RESUMO
BACKGROUND: Preterm infants face unique stress states in early life. Early-life stress has been associated with changes in cortisol reactivity and behavioral abnormalities later in childhood in non-preterm populations. The Neonatal Infant Stressor Scale (NISS) has been used to estimate infant stress in the neonatal intensive care unit (NICU) but has not been biomarker validated. The relationship between NISS scores and salivary cortisol is unknown. The aim of this study is to test the association between NISS scores and salivary cortisol in the NICU Hospital Exposures and Long-Term Health (NICU-HEALTH) preterm birth cohort. METHODS: Three hundred and eighty-six salivary cortisol specimens were collected from 125 NICU-HEALTH participants during the NICU hospitalization. NISS scores were calculated to represent the infant's experience in the 6 hours prior to specimen collection. Adjusted mixed-effect regression models were used to assess the association between each NISS score and salivary cortisol. RESULTS: Acute and total NISS scores were significantly associated with salivary cortisol level (P = 0.002 and 0.05, respectively). The chronic NISS score was not associated with salivary cortisol levels. Caffeine treatment and postmenstrual age of the infant were important covariates in all models. CONCLUSION: Acute and total NISS score are associated with salivary cortisol level in hospitalized moderately preterm infants.
Assuntos
Hidrocortisona/metabolismo , Saliva/metabolismo , Estresse Psicológico/metabolismo , Biomarcadores/metabolismo , Cafeína/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , MasculinoRESUMO
In this study, we use advanced growth modeling techniques and the rich biospecimen and data repositories of the NICU Hospital Exposures and Long-Term Health (NICU-HEALTH) study to assess the impact of NICU-based phthalate exposure on extrauterine growth trajectories between birth and NICU discharge. Repeated holdout weighed quantile sum (WQS) regression was used to assess the effect of phthalate mixtures on the latency to first growth spurt and on the rate of first growth spurt. Further, we assessed sex as an effect modifier of the relationship between a phthalate mixture and both outcomes. Nine phthalate metabolites, mono-ethyl phthalate (MEP), mono-benzyl phthalate (MBzP), mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-(3-carboxypropyl) phthalate (MCPP), mono-2-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) were measured in weekly urine specimens from 101 NICU-HEALTH participants between birth and the first growth spurt. Phthalate levels varied by species but not by infant sex, and decreased over the course of the NICU hospitalization as presented in detail in Stroustrup et al., 2018. There was evidence of nonlinearity when assessing the effect of phthalates on latency to first growth spurt. Above a threshold level, a higher phthalate mixture with dominant contributors MCPP, MBzP, and MEP predicted a shorter latency to the first inflection point, or an earlier growth spurt. A higher phthalate mixture with dominant contributors MECPP, MEHHP, and MEOHP was associated with an increased rate of growth. Results of both models were clearly different for boys and girls, consistent with other studies showing the sexually dimorphic impact of early life phthalate exposure. These results suggest that growth curve modeling facilitates evaluation of discrete periods of rapid growth during the NICU hospitalization and exposure to specific phthalates during the NICU hospitalization may both alter the timing of the first growth spurt and result in more rapid growth in a sexually dimorphic manner.
Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Exposição Ambiental , Feminino , Hospitalização , Hospitais , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Masculino , Ácidos Ftálicos/metabolismo , Ácidos Ftálicos/toxicidadeRESUMO
In the United States each year, more than 300,000 infants are admitted to neonatal intensive care units (NICU) where they are exposed to a chemical-intensive hospital environment during a developmentally vulnerable period. Although multiple studies have demonstrated elevated phthalate biomarkers in NICU patients, specific sources of NICU-based phthalate exposure have not been identified.In this study, premature newborns with birth weight <1500 g were recruited to participate in a prospective environmental health cohort during the NICU hospitalization. Exposure to specific NICU equipment was recorded daily during the NICU hospitalization. One hundred forty-nine urine specimens from 71 infants were analyzed for phthalate metabolites using high-performance liquid chromatography/tandem mass spectrometry.In initial analyses, exposure to medical equipment was directly related to phthalate levels, with DEHP biomarkers 95-132% higher for infants exposed to specific medical equipment types compared to those without that equipment exposure (p < 0.001-0.023). This association was mirrored for clinically relevant phthalate mixtures whether composed of DEHP metabolites or not (p = 0.002-0.007). In models accounting for concurrent equipment use, exposure to respiratory support was associated with DEHP biomarkers 50-136% higher in exposed compared to unexposed infants (p = 0.007-0.036). Phthalate mixtures clinically relevant to neurobehavioral development were significantly associated with non-invasive respiratory support (p = 0.008-0.026). Feeding supplies and intravenous lines were not significantly associated with clinically important phthalate mixtures.Respiratory support equipment may be a significant and clinically relevant NICU source of phthalate exposure. Although manufacturers have altered feeding and intravenous supplies to reduce DEHP exposure, other sources of exposure to common and clinically impactful phthalates persist in the NICU.
