Pre- plus postnatal exposures to di-(2-ethylhexyl)-phthalate and thyroid dysfunction in prematurely born children

Abstract

Thyroid dysfunction is frequently observed among comorbidities associated with prematurity. The main factors reported to affect thyroid function in preterm infants are the immaturity of the hypothalamic-pituitary-thyroid axis, immature thyroid hormone synthesis and metabolism, and insufficient or excessive exposure to iodine [1, 2], as well as drugs used to treat critically ill premature babies, such as caffeine, dopamine, morphine and glucocorticoids [3]. We propose further factors that may contribute to explaining disturbances of the hypothalamus-pituitarythyroid axis observed in preterm babies, i.e., preand postnatal exposures to environmental chemical compounds with thyroid-disrupting activity, such as phthalates. Phthalates are a group of chemicals with many commercial uses such as solvents, additives and particularly plasticizers to impart flexibility to an otherwise rigid polyvinylchloride (PVC). In particular, di-(2-ethylhexyl)phthalate (DEHP) is the most commonly used plasticizer in PVC medical devices, such as infusion systems, tracheal tubes, and blood bags [4]. It is well known that the developing fetus and the neonate are the most vulnerable phases of life for exposure to these environmental contaminants. It has also been shown that prenatal exposure to DEHP is associated with shorter pregnancy duration [5, 6]. According to Food and Drug Administration (FDA), due to their small body size, physical condition, and particularly multiple medical device DEHP-related exposure, neonates in the Neonatal Intensive Care Unit (NICU) environment are a population especially at risk [7]. In addition, it has been shown that neonates in the NICU environment are exposed to higher concentrations of DEHP than the general population [8], and their daily exposure to DEHP may increase up to 20-fold the tolerable daily intake [9]. Phthalates have also been reported to interfere with the endocrine system, especially when exposure begins early in life [6]. Several lines of evidence, mainly based on in vivo and in vitro studies, indicate that thyroid function is a further target of these compounds and that these chemicals may act through a number of potential mechanisms [10, 11]. In this regard, a recent review of the most recently published epidemiological studies reported that exposure to phthalates negatively impacts thyroid function in children [12]. Moreover, a positive relationship between urinary DEHP metabolites and thyroid-stimulating hormone levels has been reported, in both adults and adolescents from the general population [13]. Therefore, it is conceivable that prenatal and postnatal exposure to phthalates may have a role in producing thyroid hazards in exposed preterm babies. In conclusion, although alternative materials have been developed [14], only few DEHP–free medical devices are available on the market and their high cost is still a major limit to their exploitation. Therefore, research into alternatives to DEHP-containing medical devices that may come in contact with human tissues should be urgently encouraged. In the meantime, further studies are needed to evaluate the real impact of preand postnatal DEHP exposure G. Latini Division of Neonatology, Ospedale Perrino, Brindisi, Italy