RESUMO
OBJECTIVE: To identify perinatal clinical diseases and treatments that are associated with the development of objectively diagnosed diffuse white matter abnormality (DWMA) on structural magnetic resonance imaging (MRI) at term-equivalent age in infants born very preterm. STUDY DESIGN: A prospective cohort of 392 infants born very preterm (≤32 weeks of gestational age) was enrolled from 5 level III/IV neonatal intensive care units between September 2016 and November 2019. MRIs of the brain were collected at 39 to 45 weeks of postmenstrual age to evaluate DWMA volume. A predefined list of pertinent maternal characteristics, pregnancy/delivery data, and neonatal intensive care unit data were collected for enrolled patients to identify antecedents of objectively diagnosed DWMA. RESULTS: Of the 392 infants in the cohort, 377 (96%) had high-quality MRI data. Their mean (SD) gestational age was 29.3 (2.5) weeks. In multivariable linear regression analyses, pneumothorax (P = .027), severe bronchopulmonary dysplasia (BPD) (P = .009), severe retinopathy of prematurity (P < .001), and male sex (P = .041) were associated with increasing volume of DWMA. The following factors were associated with decreased risk of DWMA: postnatal dexamethasone therapy for severe BPD (P = .004), duration of caffeine therapy for severe BPD (P = .009), and exclusive maternal milk diet at neonatal intensive care unit discharge (P = .049). CONCLUSIONS: Severe retinopathy of prematurity and BPD exhibited the strongest adverse association with development of DWMA. We also identified treatments and nutritional factors that appear protective against the development of DWMA that also have implications for the clinical care of infants born very preterm.
Assuntos
Lactente Extremamente Prematuro , Imageamento por Ressonância Magnética , Substância Branca/anormalidades , Substância Branca/diagnóstico por imagem , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/epidemiologia , Cafeína/uso terapêutico , Estudos de Coortes , Dexametasona/uso terapêutico , Feminino , Idade Gestacional , Glucocorticoides/uso terapêutico , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Leite Humano , Análise Multivariada , Pneumotórax/epidemiologia , Fatores de Proteção , Retinopatia da Prematuridade/epidemiologia , Fatores SexuaisRESUMO
OBJECTIVE: To externally validate the independent value of objectively diagnosed diffuse white matter abnormality (DWMA; also known as diffuse excessive high signal intensity) volume to predict neurodevelopmental outcomes in very preterm infants (≤31 weeks of gestational age). STUDY DESIGN: A prospective, multicenter, regional population-based cohort study in 98 very preterm infants without severe brain injury on magnetic resonance imaging (MRI). DWMA volume was diagnosed objectively on structural MRI at term-equivalent age using our published algorithm. Multivariable linear regression was used to assess the value of DWMA volume to predict cognitive and language scores on the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 2 years corrected age. RESULTS: Of the infants who returned for follow-up (n = 74), the mean (SD) gestational age was 28.2 (2.4) weeks, and 42 (56.8%) were boys. In bivariable analyses, DWMA volume was a significant predictor of Bayley-III cognitive and language scores. In multivariable analyses, controlling for known predictors of Bayley-III scores (ie, socioeconomic status, gestational age, sex, and global brain abnormality score), DWMA volume remained a significant predictor of cognitive (P < .001) and language (P = .04) scores at 2 years. When dichotomized, objectively diagnosed severe DWMA was a significant predictor of cognitive and language impairments, whereas visual qualitative diagnosis of DWMA was a poor predictor. CONCLUSIONS: In this multicenter, prospective cohort study, we externally validated our previous findings that objectively diagnosed DWMA is an independent predictor of cognitive and language development in very preterm infants. We also demonstrated again that visually-diagnosed DWMA is not predictive of neurodevelopmental outcomes.
