Prenatal Exposure to Glyphosate and Its Environmental Degradate,Aminomethylphosphonic Acid (AMPA), and Preterm Birth: A Nested Case–Control Study in the PROTECT Cohort (Puerto Rico)

Background: Glyphosate (GLY) is the most heavily used herbicide in the world. Despite nearly ubiquitous exposure, few studies have examined prenatal GLY exposure and potentially adverse pregnancy outcomes. Preterm birth (PTB) is a risk factor for neonatal mortality and adverse health effects in childhood.Objectives: We examined prenatal exposure to GLY and a highly persistent environmental degradate of GLY, aminomethylphosphonic acid (AMPA), and odds of PTB in a nested case–control study within the ongoing Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort in northern Puerto Rico.Methods: GLY and AMPA in urine samples collected at 18±2 (Visit 1) and 26±2 (Visit 3) wk gestation (53 cases/194 randomly selected controls) were measured using gas chromatography tandem mass spectrometry. Multivariable logistic regression was used to estimate associations with PTB (delivery <37wk completed gestation).Results: Detection rates in controls were 77.4% and 77.5% for GLY and 52.8% and 47.7% for AMPA, and geometric means (geometric standard deviations) were 0.44 (2.50) and 0.41 (2.56)μg/L for GLY and 0.25 (3.06) and 0.20 (2.87)μg/L for AMPA, for Visits 1 and 3, respectively. PTB was significantly associated with specific gravity–corrected urinary GLY and AMPA at Visit 3, whereas associations with levels at Visit 1 and the Visits 1–3 average were largely null or inconsistent. Adjusted odds ratios (ORs) for an interquartile range increase in exposure at Visit 3 were 1.35 (95% CI: 0.99, 1.83) and 1.67 (95% CI: 1.26, 2.20) for GLY and AMPA, respectively. ORs for Visit 1 and the visit average were closer to the null.Discussion: Urine GLY and AMPA levels in samples collected near the 26th week of pregnancy were associated with increased odds of PTB in this modestly sized nested case–control study. Given the widespread use of GLY, multiple potential sources of AMPA, and AMPA’s persistence in the environment, as well as the potential for long-term adverse health effects in preterm infants, further investigation in other populations is warranted. https://doi.org/10.1289/EHP7295     

A Concise Panel of Biomarkers Identifies Neurocognitive Functioning Changes in HIV-Infected Individuals

Neurocognitive (NC) impairment (NCI) occurs commonly in people living with HIV. Despite substantial effort, no biomarkers have been sufficiently validated for diagnosis and prognosis of NCI in the clinic. The goal of this project was to identify diagnostic or prognostic biomarkers for NCI in a comprehensively characterized HIV cohort. Multidisciplinary case review selected 98 HIV-infected individuals and categorized them into four NC groups using normative data: stably normal (SN), stably impaired (SI), worsening (Wo), or improving (Im). All subjects underwent comprehensive NC testing, phlebotomy, and lumbar puncture at two timepoints separated by a median of 6.2 months. Eight biomarkers were measured in CSF and blood by immunoassay. Results were analyzed using mixed model linear regression and staged recursive partitioning. At the first visit, subjects were mostly middle-aged (median 45) white (58 %) men (84 %) who had AIDS (70 %). Of the 73 % who took antiretroviral therapy (ART), 54 % had HIV RNA levels below 50 c/mL in plasma. Mixed model linear regression identified that only MCP-1 in CSF was associated with neurocognitive change group. Recursive partitioning models aimed at diagnosis (i.e., correctly classifying neurocognitive status at the first visit) were complex and required most biomarkers to achieve misclassification limits. In contrast, prognostic models were more efficient. A combination of three biomarkers (sCD14, MCP-1, SDF-1α) correctly classified 82 % of Wo and SN subjects, including 88 % of SN subjects. A combination of two biomarkers (MCP-1, TNF-α) correctly classified 81 % of Im and SI subjects, including 100 % of SI subjects. This analysis of well-characterized individuals identified concise panels of biomarkers associated with NC change. Across all analyses, the two most frequently identified biomarkers were sCD14 and MCP-1, indicators of monocyte/macrophage activation. While the panels differed depending on the outcome and on the degree of misclassification, nearly all stable patients were correctly classified.     

Epidemiology of Traumatic Brain Injury and Subarachnoid Hemorrhage

Incidence rates of traumatic brain injury are high in both industrialized and non-industrialized countries and have been estimated variously to be between 150–250 cases per 100,000 population per year. The estimated incidence rates for subarachnoid hemorrhage (SAH) are between 10 to 25 cases per 100,000 population per year. Seasonal variation in the occurrence of subarachnoid hemorrhage has been reported in studies from different countries, with significant seasonal variations and peak periods for aneurysmal SAH differing widely. A differential racial distribution for SAH has been found as well as a higher mortality rate for women than for men. The cognitive and behavioral consequences of TBI and SAH are significant and affect the quality of life of patients and their families. Recent publications have informed of hypopituitary deficits in patients sustaining TBI or SAH. It is not clear whether the cognitive deficits found in these patients are due to the consequences of the brain injury itself or are related to the hypopituitary deficits. There is a need for research distinguishing the differential cognitive and behavioral effects of the brain injury and the endocrinological deficits in these patients, and for developing adequate treatment.