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1.
Acta Diabetol ; 56(9): 1073-1082, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31062097

RESUMO

AIMS: Offspring of mothers suffering from obesity and/or gestational diabetes mellitus (GDM) were reported to be at risk of higher birth weight (BW), later obesity and diabetes. We hypothesize that infant anthropometry changes related to maternal pathological status are due to dysregulated infant metabolism. METHODS: First, we inspected differences in BMI z-scores (z-BMI) between three infant groups: born to normal weight (NW; n = 49), overweight/obese (OV/OB; n = 40) and GDM mothers (n = 27) at birth and 1 year. Then, we inspected associations between cord blood metabolites and 1-year Δ z-BMI in the three infant groups at birth and 1 year. RESULTS: No statistically significant difference was detected in z-BMI between the study groups at birth; however, GDM was associated with heavier infants at 1 year. Regarding the associations between the metabolites and z-BMI, phospholipids, especially those containing polyunsaturated fatty acids, were the species most impacted by the maternal metabolic status, since numerous phosphatidylcholines-PUFA were positively associated with z-BMI in NW but negatively in OV/OB and GDM groups at birth. Conversely, the sum of lysophosphatidylcholines was only positively associated with z-BMI in NW at birth but of no relation in the other two groups. At 1 year, most of the associations seen at birth were reversed in NW and lost in OV/OB and GDM groups. In the NW group, PC-PUFA were found to be negatively associated with Δ z-BMI at 1 year in addition to some medium-chain acylcarnitines, tricarboxylic acid metabolites, Asp and Asn-to-Asp ratio. In OV/OB and GDM groups, the non-esterified fatty acid (NEFA26:0) and His correlated with Δ z-BMI at 1 year in negative and positive directions, respectively. CONCLUSIONS: GDM was associated with overweight in offspring at 1 year, independent of the BW with lack of evidence on existing correlation of this finding with metabolic alterations detected in cord blood metabolome. Associations were found between cord blood metabolites and infant anthropometry at birth and were influenced by maternal OB and GDM. However, an extension of the findings monitored at birth among the three groups was not detected longitudinally showing a lack of predictive power of cord blood metabolome for later development at least 1 year.


Assuntos
Crianças Adultas , Filho de Pais Incapacitados , Diabetes Gestacional , Sangue Fetal/metabolismo , Metaboloma , Obesidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Adulto , Crianças Adultas/estatística & dados numéricos , Peso ao Nascer/fisiologia , Índice de Massa Corporal , Estudos de Casos e Controles , Filho de Pais Incapacitados/estatística & dados numéricos , Efeito de Coortes , Diabetes Gestacional/sangue , Diabetes Gestacional/metabolismo , Características da Família , Ácidos Graxos não Esterificados/análise , Ácidos Graxos não Esterificados/sangue , Feminino , Sangue Fetal/química , Humanos , Lactente , Recém-Nascido , Masculino , Metabolômica/instrumentação , Metabolômica/métodos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/diagnóstico , Sobrepeso/complicações , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/diagnóstico
2.
Pediatrics ; 143(6)2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064798

RESUMO

Naphthalene poisoning due to exposure to mothballs is a common cause of toxicity in children worldwide. Naphthalene toxicity is known to cause hemolytic anemia, methemoglobinemia, and hepatic and renal injury. Neonates are more susceptible to the effects of oxidative stress from naphthalene because of their low glutathione stores and immaturity of hepatic enzymes. However, there are no reported cases of chronic fetal exposure to naphthalene during pregnancy. We report a novel case of chronic fetal exposure to naphthalene-containing mothballs that occurred from the second trimester through the third trimester of pregnancy. Our patient presented with hyperbilirubinemia, requiring exchange transfusion, severe hemolytic anemia, pulmonary hypertension, respiratory failure, and renal failure and progressed to develop "bronze baby" syndrome. Pregnant mothers should be diligently screened for such exposures and if found should receive psychiatric evaluation and counseling to prevent such devastating effects in neonates.


Assuntos
Ingestão de Alimentos , Naftalenos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Adulto , Anemia Hemolítica/sangue , Anemia Hemolítica/induzido quimicamente , Anemia Hemolítica/diagnóstico , Ingestão de Alimentos/fisiologia , Feminino , Humanos , Hiperbilirrubinemia/sangue , Hiperbilirrubinemia/induzido quimicamente , Hiperbilirrubinemia/diagnóstico , Recém-Nascido , Masculino , Naftalenos/administração & dosagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue
3.
Nat Commun ; 10(1): 1893, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015461

RESUMO

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.


