Phthalate esters are used widely as plasticizers for polyvinylchloride (PVC) formulations in several applications, including medical devices, toys, food wraps, and building products, to impart flexibility to an otherwise rigid PVC. Di-(2-ethylhexyl)phthalate (DEHP) is the most commonly used plasticizer. Because DEHP does not bind with the plastic, it leaches with time and use from vinyl products, thus becoming a ubiquitous environmental contaminant (Bauer and Herrmann 1997;Bradbury 1996;Giam et al. 1978;Griffiths et al. 1985;Mayer et al. 1972;Mes et al. 1974;Øie et al. 1997;Sharman et al. 1994). In particular, leaching of DEHP from PVC medical devices and deposits in tissue have been well documented (Latini 2000;Tickner et al. 2001). Because the DEHP action depends on dose, time, and age (Latini 2000) and because DEHP effects are influenced by the stage of development at exposure among animals (Akingbemi et al. 2001), the DEHP-related exposure risk is potentially higher for the developing fetus and newborn, particularly preterm. Recently, our preliminary findings indicated that the exposure to these environmental contaminants begins during intrauterine life, that these chemicals are able to cross the placental barrier, and that fetal exposure is closely related to maternal exposure (Latini et al. 2003). The aim of this study was to measure concentrations of DEHP and/or its main metabolite, mono-(2-ethylhexyl)phthalate (MEHP), in a larger population of human neonates and to evaluate possible biologic effects from prenatal exposure to DEHP and/or MEHP. Patients and MethodsSubjects. Cord blood samples were collected from 84 consecutive newborns (82 singletons, two twins), born at the general-practice Brindisi Hospital, with the following characteristics: 39 male, 45 female; maternal age at delivery, 29.5 ± 5.1 years (range = 18-42); vaginal delivery, n = 65 (77.4%); gestational age, 38.4 ± 2.2 weeks (range = 27-42); birth weight, 3,220 ± 680 g, (range = 1,150-4,350); 1-min Apgar score, 7.9 ± 0.9; 5-min Apgar score, 8.8 ± 0.5. Eleven of 84 infants were preterm; only three had very low birth weight. Moreover, four infants who were small for gestational age (SGA) were present in our population. None of the examined infants was born after in vitro fertilization pregnancy. The study was approved by the ethics committee of the Brindisi Hospital (Brindisi, Italy), and written informed consent from the parents was obtained. Blood specimens were immediately centrifuged (3,500 × g, 7 min), and serum was stored at -20°C until assay. To avoid any contamination from plasticizers in lab equipment, the serum sample collection, preservation, and treatment were performed only with glass devices. The concentrations of DEHP and MEHP were determined by highperformance liquid chromatography, at the Department of Chemistry of the University of L'Aquila, an institution certified in agreement with the International Organization for Standardization 9001 quality system, as described previously .Data analysis. Data are expressed as mean ± SD...

The present findings showed for the first time an association between DEHP plasma concentrations and endometriosis, suggesting a possible role for phthalate esters in the pathogenesis.

Inborn errors of metabolism are genetic disorders due to impaired activity of enzymes, transporters, or cofactors resulting in accumulation of abnormal metabolites proximal to the metabolic block, lack of essential products or accumulation of by-products. Many of these disorders have serious clinical consequences for affected neonates, and an early diagnosis allows presymptomatic treatment which can prevent severe permanent sequelae and in some cases death. Expanded newborn screening for these diseases is a promising field of targeted metabolomics. Here we report the application, between 2007 and 2014, of this approach to the identification of newborns in southern Italy at risk of developing a potentially fatal disease. The analysis of amino acids and acylcarnitines in dried blood spots by tandem mass spectrometry revealed 24 affected newborns among 45,466 infants evaluated between 48 and 72 hours of life (overall incidence: 1 : 1894). Diagnoses of newborns with elevated metabolites were confirmed by gas chromatography-mass spectrometry, biochemical studies, and genetic analysis. Five infants were diagnosed with medium-chain acyl CoA dehydrogenase deficiency, 1 with methylmalonic acidemia with homocystinuria type CblC, 2 with isolated methylmalonic acidemia, 1 with propionic acidemia, 1 with isovaleric academia, 1 with isobutyryl-CoA dehydrogenase deficiency, 1 with beta ketothiolase deficiency, 1 with short branched chain amino acid deficiency, 1 with 3-methlycrotonyl-CoA carboxylase deficiency, 1 with formimino-transferase cyclodeaminase deficiency, and 1 with cystathionine-beta-synthase deficiency. Seven cases of maternal vitamin B12 deficiency and 1 case of maternal carnitine uptake deficiency were detected. This study supports the widespread application of metabolomic-based newborn screening for these genetic diseases.

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