Exposure of preterm neonates receiving total parenteral nutrition to phthalates and its impact on neurodevelopment at the age of 2 months.

This prospective study assessed the exposure to phthalates of preterm neonates who received total parenteral nutrition (TPN) during their stay in the neonatal intensive care unit (NICU) and the risk of neurodevelopment delays at the age of 2 months. Our study recruited 33 preterm neonates who required TPN upon NICU admission. Urine samples for analyzing phthalate metabolites were obtained at admission and then daily until the last day of receiving TPN. Phthalates in the daily TPN received by the preterm neonates were analyzed. The neurodevelopment of the neonates was assessed using the Ages and Stages Questionnaire Edition 3 (ASQ-3). Diethyl phthalate and butyl benzyl phthalate were found in all TPN samples, while 27% and 83% contained dibutyl phthalate and di-(2-ethylhexyl) phthalate (DEHP), respectively. Yet, the daily dose of each phthalate that our preterm neonates received from TPN was much lower than the recommended tolerable limit. Urinary levels of monobenzyl phthalate and four metabolites of DEHP [i.e., mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)] and the sum of four DEHP metabolites (∑4DEHP) increased significantly in preterm neonates before discharge. However, these levels were not correlated with their phthalate parent compounds in TPN, suggesting other sources of exposure in the NICU. At 2 months, we found that urinary levels of mono-iso-butyl phthalate (MiBP), MECPP, MEHP, and ∑4DEHP were inversely related to fine motor skills. After adjusting for head circumference, the inverse relationships remained significant, suggesting direct effects from phthalates. Given the extreme vulnerability of our population, it is critical to minimize exposure to phthalates during their NICU stay.

Exposure of preterm neonates to toxic metals during their stay in the Neonatal Intensive Care Unit and its impact on neurodevelopment at 2 months of age.

BACKGROUND: Premature neonates might be exposed to toxic metals during their stay in the neonatal intensive care unit (NICU), which could adversely affect neurodevelopment; however, limited evidence is available. The present study was therefore designed to assess the exposure to mercury, lead, cadmium, arsenic, and manganese of preterm neonates who received total parenteral nutrition (TPN) and/or red blood cell (RBC) transfusions during their NICU stay and the risk of neurodevelopment delay at the age of 2 months. METHODS: We recruited 33 preterm neonates who required TPN during their NICU admission. Blood samples were collected for metal analysis at two different time points (admission and before discharge). Metals in the daily TPN received by preterm neonates were analyzed. Neurodevelopment was assessed using the Ages and Stages Questionnaire Edition 3 (ASQ-3). RESULTS: All samples of TPN had metal contamination: 96% exceeded the critical arsenic limit (0.3 µg/kg body weight/day); daily manganese intake from TPN for preterm neonates exceeded the recommended dose (1 µg/kg body weight) as it was added intentionally to TPN solutions, raising potential safety concerns. All samples of RBC transfusions exceeded the estimated intravenous reference dose for lead (0.19 µg/kg body weight). Levels of mercury, lead and manganese in preterm neonates at discharge decreased 0.867 µg/L (95% CI, 0.76, 0.988), 0.831 (95%CI, 0.779, 0.886) and 0.847 µg/L (95% CI, 0.775, 0.926), respectively. A decrease in ASQ-3-problem solving scores was associated with higher levels of blood lead in preterm neonates taken at admission (ß = -0.405, 95%CI = -0.655, -0.014), and with plasma manganese (ß = -0.562, 95%CI = -0.995, -0.172). We also observed an association between decreased personal social domain scores with higher blood lead levels of preterm neonates before discharge (ß = -0.537, 95%CI = -0.905, -0.045). CONCLUSION: Our findings provide evidence to suggest negative impacts on the neurodevelopment at 2 months of preterm infants exposed to certain metals, possibly related to TPN intake and/or blood transfusions received during their NICU stay. Preterm neonates may be exposed to levels of metals in utero.

The cumulative risk assessment of phthalates exposure in preterm neonates.

Phthalates are widely used plasticizers in various consumer products and medical devices, with some reporting as having estrogenic and anti-androgenic endocrine-disrupting effects. Premature neonates may be exposed to high levels of specific phthalates during hospitalization in the neonatal intensive care unit (NICU) because of reliance on multiple medical procedures that pose a possible health risk. The present study utilized seven urinary phthalate metabolites of dibutyl phthalate isomers [(di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP)], butylbenzyl phthalate (BBzP), and di(2-ethylhexyl) phthalate (DEHP) that had been previously measured in 33 preterm neonates sampled at hospital admission (N = 23) and daily during their NICU stay (N = 260). We aimed to perform: (1) cumulative risk assessment (CRA) using the volume and creatinine-adjusted models; (2) examine the temporal variability of CRA from repeated measures and (3) estimate the risk of cumulative exposure to phthalates based on their anti-androgenic and/or estrogenic properties. We multiplied the relative activity of individual phthalates exhibiting estrogenic or anti-androgenic effects by daily intake. For each preterm neonate, CRA was assessed based on the hazard index (HI) metric [the sum of hazard quotients] based on three reference doses for anti-androgenicity: the tolerable daily intake (TDI) from the European Food Safety Authority, the reference dose (RfD-AA) published in 2010 and newly revised published in 2020 (NRfD-AA). The metabolites of BBzP and DEHP were 2-23 fold higher in preterm neonates during their NICU stay. Median HIs increased in the order of HINRfDAA > HIRfDAA > HITDI. In the creatinine-based model, 87% (92%), 87% (96%), and 100% (100%) of preterm neonates at admission (during NICU stay) showed HITDI, HIRfD-AA, and HINRfD-AA exceeding 1, respectively with DEHP the most prevalent. The temporal reproducibility of HI (based on three reference doses) during preterm neonate stay in the NICU was high, with intra-class correlation coefficients ranging between 0.77 and 0.97, suggesting persistent exposure to phthalates. The four phthalates that preterm neonates were exposed to in the NICU exhibited estrogenic binding and anti-androgenic effects with median values (creatinine-based) of 98.7 and 56.9 µg/kg body weight/day, respectively. This was especially true for DEHP. The results indicate that preterm neonates in this NICU setting are probably at high risk of cumulative phthalate exposure with anti-androgenic properties that may have long-term adverse reproductive and developmental effects.