Assuntos
Peso ao Nascer/genética , DNA/metabolismo , Epigênese Genética , Genoma Humano , Adolescente , Adulto , Índice de Massa Corporal , Criança , Ilhas de CpG , DNA/genética , Metilação de DNA , Feminino , Desenvolvimento Fetal/genética , Feto , Ácido Fólico/sangue , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fumar/efeitos adversos , Fumar/sangue , Fumar/genética
4.
Biol Psychol ; 144: 11-19, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30885739

RESUMO

Prenatal social stress "programs" offspring immune activity in animal models, but how the prenatal social environment affects human offspring inflammation is not known. Here, we test associations between prenatal partner support quality, i.e. positive/helpful support, negative/upsetting support, and their interaction, and infant inflammatory markers. A sample of 113 women from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort were followed from early pregnancy to 3-months postpartum. Partner support quality was measured during pregnancy and the postpartum period. Three-month-old infant blood samples were assayed for inflammatory markers, i.e., adaptive immune markers IFNγ, IL12p70 and IL10. The prenatal positive-by-negative partner support interaction predicted infant IFNγ, IL12p70, and IL10, p's<.035, independent of covariates and postpartum partner support. When negative partner support was high, high positive support predicted higher infant IFNγ, IL12p70, and IL10. As such, partner support during pregnancy that is both highly negative/upsetting and also highly positive/helpful predicted adaptive immunity markers in infants at 3 months of age.


Assuntos
Mediadores da Inflamação/sangue , Complicações na Gravidez/psicologia , Efeitos Tardios da Exposição Pré-Natal/sangue , Parceiros Sexuais/psicologia , Apoio Social , Adulto , Alberta , Estudos de Coortes , Feminino , Humanos , Lactente , Inflamação , Masculino , Período Pós-Parto/psicologia , Gravidez , Resultado da Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estresse Psicológico/psicologia , Adulto Jovem
5.
Ecotoxicol Environ Saf ; 174: 263-269, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30831475

RESUMO

As endocrine disrupting chemicals, hexachlorocyclohexane (HCH) isomers were reported to impair the intrauterine growth. Although the findings of HCHs with preterm birth were well established, the associations with gestational age were limited. In the present study, we examined whether exposure to HCHs would influence gestational age. The study population included 1028 pregnant women and their offspring who were born in 2014-2015 from a birth cohort in Wuhan, China. Associations of the cord serum HCH levels with gestational age were estimated using generalized linear models. We found higher HCH levels in pregnant women, who were elder, had higher body mass index (BMI) before pregnancy, received higher education, or were exposed to smoking passively. For term birth, the 3rd tertiles of α-HCH and γ-HCH were significantly associated with shorter gestational age [crude ß = -1.017, confidence interval (CI): - 2.017, - 0.018 for α-HCH, crude ß = -1.068, CI: - 2.067, - 0.070 for γ-HCH], and relationships were similar after adjusted by covariates. Stratified analysis showed positive associations between α-HCH and gestational age for mothers younger than 25 years old (adjusted ß = 0.610, CI: 0.061, 1.158), while showing negative relationships for mothers elder than 35 years old (adjusted ß = -1.365, CI: -2.414, -0.317). In summary, our results indicated cord serum levels of HCHs were associated with gestational age at birth.


Assuntos
Disruptores Endócrinos/sangue , Sangue Fetal/química , Idade Gestacional , Hexaclorocicloexano/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Adulto , China , Feminino , Ganho de Peso na Gestação , Humanos , Recém-Nascido , Idade Materna , Exposição Materna , Gravidez , Nascimento Prematuro/sangue
6.
Anal Bioanal Chem ; 411(11): 2351-2362, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30783713

RESUMO

Metabolism of chemicals from the diet, exposures to xenobiotics, the microbiome, and lifestyle factors (e.g., smoking, alcohol intake) produce electrophiles that react with nucleophilic sites in circulating proteins, notably Cys34 of human serum albumin (HSA). To discover potential risk factors resulting from in utero exposures, we are investigating HSA-Cys34 adducts in archived newborn dried blood spots (DBS) that reflect systemic exposures during the last month of gestation. The workflow includes extraction of proteins from DBS, measurement of hemoglobin (Hb) to normalize for blood volume, addition of methanol to enrich HSA by precipitation of Hb and other interfering proteins, digestion with trypsin, and detection of HSA-Cys34 adducts via nanoflow liquid chromatography-high-resolution mass spectrometry. As proof-of-principle, we applied the method to 49 archived DBS collected from newborns whose mothers either actively smoked during pregnancy or were nonsmokers. Twenty-six HSA-Cys34 adducts were detected, including Cys34 oxidation products, mixed disulfides with low molecular weight thiols (e.g., cysteine, homocysteine, glutathione, cysteinylglycine), and other modifications. Data were normalized with a novel method ("scone") to remove unwanted technical variation arising from HSA digestion, blood volume, DBS age, mass spectrometry analysis, and batch effects. Using an ensemble of linear and nonlinear models, the Cys34 adduct of cyanide was found to consistently discriminate between newborns of smoking and nonsmoking mothers with a mean fold change (smoking/nonsmoking) of 1.31. These results indicate that DBS adductomics is suitable for investigating in utero exposures to reactive chemicals and metabolites that may influence disease risks later in life.


