Associations Between Gestational Diabetes Mellitus and Neonatal Acyl Metabolic Profiles: An Empirical Study Based on a Birth Cohort.

AIM: This study aimed to identify gestational diabetes mellitus (GDM)-associated neonatal acylcarnitines (ACs), assess maternal glycemic control's impact on these ACs, and evaluate maternal lipids' mediating role, supporting early metabolic risk stratification in offspring.

METHODS

Tandem mass spectrometry (TMS) measured AC levels in 4,974 newborns (836 GDMs,4,138 controls). Generalized linear models assessed GDM-neonatal AC associations. Non-parametric tests assessed differences among no-GDM (2769), well-controlled GDM (129), and suboptimally controlled GDM groups (425). Mediation analysis identified factors affecting neonatal ACs. Maternal clinical data were extracted from the electronic medical record (EMR) system.

RESULTS

Of the 31 acylcarnitine species, 19 were significantly associated with GDM. Relative to the control group, 18 ACs exhibited significantly elevated levels, specifically malonylcarnitine+3-hydroxybutyrylcarnitine (C3DC+C4OH), isovalerylcarnitine+methylbutyrylcarnitine (C5), glutarylcarnitine+3-hydroxyhexanoylcarnitine (C5DC+C6OH), hexanoylcarnitine (C6), methylglutarylcarnitine (C6DC), decanoylcarnitine (C10), decenoylcarnitine (C10:1), dodecanoylcarnitine (C12), dodecenoylcarnitine (C12:1), tetradecanoylcarnitine (C14), tetradecenoylcarnitine (C14:1), palmitoylcarnitine (C16), palmitoleylcarnitine (C16:1), 3-hydroxypalmitoleylcarnitine (C16:1OH), 3-hydroxypalmitoylcarnitine (C16OH), stearoylcarnitine (C18), 3-hydroxyoleoylcarnitine (C18:1-OH),and 3-hydroxystearoylcarnitine (C18OH); only linoleoylcarnitine (C18:2) showed a significant decrease. In groups with progressively impaired glycemic control, triglyceride (TG) levels (P < 0.001) and propionylcarnitine (C3) levels (P = 0.02) exhibited a significant increasing trend, whereas high-density lipoprotein cholesterol (HDL-C) (P = 0.01) and C18:2 levels (P = 0.02) showed a consistent decreasing trend. Mediation analysis further demonstrated that maternal TG levels exerted a significant positive mediating effect on the elevation of neonatal C3 levels (10.7%, 95% CI: 0.0016, 0.0182, P = 0.006), whereas a significant masking effect was observed on C10:1 levels (-14.27%, 95% CI: -0.0006, -0.0001, P < 0.001). Additionally, maternal HDL-C levels exhibited significant masking effects on most acylcarnitine indicators, with the only exception being a significant positive mediating effect on C18:2 levels (2.94%,95% CI: -0.0018, -0.0001, P = 0.0186).

CONCLUSION

GDM correlates with offspring AC levels, with TG and HDL-C partially mediating this relationship. Newborn fat oxidation metabolism is influenced by maternal factors from birth.