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1.
PLoS Med ; 17(9): e1003322, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32870921

RESUMO

BACKGROUND: Despite the widespread use, only sparse information is available on the safety of gabapentin during pregnancy. We sought to evaluate the association between gabapentin exposure during pregnancy and risk of adverse neonatal and maternal outcomes. METHODS AND FINDINGS: Using the United States Medicaid Analytic eXtract (MAX) dataset, we conducted a population-based study of 1,753,865 Medicaid-eligible pregnancies between January 2000 and December 2013. We examined the risk of major congenital malformations and cardiac defects associated with gabapentin exposure during the first trimester (T1), and the risk of preeclampsia (PE), preterm birth (PTB), small for gestational age (SGA), and neonatal intensive care unit admission (NICUa) associated with gabapentin exposure early, late, or both early and late in pregnancy. Gabapentin-unexposed pregnancies served as the reference. We estimated relative risks (RRs) and 95% confidence intervals (CIs) using fine stratification on the propensity score (PS) to control for over 70 confounders (e.g., maternal age, race/ethnicity, indications for gabapentin, other pain conditions, hypertension, diabetes, use of opioids, and specific morphine equivalents). We identified 4,642 pregnancies exposed in T1 (mean age = 28 years; 69% white), 3,745 exposed in early pregnancy only (28 years; 67% white), 556 exposed in late pregnancy only (27 years; 60% white), and 1,275 exposed in both early and late pregnancy (29 years; 75% white). The reference group consisted of 1,744,447 unexposed pregnancies (24 years; 40% white). The adjusted RR for major malformations was 1.07 (95% CI 0.94-1.21, p = 0.33) and for cardiac defects 1.12 (0.89-1.40, p = 0.35). Requiring ≥2 gabapentin dispensings moved the RR to 1.40 (1.03-1.90, p = 0.03) for cardiac defects. There was a higher risk of preterm birth among women exposed to gabapentin either late (RR, 1.28 [1.08-1.52], p < 0.01) or both early and late in pregnancy (RR, 1.22 [1.09-1.36], p < 0.001), SGA among women exposed to gabapentin early (1.17 [1.02-1.33], p = 0.02), late (1.39 [1.01-1.91], p = 0.05), or both early and late in pregnancy (RR, 1.32 [1.08-1.60], p < 0.01), and NICU admission among women exposed to gabapentin both early and late in pregnancy (RR, 1.35 [1.20-1.52], p < 0.001). There was no higher risk of preeclampsia among women exposed to gabapentin after adjustment. Study limitations include the potential for residual confounding and exposure misclassification. CONCLUSIONS: In this large population-based study, we did not find evidence for an association between gabapentin exposure during early pregnancy and major malformations overall, although there was some evidence of a higher risk of cardiac malformations. Maternal use of gabapentin, particularly late in pregnancy, was associated with a higher risk of PTB, SGA, and NICUa.


Assuntos
Gabapentina/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Anormalidades Induzidas por Medicamentos/metabolismo , Adulto , Estudos de Coortes , Feminino , Gabapentina/uso terapêutico , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Pré-Eclâmpsia/fisiopatologia , Gravidez , Complicações na Gravidez , Primeiro Trimestre da Gravidez , Nascimento Prematuro , Pontuação de Propensão , Risco , Estados Unidos
2.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913133

RESUMO

BACKGROUND: Despite the standardization of care, formula feeding varied across sites of the Ohio Perinatal Quality Collaborative (OPQC). We used orchestrated testing (OT) to learn from this variation and improve nonpharmacologic care of infants with neonatal abstinence syndrome (NAS) requiring pharmacologic treatment in Ohio. METHODS: To test the impact of formula on length of stay (LOS), treatment failure, and weight loss among infants hospitalized with NAS, we compared caloric content (high versus standard) and lactose content (low versus standard) using a 22 factorial design. During October 2015 to June 2016, OPQC sites joined 1 of 4 OT groups. We used response plots to examine the effect of each factor and control charts to track formula use and LOS. We used the OT results to revise the nonpharmacologic bundle and implemented it during 2017. RESULTS: Forty-seven sites caring for 546 NAS infants self-selected into the 4 OT groups. Response plots revealed the benefit of high-calorie formula (HCF) on weight loss, treatment failure, and LOS. The nonpharmacologic treatment bundle was updated to recommend HCF when breastfeeding was not possible. During implementation, HCF use increased, and LOS decreased from 17.1 to 16.4 days across the OPQC. CONCLUSIONS: OT revealed that HCF was associated with shorter LOS in OPQC sites. Implementation of a revised nonpharmacologic care bundle was followed by additional LOS improvement in Ohio. Despite some challenges in the implementation of OT, our findings support its usefulness for learning in improvement networks.