Assuntos
Cisteína/análise , Teste em Amostras de Sangue Seco/métodos , Albumina Sérica Humana/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Feminino , Humanos , Recém-Nascido , Exposição Materna/efeitos adversos , Oxirredução , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Fumar/efeitos adversos , Fumar/sangue
7.
BMC Med ; 17(1): 27, 2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30722777

RESUMO

BACKGROUND: Newborn telomere length (TL) is considered a potential marker for future disease and lifelong health, but few epidemiological studies have examined the determinants of TL in early life. The study aim was to investigate whether there is an association between prenatal cadmium exposure and relative cord blood TL in Chinese newborns. METHODS: Participants were 410 mother-newborn pairs drawn from a prospective birth cohort study conducted in Wuhan, China, between November 2013 and March 2015. Urine samples were collected from pregnant women during their period of institutional delivery. Urinary cadmium concentrations were measured by inductively coupled plasma mass spectrometry. The real-time quantitative polymerase chain reaction detection was used to measure relative TL using genomic DNA isolated from umbilical cord blood leukocytes. Multivariate linear regression models were used to estimate the effect of prenatal urinary cadmium concentration on relative cord blood TL. RESULTS: The geometric mean of maternal urinary cadmium concentration was 0.68 µg/g creatinine. In the multivariate-adjusted linear regression model, per doubling of maternal urinary cadmium concentration was associated with 6.83% (95% CI - 11.44%, - 1.97%; P = 0.006) shorter relative cord blood TL. Stratified analyses indicated that the inverse association between prenatal urinary cadmium and newborn relative TL was more pronounced among female infants and mothers < 29 years, while there were no significant effect modification according to infant sex (P for interaction = 0.907) and maternal age (P for interaction = 0.797). CONCLUSIONS: The findings indicated that increased maternal urinary cadmium was associated with shortened relative cord blood TL. The results provide more evidence of the negative effects of environmental cadmium exposure and suggest that accelerated aging or cadmium-related diseases may begin in early life.


Assuntos
Cádmio/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/patologia , Telômero/efeitos dos fármacos , Telômero/patologia , Adulto , Cádmio/urina , China , Estudos de Coortes , Feminino , Sangue Fetal/efeitos dos fármacos , Humanos , Recém-Nascido , Leucócitos/patologia , Modelos Lineares , Masculino , Mães , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Estudos Prospectivos
8.
Artigo em Inglês | MEDLINE | ID: mdl-30764478

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive or stereotypic behaviours. In utero exposure to environmental chemicals, such as polychlorinated biphenyls (PCBs), may play a role in the etiology of ASD. We examined the relation between plasma PCB concentrations measured during pregnancy and autistic behaviours in a subset of children aged 3⁻4 years old in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pregnancy and birth cohort of 546 mother-infant pairs from Canada (enrolled: 2008⁻2011). We quantified the concentrations of 6 PCB congeners that were detected in >40% of plasma samples collected during the 1st trimester. At age 3⁻4 years, caregivers completed the Social Responsiveness Scale-2 (SRS), a valid and reliable measure of children's reciprocal social and repetitive behaviours and restricted interests. We examined SRS scores as both a continuous and binary outcome, and we calculated Bayesian predictive odds ratios for more autistic behaviours based on a latent variable model for SRS scores >60. We found no evidence of an association between plasma PCB concentrations and autistic behaviour. However, we found small and imprecise increases in the mean SRS score and odds of more autistic behaviour for the highest category of plasma PCB concentrations compared with the lowest category; for instance, an average increase of 1.4 (95%PCI: -0.4, 3.2) in the mean SRS (exposure contrast highest versus lowest PCB category) for PCB138 translated to an odds ratio of 1.8 (95%PCI: 1.0, 2.9). Our findings illustrate the importance of measuring associations between PCBs and autistic behaviour on both continuous and binary scales.


