In a recent study, scientists found a link between MTHFR gene mutations and intraventricular hemorrhaging (IVH) in prematurely born infants. Intraventricular hemorrhaging occurs when fluid-filled spaces within the brain, called ventricles, begin to fill up with excess blood. Depending on the severity of intraventricular hemorrhaging (IVH), it can lead to brain injuries that result in long-term developmental problems, brain damage, and even death.
What Causes intraventricular hemorrhaging (IVH)?
Intraventricular hemorrhaging (IVH) is more likely to occur in premature infants, due to less developed blood vessels and an overall weak vascular system. The closer a baby is to reaching full term within the mother, the less chance there is of developing IVH because the vascular system and brain tissues are more mature. IVH in newborns brought to full term is rare but does occur. Newborns are most at risk for developing IVH within the first week of their lives. A close eye should be kept on them during this time period to ensure their safety. A close eye should especially be kept on prematurely born infants to see if they develop any of the common symptoms brought on by IVH.
What Role Does MTHFR and Other Genetic Mutations Play In The Development Of Intraventricular hemorrhaging (IVH)?
In a recent study published in the Journal of Child’s Nervous System on June 3rd, 2017, scientists found a relationship between specific genes and how they affect the coagulation (blood clotting) pathway in newborns (6). The genes they looked at were:
MTHFR A1298C, MTHFR C667T, Factor V 1691G, Factor II 20210G and Factor XIII 103G. Prematurely born infants between 24 and 32 gestational weeks of age were observed for IVH and their corresponding genetic codes were analyzed.
The results of the study are as follows:
- 45% (45 out of 100) of premature infants had IVH
- Of this 45%
- 33.33% (15 out of 45) had stage 1 IVH
- 42.22% (20 out of 45) had stage 2 IVH
- 17.77% (8 out of 45) had stage 3 IVH
- 6.66% (3 out of 45) had stage 4 IVH
- Newborns with the MTHFR A1298C mutation were 4.5 times more likely to develop stage 2-4 IVH
The scientists found newborns with the MTHFR A1298C mutation had a 4.5 greater chance of being diagnosed with IVH stages 2-4 compared to newborns without the A1298C mutation. Remember that stages 3 and 4 of IVH produce immediate and long-term neuronal damage and can significantly harm the child’s development. The link between MTHFR A1298C and other genes in the study hold true regardless of the gender of newborns.
The researchers hypothesize MTHFR plays a role in fibrinolytic activity (ability to break down blood clots) and regulation of clotting factors (control of bleeding) during embryonic development. This hypothesis is based on their experimental data showing a 4.5 increase in IVH stages 2-4 in prematurely born infants with the MTHFR A1298C mutation.
*** Recall that an MTHFR A1298C gene mutation reduces the activity of the MTHFR enzyme by 20% if there is one copy (heterozygous) of the gene present and by 40% if two copies of the gene are present (homozygous). For more info on MTHFR mutations see What Is MTHFR?
Other Genes Playing A Role In intraventricular hemorrhaging (IVH)
The study did not find any significance between IVH and other genetic polymorphisms other than MTHFR A1298C. The study had a small sample size of non-MTHFR genetic polymorphisms making it difficult to draw clear conclusions about the roles these genes in the development of IVH. They relied on previous studies to help them assess the role genetics play in the development of IVH. Further research will be able to provide a better understanding of genetic polymorphisms and the development of IVH. Below is a quick summary of other genes the scientists looked at in their study.
- The MTHFR gene converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (MTHF); the last step in the folate cycle.
- MTHF is responsible for the remethylation of homocysteine to methionine (an essential amino acid)
- The study found NO connection between the MTHFR C667T gene mutation and IVH. More studies are needed to determine the exact differences between the function of MTHFR A1298C and MTHFR C667T.
Factor V G1691A
- Also known as the Leiden mutation and plays a role in anticoagulation (removal of blood clots)
- 90% of congenital thrombophilia cases are due to this mutation
- The small sample size of prematurely born infants in this study suggests that results for the relationship between Factor V G1691A and IVH are not reliable.
