Hidden Toxicity in Neonatal Intensive Care Units: Phthalate Exposure in Very Low Birth Weight Infants

Abstract

Objective:To determine exposure to endocrine-disrupting phthalates in preterm infants in neonatal intensive care units (NICU).Methods:Urine samples (n=151) from 36 preterm infants (<32 weeks of gestation and/or <1500 g of birth weight) were collected on the first 3 days of admission to the NICU and biweekly thereafter. Diethylhexyl phthalate contents of indwelling medical devices used in various procedures and the concentrations of phthalate metabolites in the urine samples were analyzed. The relationships between urinary excretion, exposure intensity, postnatal age and birth weight were examined.Results:The mean gestational age and mean birth weight of the study infants were 28.9±1.5 weeks and 1024±262 g, respectively. Diethylhexyl phthalate was detected in umbilical catheters, endotracheal tubes, nasogastric tubes, and nasal cannula. Monoethylhydroxyhexyl phthalate (MEHHP) was the most frequently detected metabolite (81.4%); its concentration increased during the first 4 weeks and then started to decrease but never disappeared. Patients who did not need indwelling catheters (except nasogastric tubes) after 2 weeks were classified as group 1 and those who continued to have indwelling catheters as group 2. Although not of statistical significance, MEHHP levels decreased in group 1 but continued to stay high in group 2 (in the 4th week, group 1: 65.9 ng/mL and group 2: 255.3 ng/mL). Levels of MEHHP in the first urinary samples were significantly higher in infants with a birth weight <1000 g (<1000 g: 63.2±93.8 ng/mL, ≥1000 g: 10.9±22.9 ng/mL, p=0.001).Conclusion:Phthalate metabolites were detected even in the first urine samples of very low birth weight newborns. Phthalate levels were higher in the first weeks of intensive invasive procedures and in preterm infants with a birth weight less than 1000 g. MEHHP was the most frequently detected metabolite and could be a suitable biomarker for the detection of phthalate exposure in preterm infants.

Comparative Effects of Di-(2-ethylhexyl)phthalate and Di-(2-ethylhexyl)terephthalate Metabolites on Thyroid Receptors: In Vitro and In Silico Studies

“…Urinary levels of 5-OH-MEHP may exceed 0.2 µg/mL, a concentration at which we have demonstrated a TRβ agonist effect that was confirmed in vitro as being partial and has a synergistic effect with T3. The maximum values of 5-OH-MEHP measured in the urine of newborns hospitalized in NICUs range from 0.43 µg/mL to 13.1 µg/mL, i.e., 2 to 65 times higher than the concentration activating thyroid receptors [ 36 , 37 , 38 , 39 , 40 ]. Certain medical procedures, such as extracorporeal circulation (extracorporeal membrane oxygenation, cardiopulmonary bypass), respiratory assistance, and intravenous nutrition are recognized as situations with a high risk of exposure, which can explain the high values in multi-exposed patients.…”

Association between Urinary Metabolites and the Exposure of Intensive Care Newborns to Plasticizers of Medical Devices Used for Their Care Management

“…Our study of 104 neonates is the first biomonitoring study assessing this exposure to alternative-to-DEHP plasticizers of neonates hospitalized in NICU. Previous NICU studies were conducted on few patients and were intended only to measure the exposure to DEHP via MD, based on the urinary concentrations of its metabolites [ 16 , 17 , 18 , 19 ]. All the authors demonstrated a correlation between the urinary levels of some DEHP metabolites (MEHP, 5-oxo-MEHP, and 5-OH-MEHP) and the exposure of NICU patients to DEHP via MD, higher than the general population.…”

“…Moreover, fetal and neonatal periods are very sensitive periods to the effects of endocrine disruptors. Overall, multiple and intensive medical interventions and an impaired ability to excrete phthalates may explain the susceptibility of neonates, and particularly preterm infants, to high DEHP exposure, the latter being associated with the intensity and duration of invasive medical procedures [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

Bisphenols and phthalates: Plastic chemical exposures can contribute to adverse cardiovascular health outcomes

“…In the final product, DEHP can contribute up to 40% of the finished weight of plastic medical products (e.g., intravenous fluid bags, blood storage bags), and up to 80% of the weight of flexible medical tubing (Halden, 2010; Jaeger & Rubin, 1973, 2010; Plonait, Nau, Maier, Wittfoht, & Obladen, 1993). Since phthalates are not covalently bound to PVC, these chemical additives are known to leach or migrate into surrounding solutions, including blood (Table 2) (Barry et al, 1989; D'Alessandro et al, 2019; Demirel et al, 2016; Gaynor et al, 2018; Green et al, 2005; Kaestner et al, 2020; Karle et al, 1997; Mallow & Fox, 2014; Münch et al, 2020; Peck et al, 1979; Rael et al, 2009; Sjöberg, Bondesson, Sedin, & Gustafsson, 1985; Sjoberg et al, 1985; Stroustrup et al, 2018; Su et al, 2012; Takatori et al, 2008; van der Meer et al, 2014). Moreover, DEHP leaching is exacerbated under conditions of prolonged use, mechanical stress, higher temperature and/or in the presence of lipid‐containing fluids.…”