Assuntos
Transtorno do Espectro Autista/induzido quimicamente , Poluentes Ambientais/sangue , Exposição Materna/efeitos adversos , Bifenilos Policlorados/sangue , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Transtorno do Espectro Autista/sangue , Teorema de Bayes , Canadá , Estudos de Casos e Controles , Pré-Escolar , Monitoramento Ambiental , Feminino , Humanos , Masculino , Razão de Chances , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Fatores de Risco
9.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(2): 180-185, 2019 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-30744269

RESUMO

Objective: To study the dose-response relationship between maternal thyroid hormone levels in the first twenty weeks of pregnancy and the infant physical and neuropsychological development. Methods: In this prospective cohort study, a total of 945 women and their children were included. Maternal serum samples during first half of the pregnancy were collected and analyzed for levels of thyroid hormones by using the electro-chemiluminescence immunoassay. Maternal social demographic information was collected by using the a self-administered questionnaire. Physical measurements of newborns and neuropsychological evaluation of infants were performed by doctors of maternal and child health care. Results: The differences in newborns' birth length and head circumference were significant among the newborns of mothers with different percentiles of maternal serum (thyroid-stimulating hormone, TSH) levels (P<0.05). Newborns with maternal TSH level ≥P(95) or

Assuntos
Peso ao Nascer/fisiologia , Desenvolvimento Infantil/fisiologia , Hormônios Tireóideos/sangue , Tireotropina/sangue , Criança , China , Feminino , Sangue Fetal/metabolismo , Humanos , Lactente , Recém-Nascido/sangue , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Estudos Prospectivos , Glândula Tireoide/fisiologia , Hormônios Tireóideos/metabolismo
10.
Pediatrics ; 143(3)2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30804074

RESUMO

OBJECTIVES: An association between maternal smoking during pregnancy and offspring attention-deficit/hyperactivity disorder (ADHD) has been shown across several studies based on self-reports. No previous studies have investigated the association of nicotine exposure measured by cotinine levels during pregnancy and offspring ADHD. METHODS: In this population-based study, 1079 patients born between 1998 and 1999 and diagnosed with ADHD according to the International Classification of Diseases and 1079 matched controls were identified from Finnish nationwide registers. Maternal cotinine levels were measured by using quantitative immunoassays from maternal serum specimens collected during the first and second trimesters of pregnancy and archived in the national biobank. RESULTS: There was a significant association between increasing log-transformed maternal cotinine levels and offspring ADHD. The odds ratio was 1.09 (95% confidence interval [CI] 1.06-1.12) when adjusting for maternal socioeconomic status, maternal age, maternal psychopathology, paternal age, paternal psychopathology, and child's birth weight for gestational age. In the categorical analyses with cotinine levels in 3 groups, heavy nicotine exposure (cotinine level >50 ng/mL) was associated with offspring ADHD, with an odds ratio of 2.21 (95% CI 1.63-2.99) in the adjusted analyses. Analyses by deciles of cotinine levels revealed that the adjusted odds for offspring ADHD in the highest decile was 3.34 (95% CI 2.02-5.52). CONCLUSIONS: The study reveals an association with and a dose-response relationship between nicotine exposure during pregnancy and offspring ADHD. Future studies incorporating maternal smoking and environmental, genetic, and epigenetic factors are warranted.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/sangue , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Cotinina/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
11.
J Matern Fetal Neonatal Med ; 32(2): 173-178, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28851248

RESUMO

The administration of testosterone to pregnant sheep to resemble fetal programming of the polycystic ovary syndrome could alter other hormones/factors of maternal origin with known effects on fetal growth. Hence, we studied the weekly profile of insulin, progesterone and glucose during a treatment with testosterone propionate given biweekly from weeks 5 to 17 of pregnancy (term at 21 weeks) and checked the outcome of their fetuses at 17 weeks of gestation after C-section. Control dams were only exposed to the vehicle of the hormone. The testosterone administration did not cause any significant change in the maternal weekly profile of insulin, progesterone or glucose concentration, although the plasma levels of testosterone in the treated dams were inversely correlated to the levels of progesterone. Testosterone treatment also induced an inverse correlation between mean maternal insulin levels and fetal insulin levels; however, the fetal zoometric parameters, body weight, or insulin levels did not differ between exposed and not exposed fetuses. Therefore, treatment with testosterone during pregnancy does not cause significant impact on insulin levels in the mother, leading to less effect on the programming of fetal growth.


Assuntos
Glicemia/metabolismo , Insulina/sangue , Síndrome do Ovário Policístico/patologia , Efeitos Tardios da Exposição Pré-Natal/sangue , Testosterona/farmacologia , Animais , Animais Recém-Nascidos , Glicemia/análise , Glicemia/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Feto/efeitos dos fármacos , Feto/metabolismo , Síndrome do Ovário Policístico/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/veterinária , Ovinos , Fatores de Tempo
12.
Pediatr Int ; 61(2): 140-146, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30565800