Assuntos
Ingestão de Energia , Fórmulas Infantis , Tempo de Internação/estatística & dados numéricos , Síndrome de Abstinência Neonatal/terapia , Feminino , Humanos , Recém-Nascido , Lactose/administração & dosagem , Metadona/administração & dosagem , Metadona/efeitos adversos , Morfina/administração & dosagem , Morfina/efeitos adversos , Ohio , Tratamento de Substituição de Opiáceos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Melhoria de Qualidade/organização & administração , Ganho de Peso
3.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32938776

RESUMO

For healthy individuals, it is increasingly accepted that lung function follows along an individual percentile established early in life and that the level of maximal function reached as a young adult can affect the subsequent development of lung disease that occurs with the normal aging process. This emphasizes the need to maximize early lung function. The trajectories of lung function are at least partially established by perinatal factors, including prematurity and in utero exposures (tobacco exposure, nutrition, inflammation, etc), although they can also be affected by a variety of additional factors and exposures throughout the life span. Whether lung function trajectories can be impacted or reset if established under suboptimal conditions is an unanswered question, offering new avenues for research. In this review, we will summarize important articles outlining lung function trajectories and linking pediatric lung function tests to adult lung function tests decades later. We will focus on perinatal factors and outline progress and opportunities for further investigation into the potential ability to reset trajectories to impact long-term lung health.


Assuntos
Pneumopatias/fisiopatologia , Pulmão/fisiologia , Criança , Feminino , Humanos , Lactente , Recém-Nascido Prematuro , Doenças do Prematuro , Pulmão/embriologia , Pneumopatias/prevenção & controle , Assistência Perinatal , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Testes de Função Respiratória
4.
Ecotoxicol Environ Saf ; 203: 111053, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888615

RESUMO

Vinclozolin is a common dicarboximide fungicide used to protect crops from diseases. It is also an endocrine disruptor and is thought to be related to abnormalities of the reproductive tract. However, its mechanism of inducing abnormalities of the male reproductive tract is still unclear. The purpose of this study was to study the effect of gestational vinclozolin exposure on the development of rat fetal Leydig cells. Female pregnant Sprague-Dawley rats were exposed to vinclozolin (0, 25, 50, and 100 mg/kg body weight/day) by gavage from gestational day 14-21. Vinclozolin dose-dependently reduced serum testosterone levels at doses of 50 and 100 mg/kg and the anogenital distance at 100 mg/kg. RNA-seq, qPCR, and Western blotting showed that vinclozolin down-regulated the expression of Nr5a1, Sox9, Lhcgr, Cyp11a1, Hsd3b1, Hsd17b3, Amh, Pdgfa, and Dhh and their encoded proteins. Vinclozolin reduced the number of NR2F2-positive stem Leydig cells at a dose of 100 mg/kg and enhanced autophagy in the testes. In conclusion, vinclozolin disrupts reproductive tract development and testis development in male fetal rats via several pathways.


Assuntos
Disruptores Endócrinos/toxicidade , Fungicidas Industriais/toxicidade , Organogênese/efeitos dos fármacos , Oxazóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Testículo/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Testículo/embriologia , Testículo/patologia , Testosterona/sangue
5.
PLoS One ; 15(8): e0238223, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853260

RESUMO

Being delivered as a low birthweight (LBW) infant is a risk factor for elevated blood pressure and future problems with cardiovascular and cerebellar diseases. Although premature babies are reported to have low numbers of nephrons, some unclear questions remain about the mechanisms underlying elevated blood pressure in full-term LBW infants. We previously reported that glucocorticoids increased miR-449a expression, and increased miR-449a expression suppressed Crhr1 expression and caused negative glucocorticoid feedback. Therefore, we conducted this study to clarify the involvement of pituitary miR-449a in the increase in blood pressure caused by higher glucocorticoids in LBW rats. We generated a fetal low-carbohydrate and calorie-restricted model rat (60% of standard chow), and some individuals showed postnatal growth failure caused by growth hormone receptor expression. Using this model, we examined how a high-fat diet (lard-based 45kcal% fat)-induced mismatch between prenatal and postnatal environments could elevate blood pressure after growth. Although LBW rats fed standard chow had slightly higher blood pressure than control rats, their blood pressure was significantly higher than controls when exposed to a high-fat diet. Observation of glomeruli subjected to periodic acid methenamine silver (PAM) staining showed no difference in number or size. Aortic and cardiac angiotensin II receptor expression was altered with compensatory responses. Blood aldosterone levels were not different between control and LBW rats, but blood corticosterone levels were significantly higher in the latter with high-fat diet exposure. Administration of metyrapone, a steroid synthesis inhibitor, reduced blood pressure to levels comparable to controls. We showed that high-fat diet exposure causes impairment of the pituitary glucocorticoid negative feedback via miR-449a. These results clarify that LBW rats have increased blood pressure due to high glucocorticoid levels when they are exposed to a high-fat diet. These findings suggest a new therapeutic target for hypertension of LBW individuals.


