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)

Abstract

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 $18\pm 2$ (Visit 1) and $26\pm 2$ (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 $<37\mathrm{wk}$ 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 $\left(2.56\right)\mu g/L$ for GLY and 0.25 (3.06) and 0.20 $\left(2.87\right)\mu g/L$ 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.

Figure 1.

Odds ratios by level of urinary GLY and AMPA concentrations measured in maternal urine at Visit 3 ($26\pm 2$ wk gestation) and preterm birth. Corresponding numeric data for Visit 1, Visit 3, and the pregnancy average are provided in Table S3. Biomarkers are adjusted for specific gravity using the formula: ${\text{GA}}_{\text{SG}}=\text{GA}\left[\left(1.019–1\right)/\left(\text{SG}-1\right)\right]$, where ${\text{GA}}_{\text{SG}}$ is the SG-adjusted GLY or AMPA concentration ($\mathrm{\mu }\mathrm{g}/\mathrm{L}$); GA is the observed GLY or AMPA concentration; 1.019 is the population median specific gravity; and SG is the specific gravity of the urine sample; $n=208$; 53 cases, 155 controls. Adjusted models are adjusted for maternal age, education, prepregnancy BMI, and smoking; $n=198$; 50 cases, 148 controls. The x-axes are shown on a log-10 scale. Note: AMPA, aminomethylphosphonic acid; BMI, body mass index; CI, confidence interval; GLY, glyphosate; OR, odds ratio.

Figure 2.

Odds ratios by level of urinary GLY and AMPA concentrations measured in maternal urine at Visit 3 ($26\pm 2$ wk gestation) and spontaneous preterm birth. Corresponding numeric data for Visit 1, Visit 3, and the pregnancy average are provided in Table S3. Biomarkers are adjusted for specific gravity using the formula: ${\text{GA}}_{\text{SG}}=\text{GA}\left[\left(1.019–1\right)/\left(\text{SG}-1\right)\right]$, where ${\text{GA}}_{\text{SG}}$ is the SG-adjusted GLY or AMPA concentration ($\mathrm{\mu }\mathrm{g}/\mathrm{L}$); GA is the observed GLY or AMPA concentration; 1.019 is the population median specific gravity; and SG is the specific gravity of the urine sample; $n=208$; 35 cases, 155 controls. Adjusted models are adjusted for maternal age, education, prepregnancy BMI, and smoking; $n=180$; 32 cases, 148 controls. The x-axes are shown on a log-10 scale. Note: AMPA, aminomethylphosphonic acid; BMI, body mass index; CI, confidence interval; GLY, glyphosate; OR, odds ratio.