RESUMO

BACKGROUND: We investigated the association between the hormone environment during the prenatal period using cord blood, and gender-role play behavior in school-aged children. METHODS: A total of 879 school-aged children (433 boys and 446 girls) in a prospective birth cohort study in Hokkaido were enrolled to analyze the relationship between cord blood level of the sex hormones estradiol (E), testosterone (T), progesterone (P), and dehydroepiandrosterone (DHEA), and the Pre-School Activities Inventory (PSAI) score. The PSAI evaluated sex-typical characteristics, the type of preferred toys and play activities. The PSAI consists of 12 masculine and 12 feminine items, and the composite scores were calculated by subtracting the feminine score from the masculine score. Higher scores indicated male-typical behavior. RESULTS: Composite and masculine PSAI scores were significantly higher in boys. Meanwhile, the feminine score was significantly lower in boys. Although T and P were significantly higher in boys, E/T was significantly higher in girls. In a multivariate regression model, including covariates of social factors, there was no correlation between any of the hormones and PSAI score in boys. In girls, only P and E/T were positively correlated with the feminine score. CONCLUSIONS: Prenatal sex hormone exposure may influence the dimorphic brain development and behavior in school-aged girls. Furthermore, the cord blood hormone levels may not fully reflect the hormone environment during the prenatal period.


Assuntos
Comportamento Infantil/fisiologia , Sangue Fetal/metabolismo , Identidade de Gênero , Hormônios Esteroides Gonadais/sangue , Jogos e Brinquedos/psicologia , Efeitos Tardios da Exposição Pré-Natal/sangue , Biomarcadores/sangue , Criança , Comportamento Infantil/psicologia , Feminino , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia , Estudos Prospectivos
13.
Food Chem Toxicol ; 123: 546-552, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30543894

RESUMO

We studied in rats the effects of cafeteria diet (CD) supplemented (or not) with fish oil (FO) during just the first 12 days of pregnancy, or during the whole of pregnancy and lactation in 14-month old offspring. Female rats were given standard diet (STD) or CD and after mating some animals remained on STD or CD; for some CD rats the diet was supplemented with 8.78% FO. After 12 days, half of the CD-FO group returned to CD (CD-FO12) and the others remained on CD-FO. From weaning all offspring were given STD. The adiposity index of male offspring of CD dams increased but was normal in CD-FO males. Plasma triacylglycerols (TAG) and individual fatty acid concentrations were similar among the groups. Liver total lipids, TAG, fatty acid concentrations, Δ9-desaturase indices and the mRNA expression of fatty acid synthase were higher in male offspring of CD than in those of STD; most of these differences disappeared in male offspring of CD-FO12 and CD-FO dams. Female offspring showed smaller changes. Thus, a moderate supplement with FO during just the first half of gestation or during pregnancy and lactation in rats on CD decreases the liver steatosis in male adult offspring.


Assuntos
Dieta/efeitos adversos , Suplementos Nutricionais/análise , Fígado Gorduroso/prevenção & controle , Óleos de Peixe/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Animais , Ácidos Graxos/sangue , Fígado Gorduroso/sangue , Fígado Gorduroso/etiologia , Feminino , Humanos , Fígado/metabolismo , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/etiologia , Ratos , Ratos Sprague-Dawley , Fatores Sexuais , Triglicerídeos/sangue
14.
Mol Cell Endocrinol ; 482: 45-56, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30550814

RESUMO

The aim of the present study was to compare the effect of oral and subcutaneous exposure to a glyphosate-based herbicide (GBH) on the female reproductive system, specifically in the ovaries and uterus of prepubertal lambs. To this end, ewe lambs were exposed to a s.c. (n: 5) or an oral (n: 5) environmentally relevant dose of GBH (2 mg/kg/day) or to vehicle (controls, n: 12), from postnatal day (PND) 1 to PND14. Serum glyphosate and aminomethylphosphonic acid (AMPA) concentrations were measured on PND15 and PND45. The ovaries and uterus were obtained and weighed on PND45. Ovarian follicular dynamics and uterine morphological features were determined by picrosirius-hematoxylin staining. The proliferation marker Ki67 was evaluated by immunohistochemistry in ovarian and uterine samples. Glyphosate but not AMPA was detected in serum of exposed lambs on PND15, whereas neither glyphosate nor AMPA were detected on PND45. Controls were negative for glyphosate and AMPA on PND15 and PND45. GBH exposure did not affect ovarian or uterine weight. However, on PND45, the ovary of GBH-exposed lambs showed altered follicular dynamics, increased proliferation of granulosa and theca cells, and decreased mRNA expression of FSHR and GDF9, whereas their uterus showed decreased cell proliferation but no alterations in the histomorphology or gene expression. In conclusion, GBH exposure altered the ovarian follicular dynamics and gene expression, and the proliferative activity of the ovaries and uterus of lambs. It is noteworthy that all the adverse effects found in the ovaries and uterus of both GBH-exposed groups were similar, independently of the administration route.