Assuntos
Pressão Sanguínea/fisiologia , Retroalimentação Fisiológica/fisiologia , Glucocorticoides/sangue , Doenças da Hipófise/sangue , Doenças da Hipófise/fisiopatologia , Hipófise/fisiologia , Animais , Peso ao Nascer/efeitos dos fármacos , Peso ao Nascer/fisiologia , Pressão Sanguínea/efeitos dos fármacos , Corticosterona/sangue , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Recém-Nascido de Baixo Peso/sangue , Recém-Nascido de Baixo Peso/fisiologia , Recém-Nascido , Masculino , Metirapona/uso terapêutico , Doenças da Hipófise/tratamento farmacológico , Hipófise/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Wistar
6.
PLoS One ; 15(8): e0237708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817646

RESUMO

Parental high-fat diet (HFD) programs for obesity and hypertension in female offspring in rats, but it is unknown how the pregnancies of these offspring are impacted. Therefore, the hypothesis was tested that parental HFD exaggerates obesity and hypertension during pregnancy of the offspring. Wistar Hannover rat dams (the parental, P generation) were maintained on normal-fat diet (NFD) or HFD from weaning and were kept on respective diets through pregnancy and lactation. Their offspring (the first filial, F1 generation) were weaned onto the same diet as the P generation, or they were changed to the other diet to determine if combined HFD in the P and F1 generations exaggerates body weight and blood pressure levels during pregnancy in these offspring. This diet paradigm resulted in the following groups of pregnant F1 offspring: P-NFD/F1-NFD, P-HFD/F1-NFD, P-NFD/F1-HFD, and P-HFD/F1-HFD. Maternal body and adipose tissue weights were greatest in the P-HFD/F1-HFD group compared to the other 3 groups by the end of pregnancy. Plasma leptin and conscious mean arterial blood pressure were not significantly different between any group, although there was a main effect for increased blood pressure in the F1-HFD groups. Circulating levels of the antihypertensive pregnancy factor, placental growth factor (PlGF), were assessed. Although average PlGF levels were similar among all groups, correlative studies revealed that lower levels of PlGF were associated with higher blood pressure only in the P-HFD/F1-HFD group. In summary, HFD feeding from the P generation exaggerated HFD-induced body and adipose tissue weights in the pregnant offspring.


Assuntos
Hipertensão/sangue , Leptina/sangue , Obesidade/sangue , Fator de Crescimento Placentário/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Adiposidade/genética , Animais , Pressão Sanguínea/genética , Peso Corporal/genética , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Humanos , Hipertensão/genética , Hipertensão/fisiopatologia , Masculino , Herança Materna/genética , Obesidade/genética , Obesidade/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Desmame
7.
Ecotoxicol Environ Saf ; 202: 110911, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800246

RESUMO

Applications of TiO2 nanoparticles (NPs) in food, personal care products and industries pose risks on human health, particularly on vulnerable populations including pregnant women and infants. Fetus, deficient in mature defense system, is more susceptible to NPs. Publications on the developmental toxicity of TiO2 NPs on the maternal-exposed progeny have emerged. This review presents the main exposure routes of TiO2 NPs during pregnancy, including skin penetration, ingestion and inhalation, followed by transport of TiO2 NPs to the placenta. Accumulation of TiO2 NPs in placenta may cause dysfunction in nutrient transfer. TiO2 NPs can be even transported to the fetus and generate toxicities, such as impairments of nervous and reproductive system, and failure in lung and cardiovascular development. The toxicities rely on the crystalline phase and concentrations, and the main mechanisms include the accumulation of excessive reactive oxygen species, DNA damage, and over-activation of signaling pathways such as MAPK which impairs neurotransmission. Finally, this review remarks on the significance for identifying TiO2 NPs dosage safe for both mother and fetus, and particular attention should be paid at TiO2 NPs concentrations safe for mother but toxic to fetus. Importantly, research on the epigenetic trans-generational inheritance of TiO2 NPs is urgently needed to provide insights for deciding the prospects of TiO2 NPs applications.


Assuntos
Nanopartículas Metálicas/toxicidade , Titânio/toxicidade , Animais , Feminino , Feto , Humanos , Nanopartículas/toxicidade , Organogênese , Placenta/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade
8.
Adv Exp Med Biol ; 1265: 153-165, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761575

RESUMO

Severe undernutrition and famine continue to be a worldwide concern, as cases have been increasing in the past 5 years, particularly in developing countries. The occurrence of nutrient restriction (NR) during pregnancy affects fetal growth, leading to small for gestational age (SGA) or intrauterine growth restricted (IUGR) offspring. During adulthood, SGA and IUGR offspring are at a higher risk for the development of metabolic syndrome. Skeletal muscle is particularly sensitive to prenatal NR. This tissue plays an essential role in oxidation and glucose metabolism because roughly 80% of insulin-mediated glucose uptake occurs in muscle, and it represents around 40% of body weight. Alterations in myofiber number, hypertrophy and myofiber type composition, decreased protein synthesis, lower mitochondrial content and activity of oxidative enzymes, and increased accumulation of intramuscular triglycerides are among the described programming effects of maternal NR on skeletal muscle. Together, these features would add to a phenotype that is prone to insulin resistance, type 2 diabetes, obesity, and metabolic syndrome. Insights from diverse animal models (i.e. ovine, swine, and rodent) have provided valuable information regarding the molecular mechanisms behind those altered developmental pathways. Understanding those molecular signatures supports the development of efficient treatments to counteract the effects of maternal NR on skeletal muscle, and its negative implications for postnatal health.


