Temporary Increased LDL-C in Offspring with Extreme Elevation of Maternal Preconception Estradiol: A Retrospective Cohort Study

OBJECTIVE: To investigate the effect of maternal estradiol (E(2)) elevation on long-term metabolic manifestations in the offspring. STUDY DESIGN AND SETTING: This was a retrospective cohort study. Overall, 3690 children conceived by in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) between July 2014 and December 2017 were recruited and divided into four groups categorized by maternal E(2) quartiles (Q1, <2420; Q2, 2420–3839; Q3, 3839–5599; and Q4, ≥5599 pg/mL). The metabolic profiles were measured during childhood. Linear mixed models were used to evaluate the association between maternal E(2) elevation and metabolic phenotypes of the offspring. RESULTS: Lipoprotein cholesterol (LDL-C) was significantly higher in the highest quartile group than in the lowest quartile group during infancy (adjusted mean difference [95% confidence interval, CI]): 0.11 [0.02, 0.20], P = 0.005), but the difference disappeared in the later childhood phase. In children born after fresh embryo transfer, LDL-C showed an increasing trend with the increase in maternal E(2) level (adjusted mean difference [95% CI]: Q2 vs Q1, −0.01 [−0.11, 0.08], Q3 vs Q1, 0.06 [−0.04, 0.15], Q4 vs Q1, 0.10 [0, 0.20]). Other metabolic variables were comparable across increasing quartiles of maternal E(2) levels. CONCLUSION: This study demonstrates a temporary increase in LDL-C levels in infants with higher levels of maternal preconception E(2) levels. However, the long-term safety of hyperestrogens after ovarian stimulation in the next generation is favorable. The mechanism underlying the transiently increased metabolic dysfunction risk in infants conceived by IVF/ICSI requires investigation in future studies.