) (n = 49). The Spearman correlation coefficient between 2,3-diHOPr-Val levels in cord and maternal blood samples was 0.63 (p < 0.001) among all mother-newborn pairs and 0.59 (p < 0.001) among mother-newborn pairs of non-smoking mothers. DISCUSSION: Maternal data confirm widespread exposure to glycidol, also in non-smokers. Neonatal levels indicate prenatal exposure to glycidol, due to an obviously relatively unhindered passive transfer through the placental barrier. Possible health effects of fetal (and postnatal) glycidol exposure in children may be addressed in epidemiological studies.


Assuntos
Compostos de Epóxi/metabolismo , Sangue Fetal/química , Hemoglobinas/metabolismo , Troca Materno-Fetal , Propanóis/metabolismo , Valina/análogos & derivados , Adulto , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Eritrócitos/química , Feminino , Hemoglobinas/análise , Humanos , Recém-Nascido , Gravidez , Fumar/sangue , Espectrometria de Massas em Tandem , Valina/sangue
12.
Metabolism ; 110: 154292, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32553738

RESUMO

BACKGROUND: Birthweight reflects in utero exposures and later health evolution. Despite existing studies employing high-dimensional molecular measurements, the understanding of underlying mechanisms of birthweight remains limited. METHODS: To investigate the systems biology of birthweight, we cross-sectionally integrated the methylome, the transcriptome, the metabolome and a set of inflammatory proteins measured in cord blood samples, collected from four birth-cohorts (n = 489). We focused on two sets of 68 metabolites and 903 CpGs previously related to birthweight and investigated the correlation structures existing between these two sets and all other omic features via bipartite Pearson correlations. RESULTS: This dataset revealed that the set of metabolome and methylome signatures of birthweight have seven signals in common, including three metabolites [PC(34:2), plasmalogen PC(36:4)/PC(O-36:5), and a compound with m/z of 781.0545], two CpGs (on the DHCR24 and SC4MOL gene), and two proteins (periostin and CCL22). CCL22, a macrophage-derived chemokine has not been previously identified in relation to birthweight. Since the results of the omics integration indicated the central role of cholesterol metabolism, we explored the association of cholesterol levels in cord blood with birthweight in the ENVIRONAGE cohort (n = 1097), finding that higher birthweight was associated with increased high-density lipoprotein cholesterol and that high-density lipoprotein cholesterol was lower in small versus large for gestational age newborns. CONCLUSIONS: Our data suggests that an integration of different omic-layers in addition to single omics studies is a useful approach to generate new hypotheses regarding biological mechanisms. CCL22 and cholesterol metabolism in cord blood play a mechanistic role in birthweight.


Assuntos
Peso ao Nascer , Colesterol/metabolismo , Sangue Fetal/química , Quimiocina CCL22/metabolismo , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Masculino , Metaboloma , Metilação
13.
Am J Obstet Gynecol ; 223(3): 440.e1-440.e7, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32497605

RESUMO

BACKGROUND: Maternal oxygen (O2) administration is a commonly performed intrauterine resuscitation technique though to improve fetal oxygenation. However, hyperoxygenation is known to be harmful in both neonates and adults. Currently, there are no formal recommendations on whether a certain dose or duration of O2 may be most helpful in improving umbilical cord gases or neonatal outcomes. OBJECTIVE: We tested the hypothesis that prolonged supplemental O2 exposure during labor is associated with increased umbilical cord O2 concentrations. STUDY DESIGN: This was a planned secondary analysis of a randomized noninferiority trial comparing O2 with room air in laboring patients. Patients were randomized to receive either 10 L/min O2 or room air at any point during active labor when they developed a category II fetal heart tracing that would otherwise require resuscitation. The primary outcome variable for this analysis was partial pressure of O2 in the umbilical vein. The secondary outcome variable was partial pressure of O2 in the umbilical artery. These outcome variables were compared between patients with short durations of O2 exposure and those with long durations of O2 exposure, defined as <75th percentile and ≥75th percentile of duration, respectively. The outcomes were also compared among the groups that received room air, O2 for short durations, and O2 for long durations. RESULTS: Among the 99 patients with paired and validated cord gases who were included in this analysis, the partial pressure of O2 in the umbilical vein was significantly lower in patients who received O2 supplementation for longer durations than in those who received O2 for shorter durations (median interquartile range 25.5 [21.5-33] vs 32.5 [26.5-37.5] mm Hg; P<.03). There was no difference in the partial pressure of O2 in the umbilical artery or other cord gases between the short and long duration O2 supplementation groups. Other methods of intrauterine resuscitation were similar between the short and long duration O2 supplementation groups. There was no difference in the partial pressure of O2 in the umbilical artery or in the umbilical vein when the room air, short duration O2 supplementation, and long duration O2 supplementation groups were compared. CONCLUSION: Longer durations of O2 exposure are not associated with a higher partial pressure of O2 in the umbilical cord. In fact, patients with longer durations of O2 exposure had lower partial pressure of O2 in the umbilical vein, suggesting impaired placental O2 transfer with prolonged O2 exposure.