Assuntos
Glicina/análogos & derivados , Herbicidas/efeitos adversos , Ovário/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Útero/efeitos dos fármacos , Administração Oral , Animais , Animais Recém-Nascidos , Proliferação de Células , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Glicina/efeitos adversos , Glicina/sangue , Glicina/farmacologia , Fator 9 de Diferenciação de Crescimento/genética , Herbicidas/sangue , Herbicidas/farmacologia , Injeções Subcutâneas , Isoxazóis/sangue , Tamanho do Órgão/efeitos dos fármacos , Ovário/citologia , Ovário/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/genética , Receptores do FSH/genética , Carneiro Doméstico , Tetrazóis/sangue , Útero/citologia , Útero/metabolismo
15.
Psychoneuroendocrinology ; 99: 257-264, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30390444

RESUMO

Background Adipocytokines may play a role in fetal programming of neurodevelopment. We aimed to investigate the associations between cord blood adipocytokine concentrations and children's intelligence test scores. Methods We used data from two ongoing pregnancy cohorts in North America: the Maternal-Infant Research on Environmental Chemicals (MIREC, n = 429) and Health Outcomes and Measures of the Environment (HOME, n = 183) Studies. Umbilical cord blood adipocytokine concentrations were measured using enzyme-linked immunosorbent assays. We assessed children's Intelligence Quotient (IQ) and its components using the Wechsler Preschool and Primary Scales of Intelligence-III or Wechsler Intelligence Scale for Children-IV. We used linear regression and linear mixed models to estimate associations between log2-transformed adipocytokine concentrations and children's IQ after adjusting for sociodemographic, perinatal, and child factors. Results After adjusting for covariates, cord blood adiponectin was positively associated with children's full-scale IQ scores at age 3 years in the MIREC Study (ß = 1.4, 95% confidence interval [CI]: 0.2, 2.5) and at ages 5 and 8 years in the HOME Study (ß = 1.7, CI: -0.1, 3.5). Adiponectin was positively associated with performance IQ in both studies (MIREC: ß = 2.0, CI: 0.7, 3.3; HOME: ß = 2.2, CI: 0.5, 3.9). Adiponectin was positively associated with working memory composite scores at age 8 in the HOME Study (ß = 3.1, CI: 1.0, 5.2). Leptin was not associated with children's IQ in either study. Conclusions Cord blood adiponectin was associated with higher full-scale and performance IQ and working memory composite scores in children. Future studies are needed to explore the mechanisms underlying these associations.


Assuntos
Adiponectina/fisiologia , Cognição/fisiologia , Leptina/fisiologia , Adiponectina/metabolismo , Biomarcadores/sangue , Desenvolvimento Infantil , Pré-Escolar , Feminino , Sangue Fetal/química , Humanos , Inteligência/fisiologia , Testes de Inteligência , Leptina/metabolismo , Masculino , Memória de Curto Prazo/fisiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue
16.
J Matern Fetal Neonatal Med ; 32(3): 448-454, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28922987

RESUMO

BACKGROUND: Hypoglycaemia accounts for approximately one-tenth of term admissions to neonatal units can cause long-term neurodevelopmental impairment and is associated with the significant burden to the affected infants, families and the health system. OBJECTIVE: To define the prevalence, length and cost of admissions for hypoglycaemia in infants born at greater than 35 weeks gestation and to identify antenatal and perinatal predictors of those outcomes. MATERIALS AND METHODS: This was a retrospective audit of infants admitted for hypoglycaemia between 1 January 2012 and 31 December 2015, in a level three neonatal intensive care unit at King's College Hospital NHS Foundation Trust, London. The main outcome measures were the prevalence, length and cost of admissions for hypoglycaemia and antenatal and postnatal predictors of the length and cost of the stay. RESULTS: There were 474 admissions for hypoglycaemia (17.8% of total admissions). Their median (IQR) blood glucose on admission was 2.1 (1.7-2.4) mmol/l, gestation at delivery 38.1 (36.7-39.3) weeks, birthweight percentile 31.4 (5.4-68.9), their length of stay was 3.0 (2.0-5.0). Admissions equated to a total of 2107 hospital days. The total cost of the stay was 1,316,591 Great Britain pound. The antenatal factors associated with admission for hypoglycaemia were maternal hypertension (19.8%), maternal diabetes (24.5%), foetal growth restriction (FGR) (25.9%) and pathological intrapartum cardiotocograph (23.4%). In 13.7% of cases, there was no associated pregnancy complication. Multivariate logistic regression analysis demonstrated lower gestational age, z-score birthweight squared, exclusive breastfeeding and maternal prescribed nifedipine were independently associated with the length and cost of the stay. CONCLUSION: Hypoglycaemia accounted for approximately one-fifth of admissions after 35-week gestation. Lower gestational age and admission blood glucose, low and high z-score birthweight, maternal nifedipine and exclusive breastfeeding are associated with longer duration of stay.