Assuntos
Retardo do Crescimento Fetal/metabolismo , Músculo Esquelético/embriologia , Músculo Esquelético/metabolismo , Nutrientes/deficiência , Nutrientes/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Resistência à Insulina , Síndrome Metabólica , Obesidade , Gravidez
9.
Life Sci ; 258: 118197, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32781059

RESUMO

AIMS: Patients with neurodevelopmental disorders, usually suffer from bone diseases. Many studies have revealed a higher risk of fracture after atypical antipsychotic drug Risperidone (RIS) treatment, which is usually used to treat such disorders. It remains debatable whether neurodevelopmental disorders by itself are the cause of bone diseases or pharmacotherapy may be the reason. MATERIALS AND METHODS: This study attempts to evaluate the biomechanical, histological, stereological, and molecular properties of bones in the offspring of Lipopolysaccharide (LPS) and saline-treated mothers that received saline, drug vehicle or the atypical antipsychotic drug risperidone (RIS) at different days of postnatal development. After postnatal drug treatment, animals were assessed for autistic-like behaviors. Then their bones were taken for evaluations. RESULTS: Maternal LPS exposure resulted in deficits in all behavioral tests and RIS ameliorated these behaviors (p < 0.01& p < 0.05). The administration of LPS and RIS individually led to a significant decrease in the biomechanical parameters such as bone stiffness, strength and the energy used to fracture of bone. The numerical density of osteocalcin-positive cells were significantly decreased in these groups. These rats also had decreased RUNX2 and osteocalcin gene expression. When LPS rats were treated with RIS, these conditions were accelerated (p < 0.001). DISCUSSIONS: The results of our preclinical study, consistent with previous studies in animals, explore that autistic-like deficits induced by prenatal exposure to LPS, can reduce bone stability and bone mass similar to those observed in neurodevelopmental disorders, and, for the first time, reveal that this condition worsened when these animals were treated with RIS.


Assuntos
Transtorno Autístico/induzido quimicamente , Reabsorção Óssea/induzido quimicamente , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal/patologia , Risperidona/efeitos adversos , Animais , Animais Recém-Nascidos , Transtorno Autístico/sangue , Transtorno Autístico/complicações , Comportamento Animal , Fenômenos Biomecânicos , Reabsorção Óssea/sangue , Reabsorção Óssea/fisiopatologia , Citocinas/sangue , Citocinas/genética , Feminino , Lipopolissacarídeos/administração & dosagem , Masculino , Atividade Motora , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Risperidona/administração & dosagem , Comportamento Estereotipado
10.
Environ Health Prev Med ; 25(1): 38, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-32770943

RESUMO

BACKGROUND: Many studies have investigated heavy metal exposure could increase the occurrence of congenital heart defects (CHDs). However, there are limited data regarding the relationship between cobalt exposure and CHD occurrence in offspring. The aim of this study was to analyze the association between cobalt exposure in mothers and the risk of CHDs in offspring. MATERIALS AND METHODS: In order to explore the association between cobalt exposure and occurrence of congenital heart defect (CHD), a case-control study with 490 controls and 399 cases with CHDs in China were developed. The concentrations of cobalt in hair of pregnant woman and fetal placental tissue were measured and processed by a logistic regression analysis to explore the relationship between cobalt exposure and risk of CHDs. RESULTS: The median concentration of hair cobalt in the control and case group was 0.023 ng/mg and 0.033 ng/mg (aOR, 1.837; 95% CI, 1.468-2.299; P < 0.001), respectively. And the median (5-95% range) fetal placental cobalt concentrations were 19.350 ng/g and 42.500 ng/g (aOR, 2.924; 95% CI, 2.211-3.868; P < 0.001) in the control and case groups, respectively. Significant differences in the middle level of cobalt in hair were found in the different CHD subtypes, including septal defects, conotruncal defects, right ventricular outflow tract obstruction, and left ventricular outflow tract obstruction (P < 0.001). Dramatically, different cobalt concentrations in fetal placental tissue were found in all subtypes of cases with CHDs (P < 0.01). CONCLUSIONS: The finding suggested that the occurrence of CHDs may be associated with cobalt exposure.


