Human Placental Lactogen in Relation to Maternal Metabolic Health and Fetal Outcomes: A Systematic Review and Meta-Analysis

Abstract

Human placental lactogen (hPL) is a placental hormone which appears to have key metabolic functions in pregnancy. Preclinical studies have putatively linked hPL to maternal and fetal outcomes, yet—despite human observational data spanning several decades—evidence on the role and importance of this hormone remains disparate and conflicting. We aimed to explore (via systematic review and meta-analysis) the relationship between hPL levels, maternal pre-existing and gestational metabolic conditions, and fetal growth. MEDLINE via OVID, CINAHL plus, and Embase were searched from inception through 9 May 2022. Eligible studies included women who were pregnant or up to 12 months post-partum, and reported at least one endogenous maternal serum hPL level during pregnancy in relation to pre-specified metabolic outcomes. Two independent reviewers extracted data. Meta-analysis was conducted where possible; for other outcomes narrative synthesis was performed. 35 studies met eligibility criteria. No relationship was noted between hPL and gestational diabetes status. In type 1 diabetes mellitus, hPL levels appeared lower in early pregnancy (possibly reflecting delayed placental development) and higher in late pregnancy (possibly reflecting increased placental mass). Limited data were found in other pre-existing metabolic conditions. Levels of hPL appear to be positively related to placental mass and infant birthweight in pregnancies affected by maternal diabetes. The relationship between hPL, a purported pregnancy metabolic hormone, and maternal metabolism in human pregnancy is complex and remains unclear. This antenatal biomarker may offer value, but future studies in well-defined contemporary populations are required.

Recent insights into the role of hormones during development and their functional regulation

“…Human chorionic somatomammotropin (hCS), formerly referred to as human placental lactogen (hPL), increases delivery of glucose to the fetus by down-regulating maternal utilization of glucose and by stimulating fatty acid metabolism. hCS’s exact role in pregnancy outcomes is a topic of ongoing study with current evidence suggesting its association with placental mass and infant birthweight ( 6 ). Due to its critical role, hCS is used as a marker for the effects of glucose transporters during fetal development ( 7 ).…”

Recent progress in metabolic reprogramming in gestational diabetes mellitus: a review

“…This unstable metabolic state increases blood glucose and free fatty acid levels, further contributing to GDM development. However, no consensus exists on whether these hormones contribute to GDM, as some systematic reviews have discovered no association between placental prolactin and prolactin and an increased GDM risk ( 43 , 61 ). Therefore, further large-scale studies are needed.…”

The Placental Role in Gestational Diabetes Mellitus: A Molecular Perspective

“… 36 Nevertheless, even though the current evidence is not conclusive, it suggests a possible secondary role within the pathogenesis of this metabolic disease, with a greater emphasis on PGH dysregulation. 37 …”