A Randomized Controlled Trial of the Use of Oral Glucose with or without Gentle Facilitated Tucking of Infants during Neonatal Echocardiography.

OBJECTIVE: To compare the effect of oral glucose given with or without facilitated tucking (FT), versus placebo (water) to facilitate image acquisition during a targeted neonatal echocardiography (TNE). DESIGN: Factorial, double blind, randomized controlled trial. SETTING: Tertiary neonatal intensive care unit (NICU). PATIENTS: Infants born between 26 and 42 weeks of gestation (GA). INTERVENTIONS: One of four treatment groups: oral water (placebo), oral glucose (25%), facilitated tucking with oral water or facilitated tucking with oral glucose, during a single, structured TNE. All infants received a soother. MAIN OUTCOME MEASURE: Change in Behavioral Indicators of Infant Pain (BIIP) scores. RESULTS: 104 preterm infants were randomized (mean ± SD GA: 33.4 ± 3.5 weeks). BIIP scores remained low during the echocardiography scan (median, [IQ range]: 0, [0 to 1]). There were no differences in the level of agitation of infants amongst the treatment groups, with estimated reductions in mean BIIP relative to control of 0.27 (95%CI -0.40 to 0.94) with use of oral glucose and .04 (-0.63 to 0.70) with facilitated tucking. There were also no differences between treatment groups in the quality and duration of the echocardiography scans. CONCLUSIONS: In stable infants in the NICU, a TNE can be performed with minimal disruption in a majority of cases, simply by providing a soother. The use of 25% glucose water in this context did not provide further benefit in reducing agitation and improving image acquisition. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov: NCT01253889.

Preferential cephalic redistribution of left ventricular cardiac output during therapeutic hypothermia for perinatal hypoxic-ischemic encephalopathy.

OBJECTIVE: To determine the relationship between left ventricular cardiac output (LVCO), superior vena cava (SVC) flow, and brain injury during whole-body therapeutic hypothermia. STUDY DESIGN: Sixteen newborns with moderate or severe hypoxic-ischemic encephalopathy were studied using echocardiography during and immediately after therapeutic hypothermia. Measures were also compared with 12 healthy newborns of similar postnatal age. Newborns undergoing therapeutic hypothermia also had cerebral magnetic resonance imaging as part of routine clinical care on postnatal day 3-4. RESULTS: LVCO was markedly reduced (mean ± SD 126 ± 38 mL/kg/min) during therapeutic hypothermia, whereas SVC flow was maintained within expected normal values (88 ± 27 mL/kg/min) such that SVC flow represented 70% of the LVCO. The reduction in LVCO during therapeutic hypothermia was mainly accounted by a reduction in heart rate (99 ± 13 vs 123 ± 17 beats/min; P < .001) compared with immediately postwarming in the context of myocardial dysfunction. Neonates with brain injury on magnetic resonance imaging had higher SVC flow prerewarming, compared with newborns without brain injury (P = .013). CONCLUSION: Newborns with perinatal hypoxic-ischemic encephalopathy showed a preferential systemic-to-cerebral redistribution of cardiac blood flow during whole-body therapeutic hypothermia, which may reflect a lack of cerebral vascular adaptation in newborns with more severe brain injury.

The use of herbal preparations as complementary and alternative medicine (CAM) in a sample of patients with cancer in Jordan.

PURPOSE: This study sought to describe the type, frequency, purpose and pattern of herbal preparation use as complementary medicine in a sample of patients with cancer in Jordan. METHOD: The study took the form of a cross-sectional survey of patients attending the outpatient departments at King Hussein Cancer Centre (KHCC), a specialist cancer centre in Amman. The method was based on using a semi-structured questionnaire. RESULTS: A total of 1138 patients with cancer were interviewed, out of which 404 (35.5%) reported using botanicals based complementary and alternative medicine (CAM) primarily bought form Jordan (85.1%) and used in the crude form as infusions (73.3%). Only 6.8% used herbal products in a dosage form. Most of CAM users were above 40 years of age (63.1%). Recommendation of a friend was the main factor that prompted them to use CAM (41.8%). CONCLUSION: This study revealed that CAM use is common among patients with cancer in Jordan.