Prenatal exposure to heavy metal mixtures and anthropometric birth outcomes: a cross-sectional study.

BACKGROUND: Numerous studies have suggested significant associations between prenatal exposure to heavy metals and newborn anthropometric measures. However, little is known about the effect of various heavy metal mixtures at relatively low concentrations. Hence, this study aimed to investigate associations between prenatal exposures to a wide range of individual heavy metals and heavy metal mixtures with anthropometric measures of newborns. METHODS: We recruited 975 mother-term infant pairs from two major hospitals in Israel. Associations between eight heavy metals (arsenic, cadmium, chromium, mercury, nickel, lead, selenium, and thallium) detected in maternal urine samples on the day of delivery with weight, length, and head circumference at birth were estimated using linear and Bayesian kernel machine regression (BKMR) models. RESULTS: Most heavy metals examined in our study were observed in lower concentrations than in other studies, except for selenium. In the linear as well as the BKMR models, birth weight and length were negatively associated with levels of chromium. Birth weight was found to be negatively associated with thallium and positively associated with nickel. CONCLUSION: By using a large sample size and advanced statistical models, we could examine the association between prenatal exposure to metals in relatively low concentrations and anthropometric measures of newborns. Chromium was suggested to be the most influential metal in the mixture, and its associations with birth weight and length were found negative. Head circumference was neither associated with any of the metals, yet the levels of metals detected in our sample were relatively low. The suggested associations should be further investigated and could shed light on complex biochemical processes involved in intrauterine fetal development.

Maternal Exposure to Polychlorinated Biphenyls and Asthma, Allergic Rhinitis and Atopic Dermatitis in the Offspring: The Environmental Health Fund Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are persistent organic pollutants banned for use worldwide. Due to their biodegradation resistance, they accumulate along the food chain and in the environment. Maternal exposure to PCBs may affect the fetus and the infant. PCBs are immunotoxic and may damage the developing immune system. PCBs are associated with elevated IgE antibodies in cord blood and are considered to be predictive of atopic reactions. Several studies on the association between prenatal exposure to PCBs and atopic reactions were previously published, albeit with conflicting results. Objectives: To examine the association between maternal PCBs levels and atopic reactions in their offspring. Methods: During the years 2013-2015, a prospective birth cohort was recruited at the delivery rooms of Shamir Medical Center (Assaf Harofeh) and "Dana Dwek" Children's Hospital. Four PCBs congeners were investigated: PCBs 118, 138, 153, and 180. In 2019, when children reached the age of 4-6 years, mothers were interviewed using the ISAAC questionnaire to assess symptoms of atopic reactions, including asthma, allergic rhinitis, and atopic dermatitis. Results: One hundred and fifty mother-child dyads were analyzed. No significant differences were found in the median serum PCBs concentrations of each studied congener or total PCBs for asthma, allergic rhinitis, atopic dermatitis diagnosis, or parent-reported symptoms. No association was found between exposure to total PCBs and the risk for asthma symptoms or diagnosis, adjusted to maternal age and family member with atopic condition: aOR = 0.94, 95%CI: (0.88; 0.99). No association was observed between each studied PCB congener and asthma symptoms or diagnosis. The same results were found also for other studied outcomes-allergic rhinitis and atopic dermatitis. Conclusion: Our study joins a series of previous studies that attempt to shed light on environmental exposures in utero as influencing factors for atopic conditions in children. Our results reflect the complexity of the pathophysiology of these phenomena. No relationship between maternal serum PCBs levels was demonstrated for asthma, allergic rhinitis, or atopic dermatitis. However, additional multi-participant studies, with longer, spanning into later pediatric age follow up are needed.

