Maternal Blood MFSD2a Levels as a Fetal Neurodevelopment Biomarker

Pregnant woman getting blood test
Nurse getting blood from on a pregnant woman
The level of MFSD2a in maternal blood is a possible biomarker for disturbances of MFSD2a gene expression and may assist in predicting fetal neurodevelopment.

The level of major family super domain 2a (MFSD2a) in maternal blood is a possible biomarker for disturbances of MFSD2a gene expression during pregnancy and may assist in predicting fetal neurodevelopment and identifying an appropriate treatment, according to study results published in Frontiers in Endocrinology.

The protein MFSD2a is a carrier for the uptake of docosahexaenoic acid (DHA) and other long-chain fatty acids into the brain and the eye. Intellectual impairments and microcephaly were reported in humans with homozygous inactivating variants in the MFSD2a gene. The expression of the DHA membrane transporter MFSD2a is lower in gestational diabetes mellitus (GDM) placentas, which could affect maternofetal DHA transport. Abnormal levels of MFSD2a have also been associated with preeclampsia.

The goal of the study was to explore the association between MFSD2a level in maternal blood during the third trimester of pregnancy as a potential predictor for disturbances in the expression of MFSD2a in placental tissue and fetal neurodevelopment.

The study included pregnant women aged 18 to 40 years with singleton pregnancy, recruited in their third trimester of gestation (28-32 weeks) between 2008 and 2010. The researchers established 3 groups of pregnant women: 25 healthy control individuals, 23 women with diagnosed GDM who were receiving dietary treatment, and 20 women with diagnosed GDM who required insulin treatment. The control group was recruited from healthy pregnant women who underwent routine ultrasound in weeks 20 to 22 of gestation. Maternal blood samples were collected at recruitment and during labor.

MFSD2a was analyzed in the placenta, blood, and serum and its expression was significantly lower in maternal blood from both GDM groups (control, 3.54±0.50; GDM receiving dietary treatment, 0.89±0.17; GDM receiving insulin, 1.60±0.42; P <.001). There was a weak but statistically positive correlation between maternal blood and placental MFSD2a levels (P =.035), “pointing toward the possibility of using maternal blood samples for the early detection of disturbances in placental MFSD2a expression during pregnancy,” noted the investigators.

Levels of MFSD2a in maternal blood were positively correlated with the z score of head circumference in children at age 6 months (P =.012) and at several time points during the first year of life.

Levels of MFSD2a in maternal blood also correlated with cord blood levels of triglycerides and insulin, but not with cord adiponectin levels. The ratio of cord to maternal serum DHA, an indicator of maternofetal DHA transport, was reduced in both GDM groups and correlated with MFSD2a expression in both maternal blood at the third trimester and in the placenta at delivery. This indicated that altered MFSD2a levels in maternal blood during pregnancy might influence placental nutrient transport and fetal neurodevelopment.

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Levels of MFSD2a in maternal blood during the third trimester were inversely correlated with DHA in maternal serum lysophospholipids, suggesting a less efficient transport of lysophospholipid DHA from the maternal serum to tissue cells, such as blood, placental, or brain cells or eye photoreceptors.

The study had several limitations according to the researchers, including the small sample size. In addition, there was no option to determine by flow cyotmetry or microscopy which cells were expressing MFSD2a or if there were differences in cellular profile expression of MFSD2a in patients with GDM vs control individuals.

“[T]he early detection of the MFSD2a level in blood during pregnancy related with placenta and DHA materno-fetal transport could be regarded as a potential and feasible biomarker of brain development before delivery. The analysis of this blood biomarker at the third trimester could be of great importance to detect problems in MFSD2a expression during pregnancy that would ultimately affect the offspring development,” concluded the researchers. “[T]his early data would be useful to select the best treatment options for the affected subjects.”


Sánchez-Campillo M, Ruiz-Palacios M, Ruiz-Alcaraz AJ, et al. Child head circumference and placental MFSD2a expression are associated to the level of MFSD2a in maternal blood during pregnancy [published online February 5, 2020]. Front Endocrinol (Lausanne). doi:10.3389/fendo.2020.00038