First trimester PAPP-A serum levels and long-term metabolic outcome of mothers and their offspring

Abstract

Low maternal serum levels of pregnancy associated plasma protein A (PAPP-A) are known to be associated with the development of pregnancy-related complications like small for gestational age infants, intrauterine fetal demise, gestational diabetes and preeclampsia. The study aims to find possible long-term correlations with the development of metabolic and cardiovascular complications in the mothers and their progeny in later life. This is a retrospective cohort study conducted on consecutive unselected women screened for chromosomal anomalies in the first trimester of pregnancy between 2004 and 2010. PAPP-A values as well as clinical data collected at childbirth were considered. A maternal and neonatal follow-up was performed through a telephone interview with the mother during 2015. The body-mass-index and the presence of cardiovascular diseases, dyslipidaemia and diabetes mellitus were evaluated. The analysis included 988 patients. The median time of follow-up was 7 years (IQR 6-9). Lower first trimester maternal blood PAPP-A quartiles were associated with small stature of the offspring (z-score 1st-2nd quartile 0.37 IQR -0.42 and 1.17 vs 3rd-4th quartile 0.67 IQR -0.17 and 1.36, p < 0.05). Furthermore, low first trimester PAPP-A in pregnancy without other gestations following the index one, in Kaplan-Meier analysis was associated to a significant increase of hypoglycemic agents use at 7 and 10 years (respectively 1.12% CI.95 0-2.38% and 5.45% CI.95 0-10.82%) compared to the control group of high first trimester PAPP-A values (0% CI.95 0-0%) (p < 0.05). Low PAPP-A serum levels in the first trimester of pregnancy are associated with short stature in offspring and de-novo development of maternal diabetes mellitus in later life.

Figure 1

(Panel A) Cumulative events of hypoglycemic agents/insulin use in the years after birth according to the PAPP-A value in the first trimester of the index pregnancy. Log-rank test p = 0.080. It should be noted that cases of pre-gestational diabetes mellitus were excluded prior to analysis. (Panel B) Cumulative events of hypoglycemic agents/insulin use in the years after birth, in the subgroup without pregnancies following the index pregnancy, according to the PAPP-A value in the first trimester of the index pregnancy. Log-rank test p < 0.05. It should be noted that cases of pre-gestational diabetes mellitus were excluded prior to analysis. (Panel C) Correlation between Z scores of offspring height and maternal blood value of PAPP-A corrected MoM in the first trimester of pregnancy.