RESUMEN
The accumulation of fatty acid ethyl esters (FAEEs) in meconium of term newborns has been described as one potential biomarker of maternal alcohol use during pregnancy. FAEEs accumulate in multiple alcohol-exposed fetal tissues and in the placenta. Limited research has focused on the identification of the premature newborn exposed to alcohol in utero. We hypothesized that maternal alcohol use occurs in a significant proportion of premature deliveries and that this exposure can be detected as elevated placental FAEEs. The goals of this study were to 1) determine the prevalence of maternal alcohol use in the premature newborn and 2) investigate whether placental FAEEs could identify those newborns with fetal alcohol exposure. This prospective observational study evaluated 80 placentas from 80 women after premature delivery. Subjects were interviewed for alcohol intake and placental FAEEs were quantified via GC/MS. Receiver Operator Characteristic (ROC) Curves were generated to evaluate the ability of placental FAEEs to predict maternal drinking during pregnancy. Adjusted ROC curves were generated to adjust for gestational age, maternal smoking, and illicit drug use. 30% of the subjects admitted to drinking alcohol during pregnancy and approximately 14% answered questions indicative of problem drinking (designated AUDIT+). The specific FAEEs ethyl stearate and linoleate, as well as combinations of oleate + linoleate + linolenate (OLL) and of OLL + stearate, were significantly (p<0.05) elevated in placentas from AUDIT+ pregnancies. Adjusted ROC Curves generated areas under the curve ranging from 88-93% with negative predictive values of 97% for AUDIT+ pregnancies. We conclude that nearly one third of premature pregnancies were alcohol-exposed, and that elevated placental FAEEs hold great promise to accurately determine maternal alcohol use, particularly heavy use, in pregnancies complicated by premature delivery.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Ésteres/análisis , Ésteres/metabolismo , Ácidos Grasos/metabolismo , Recien Nacido Prematuro/metabolismo , Meconio/metabolismo , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Estudios Prospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Chronic alcohol exposure alters the function of alveolar macrophages (AM), impairing immune defenses in both adult and neonatal lungs. Fatty acid ethyl esters (FAEEs) are biological markers of prenatal alcohol exposure in newborns. FAEEs contribute to alcohol-induced mitochondrial (MT) damage in multiple organs. We hypothesized that in utero ethanol exposure would increase FAEEs in the neonatal lung and that direct exposure of neonatal AM to FAEEs would contribute to MT injury and cellular dysfunction. METHODS: FAEEs were measured in neonatal guinea pig lungs after ± in utero ethanol exposure via gas chromatography/mass spectrometry. The NR8383 cell line and freshly isolated neonatal guinea pig AM were exposed to ethyl oleate (EO) in vitro. MT membrane potential, MT reactive oxygen species generation (mROS), phagocytosis, and apoptosis were evaluated after exposure to EO ± the MT-specific antioxidant mito-TEMPO (mitoT) or ± the pan-caspase inhibitor Z-VAD-FMK. Whole lung FAEEs were compared using the Mann-Whitney U-test. Cellular results were analyzed using 1-way analysis of variance, followed by the Student-Newman-Keuls Method for post hoc comparisons. RESULTS: In utero ethanol significantly increased ethyl linoleate and the combinations of ethyl oleate + linoleate + linolenate (OLL), and OLL + stearate in the neonatal lung. In vitro EO caused significant MT dysfunction in both NR8383 and primary neonatal AM, as indicated by increased mROS and loss of MT membrane potential. Impaired phagocytosis and apoptosis were significantly increased in both the cell line and primary AM after EO exposure. MitoT conferred significant but only partial protection against EO-induced MT injury, as did caspase inhibition with Z-VAD-FMK. CONCLUSIONS: In utero ethanol exposure increased FAEEs in the neonatal guinea pig lung. Direct exposure to the FAEE EO significantly contributed to AM dysfunction, in part via oxidant injury to the MT and in part via secondary apoptosis.
Asunto(s)
Etanol/toxicidad , Ácidos Grasos no Esterificados/toxicidad , Pulmón/citología , Pulmón/efectos de los fármacos , Macrófagos Alveolares/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Animales , Animales Recién Nacidos , Femenino , Cobayas , Pulmón/metabolismo , Macrófagos Alveolares/metabolismo , Mitocondrias/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismoRESUMEN
In utero alcohol exposure dramatically increases the risk of premature delivery. However, the majority of premature and term newborns exposed to alcohol remain undetected by medical caregivers. There is a desperate need for reliable and accurate biomarkers of alcohol exposure for the term and premature newborn population. The inability to identify the exposed newborn severely limits our understanding of alcohol's pathophysiological effects on developing organs such as the lung. This chapter will review potential advancements in future biomarkers of alcohol exposure for the newborn population. We will discuss alcohol's effects on redox homeostasis and cellular development of the neonatal lung. Finally, we will present the evidence describing in utero alcohol's derangement of innate and adaptive immunity and risk for infectious complications in the lung. Continued investigations into the identification and understanding of the mechanisms of alcohol-induced alterations in the premature lung will advance the care of this vulnerable patient population.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Etanol/efectos adversos , Enfermedades Pulmonares , Pulmón/efectos de los fármacos , Pulmón/embriología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Consumo de Bebidas Alcohólicas/epidemiología , Femenino , Salud Global , Humanos , Incidencia , Recién Nacido , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/fisiopatología , EmbarazoRESUMEN
Prematurity is one of the leading causes of infant morbidity and mortality globally. Over the years, however, advances in medicine and technology have enhanced the ability to care for babies at very early gestations. There has also been a shift in the distribution of births away from term/post-term gestations and toward earlier gestational ages. These changes have added to the burden of premature births. The focus of this article is to present both sides of the story, one that highlights the many problems and morbidities faced by this subgroup of premature infants and the other that justifies their early delivery.