Assuntos
Sangue Fetal/química , Hipóxia Fetal/terapia , Trabalho de Parto , Oxigenoterapia , Assistência Perinatal , Adulto , Gasometria , Feminino , Humanos , Gravidez , Ressuscitação
14.
Environ Sci Pollut Res Int ; 27(27): 33703-33711, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32533481

RESUMO

Being the largest agriculture country in the Arab world, Egypt was one of the major consumer of organochlorine pesticides (OCPs) in this area, continued to have a heavy burden of OCPs in the environment. There is growing concern that OCPs could pass from the maternal circulation through the placenta to the fetal circulation and pose several health risks to their fetuses. The current study was intended to identify OCPs residue exposure in healthy pregnant women and to justify the potential impacts of these residues on their fetuses. In this study, the prevalence of 18 OCPs was estimated in 81 maternal and cord blood samples, using Agilent 7890, gas chromatograph equipped with micro-electron capture detector (GC-µECD). Our data signposted that the heptachlor epoxide has the highest detection rate among all residues in both maternal (32%) and cord blood serum (27.16%). DDTs were still quantifiable, but with the lowest quantifiable percentage. More than 85% of mothers' serum with detectable residues transfer OCPs residue to their fetuses in a statistically significant manner (x = 42.9, p value < 0.001). The present findings showed no significant growth retardation, or preterm delivery induced by in utero exposure to the most abundant residues. There is growing evidence that exposure to OCPs residue has profound impact on sex ratio. Methoxychlor, in this study be deemed as testosterone triggers which yields high boys ratio (x = 4.37, p < 0.05). In conclusion, Egypt continued to have a heavy burden of OCPs residues, and fetuses and infants are especially the most vulnerable groups to their adverse health effects. Exposure to OCPs may disrupt the maternal hormones, which regulate the offspring gender, but these results need to be validated in larger sample sizes.


Assuntos
Hidrocarbonetos Clorados/análise , Resíduos de Praguicidas/análise , Praguicidas/análise , China , Egito , Monitoramento Ambiental , Feminino , Sangue Fetal/química , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez
15.
Environ Health ; 19(1): 55, 2020 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448197

RESUMO

BACKGROUND: Organophosphate esters (OPEs) are synthetic chemicals used as flame retardants and plasticizers in a variety of goods. Despite ubiquitous human exposures and laboratory evidence that prenatal OPE exposures may disrupt offspring metabolism, perinatal studies of OPE health effects are limited. The objectives of this study were to: 1) Determine predictors and reproducibility of urinary OPE biomarker concentrations during pregnancy, and 2) Estimate the relation of prenatal OPE exposures with birth outcomes and cord blood adipokine and insulin concentrations. METHODS: We analyzed five OPE metabolites in urine samples collected at up to three visits during pregnancy from 90 women enrolled in the ORigins of Child Health And Resilience in Development (ORCHARD) pregnancy cohort in Baltimore, MD from 2017 to 2019. To quantify the variability of metabolite concentrations during pregnancy, we calculated intraclass correlation coefficients (ICCs) for each metabolite using mixed effects regression models. Using self-reported questionnaire data collected during gestation, we assessed possible sociodemographic and environmental/behavioral predictors of each OPE metabolite using generalized estimating equations to account for repeated exposure measures. We ascertained birth outcomes of 76 offspring from medical records, including weight-for-gestational age, length, ponderal index, and gestational age. In a subset of 37 infants, we measured cord blood concentrations of leptin, adiponectin, and insulin. To account for repeated exposure measures, we used linear structural equation models to assess the relations of standard deviation (SD) increases in prenatal OPE metabolite factor scores with continuous birth outcomes and cord blood biomarker concentrations. RESULTS: ICCs ranged from 0.09 for isopropylphenyl-phenyl phosphate (ip-PPP) to 0.59 for bis(1,3-dichloro-2-propyl) phosphate (BDCIPP). We observed little consistency in environmental or behavioral predictors of OPE exposures, although concentrations were generally lower for samples collected in the afternoon compared to morning and winter compared to other seasons. In adjusted analyses, a SD increase in BDCIPP concentration was associated with a 0.06 g/cm3 (95% CI: 0.00, 0.12) greater ponderal index. A SD increase in BDCIPP was associated with a 0.37 (95% CI: - 0.62, - 0.13) SD lower insulin concentration and 0.24 (95% CI: - 0.39, - 0.08) SD lower leptin concentration. Other OPEs were not associated with infant outcomes. CONCLUSIONS: These findings suggest some OPEs may be metabolic disruptors warranting investigation in larger studies.