Assuntos
Cobalto/efeitos adversos , Cabelo/química , Cardiopatias Congênitas/induzido quimicamente , Exposição Materna/efeitos adversos , Placenta/química , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Adolescente , Adulto , Estudos de Casos e Controles , China , Feminino , Humanos , Gravidez , Fatores de Risco , Adulto Jovem
11.
Chem Biol Interact ; 329: 109217, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32750324

RESUMO

Developing brain is very sensitive to the influence of environmental factors during gestation and the neonatal period. The aim of the study is to assess cobalt and iron accumulation in the brain as well as changes in the expression of iron-regulatory proteins transferrin receptor 1, hepcidin, and ferroportin in suckling mice. Perinatal exposure to cobalt chloride increased significantly cobalt content in brain tissue homogenates of 18-day-old (d18) and 25-day-old (d25) mice inducing alterations in brain iron homeostasis. Higher degree of transferrin receptor 1 expression was demonstrated in cobalt chloride-exposed mice with no substantial changes between d18 and d25 mice. A weak ferroportin expression was found in 18-day-old control and cobalt-treated mouse brain. Cobalt exposure of d25 mice resulted in increased ferroportin expression in brain compared to the untreated age-matched control group. Hepcidin level in cobalt-exposed groups was decreased in d18 mice and slightly increased in d25 mice. The obtained data contribute for the better understanding of metal toxicity impact on iron homeostasis in the developing brain with further possible implications in neurodegeneration.


Assuntos
Encéfalo/metabolismo , Cobalto/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Proteínas Reguladoras do Ferro/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Cobalto/metabolismo , Feminino , Hepcidinas/genética , Hepcidinas/metabolismo , Ferro/metabolismo , Proteínas Reguladoras do Ferro/genética , Camundongos , Camundongos Endogâmicos ICR , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo
12.
Environ Health ; 19(1): 90, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847589

RESUMO

BACKGROUND: Lower respiratory tract infections (LRTI) in early life, including pneumonia, bronchitis and bronchiolitis, can lead to decreased lung function, persistent lung damage and increased susceptibility to various respiratory diseases such as asthma. In-utero exposure to particulate matter (PM) during pregnancy may disrupt biological mechanisms that regulate fetal growth, maturation and development. We aimed to estimate the association between intrauterine exposure to PM of size < 2.5 µm in diameter (PM2.5) and incidence of LRTIs during the first year of life. METHODS: A retrospective population-based cohort study in a population of mothers and infants born in Soroka University Medical Center (SUMC) in the years 2004-2012. All infants < 1 year old that were hospitalized due to LRTIs were included. The main exposure assessment was based on a hybrid model incorporating daily satellite-based predictions at 1 km2 spatial resolution. Data from monitoring stations was used for imputation of main exposure and other pollutants. Levels of environmental exposures were assigned to subjects based on their residential addresses and averaged for each trimester. Analysis was conducted by a multivariable generalized estimating equation (GEE) Poisson regression. Data was analyzed separately for the two main ethnic groups in the region, Jewish and Arab-Bedouin. RESULTS: The study cohort included 57,331 deliveries that met the inclusion criteria. Overall, 1871 hospitalizations of infants < 1 year old due to pneumonia or bronchiolitis were documented. In a multivariable analysis, intrauterine exposure to high levels of PM2.5 (> 24 µg/m3) in the first and second trimesters was found to be adversely associated with LRTIs in the Arab-Bedouin population (1st trimester, RR = 1.31, CI 95% 1.08-1.60; 2nd trimester: RR = 1.34, CI 95% 1.09-1.66). CONCLUSION: Intrauterine exposure to high levels of PM2.5 is associated with a higher risk of hospitalizations due to lower respiratory tract infections in Arab-Bedouin infants.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Exposição Materna/efeitos adversos , Material Particulado/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Infecções Respiratórias/epidemiologia , Feminino , Hospitalização , Humanos , Incidência , Lactente , Recém-Nascido , Israel/epidemiologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Infecções Respiratórias/induzido quimicamente
13.
PLoS Med ; 17(8): e1003158, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32810187

