# Investigation of Netrin-1 Levels in Maternal and Umbilical Cord Serum in Preeclampsia and Their Relationship With Vitamin D, Vitamin B12, and Folic Acid

**Authors:** Gulsah Cetindari Demirci, Soner Gök, Berfin Gök, Esin Avci

PMC · DOI: 10.7759/cureus.102489 · Cureus · 2026-01-28

## TL;DR

This study found higher Netrin-1 levels in mothers with preeclampsia and a link to proteinuria, but no changes in umbilical cord levels.

## Contribution

The study is the first to investigate Netrin-1 in maternal and umbilical cord serum in relation to preeclampsia and vitamin levels.

## Key findings

- Maternal Netrin-1 levels were significantly higher in preeclampsia patients compared to controls.
- A significant positive correlation was found between maternal Netrin-1 levels and proteinuria in preeclampsia.
- No significant changes were observed in umbilical cord Netrin-1 levels between the groups.

## Abstract

Background

The purpose of this study was to compare maternal blood and umbilical cord Netrin-1 levels at delivery in severe preeclampsia (PE) patients to a control group, investigate their relationship with clinical parameters, and look into the potential link between maternal vitamin D, vitamin B12, and folic acid levels.

Methods

This is a case-control observational study that included 22 pregnant women with severe PE and a control group of 22 healthy pregnant women of the same gestational age. We measured Netrin-1 levels in serum samples collected from maternal blood and umbilical cords during cesarean section in both groups. Vitamin D, B12, and folic acid levels in maternal blood were also measured in both groups. An enzyme-linked immunosorbent assay was used to measure Netrin-1 levels.

Results

The maternal Netrin-1 levels were significantly higher in the PE group compared to the control group (p = 0.006). We found a significant positive correlation between maternal Netrin-1 levels and proteinuria in the PE group (p = 0.001). The control group, on the other hand, did not exhibit this relationship.

Conclusion

We discovered that PE cases had higher levels of maternal Netrin-1, and that maternal Netrin-1 levels and proteinuria were significantly positively correlated. Nevertheless, we did not find any correlation or increase in umbilical cord Netrin-1 levels. We believe that the primary reason for these changes is to protect the fetus from microvascular and endothelial injury.

## Linked entities

- **Proteins:** Ntn1 (netrin 1)
- **Chemicals:** vitamin B12 (PubChem CID 73415824), folic acid (PubChem CID 135398658)
- **Diseases:** preeclampsia (MONDO:0005081)

## Full-text entities

- **Genes:** MTR (5-methyltetrahydrofolate-homocysteine methyltransferase) [NCBI Gene 4548] {aka HMAG, MS, cblG}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, PGF (placental growth factor) [NCBI Gene 5228] {aka D12S1900, PGFL, PIGF, PLGF, PlGF-2, SHGC-10760}, VDR (vitamin D receptor) [NCBI Gene 7421] {aka NR1I1, PPP1R163}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, NTN1 (netrin 1) [NCBI Gene 9423] {aka MRMV4, NET1, NTN1L}
- **Diseases:** hypertension (MESH:D006973), prenatal death (MESH:D003643), reperfusion injury (MESH:D015427), placental insufficiency (MESH:D010927), insulin resistance (MESH:D007333), urinary tract infections (MESH:D014552), premature membrane rupture (MESH:D005322), eclampsia (MESH:D004461), thrombocytopenia (MESH:D013921), abortions (MESH:D000026), premature delivery (MESH:C536271), liver failure (MESH:D017093), hyperhomocysteinemia (MESH:D020138), renal illness (MESH:D007674), maternal disease (MESH:D000079262), epigastric pain (MESH:D010146), abnormalities in vision and cognition (MESH:D014786), intrauterine growth restriction (MESH:D005317), headache (MESH:D006261), impaired liver function (MESH:D008107), inflammation (MESH:D007249), chronic renal disease (MESH:D051436), PE (MESH:D011225), Pulmonary edema (MESH:D011654), endothelial dysfunction (MESH:D014652), ischemic (MESH:D002545), cancer (MESH:D009369), renal failure (MESH:D051437), inflammatory damage (MESH:D018746), Vitamin D deficiency (MESH:D014808), GDM (MESH:D016640), obesity (MESH:D009765), hypoxia (MESH:D000860), systemic diseases (MESH:D034721), preeclamptic (MESH:C538543), Proteinuria (MESH:D011507), ischemia (MESH:D007511), neural tube defects (MESH:D009436)
- **Chemicals:** 25-hydroxyvitamin D (MESH:C104450), amino acid (MESH:D000596), Homocysteine (MESH:D006710), Vitamin B12 (MESH:D014805), cysteine (MESH:D003545), steroids (MESH:D013256), 1,25(OH)2D (MESH:C097949), Folic Acid (MESH:D005492), creatinine (MESH:D003404), Vitamin D (MESH:D014807), methionine (MESH:D008715), B12 (MESH:C034730), nitric oxide (MESH:D009569)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

29 references — full list in the complete paper: https://tomesphere.com/paper/PMC12947975/full.md

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Source: https://tomesphere.com/paper/PMC12947975