Can placental growth factors explain birthweight variation in offspring of women with type 1 diabetes?

• Published in: Diabetologia 2021-07, Vol.64 (7), p.1527-1537
• Main Authors: Bacon, Siobhan, Burger, Dylan, Tailor, Mayur, Sanchez, J. Johanna, Tomlinson, George, Murphy, Helen R., Feig, Denice S.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Angiogenesis; Biological Variation, Individual; Biomarkers - blood; Birth Weight; Blood glucose; Child of Impaired Parents; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - diagnosis; Female; Follow-Up Studies; Gestation; Glucose; Glucose monitoring; Growth factors; Human Physiology; Humans; Hyperglycemia; Infant, Newborn; Infants; Internal Medicine; Maternal & child health; Medicine; Medicine & Public Health; Metabolic Diseases; Newborn babies; Offspring; Placenta; Placenta Growth Factor - blood; Placenta Growth Factor - physiology; Pregnancy; Pregnancy in Diabetics - blood; Pregnancy in Diabetics - diagnosis; Pregnancy Outcome; Prognosis; Protein-tyrosine kinase; Vascular Endothelial Growth Factor Receptor-1 - blood; Womens health; Young Adult
• ISSN: 0012-186X; 1432-0428; 1432-0428
• DOI: 10.1007/s00125-021-05438-y

Aims/hypothesis Maternal hyperglycaemia alone does not explain the incidence of large offspring amongst women with type 1 diabetes. The objective of the study was to determine if there is an association between placental function, as measured by angiogenic factors, and offspring birthweight z score in women with type 1 diabetes. Methods This cohort study included samples from 157 Continuous Glucose Monitoring in Pregnant Women with Type 1 Diabetes (CONCEPTT) trial participants. Correlations were estimated between birthweight z score and placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) levels measured at baseline and at 24 and 34 weeks of gestation. Linear regression was used to assess the relationship between birthweight z score and placental health, as measured by PlGF and sFlt-1/PlGF ratio, stratified by glycaemic status (continuous glucose monitoring and HbA 1c measures) and adjusted for potential confounders of maternal BMI, smoking and weight gain. Higher PlGF levels and lower sFlt-1/PlGF ratios represent healthy placentas, while lower PlGF levels and higher sFlt-1/PlGF ratios represent unhealthy placentas. Results Among CONCEPTT participants, the slopes relating PlGF levels to birthweight z scores differed according to maternal glycaemia at 34 weeks of gestation ( p  = 0.003). With optimal maternal glycaemia (HbA 1c   30%), increasing PlGF values were associated with heavier infants. Those with a healthy placenta (PlGF > 100) and suboptimal glycaemic control had a higher mean z score (2.45) than those with an unhealthy placenta (mean z score = 1.86). Similar relationships were seen when using sFlt-1/PlGF ratio as a marker for a healthy vs unhealthy placenta. Conclusions/interpretation In women with type 1 diabetes, infant birthweight is influenced by both glycaemic status and placental function. In women with suboptimal glycaemia, infant birthweight was heavier when placentas were healthy. Suboptimal placental function should be considered in the setting of suboptimal glycaemia and apparently ‘normal’ birthweight. Graphical abstract