RESUMO

BACKGROUND: Most of the women who smoke before pregnancy continue smoking during pregnancy, and some start to quit smoking after being pregnant, although existing guidelines for pregnancy recommend that women who smoke should quit smoking before pregnancy. Findings about the timing and intensity of maternal smoking, especially low-intensity smoking (1-9 cigarettes per day), and preterm birth are still inconsistent and ambiguous. This study aimed to examine the association of the timing of smoking and doses of smoking before pregnancy and during the first or second trimester of pregnancy with preterm birth in a large-scale population-based retrospective cohort study. METHODS AND FINDINGS: We used nationwide birth certificate data from singleton mother-infant pairs in the United States National Vital Statistics System, 2011-2018. All adult women with live singleton births, without preexisting hypertension or diabetes, and with complete data on smoking and gestational age at delivery were included. Participants reported their smoking status (yes or no) and daily number of cigarettes consumed before and during each trimester of pregnancy. The outcome of interest was preterm birth, defined as a birth before 37 weeks of gestation. Logistic regression models were used to estimate the odds ratio (OR) with 95% confidence intervals (CIs) of preterm birth associated with smoking status and the number of cigarettes consumed, adjusting for maternal age, race/ethnicity, parity, education levels, prepregnancy BMI, previous history of preterm birth, marital status, infant sex, and initiation of prenatal care. This study included 25,623,479 women, with a mean age of 29 years (range 20-50 years); 13,742,486 (53.6%) participants were of non-Hispanic white ancestry, 5,971,598 (23.3%) of Hispanic ancestry, and 3,417,456 (13.34%) of non-Hispanic black ancestry. The prevalence of preterm birth was 9.3% (n = 2,378,398). We found that maternal smoking during pregnancy, even at a very low level of intensity, was associated with an increased risk of preterm delivery. The adjusted ORs (95% CI) of preterm birth for mothers who smoked 1-2, 3-5, 6-9, 10-19, and ≥20 cigarettes per day during the first trimester compared with mothers who did not smoke were 1.31 (1.29-1.33), 1.31 (1.30-1.32), 1.33 (1.31-1.35), 1.44 (1.43-1.45), and 1.53 (1.52-1.55), respectively (all P values < 0.001), whereas for those who smoked during the second trimester, the corresponding ORs were 1.37 (1.35-1.39), 1.36 (1.35-1.38), 1.36 (1.34-1.38), 1.48 (1.47-1.49), and 1.59 (1.58-1.61), respectively (all P values < 0.001). Furthermore, smokers who quit before pregnancy, regardless of smoking intensity, had a comparable risk of preterm birth with nonsmokers, although this was not the case when cessation occurred in the first or second trimester of pregnancy. The major limitation of this study is the self-reported information about smoking, which may be subject to information bias. In addition, we cannot rule out the possibility of residual confounding caused by unmeasured factors in an observational research design. CONCLUSIONS: In this study, we observed that low-intensity cigarette consumption during either the first or second trimester of pregnancy, even as low as 1-2 cigarettes per day, was associated with an increased risk of preterm birth. These findings suggest that there is no safe level or safe trimester for maternal smoking during pregnancy. Women of reproductive age who smoke should be strongly encouraged and supported to quit smoking before pregnancy.


Assuntos
Fumar Cigarros/efeitos adversos , Fumar Cigarros/epidemiologia , Comportamento Materno , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , Fumar Cigarros/tendências , Relação Dose-Resposta a Droga , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Nascimento Prematuro/diagnóstico , Nascimento Prematuro/etiologia , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/etiologia , Fatores de Risco , Autorrelato , Estados Unidos/epidemiologia , Adulto Jovem
14.
PLoS Med ; 17(8): e1003182, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32810184

RESUMO

BACKGROUND: Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. METHODS AND FINDINGS: We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. CONCLUSIONS: We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.


Assuntos
Pais , Obesidade Pediátrica/epidemiologia , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/efeitos adversos , Fumar/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , América do Norte/epidemiologia , Obesidade Pediátrica/diagnóstico , Gravidez , Nascimento Prematuro/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Fatores de Risco , Fumar/tendências
15.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(6): 644-650, 2020 Jun 06.
Artigo em Chinês | MEDLINE | ID: mdl-32842280

RESUMO

Objective: To explore the association between maternal bisphenol A (BPA) exposure during pregnancy and neurobehavioral development in infant. Methods: Participants were from the Ma'anshan Birth Cohort, which was established from October 2008 to October 2010 based on four municipal medical and health institutions in Ma'anshan. High-performance liquid chromatography-tandem mass spectrometry was applied for the determination of serum BPA concentration in 1 783 pregnant women sampled at their first filing, and during 2.97 to 28.1 months age of the infants. Neurobehavioral development were assessed by 0-6-year-old pediatric examination table of neuropsychological development. Generalized linear model was used to analyze the association between serum BPA levels during pregnancy and infants' neurobehavioral development. Results: A total of 931 mother-child pairs had complete data on serum BPA detection during pregnancy and assessment of infants' neurobehavioral development status. The age of pregnant women at their first filing was (26.67±3.45) years old, and the M (P25,P75) of serum BPA concentration (ng/ml) was 0.23 (0.11, 0.52), with a detection rate of 84.1% (783/931). The age of infants was (13.18±5.46) months, and 53.5% (498) were boys. The developmental quotient scores of large motor, fine motor, adaptive ability, language ability and social behaviors of infants were (97.88±16.32), (97.16±15.35), (99.64±15.47), (95.3±16.04) and (98.95±14.76) points, respectively. Generalized linear model showed that after adjusting for factors such as delivery mode, feeding mode, family per capita monthly income, preterm delivery, gender, maternal age, residence, pre-pregnancy body mass index and residence time, serum BPA level in pregnancy was negatively associated with infant's development of social behavior [ß (95%CI):-2.42 (-4.71, -0.12)]. The post-stratification analysis by infant age revealed that the serum BPA level in pregnancy was only negatively associated with the development of language and social behavior developmental quotient scores in infants between the ages of 12 and 18 months, with ß (95%CI) about -6.66 (-13.06, -0.25) and -7.401 (-12.97, -1.83), respectively. Conclusion: BPA exposure during pregnancy affects language and social behavior development in infants, and the detection window is between 12 and 18 months old of the infant.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Adulto , Compostos Benzidrílicos , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fenóis , Gravidez , Adulto Jovem
16.
PLoS One ; 15(8): e0231609, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760152

