Newborns from Mothers Who Intensely Consumed Sucralose during Pregnancy Are Heavier and Exhibit Markers of Metabolic Alteration and Low-Grade Systemic Inflammation: A Cross-Sectional, Prospective Study

Abstract

Robust data in animals show that sucralose intake during gestation can predispose the offspring to weight gain, metabolic disturbances, and low-grade systemic inflammation; however, concluding information remains elusive in humans. In this cross-sectional, prospective study, we examined the birth weight, glucose and insulin cord blood levels, monocyte subsets, and inflammatory cytokine profile in 292 neonates at term from mothers with light sucralose ingestion (LSI) of less than 60 mg sucralose/week or heavy sucralose intake (HSI) of more than 36 mg sucralose/day during pregnancy. Mothers in the LSI (n = 205) or HSI (n = 87) groups showed no differences in age, pregestational body mass index, blood pressure, and glucose tolerance. Although there were no differences in glucose, infants from HSI mothers displayed significant increases in birth weight and insulin compared to newborns from LSI mothers. Newborns from HSI mothers showed a substantial increase in the percentage of inflammatory nonclassical monocytes compared to neonates from LSI mothers. Umbilical cord tissue of infants from HSI mothers exhibited higher IL-1 beta and TNF-alpha with lower IL-10 expression than that found in newborns from LSI mothers. Present results demonstrate that heavy sucralose ingestion during pregnancy affects neonates' anthropometric, metabolic, and inflammatory features.

Keywords: IL-10; TNF-alpha; birth weight; cord blood; insulin; monocyte subset; neonate; pregnancy; sucralose.

Figure 1

Glucose and insulin levels in neonates lightly or heavily exposed to sucralose during pregnancy. (A) Cord blood glucose levels in newborns lightly or heavily exposed to sucralose. (B) Cord blood insulin levels in neonates lightly or heavily exposed to sucralose. We measured glucose and insulin in umbilical cord blood from all infants. We expressed data as mean ± standard deviation. We compared data by the unpaired Student’s t-test, considering differences significant when p < 0.05.

Figure 2

Gating strategy for detecting classical, intermediate, and nonclassical monocyte subsets in neonates lightly or heavily exposed to sucralose during pregnancy. CD14++CD16- cells were recognized as classical monocytes, CD14++CD16+ cells were identified as intermediate monocytes, and CD14+CD16+ cells were distinguished as nonclassical monocytes. The last panel illustrates how nonclassical monocytes significantly increase in neonates from mothers who intensely consumed sucralose during pregnancy. We acquired 1 × 10⁴ cell events per test in triplicate corresponding to the HLA-DR+ cell population on a BD influx flow cytometer.

Figure 3

Percentages of classical, intermediate, and nonclassical monocytes in neonates lightly or heavily exposed to sucralose during pregnancy. (A) Classical monocyte percentage in newborns lightly or heavily exposed to sucralose. (B) Intermediate monocyte percentage in neonates lightly or heavily exposed to sucralose. (C) Nonclassical monocyte percentage in newborns lightly or heavily exposed to sucralose. We measured percentages of monocyte subsets in umbilical cord blood from all infants. We expressed data as mean ± standard deviation. We compared data by the unpaired Student’s t-test, considering differences significant when p < 0.05.

Figure 4

IL-1 beta, TNF-alpha, and IL-10 expression in umbilical cord specimens from neonates lightly or heavily exposed to sucralose during pregnancy. (A) IL-1 beta expression in umbilical cord tissue from newborns lightly or heavily exposed to sucralose. (B) TNF-alpha expression in umbilical cord samples from neonates lightly or heavily exposed to sucralose. (C) IL-10 expression in umbilical cord specimens from infants lightly or heavily exposed to sucralose. We expressed data as mean ± standard deviation. We compared data by the unpaired Student’s t-test, considering differences significant when p < 0.05. IL-1 beta, interleukin 1 beta; TNF-alpha, tumor necrosis factor alpha; IL-10, interleukin 10.