Assuntos
Transtornos Cognitivos/diagnóstico , Lactente Extremamente Prematuro , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Imageamento por Ressonância Magnética , Substância Branca/anormalidades , Substância Branca/diagnóstico por imagem , Algoritmos , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Análise Multivariada , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: This retrospective cohort study examined whether bariatric surgery is associated with reduced risk of breast cancer among pre- and postmenopausal women. BACKGROUND: Obesity is associated with increased risk of breast cancer, but the impact of weight loss on breast cancer risk has been difficult to quantify. METHODS: The cohort included obese (body mass index ≥35âkg/m) patients enrolled in an integrated health care delivery system between 2005 and 2012 (with follow-up through 2014). Female bariatric surgery patients (N = 17,998) were matched on body mass index, age, study site, and comorbidity index to 53,889 women with no bariatric surgery. Kaplan-Meier curves and Cox proportional hazards models were used to examine incident breast cancer up to 10 years after bariatric surgery. Pre- and postmenopausal women were examined separately, and further classified by estrogen receptor (ER) status. RESULTS: The analysis included 301 premenopausal and 399 postmenopausal breast cancer cases. In multivariable adjusted models, bariatric surgery was associated with a reduced risk of both premenopausal (HR = 0.72, 95% CI, 0.54-0.94) and postmenopausal (HR = 0.55, 95% CI, 0.42-0.72) breast cancer. Among premenopausal women, the effect of bariatric surgery was more pronounced among ER-negative cases (HR = 0.36, 95% CI, 0.16-0.79). Among postmenopausal women, the effect was more pronounced in ER-positive cases (HR = 0.52, 95% CI, 0.39-0.70). CONCLUSIONS: Bariatric surgery was associated with a reduced risk of breast cancer among severely obese women. These findings have significant public health relevance because the prevalence of obesity continues to rise, and few modifiable breast cancer risk factors have been identified, especially for premenopausal women.
Assuntos
Cirurgia Bariátrica , Neoplasias da Mama/prevenção & controle , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Pós-Menopausa , Pré-Menopausa , Estudos Retrospectivos , Medição de RiscoRESUMO
OBJECTIVE: To explore the relationship between maternal shared reading quality (verbal interactivity and engagement) and brain function during story listening in at-risk, preschool-age children, in the context of behavioral evidence and American Academy of Pediatrics, recommendations. STUDY DESIGN: In this cross-sectional study, 22 healthy, 4-year-old girls from low socioeconomic status households completed functional magnetic resonance imaging using an established story listening task, followed by videotaped observation of uncoached mother-daughter reading of the same, age-appropriate picture book. Shared reading quality was independently scored applying dialogic reading and other evidence-based criteria reflecting interactivity and engagement, and applied as a predictor of neural activation during the functional magnetic resonance imaging task, controlling for income and maternal education. RESULTS: Shared reading quality scores were generally low and negatively correlated with maternal distraction by smartphones (P < .05). Scores were positively correlated with activation in left-sided brain areas supporting expressive and complex language, social-emotional integration, and working memory (P <.05, false discovery rate corrected). CONCLUSIONS: Maternal shared reading quality is positively correlated with brain activation supporting complex language, executive function, and social-emotional processing in at-risk, preschool-age children. These findings represent novel neural biomarkers of how this modifiable aspect of home reading environment may influence foundational emergent literacy skills, reinforce behavioral evidence and American Academy of Pediatrics, recommendations, and underscore the potential of dialogic reading interventions to promote healthy brain development, especially in at-risk households.
Assuntos
Encéfalo/fisiologia , Neuroimagem Funcional , Imageamento por Ressonância Magnética , Comportamento Materno , Relações Mãe-Filho/psicologia , Leitura , Comportamento Verbal/fisiologia , Adulto , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Alfabetização , Classe SocialRESUMO
OBJECTIVES: To determine the impact of empiric ampicillin and gentamicin use in the first week of life on microbial colonization and diversity in preterm infants. STUDY DESIGN: The 16s ribosomal DNA community profiling was used to compare the microbiota of 74 infants born ≤32 weeks gestational age by degree of antibiotic use in the first week of life. The degree of antibiotic use was classified as 0 days, 1-4 days, and 5-7 days of antibiotic administration. All of the antibiotic use was empiric, defined as treatment based solely on clinical suspicion of infection without a positive culture result. RESULTS: Infants who received 5-7 days of empiric antimicrobial agents in the first week had increased relative abundance of Enterobacter (P = .016) and lower bacterial diversity in the second and third weeks of life. Infants receiving early antibiotics also experienced more cases of necrotizing enterocolitis, sepsis, or death than those not exposed to antibiotics. CONCLUSIONS: Early empiric antibiotics have sustained effects on the intestinal microbiota of preterm infants. Intestinal dysbiosis in this population has been found to be associated with elevated risk of necrotizing enterocolitis, sepsis, or death.