- Another study of IVH and Factor V G1691A found that patients with this mutation are at 2.65 times greater risk of developing more severe cases of IVH (3)
Factor II G20210A
- Factor II converts fibrinogen to fibrin, a protein that forms a kind of biological mesh that impedes the flow of blood
- Individuals with the Factor II G20210A gene mutation are more likely to have thrombotic events (obstruction of blood flow somewhere in the body) (4)
- Babies born with a very low birth weight who have the Factor II G20210A mutation are more likely to develop IVH within the first several days after birth (3)
Factor XIII G103T
- Factor XII helps blood clots stay resistant to breaking down by stabilizing blood clots and the Factor XIII G103T gene mutation creates more dense blood clots that are harder to break down by the body
- People who have the Factor XIII G103T mutation are more likely to have hemorrhagic strokes (1)
- A moderate increase in IVH risk occurs in newborns who are born with a very low birth weight and have the Factor XIII mutation (2)
Our understanding of genetics and the role they play in intraventricular hemorrhaging (IVH), and fertility at large, is developing at a rapid pace. This pace is often too fast for medical professionals to keep up with which is why it’s important to try and see genetic counselors or professionals with specialties in fields such as fertility who keep up to date with the newest scientific research.
Everyday new connections are made between genetics and human health that were previously unknown. Knowing your genome makes you become less of a statistic and more of a unique individual, you move from basic treatment to a treatment that is meant for you. There has been little progress in preventing IVH, especially in preterm infants. Identifying genetic risk factors for IVH and preterm birth will help understand the biological mechanisms behind it and create better preventative strategies in the future. The better job you do at preparing for pregnancy, the more you reduce the risk of IVH in your child. Pregnancy preparation is the best strategy to not only prevent IVH but many of the complications that can happen during and after pregnancy.
The cost of genetic testing has dropped exponentially over the past couple decades. The human genome project (where scientists sequenced the human genome) took years and billions of dollars to do. Now you can get your genome sequenced for ~ $129USD with https://www.ancestry.com/. Knowing your genome gets your into the club of personalized medicine, creating a more personalized approach to your health and pregnancy.
If you are looking to become pregnant, there is so much information out there that it’s hard to keep track of what you should and should not be doing. That is why we have created the “10 most important things you need to do before you become pregnant” checklist. We walk you through the ten most important things you can do right now to start improving your fertility and your future pregnancy.
- Antalfi, B., Pongrácz, E., Csiki, Z., Mezei, Z. A., & Shemirani, A. H. (2013). Factor XIII‐A subunit Val34Leu polymorphism in fatal hemorrhagic stroke. International journal of laboratory hematology, 35(1), 88-91. (34)
- Göpel, W., Kattner, E., Seidenberg, J., Kohlmann, T., Segerer, H., Möller, J., & Genetic Factors in Neonatology Study Group. (2002). The effect of the Val34Leu polymorphism in the factor XIII gene in infants with a birth weight below 1500 g. The Journal of pediatrics, 140(6), 688-692. (36)
- Ramenghi, L. A., Fumagalli, M., Groppo, M., Consonni, D., Gatti, L., Bertazzi, P. A., … & Mosca, F. (2011). Germinal Matrix Hemorrhage: Intraventricular Hemorrhage in Very-Low-Birth-Weight Infants. Stroke, 42(7), 1889-1893. (26)
- Seremak-Mrozikiewicz, A., Drews, K., Wender-Ożegowska, E., & Mrozikiewicz, P. M. (2010). The significance of genetic polymorphisms of factor V Leiden and prothrombin in the preeclamptic Polish women. Journal of thrombosis and thrombolysis, 30(1), 97-104. (30)
- Szpecht, D., Gadzinowski, J., Seremak-Mrozikiewicz, A., Kurzawińska, G., Drews, K., & Szymankiewicz, M. (2017). The role of FV 1691G> A, FII 20210G> A mutations and MTHFR 677C> T; 1298A> C and 103G> T FXIII gene polymorphisms in pathogenesis of intraventricular hemorrhage in infants born before 32 weeks of gestation. Child’s Nervous System, 1-8.