Assuntos
Biomarcadores/sangue , Poluentes Ambientais/urina , Ésteres/urina , Sangue Fetal/química , Organofosfatos/urina , Gravidez/urina , Adolescente , Adulto , Baltimore , Feminino , Retardadores de Chama/metabolismo , Humanos , Recém-Nascido , Masculino , Exposição Materna , Pessoa de Meia-Idade , Plastificantes/metabolismo , Reprodutibilidade dos Testes , População Urbana/estatística & dados numéricos , Adulto Jovem
16.
PLoS One ; 15(5): e0232002, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379777

RESUMO

BACKGROUND: In pregnant women with gestational diabetes, glyburide can be an alternative to insulin despite concerns about its transplacental transfer. However, transplacental transfer of glyburide is poorly quantified and the relationship between cord blood glyburide concentration and hypoglycemia has not been studied. Our objective was to quantify the transplacental transfer of glyburide at delivery and to study the association between the cord blood glyburide concentration and the risk of neonatal hypoglycemia in patients with gestational diabetes treated with glyburide. METHODS AND FINDINGS: INDAO was a multicenter, noninferiority, randomized trial conducted between May 2012 and November 2016 in 914 women with singleton pregnancies and gestational diabetes. An ancillary study was conducted in the 87 patients of the Bicêtre University Hospital Center. The sample consisted of 46 patients with utilizable assays at delivery. The relationships between glyburide concentration and the time since the last intake of glyburide and between fetal glyburide concentration and neonatal hypoglycemia were modeled with linear or logistic regressions using fractional polynomials. There was placental transfer of glyburide at a fetal to maternal ratio of 62% (95% CI [50; 74]). Umbilical cord blood glyburide concentration decreased steeply after the last maternal glyburide intake. After 24 hours, the mean umbilical cord blood concentration was less than 5 ng/mL. Neonatal hypoglycemia risk was increased with an odds ratio of hypoglycemia equal to 3.70 [1.40-9.77] for each 10 ng/mL increase in the cord blood glyburide concentration. However, no newborns were admitted to the NICU because of clinical signs of hypoglycemia or for treatment of hypoglycemia. CONCLUSION: Considering that neonatal glyburide exposure may be limited by stopping treatment a sufficient time before labor, there may still be a place for glyburide in the management of gestational diabetes.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Glibureto/efeitos adversos , Hipoglicemia/etiologia , Hipoglicemiantes/uso terapêutico , Doenças do Recém-Nascido/etiologia , Administração Oral , Adulto , Relação Dose-Resposta a Droga , Feminino , Sangue Fetal/química , Sangue Fetal/metabolismo , Glibureto/análise , Glibureto/uso terapêutico , Humanos , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/análise , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Modelos Lineares , Modelos Logísticos , Troca Materno-Fetal , Razão de Chances , Gravidez
17.
JAMA Netw Open ; 3(5): e205156, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32421184

