Serum Zn and Ca correlate with false positive non-invasive prenatal test results

The precise cause of false-positive results in non-invasive prenatal testing (NIPT) associated with suspected placental chimerism - where the placenta exhibits chromosomal abnormalities absent in the fetus, is not well understood. It is also unclear whether serum minerals such as zinc (Zn) and calcium (Ca), which are essential for maternal and fetal health, influence these false positives.

In this retrospective analysis, 16,270 pregnant women were evaluated for serum mineral concentrations at 14 weeks of gestation, while NIPT was conducted between 12 and 22 weeks of gestation. Positive NIPT results prompted amniotic fluid karyotyping to confirm the diagnosis. Binary logistic regression analysis and restricted cubic spline (RCS) methods were used to assess the association between individual serum mineral levels and false-positive NIPT results.

The false-positive NIPT group exhibited altered serum mineral levels compared to the normal group, with increased sodium (Na), potassium (K), and Zn and decreased Ca, phosphorus (P), and iron (Fe). Multifactor regression analysis confirmed these trends. RCS analysis revealed a non-linear relationship between Zn and Ca levels and NIPT false-positive rates. Specifically, false-positive rates decreased with increasing Zn levels up to 13.1 μmol/L but rose beyond this threshold. Conversely, false-positive rates increased with higher Ca concentrations up to 2.31 mmol/L and then declined. These associations remained significant after adjusting for confounding factors. Additionally, a strong correlation was observed between NIPT false positivity and restrictive placental chimerism, highlighting a significant link between maternal serum Zn and Ca levels and the occurrence of restrictive placental chimerism.

This study uncovers a non-linear relationship between maternal serum Zn and Ca levels and NIPT false positives, which are suspected to be linked to restrictive placental chimerism. Moreover, moderate Zn and Ca supplementation may contribute to the development of a more precise nutritional management program for pregnancy.