Maternal and Newborn Thyroid Hormone, and the Association With Polychlorinated Biphenyls (PCBs) Burden: The EHF (Environmental Health Fund) Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants found in human tissues. PCBs can be transferred through the placenta and may disrupt the maternal thyroid homeostasis, and affect fetal thyroid hormone production. Several studies have shown that intrauterine exposure to PCBs might be associated with abnormal levels of thyroid hormones in mothers and their offspring. Objectives: To examine the associations between environmental exposure to PCBs and thyroid hormone levels in mothers and newborns. Methods: The EHF-Assaf-Harofeh-Ichilov cohort includes 263 mothers-newborns dyads. A total of 157 mother-newborn dyads had both PCBs and thyroid function measures. Regression models were used to estimate associations between maternal PCB exposure and maternal and newborn thyroid function, controlling for possible confounders. Results: Four PCBs congeners were analyzed: PCBs 118, 138, 153, and 180. ∑PCBs median (IQR) level was 14.65 (2.83-68.14) ng/g lipids. The median maternal thyroid-stimulating hormone (TSH) level was 2.66 (0.70-8.23) µIU/ml, the median maternal free thyroxine (FT4) level was 12.44 (11.27-13.53) µg/dL, the median maternal thyroid peroxidase antibodies (TPO Ab) level was 9.6 (7.36-12.51) IU/mL. Newborns' median total thyroxine (T4) level was 14.8 (7.6-24.9) µg/dL. No association was found between exposure to different congeners or to ∑PCBs and maternal TSH, FT4, thyroglobulin autoantibodies (Tg Ab), TPO Ab and newborn total T4 levels. In multivariable analysis a 1% change in ∑PCBs level was significantly associated with a 0.57% change in maternal TSH levels in women with body mass index (BMI) < 19. The same association was observed for each of the studied PCB congeners. Maternal TPO Ab levels statistically significantly increased by 0.53 and 0.46% for 1% increase in PCB 118 and 153 congeners, respectively. In women with BMI > 25, the association between the PCBs levels and maternal TSH levels was in the opposite direction. No association was found in women with normal BMI (19-24.9). Conclusions: Background exposure to environmentally relevant concentrations of some PCBs can alter thyroid hormone homeostasis in pregnant women and might be associated with abnormal TSH levels and TPO-Ab in women with low BMI. However, these findings require further investigation.

Antiepileptic Drug Treatment in Community-Dwelling Older Patients with Epilepsy: A Retrospective Observational Study of Old- Versus New-Generation Antiepileptic Drugs.

INTRODUCTION: The use of antiepileptic drugs (AEDs) in older patients with epilepsy is challenged by polypharmacy and decreased drug elimination. Newer AEDs have a lower potential for drug interactions and are reported to be better tolerated by the elderly than old-generation AEDs. OBJECTIVE: The objective of this study was to evaluate AED use and the related adverse event rate in an outpatient cohort of older patients with epilepsy. METHODS: We retrospectively reviewed the computerized database and medical records of all the patients aged ≥60 years who visited our epilepsy outpatient clinic (Assaf Harofeh Medical Center, Zerifin, Israel) during a 4-year period from February 2012 to February 2016. In this study, phenytoin, valproic acid, carbamazepine, phenobarbital, clobazam, and clonazepam were defined as old-generation AEDs. Gabapentin, levetiracetam, lamotrigine, topiramate, oxcarbazepine, lacosamide, and perampanel were defined as new-generation AEDs. RESULTS: The study group included 115 patients aged 60-90 years (mean 70.5 ± 7.8 years), 70 (61%) of whom were men. Co-morbidities were present in 98.3% of the patients, including neuropsychiatric illnesses in 21.2%. Present medical treatment included new-generation AEDs in 49 (44.5%) and both old- and new-generation AEDs in 20 (18.2%) patients. The most commonly used current AEDs were phenytoin, gabapentin, levetiracetam, and lamotrigine. Adverse reactions mainly included fatigue and CNS-related symptoms, and were more frequent among patients treated with new-generation AEDs than in those treated with old-generation AEDs or a combination of old- and new-generation AEDs; however, these reactions were mostly related to levetiracetam treatment. The likelihood of levetiracetam-related adverse events was increased by slow levetiracetam titration [defined as a weekly dose increase of ≤250 mg/day in this study; odds ratio (OR) 16.35, 95% confidence interval (CI) 2.94-90.98], and by low- (OR 5.68, 95% CI 1.40-22.95) and high (OR 4.24, 95% CI 1.28-14.02) levetiracetam dosages compared with patients treated with lamotrigine or gabapentin. CONCLUSIONS: New-generation AEDs were administered to most of the patients in this outpatient clinic-based cohort of older patients with epilepsy. In order to decrease levetiracetam-related adverse events in this age group, we suggest that a slower titration rate (e.g., an increase of ≤125 mg/day each week) and lower maximal dosage (e.g., 1500 mg/day) of the drug should be considered.