Prolactin in relation to gestational diabetes and metabolic risk in pregnancy and postpartum: A systematic review and meta-analysis

CONTEXT: Pre-clinical evidence suggests that prolactin has important metabolic functions in pregnancy and postpartum, in addition to lactogenic actions. OBJECTIVE: To explore the relationship between prolactin and maternal metabolic outcomes in human pregnancy and postpartum, particularly in relation to gestational diabetes mellitus (GDM). DATA SOURCES: MEDLINE via OVID, CINAHL plus, Embase. STUDY SELECTION: Eligible studies included women who were pregnant or up to 12 months postpartum, reporting at least one maternal serum prolactin level in relation to key metabolic outcomes including GDM, glycaemic parameters, obesity, and gestational weight gain. DATA EXTRACTION: Two independent reviewers extracted data. DATA SYNTHESIS: Twenty-six articles were included. Meta-analysis showed no relationship between maternal prolactin levels and GDM status, with a weighted mean difference of -2.14 ng/mL (95% CI -12.54 to 8.27 ng/mL, p=0.7) between GDM and controls in early pregnancy (n=3 studies) and -3.89 ng/mL (95% CI, -15.20 to 7.41 ng/mL, p=0.5) in late pregnancy (n=11 studies). In narrative synthesis of other outcomes (due to study heterogeneity and/or lack of data), prolactin levels were not associated with maternal glycaemic or weight-related parameters during pregnancy, but in the postpartum period (particularly with lactation) a high-prolactin environment was associated with low circulating insulin and beta-cell function, and increased insulin sensitivity. CONCLUSIONS: Current evidence from human studies does not clearly support a relationship between prolactin and metabolic parameters during pregnancy, including with GDM status. Elevated prolactin was associated with lower insulin and beta-cell function and higher insulin sensitivity in the post-partum period, but the direction of causality remains unclear. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier [CRD42021262771].