Assuntos
Antibacterianos/uso terapêutico , Enterobacter/efeitos dos fármacos , Recém-Nascido Prematuro , Intestinos/microbiologia , Microbiota/efeitos dos fármacos , Ampicilina/efeitos adversos , Ampicilina/uso terapêutico , Antibacterianos/efeitos adversos , Biodiversidade , Estudos de Coortes , Impressões Digitais de DNA , DNA Ribossômico/genética , Feminino , Gentamicinas/efeitos adversos , Gentamicinas/uso terapêutico , Idade Gestacional , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Ohio , RNA Ribossômico 16S/genéticaRESUMO
OBJECTIVE: To test the hypothesis that international adoption of Chinese and Eastern European girls after 9 months of age results in long-term changes in the neural circuitry supporting monolingual English in later childhood. STUDY DESIGN: Functional magnetic resonance imaging was used to test this hypothesis by comparison with a control group of American-born English speakers (n = 13). Girls now aged 6-10 years adopted from China (n = 13) and Eastern Europe (n = 12) by English-speaking families were recruited through a pediatric hospital-based international adoption center after spending more than 6 months in an orphanage or other institution, a measure of early environmental deprivation. Functional magnetic resonance imaging scans were performed on a 3 Tesla MRI scanner using a verb generation language fluency task. Composite activation maps were computed for each group using a general linear model with random effects analysis. RESULTS: Chinese born adoptees demonstrate atypical lateralization of language function with an apparent shift of temporal-parietal and frontal areas of brain activity toward the right hemisphere. Eastern European adoptees exhibited a rightward shift relative to controls in both frontal and temporal-parietal brain regions. CONCLUSIONS: Significant differences in lateralization between the Chinese and American-born groups in temporal-parietal language areas highlight the possible impact of early tonal Asian language exposure on neural circuitry. Findings suggest that exposure to an Asian language during infancy can leave a long-term imprint on the neural circuitry supporting English language development.
Assuntos
Adoção , Mapeamento Encefálico/métodos , Desenvolvimento da Linguagem , Idioma , Imageamento por Ressonância Magnética/métodos , Criança , China , Emigrantes e Imigrantes , Europa Oriental , Feminino , Lobo Frontal/fisiologia , Humanos , Lobo Parietal/fisiologia , Lobo Temporal/fisiologia , Fatores de Tempo , Estados UnidosRESUMO
BACKGROUND: Adiponectin, a circulating adipocyte protein, is associated with lower obesity. We have previously shown that adiponectin is present in human milk. This study determined whether higher milk adiponectin is associated with infant growth and investigated milk adiponectin's oligomeric form. DESIGN AND METHODS: This is a study of two parallel longitudinal cohorts of breastfed infants born between 1998 and 2005. Forty-five mother-infant pairs from Cincinnati, OH and 277 mother-infant pairs from Mexico City, Mexico were analyzed. All participants were healthy, term infants breastfed at least 1 month who completed 6 months of follow-up. Monthly milk samples (n = 1,379) up to 6 months were assayed for adiponectin by radioimmunoassay. Infant weight-for-age, length-for-age, and weight-for-length Z-scores up to 6 months of age were calculated using World Health Organization standards. Repeated-measures analysis was conducted. The structural form of human milk adiponectin was assessed by western blot. RESULTS: In the population studies, initial milk adiponectin was 24.0 +/- 8.6 microg/L and did not differ by cohort. Over the first 6 months, higher milk adiponectin was associated with lower infant weight-for-age Z-score (-0.20 +/- 0.04, p < 0.0001) and weight-for-length Z-score (-0.29 +/- 0.08, p = 0.0002) but not length-for-age Z-score, adjusted for covariates, with no difference by cohort. By western blot, human milk adiponectin was predominantly in the biologically active high-molecular-weight form. CONCLUSIONS: Our data suggest milk adiponectin may play a role in the early growth and development of breastfed infants.
Assuntos
Adiponectina/análise , Crescimento , Recém-Nascido/crescimento & desenvolvimento , Leite Humano/química , Adiponectina/química , Adulto , Fatores Etários , Estatura/fisiologia , Peso Corporal/fisiologia , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , México , Peso Molecular , Obesidade/epidemiologia , Obesidade/etiologia , Obesidade/prevenção & controle , Ohio , RadioimunoensaioRESUMO
BACKGROUND: Previous studies have shown that human milk has a role in the gastrointestinal, neural, and immune development of neonates. If present in milk, adiponectin would be a promising candidate for influencing infant development, given its metabolic functions. OBJECTIVES: Our objectives were to determine whether adiponectin is present in human milk and to characterize maternal factors associated with potential variation in milk adiponectin concentrations. DESIGN: We quantified adiponectin concentrations in human milk samples from donors to the Cincinnati Children's Research Human Milk Bank and randomly selected participants in a cohort study in Mexico City funded by the National Institutes of Health. Using cross-sectional and longitudinal data, we examined milk adiponectin concentrations in relation to lactation duration, maternal body mass index (BMI; in kg/m(2)), and ethnicity. RESULTS: Adiponectin was detected in human skim milk (range: 4.2-87.9 ng/mL). In cross-sectional and longitudinal analyses, duration of lactation was negatively associated with milk adiponectin concentrations (beta = -0.059 +/- 0.024 and -0.059 +/- 0.007, respectively; P < 0.02 for both). Maternal postpregnancy BMI was positively associated with milk adiponectin concentrations (beta = 0.08 +/- 0.02, P < 0.0001; longitudinal analysis). Mexican mothers had lower median milk adiponectin concentrations at 1 mo than did the non-Hispanic white subjects from Cincinnati (11.5 and 19.8 ng/mL; P = 0.003). CONCLUSIONS: Adiponectin is present in human milk and its concentrations are associated with duration of lactation, maternal adiposity, and ethnicity. Given the importance of adiponectin in inflammation, insulin sensitivity, and fatty acid metabolism, future studies should examine milk adiponectin's role in infant metabolic development.