RESUMO

Maternal immune activation (MIA) during pregnancy induces a cytokine storm that alters neurodevelopment and behavior in the progeny. In humans, MIA increases the odds of developing neuropsychiatric disorders such as autism spectrum disorder (ASD). In mice, MIA can be induced by injecting the viral mimic polyinosinic:polycytidylic acid (poly(I:C)) to pregnant dams. Although the murine model of MIA has been extensively studied, it is not clear whether MIA results in cytokine changes in the progeny at early postnatal stages. Further, the murine model of MIA suffers from a lack of reproducibility and high inter-individual variability. Multivariable (MV) statistical analysis is widely used in human studies to control for confounders and covariates such as sex, age and exposure to environmental factors. We therefore reasoned that animal studies in general and studies on the MIA model in particular could benefit from MV analyses to account for complex phenotype interactions and high inter-individual variability. Here, we used MV statistical analysis to identify cytokines associated with MIA after adjustment for covariates. Besides confirming the association between previously described variables and MIA, we identified new cytokines that could play a role in behavioural alterations in the progeny during the early postnatal period.


Assuntos
Transtorno Autístico/etiologia , Citocinas/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , Animais , Transtorno do Espectro Autista/induzido quimicamente , Comportamento Animal/fisiologia , Citocinas/efeitos adversos , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Análise Multivariada , Poli I-C/farmacologia , Gravidez , Reprodutibilidade dos Testes
17.
PLoS One ; 15(8): e0236510, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790765

RESUMO

BACKGROUND: Poor vitamin D status is a global health problem and common in patients with human immunodeficiency virus (HIV) in high-income countries. There is less evidence on prevalence of vitamin D deficiency and nutrition and growth in HIV-infected and -exposed children in low- and middle-income countries. OBJECTIVES: To determine the vitamin D status in Batswana HIV-infected mothers and their children, differences among HIV-infected mothers and between HIV-exposed and -infected infants and children, and associations between vitamin D and disease-related outcomes, nutrition, and growth. METHODS: This was a cross-sectional study of HIV+ mothers and HIV-exposed infants and unrelated children (1-7.9 years). Serum 25-hydroxyvitamin D (25(OH)D) was measured, among other nutritional indicators, for mothers, infants and children. Vitamin D status for HIV-infected mothers and children, and an immune panel was assessed. History of HIV anti-retroviral medications and breastfeeding were obtained. Data were collected prior to universal combination antiretroviral therapy in pregnancy. RESULTS: Mothers (n = 36) had a mean serum 25(OH)D of 37.2±12.4ng/mL; 11% had insufficient (<20ng/mL), 17% moderately low (20.0-29.9ng/mL) and 72% sufficient (≥30ng/mL) concentrations. No infants (n = 36) or children (n = 48) were vitamin D insufficient; 22% of HIV- and no HIV+ infants had moderately low concentrations and 78% of HIV- and 100% of HIV+ infants had sufficient status, 8% of HIV- and no HIV+ children had moderately low concentrations and 92% of HIV- and 100% HIV+ children had sufficient concentrations. HIV+ children had significantly lower length/height Z scores compared to HIV- children. Length/height Z score was positively correlated with serum 25(OH)D in all children (r = 0.33, p = 0.023), with a stronger correlation in the HIV+ children (r = 0.47 p = 0.021). In mothers, serum 25(OH)D was positively associated with CD4% (r = 0.40, p = 0.016). CONCLUSIONS: Results showed a low prevalence of vitamin D insufficiency in Botswana. Growth was positively correlated with vitamin D status in HIV-exposed children, and HIV+ children had poorer linear growth than HIV- children.


Assuntos
Infecções por HIV/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adulto , Botsuana/epidemiologia , Criança , Desenvolvimento Infantil , Saúde da Criança , Pré-Escolar , Estudos Transversais , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Humanos , Lactente , Mães , Estado Nutricional , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Adulto Jovem
18.
Pediatrics ; 146(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32719088

RESUMO

CONTEXT: Vaccination during pregnancy is an effective strategy for preventing infant disease; however, little is known about early childhood health after maternal vaccination. OBJECTIVES: To systematically review the literature on early childhood health associated with exposure to influenza vaccines in utero. DATA SOURCES: We searched CINAHL Plus, Embase, Medline, Scopus, and Web of Science for relevant articles published from inception to July 24, 2019. STUDY SELECTION: We included studies published in English reporting original data with measurement of in utero exposure to influenza vaccines and health outcomes among children <5 years of age. DATA EXTRACTION: Two authors independently assessed eligibility and extracted data on study design, setting, population, vaccines, outcomes, and results. RESULTS: The search yielded 3647 records, of which 9 studies met the inclusion criteria. Studies examined infectious, atopic, autoimmune, and neurodevelopmental outcomes, and all-cause morbidity and mortality. Authors of 2 studies reported an inverse association between pandemic influenza vaccination and upper respiratory tract infections, gastrointestinal infections, and all-cause hospitalizations; and authors of 2 studies reported modest increased association between several childhood disorders and pandemic or seasonal influenza vaccination, which, after adjusting for confounding and multiple comparisons, were not statistically significant. LIMITATIONS: Given the small number of studies addressing similarly defined outcomes, meta-analyses were deemed not possible. CONCLUSIONS: Results from the few studies in which researchers have examined outcomes in children older than 6 months of age did not identify an association between exposure to influenza vaccines in utero and adverse childhood health outcomes.