Assuntos
Exposição Ambiental/estatística & dados numéricos , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Biomarcadores , Peso ao Nascer , Cromatografia Líquida de Alta Pressão , Dietilexilftalato/metabolismo , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Ácidos Ftálicos , Estudos ProspectivosRESUMO
PURPOSE: The Neonatal Intensive Care Unit Hospital Exposures and Long-Term Health (NICU-HEALTH) longitudinal preterm birth cohort studies the impact of the NICU exposome on early-life development. NICU-HEALTH collects multiple biospecimens, complex observational and survey data and comprehensive multisystem outcome assessments to allow measurement of the impact of modifiable environmental exposures during the preterm period on neurodevelopmental, pulmonary and growth outcomes. PARTICIPANTS: Moderately preterm infants without genetic or congenital anomalies and their mothers are recruited from an urban academic medical centre level IV NICU in New York City, New York, USA. Recruitment began in 2011 and continues through multiple enrolment phases to the present with goal enrolment of 400 infants. Follow-up includes daily data collection throughout the NICU stay and six follow-up visits in the first 2 years. Study retention is 77% to date, with the oldest patients turning age 8 in 2019. FINDINGS TO DATE: NICU-HEALTH has already contributed significantly to our understanding of phthalate exposure in the NICU. Phase I produced the first evidence of the clinical impact of phthalate exposure in the NICU population. Further study identified specific sources of exposure to clinically relevant phthalate mixtures in the NICU. FUTURE PLANS: Follow-up from age 3 to 12 is co-ordinated through integration with the Environmental Influences on Child Health Outcomes (ECHO) programme. The NICU-HEALTH cohort will generate a wealth of biomarker, clinical and outcome data from which future studies of the impact of early-life chemical and non-chemical environmental exposures can benefit. Findings from study of this cohort and other collaborating environmental health cohorts will likely translate into improvements in the hospital environment for infant development. TRIAL REGISTRATION NUMBERS: This observational cohort is registered with ClinicalTrials.gov (NCT01420029 and NCT01963065).
Assuntos
Exposição Ambiental/efeitos adversos , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal , Ácidos Ftálicos/efeitos adversos , Desenvolvimento Infantil , Deficiências do Desenvolvimento/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Cidade de Nova Iorque , Estudos Prospectivos , Projetos de PesquisaRESUMO
Every year in the United States, more than 300,000 infants are admitted to neonatal intensive care units (NICU) where they are exposed to a chemical-intensive hospital environment during a developmentally vulnerable period. The neurodevelopmental impact of environmental exposure to phthalates during the NICU stay is unknown. As phthalate exposure during the third trimester developmental window has been implicated in neurobehavioral deficits in term-born children that are strikingly similar to a phenotype of neurobehavioral morbidity common among children born premature, the role of early-life phthalate exposure on the neurodevelopmental trajectory of premature infants may be clinically important. In this study, premature newborns with birth weight <1500g were recruited to participate in a prospective environmental health cohort study, NICU-HEALTH (Hospital Exposures and Long-Term Health), part of the DINE (Developmental Impact of NICU Exposures) cohort of the ECHO (Environmental influences on Child Health Outcomes) program. Seventy-six percent of eligible infants enrolled in the study. Sixty-four of 81 infants survived and are included in this analysis. 164 urine specimens were analyzed for phthalate metabolites using high-performance liquid chromatography/tandem mass spectrometry. The NICU Network Neurobehavioral Scale (NNNS) was performed prior to NICU discharge. Linear and weighted quantile sum regression quantified associations between phthalate biomarkers and NNNS performance, and between phthalate biomarkers and intensity of medical intervention. The sum of di(2-ethylhexyl) phthalate metabolites (∑DEHP) was associated with improved performance on the Attention and Regulation scales. Specific mixtures of phthalate biomarkers were also associated with improved NNNS performance. More intense medical intervention was associated with higher ∑DEHP exposure. NICU-based exposure to phthalates mixtures was associated with improved attention and social response. This suggests that the impact of phthalate exposure on neurodevelopment may follow a non-linear trajectory, perhaps accelerating the development of certain neural networks. The long-term neurodevelopmental impact of NICU-based phthalate exposure needs to be evaluated.
Assuntos
Deficiências do Desenvolvimento/epidemiologia , Exposição Ambiental , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal , Ácidos Ftálicos , Atenção/efeitos dos fármacos , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Deficiências do Desenvolvimento/urina , Exposição Ambiental/análise , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Testes Neuropsicológicos , Ácidos Ftálicos/metabolismo , Estudos Prospectivos , Comportamento Social , Espectrometria de Massas em Tandem , Urina/químicaRESUMO
The goal of molecular cytogenetic testing for children presenting with developmental delay (DD) is to identify or exclude genetic abnormalities that are associated with cognitive, behavioral and/or motor symptoms. Until 2010, chromosome analysis was the standard first-line genetic screening test for evaluation of patients with DD when a specific syndrome was not suspected. In 2010, The American College of Medical Genetics and several other groups recommended chromosomal microarray as the first-line test in children with DDs, multiple congenital anomalies and/or autism. This test is able to detect regions of genomic imbalances at a much finer resolution than G-banded karyotyping. Until recently, no chromosomal microarray testing had been approved by the US FDA. This article focuses on the use of the Affymetrix CytoScan(®) Dx Assay (Santa Clara, CA, USA), the first chromosomal microarray to receive FDA approval for the genetic evaluation of individuals with DD.