RESUMO

Importance: Exposure to ambient air pollution has been associated with the risk of carcinogenesis in later life. Changes in histone modifications might have long-term adverse health effects. Objective: To investigate the association of prenatal exposure to ambient air pollution with levels of circulating total histone H3 and specific trimethylation marks (ie, H3 lysine 4, H3 lysine 36) in maternal cord blood. Design, Setting, and Participants: The Environmental Influence on Aging (ENVIRONAGE) birth cohort study included 609 mothers and their newborns. Participants were recruited when mothers entered the Hospital East Limburg (Genk, Belgium) for delivery between February 2010 and January 2017. The inclusion criteria were singleton pregnancies and the ability to fill out questionnaires in Dutch. Data analysis was conducted from March to August 2019. Exposures: Exposure to particulate matter with a diameter less than 2.5 µm (PM2.5), black carbon, and nitrogen dioxide during pregnancy was modeled with a high-resolution air pollution model on the basis of maternal address for each trimester of pregnancy as well as for the entire pregnancy. Main Outcomes and Measures: Circulating total histone H3 levels and specific trimethylation marks (ie, trimethylated H3 lysine 4 and trimethylated H3 lysine 36) in cord blood. Results: A total of 609 mother-newborn pairs were included in the study. Mean (SD) maternal age was 29.3 (4.6) years, 391 mothers (64.2%) never smoked, and 314 (51.3%) had a high education level. Overall, 322 newborns (52.4%) were boys, and mean (SD) birth weight was 3414 (485) g. Participants experienced mean (SD) exposure to PM2.5, black carbon, and nitrogen dioxide of 13.4 (2.6) µg/m3, 1.29 (0.31) µg/m3, and 17.98 (4.57) µg/m3, respectively, during their entire pregnancies. Trimethylated H3 lysine 4 and total histone H3 were positively associated with gestational PM2.5 exposure, with a 74.4% increment (95% CI, 26.7% to 140.2%, P < .001) and a 40.2% increment (95% CI, 24.1% to 58.3%, P < .001), respectively, observed for each 5-µg/m3 increase in PM2.5 exposure during the entire pregnancy. For the same exposure window, trimethylated H3 lysine 36 levels were inversely associated with PM2.5 exposure (-34.4%; 95% CI, -50.1% to -13.7%; P = .003). Exposure to black carbon during the entire pregnancy was positively associated with trimethylated H3 lysine 4 (38.4%; 95% CI, 6.2% to 80.3%; P = .003). Conclusions and Relevance: Associations of ambient air pollution with cord plasma histone H3 modifications during early life might indicate that circulating histones are a risk factor in the development of air pollution-associated disease later in life. Additional study is required to correctly estimate the long-term consequences of our findings.


Assuntos
Poluição do Ar/efeitos adversos , Sangue Fetal/química , Histonas/sangue , Exposição Materna , Adulto , Bélgica , Feminino , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Fatores de Risco
18.
Arch Gynecol Obstet ; 301(6): 1417-1422, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32347355

RESUMO

PURPOSE: To determine the influence of maternal diets on maternal and umbilical cord blood levels of vitamin B12, folic acid, ferritin, and hemoglobin. METHODS: A prospective observational study on women who maintained the same diet for at least 3 months prior to, and throughout current pregnancy. Women were divided according to their diet. Diet questionnaires were filled in during the 3rd trimester. Blood samples for complete blood counts and levels of ferritin, vitamin B12, folate, and albumin were taken from the women prior to delivery and from the umbilical cord immediately after delivery. RESULTS: The 273 enrolled women included 112 omnivores, 37 pescatarians, 64 vegetarians, and 60 vegans. There were no significant differences in the maternal B12 levels between the study groups (P = 0.426). Vegans had lower maternal ferritin levels compared to pescatarians (27 ± 17 vs 60 ± 74 ng/ml, respectively, P = 0.034), but not compared to vegetarians (P = 0.597), or omnivores (P = 1.000). There were no significant differences in the umbilical cord B12, folate, ferritin, and hemoglobin levels between the study groups. A sub-analysis that compared women who consumed multivitamins, B12 and iron supplements during pregnancy to women who did not, revealed differences in the levels of umbilical-cord B12 (1002 ± 608 vs 442 ± 151 pg/ml, respectively, P = 0.000) and maternal blood B12 (388 ± 209 vs 219 ± 95 pg/ml, respectively, P = 0.030) only among vegans, but not among omnivores. CONCLUSION: Vegan diet does not change the umbilical cord levels of B12, folic acid, ferritin, and hemoglobin. Vegans who do not take any vitamin supplementation are at greater risk for B12 deficiency than omnivores.


Assuntos
Dieta Vegana/métodos , Ferritinas/sangue , Sangue Fetal/química , Ácido Fólico/sangue , Vitamina B 12/sangue , Adulto , Feminino , Humanos , Masculino , Gravidez , Estudos Prospectivos
19.
Acta Obstet Gynecol Scand ; 99(10): 1396-1402, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32311758