Assuntos
Hipoglicemia , Doenças do Recém-Nascido , Tempo de Internação , Admissão do Paciente , Complicações na Gravidez/diagnóstico , Custos e Análise de Custo , Feminino , Idade Gestacional , Humanos , Hipoglicemia/diagnóstico , Hipoglicemia/economia , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/economia , Doenças do Recém-Nascido/epidemiologia , Unidades de Terapia Intensiva Neonatal/economia , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Admissão do Paciente/economia , Admissão do Paciente/estatística & dados numéricos , Gravidez , Complicações na Gravidez/epidemiologia , Diagnóstico Pré-Natal , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/economia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco
17.
Neuroimage ; 185: 825-835, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29654875

RESUMO

Maternal inflammation during pregnancy can alter the trajectory of fetal brain development and increase risk for offspring psychiatric disorders. However, the majority of relevant research to date has been conducted in animal models. Here, in humans, we focus on the structural connectivity of frontolimbic circuitry as it is both critical for socioemotional and cognitive development, and commonly altered in a range of psychiatric disorders associated with intrauterine inflammation. Specifically, we test the hypothesis that elevated maternal concentration of the proinflammatory cytokine interleukin-6 (IL-6) during pregnancy will be associated with variation in microstructural properties of this circuitry in the neonatal period and across the first year of life. Pregnant mothers were recruited in early pregnancy and maternal blood samples were obtained for assessment of maternal IL-6 concentrations in early (12.6 ±â€¯2.8 weeks [S.D.]), mid (20.4 ±â€¯1.5 weeks [S.D.]) and late (30.3 ±â€¯1.3 weeks [S.D.]) gestation. Offspring brain MRI scans were acquired shortly after birth (N = 86, scan age = 3.7 ±â€¯1.7 weeks [S.D.]) and again at 12-mo age (N = 32, scan age = 54.0 ±â€¯3.1 weeks [S.D.]). Diffusion Tensor Imaging (DTI) was used to characterize fractional anisotropy (FA) along the left and right uncinate fasciculus (UF), representing the main frontolimbic fiber tract. In N = 30 of the infants with serial MRI data at birth and 12-mo age, cognitive and socioemotional developmental status was characterized using the Bayley Scales of Infant Development. All analyses tested for potentially confounding influences of household income, prepregnancy Body-Mass-Index, obstetric risk, smoking during pregnancy, and infant sex, and outcomes at 12-mo age were additionally adjusted for the quality of the postnatal caregiving environment. Maternal IL-6 concentration (averaged across pregnancy) was prospectively and inversely associated with FA (suggestive of reduced integrity under high inflammatory conditions) in the newborn offspring (bi-lateral, p < 0.01) in the central portion of the UF proximal to the amygdala. Furthermore, maternal IL-6 concentration was positively associated with rate of FA increase across the first year of life (bi-lateral, p < 0.05), resulting in a null association between maternal IL-6 and UF FA at 12-mo age. Maternal IL-6 was also inversely associated with offspring cognition at 12-mo age, and this association was mediated by FA growth across the first year of postnatal life. Findings from the current study support the premise that susceptibility for cognitive impairment and potentially psychiatric disorders may be affected in utero, and that maternal inflammation may constitute an intrauterine condition of particular importance in this context.


Assuntos
Encéfalo/crescimento & desenvolvimento , Cognição/fisiologia , Interleucina-6/sangue , Rede Nervosa/crescimento & desenvolvimento , Efeitos Tardios da Exposição Pré-Natal , Anisotropia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Inflamação/complicações , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Mães , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Substância Branca/crescimento & desenvolvimento
18.
PLoS One ; 13(12): e0208846, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30557361

RESUMO

There is evidence from longitudinal studies that being light at birth and weaning is associated with subsequent rapid weight gain in infants. This is referred to as "centile crossing", which can lead to increased risk of lifetime obesity, glucose dysregulation and type 2 diabetes. Here, pregnant CD-1 mice were hemi-ovariectomized so that the entire litter was contained in one uterine horn to increase variability in fetal growth rate. Pregnant females were implanted on gestation day (GD) 9 with a Silastic capsule containing 6, 60 or 600 µg bisphenol A (BPA). On GD 18 the mean fetal serum unconjugated BPA concentrations were 17, 177 and 1858 pg/ml, respectively. Capsules were not removed, to avoid maternal stress, and were predicted to release BPA for at least 3 weeks. Body weight at weaning was strongly negatively correlated with post-weaning weight gain in both control and BPA-treated male mice, consistent with human data; female offspring were excluded, avoiding complications associated with postpubertal estrogens. Within each treatment group, male offspring were sorted into tertiles based on relative weight gain during the two weeks after weaning, designated as having Rapid (R), Medium (M) or Slow (S) growth rate. BPA exposure was associated with altered growth rate between weaning and postnatal week 12 (young adulthood), when a low-dose (20 mg/kg, i.p.) glucose tolerance test (GTT) was performed. We found altered glucose regulation in response to all doses of BPA. However, glucose tolerance was only significantly impaired (blood glucose levels were elevated) compared to controls in males in the rapid post-weaning growth group exposed perinatally to BPA. We conclude that male mice that are light at weaning, but then experience rapid catch-up growth immediately after weaning, represent a sensitive sub-population that is vulnerable to the metabolic disrupting effects of very low pg/ml fetal serum concentrations of BPA.