Assuntos
Vacinas contra Influenza , Efeitos Tardios da Exposição Pré-Natal , Feminino , Gastroenteropatias/epidemiologia , Humanos , Gravidez , Infecções Respiratórias/epidemiologia
19.
Environ Pollut ; 266(Pt 1): 115117, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32650159

RESUMO

Triclosan (TCS) and Triclocarbon (TCC) are chlorinated synthetic antimicrobial agents formaternal urinelated in quantities of consumer products. However, the biomonitoring of direct exposure reflection for fetuses are rare. In this study, we determine the concentrations of TCS and TCC in paired maternal serum, cord serum, maternal urine, and amniotic fluid samples collected from a cohort of 95 expecting mother-fetal pairs in Southern China. TCS and TCC are detected widely (detection rates: >76.9%) in maternal serum, cord serum, maternal urine, and amniotic fluid samples. TCS is found to be the predominant antimicrobial agent with median concentrations in maternal serum (1.5 ng/mL) and cord serum (1.8 ng/mL) that are one order of magnitude higher than those of tcc in maternal serum (0.085 ng/mL) and cord serum (0.052 ng/mL), respectively. Cord serum concentrations of tcs and tcc correlated well with the concentrations in maternal serum, which reflect the mothers' contribution to fetal exposure. The higher median ratio of cord serum/maternal serumTCS (0.95) compared to that of cord serum/maternal serumTCC (0.53) indicates high placental transmission ability of TCS. Moreover, the facility to penetrate the placental barrier and hard to depurate characteristics lead to the long residence of TCS in the fetal environment, causing great concern over the prenatal exposure risks during the critical window of fetal development. This study provides a novel contribution by increasing existing knowledge on the exposure assessment of TCS and TCC during pregnancy through the exploration of matched maternal-fetal samples.


Assuntos
Carbanilidas/análise , Efeitos Tardios da Exposição Pré-Natal , Triclosan/análise , Líquido Amniótico/química , China , Feminino , Humanos , Gravidez
20.
Chem Biol Interact ; 328: 109188, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32679048

RESUMO

We have reported that gestational exposure to hexavalent chromium (CrVI) represses androgen receptor (Ar) and follicle stimulating hormone receptor (Fshr) in Sertoli cells (SCs) of adult rats, while the mechanism underlying remains obscure. We tested the hypothesis "transient gestational exposure to CrVI during the critical embryonic windows of testicular differentiation and growth may have adverse impact on transcription factors controlling the expression of Ar and Fshr in SCs of the F1 progeny". CrVI (K2Cr2O7) was given through drinking water (50 ppm, 100 ppm and 200 ppm), to pregnant rats from gestational day 9-14 (testicular differentiation) and 15 to 21 (prenatal differentiation and proliferation of SC); male progenies were sacrificed on postnatal day 30 (Completion of postnatal SC maturation). A significant increase in free radicals and decrease in enzymatic and non-enzymatic antioxidants were observed in SCs of experimental rats. Real time PCR and western blot data showed decreased expression of Ar, Fshr, Inhibin B, Transferrin, Androgen binding protein, Claudin 11 and Occludin in SCs of experimental rats; concentrations of lactate, pyruvate and retinoic acid also decreased. Serum FSH, luteinizing hormone and estradiol increased, whereas testosterone and prolactin decreased in experimental rats. Western blot detection revealed decreased levels of transcription factors regulating Fshr viz., USF-1, USF-2, SF-1, c-fos, c-jun and GATA 1, and those of Ar viz., Sp-1, ARA54, SRC-1 and CBP in experimental rats, whereas the levels of cyclinD1 and p53, repressors of Ar increased. ChIP assay detected decreased USF-1 and USF-2 binding to Fshr promoter, and binding of Sp-1 to Ar promoter. We conclude that gestational exposure to CrVI affects SC structure and function in F1 progeny by inducing oxidative stress and diminishing the expression of Ar and Fshr through attenuation of their specific transcriptional regulators and their interaction with the respective promoter.


Assuntos
Cromo/toxicidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Receptores Androgênicos/metabolismo , Receptores do FSH/metabolismo , Células de Sertoli/metabolismo , Maturidade Sexual , Fatores de Transcrição/metabolismo , Animais , Antioxidantes/metabolismo , Disponibilidade Biológica , Feminino , Radicais Livres/metabolismo , Hormônios/sangue , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Ratos Wistar , Receptores Androgênicos/genética , Receptores do FSH/genética , Células de Sertoli/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Proteínas de Junções Íntimas/metabolismo
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