RESUMO

INTRODUCTION: Induction of labor (IOL) is used to improve the outcome of pregnancy for mother and child. Since 2013, oral misoprostol has been used for IOL at Aarhus University Hospital, Denmark. The purpose of the present paper is to describe our experience of the use of a new, 25-µg misoprostol tablet commercially manufactured for the purpose of IOL regarding efficacy and outcome for mother and neonate in both an inpatient and an outpatient regimen. MATERIAL AND METHODS: We performed an audit from 1 April 2016, including data on all IOL in women with singleton pregnancies until 1000 consecutive women were registered. Data from 976 consecutive women with gestational age ≥37+0  weeks induced in accordance with the "Aarhus protocol" were included in the present analyses. All inductions were by oral misoprostol. Outpatient induction is standard procedure in low-risk pregnancies, that is, pregnancies with a healthy mother and no signs of placental insufficiency. In the outpatient IOL, the first dose of misoprostol is administered after a normal cardiotocography registration at the hospital. Subsequent doses are taken at home according to a predefined regimen. Following delivery, data on baseline variables and outcome variables for the mother and neonate were retrieved from the medical records. RESULTS: In 71.9% of cases, the women were induced in an outpatient regimen. Delivery within 24 hours was achieved in 38.8% of women (nulliparous 32.3%, multiparous 50.9%) and within 48 hours in 70.1% (nulliparous 66.2%, multiparous 77.2%). Hyperstimulation during induction occurred in 0.6%. The mode of delivery was spontaneous vaginal in 75.5% of cases. The cesarean section rate was 14.9% (nulliparous 20.7%, multiparous 4.1%). Apgar <7 at 5 minutes and pH <7.0 in the umbilical artery was seen in 0.9% and 0.7%, respectively. CONCLUSIONS: Induction of labor by a commercially produced low-dose (25 µg) misoprostol tablet for oral induction according to the "Aarhus protocol" is feasible in an outpatient as well as an inpatient regimen. Delivery was achieved within 48 hours for 70.1% of women. Few adverse events were seen; however, the audit was underpowered for safety.


Assuntos
Auditoria Clínica , Trabalho de Parto Induzido/métodos , Misoprostol/administração & dosagem , Ocitócicos/administração & dosagem , Administração Oral , Adulto , Assistência Ambulatorial/estatística & dados numéricos , Índice de Apgar , Cesárea/estatística & dados numéricos , Parto Obstétrico , Dinamarca/epidemiologia , Feminino , Sangue Fetal/química , Hospitalização/estatística & dados numéricos , Hospitais Universitários , Humanos , Concentração de Íons de Hidrogênio , Paridade , Gravidez
20.
Ecotoxicol Environ Saf ; 197: 110643, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32315786

RESUMO

Meteorological conditions during pregnancy can affect birth outcome, which has been linked to the H19/H19-differentially methylated region (DMR). However, the detailed mechanisms underlying this association are unclear. This was investigated in the present study to provide epidemiological evidence for elucidating the pathogenesis of adverse birth outcomes. A total of 550 mother-newborn pairs were recruited in Zhengzhou, China from January 2010 to January 2012. Meteorological data including temperature (T), relative humidity (RH), and sunshine duration (SSD) were obtained from the China Meteorological Data Sharing Service System. Bisulfite sequencing PCR was performed to determine the methylation levels of H19/H19-DMR using genomic DNA extracted from maternal peripheral and umbilical cord blood. The results showed that H19-DMR methylation status in cord blood was positively associated with that in maternal blood. Neonatal H19-DMR methylation was negatively associated with T and RH during the first trimester and positively associated with these variables during the third trimester. There was a positive correlation between neonatal H19-DMR methylation and SSD during the second trimester and a negative correlation during the third trimester. Similar associations were observed between maternal H19-DMR methylation and prenatal meteorological conditions. We also observed significant interaction effects of maternal H19/H19-DMR methylation and most prenatal meteorological factors on neonatal methylation, and found that changes in the methylation status of maternal H19-DMR were responsible for the effects of prenatal meteorological conditions on neonatal methylation. In summary, neonatal H19-DMR methylation was significantly associated with prenatal meteorological conditions, which was modified and mediated by maternal H19-DMR methylation changes. These findings provide insights into the relationship between meteorological factors during pregnancy and adverse birth outcomes or disease susceptibility in offspring, and can serve as a reference for environmental policy-making.


Assuntos
Metilação de DNA , Sangue Fetal/química , Exposição Materna/efeitos adversos , Conceitos Meteorológicos , RNA Longo não Codificante/genética , Adulto , China , DNA/sangue , Feminino , Impressão Genômica , Humanos , Recém-Nascido , Gravidez , Regiões Promotoras Genéticas , RNA Longo não Codificante/sangue , Adulto Jovem
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