Assuntos
Compostos Benzidrílicos/farmacologia , Peso Corporal/efeitos dos fármacos , Intolerância à Glucose/sangue , Fenóis/farmacologia , Ganho de Peso/efeitos dos fármacos , Animais , Compostos Benzidrílicos/sangue , Feminino , Teste de Tolerância a Glucose , Masculino , Camundongos , Fenóis/sangue , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Desmame
19.
Rev Esp Salud Publica ; 922018 06 04.
Artigo em Espanhol | MEDLINE | ID: mdl-29863107

RESUMO

The increase in C5-carnitin (C5) quantified by tandem mass spectrometry allows for early detection of isovaleric acidemia (IVA) in newborns. The administration of pro- drugs like cefditoren pivoxil (CFP) composed by pivalic acid esters also causes increases of C5 in blood. This work shows the experience of the Laboratorio de Cribado Neonatal of the Comunidad de Madrid in the newborn screening for IVA. 418.863 newborns have been analyzed and no cases of IVA have been detected, but there were 18 cases of increase of C5 in newborns from mothers treated with CFP before labour. The concentrations of C5 obtained in these cases were comparable to those from cases diagnosed of IVA in other countries. We also studied the concentration of C5 the blood of a patient who was treated with CFP, in whom we observed an elevation which was restored after treatment was finished. CFP is an antibiotic prescribed to pregnant women in Spain and can cause elevation of C5 in blood that can induce to suspect a case of IVA, causing alarm in the newborn family and forcing to a follow-up.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Antibacterianos/efeitos adversos , Carnitina/sangue , Cefalosporinas/efeitos adversos , Isovaleril-CoA Desidrogenase/deficiência , Triagem Neonatal , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Erros Inatos do Metabolismo dos Aminoácidos/sangue , Antibacterianos/administração & dosagem , Biomarcadores/sangue , Cefalosporinas/administração & dosagem , Reações Falso-Positivas , Feminino , Seguimentos , Humanos , Recém-Nascido , Isovaleril-CoA Desidrogenase/sangue , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Espanha , Espectrometria de Massas em Tandem
20.
PLoS One ; 13(5): e0196862, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29723293

RESUMO

BACKGROUND: Elevated testosterone (T) is routinely reported as a marker of hyperandrogenemia in rodent models for polycystic ovary syndrome (PCOS). In women with PCOS, elevated serum androstenedione (A4) is associated with more severe phenotypes, including a positive correlation with serum T, DHEAS, free androgen index (FAI), LH, and LH/FSH ratio. Furthermore, A4, along with calculated free T and FAI, was identified as one of the best predictors of PCOS in adult women of all ages (18 to > 50 y). OBJECTIVE: The objective of this study was to investigate serum A4 levels in early adolescent and young adult prenatally androgenized (PNA) female rats, a model for PCOS. METHODS: Pregnant rats were injected with 5 mg T daily during gestational days 16-19 (PNA rats, experimental group) or an equal volume of vehicle (control group). Female offspring of both groups had tail vein blood drawn for serum analysis at 8 and 16 weeks of age. ELISAs were used to quantify serum A4 and T levels. RESULTS: Serum A4 and T were elevated in 16-week-old PNA rats compared to controls. There was no significant difference in either hormone at 8 weeks of age. CONCLUSIONS: The PNA rats demonstrated elevated serum A4 and T in young adulthood, as has been observed in women with PCOS, further validating this as a model for PCOS and underscoring the importance of serum A4 elevation as a parameter inherent to PCOS and a rodent model for the disorder. Significant A4 elevation develops between early adolescence and early adulthood in this PNA rat model.


Assuntos
Envelhecimento/sangue , Androstenodiona/sangue , Hiperandrogenismo/sangue , Síndrome do Ovário Policístico/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Testosterona/administração & dosagem , Animais , Animais Recém-Nascidos , Biomarcadores/sangue , Modelos Animais de Doenças , Feminino , Hormônio Foliculoestimulante/sangue , Hiperandrogenismo/induzido quimicamente , Hiperandrogenismo/patologia , Hormônio Luteinizante/sangue , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/patologia , Ratos , Ratos Sprague-Dawley , Maturidade Sexual , Testosterona/sangue
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