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Adiponectina/análise , Leite Humano/química , Índice de Massa Corporal , Peso Corporal , Estudos de Coortes , Estudos Transversais , Etnicidade , Feminino , Humanos , Lactação , Leptina/análise , Estudos Longitudinais , México , Ohio , Período Pós-Parto , Fatores de TempoRESUMO
The WHO recommends exclusive breast-feeding (EBF) for the first 6 mo of life to decrease the burden of infectious disease. However, some are concerned about the effect of EBF >6 mo on iron status of children in developing countries in which anemia is prevalent. This study examines the risk of anemia in relation to the duration of EBF and maternal anemia in a birth cohort studied between March 1998 and April 2003. All infant birth weights were >or=2.2 kg. All mothers received home-based peer counseling to promote EBF. Infant feeding data were collected weekly. Nurses measured hemoglobin (Hb) values every 3 mo. Hb was measured in 183 infants at 9 mo of age. Anemia at 9 mo was defined as a Hb value <100 g/L. EBF was defined by WHO criteria and ranged in duration from 0 to 31 wk. At 9 mo, Hb (mean +/- SEM) was 114 +/- 0.9 g/L; 23 children (12.5%) had Hb levels <100 g/L. EBF >6 mo, but not EBF 4-6 mo, was associated with increased risk of infant anemia compared with EBF <4 mo (odds ratio=18.4, 95% CI=1.9, 174.0). Maternal anemia was independently (P=0.03) associated with a 3-fold increased risk of infant anemia. These associations were not explained by confounding with other maternal or infant factors. By linear regression, a lower infant Hb at 9 mo was associated with increased EBF duration among mothers who had a history of anemia (beta=-0.07, P=0.003), but not among mothers with no history of anemia. Infants who are exclusively breast-fed for >6 mo in developing countries may be at increased risk of anemia, especially among mothers with a poor iron status; greater attention to this issue is warranted.
Assuntos
Anemia/congênito , Anemia/etiologia , Aleitamento Materno/efeitos adversos , Mães , Anemia/sangue , Anemia/epidemiologia , Pré-Escolar , Estudos de Coortes , Feminino , Hemoglobinas/metabolismo , Humanos , Lactente , Recém-Nascido , Ferro/sangue , Masculino , México/epidemiologia , Fatores de Risco , Organização Mundial da SaúdeRESUMO
OBJECTIVE: To determine the association between maternal milk levels of 2-linked fucosylated oligosaccharide and prevention of diarrhea as a result of Campylobacter, caliciviruses, and diarrhea of all causes in breast-fed infants. STUDY DESIGN: Data and banked samples were analyzed from 93 breast-feeding mother-infant pairs who were prospectively studied during 1988-1991 from birth to 2 years with infant feeding and diarrhea data collected weekly; diarrhea was diagnosed by a study physician. Milk samples obtained 1 to 5 weeks postpartum were analyzed for oligosaccharide content. Data were analyzed by Poisson regression. RESULTS: Total 2-linked fucosyloligosaccharide in maternal milk ranged from 0.8 to 20.8 mmol/L (50%-92% of milk oligosaccharide). Moderate-to-severe diarrhea of all causes (n=77 cases) occurred less often (P=.001) in infants whose milk contained high levels of total 2-linked fucosyloligosaccharide as a percent of milk oligosaccharide. Campylobacter diarrhea (n=31 cases) occurred less often (P=.004) in infants whose mother's milk contained high levels of 2'-FL, a specific 2-linked fucosyloligosaccharide, and calicivirus diarrhea (n=16 cases) occurred less often (P=.012) in infants whose mother's milk contained high levels of lacto-N-difucohexaose (LDFH-I), another 2-linked fucosyloligosaccharide. CONCLUSION: This study provides novel evidence suggesting that human milk oligosaccharides are clinically relevant to protection against infant diarrhea.