Placental Fatty Acid ethyl esters are elevated with maternal alcohol use in pregnancies complicated by prematurity

Abstract

The accumulation of fatty acid ethyl esters (FAEEs) in meconium of term newborns has been described as one potential biomarker of maternal alcohol use during pregnancy. FAEEs accumulate in multiple alcohol-exposed fetal tissues and in the placenta. Limited research has focused on the identification of the premature newborn exposed to alcohol in utero. We hypothesized that maternal alcohol use occurs in a significant proportion of premature deliveries and that this exposure can be detected as elevated placental FAEEs. The goals of this study were to 1) determine the prevalence of maternal alcohol use in the premature newborn and 2) investigate whether placental FAEEs could identify those newborns with fetal alcohol exposure. This prospective observational study evaluated 80 placentas from 80 women after premature delivery. Subjects were interviewed for alcohol intake and placental FAEEs were quantified via GC/MS. Receiver Operator Characteristic (ROC) Curves were generated to evaluate the ability of placental FAEEs to predict maternal drinking during pregnancy. Adjusted ROC curves were generated to adjust for gestational age, maternal smoking, and illicit drug use. 30% of the subjects admitted to drinking alcohol during pregnancy and approximately 14% answered questions indicative of problem drinking (designated AUDIT+). The specific FAEEs ethyl stearate and linoleate, as well as combinations of oleate + linoleate + linolenate (OLL) and of OLL + stearate, were significantly (p<0.05) elevated in placentas from AUDIT+ pregnancies. Adjusted ROC Curves generated areas under the curve ranging from 88-93% with negative predictive values of 97% for AUDIT+ pregnancies. We conclude that nearly one third of premature pregnancies were alcohol-exposed, and that elevated placental FAEEs hold great promise to accurately determine maternal alcohol use, particularly heavy use, in pregnancies complicated by premature delivery.

Fig 1. Combinations of FAEEs in placental tissue.

The Y axis represents the placental FAEE combinations (μg/gm dry weight in logarithmic scale) of OLL (Panels A and B) and OLL + Stearate (Panels C and D) while the X axis denotes maternal drinking groups. The box plots depict the median line and the first and third quartiles are represented by the lower and upper box edge, respectively. The whiskers indicate the smallest and largest values measured with outliers depicted by a small circle. * denotes p ≤ 0.05 AUDIT+ versus Non-Drinker.

Fig 2. Receiver Operating Characteristic curves for AUDIT+.

Unadjusted and adjusted ROC curves were generated for (A) Ethyl Stearate, (B) Ethyl Linoleate, (C) OLL and (D) OLL + Stearate. The Y axis denotes Sensitivity and the X axis denotes 1- Specificity. The red line denotes the unadjusted curve and the blue line denotes the curve adjusted for gestational age, maternal smoking and illicit drug use. A green diagonal reference line (line of no discrimination) corresponds to an area under the curve (AUC) of 0.5.