Impact of Maternal Diabetes on Neural Tube Defects

Introduction to Maternal Diabetes and Neural Tube Defects

Maternal diabetes, encompassing both type 1 and type 2 diabetes, has been associated with a range of adverse pregnancy outcomes, including congenital anomalies such as neural tube defects (NTDs). NTDs, which result from the incomplete closure of the neural tube during early embryonic development, are among the most prevalent birth defects globally, affecting approximately 300,000 to 400,000 newborns each year (Cao et al., 2025). The mechanism through which maternal diabetes contributes to NTDs is multifactorial, with hyperglycemia, oxidative stress, and genetic predispositions playing critical roles (Cao et al., 2025).

Recent studies have highlighted that poorly controlled blood glucose levels during pregnancy can significantly increase the likelihood of NTDs, particularly when maternal diabetes is not adequately managed (Cao et al., 2025). This underscores the importance of effective prenatal care and the management of blood sugar levels in pregnant women with diabetes.

Genetic Mutations Associated with Microspherophakia

Microspherophakia (MSP) is a rare ocular condition characterized by an abnormal lens shape, often associated with various genetic mutations. Recent research has identified several genes implicated in MSP, including FBN1, ADAMTS17, and LTBP2 (Liu et al., 2025). The FBN1 gene, responsible for encoding fibrillin-1, is particularly notable, as mutations in this gene are linked to Marfan syndrome and other connective tissue disorders. Patients with FBN1 mutations often exhibit significant ocular abnormalities, including MSP and ectopia lentis, which can further complicate pregnancy outcomes in cases where maternal diabetes is also present (Liu et al., 2025).

Moreover, the presence of these genetic mutations in mothers can exacerbate the risk of NTDs in their offspring. The interplay between maternal diabetes and genetic factors underscores the necessity for comprehensive screening and genetic counseling for pregnant women at risk of both diabetes and congenital anomalies.

Ocular Biometric Correlations in Patients with MSP

Research has demonstrated significant correlations between specific genetic mutations and ocular biometric parameters in patients with MSP (Liu et al., 2025). In a cohort study involving 59 patients, variations in axial length (AL), white-to-white (WTW) measurements, and lens thickness (LT) were observed based on the underlying genetic mutations. For instance, patients with FBN1 mutations exhibited longer AL measurements, while those with ADAMTS17 mutations showed alterations in WTW dimensions and lens thickness, which can influence visual outcomes and overall ocular health (Liu et al., 2025).

These correlations suggest that genetic mutations not only impact the development of MSP but also predict the severity of ocular manifestations, which may have implications for the management of maternal diabetes and the potential risk for NTDs.

Role of Oxidative Stress and Endoplasmic Reticulum Stress

The pathophysiology of diabetes-induced NTDs involves oxidative stress and endoplasmic reticulum (ER) stress, both of which are exacerbated by high glucose levels. Maternal diabetes can lead to increased production of reactive oxygen species (ROS), resulting in cellular damage and the activation of apoptotic pathways that contribute to NTDs (Cao et al., 2025). Studies have shown that high glucose conditions initiate a cascade of events that disrupt normal cellular functions, including mitochondrial dysfunction and impaired autophagy, leading to the accumulation of misfolded proteins in the ER (Cao et al., 2025).

Furthermore, the unfolded protein response (UPR), a cellular stress response related to the ER, can become activated under conditions of oxidative stress, further promoting apoptosis in neuroepithelial cells during critical periods of neural tube development (Cao et al., 2025).

Importance of Folic Acid in Preventing Neural Tube Defects

Folic acid is a crucial nutrient in preventing NTDs and is particularly important for women with diabetes. The role of folic acid in nucleotide synthesis and DNA repair mechanisms is essential during early embryonic development, and supplementation has been shown to significantly reduce the incidence of NTDs (Cao et al., 2025). For women with diabetes, the need for adequate folic acid intake is even more pronounced, as underlying metabolic disturbances may increase the risk of birth defects.

The recommended dosage of folic acid for pregnant women is 400 to 800 micrograms daily, with higher doses often advised for those with a history of NTDs or pregestational diabetes (Cao et al., 2025). Ensuring proper folate status before and during pregnancy can effectively mitigate the risk of NTDs in infants born to mothers with diabetes.

Recommendations for Clinical Management of Maternal Diabetes

To reduce the risk of NTDs and improve pregnancy outcomes for women with diabetes, several clinical management strategies should be implemented:

1. Preconception Counseling: Women with diabetes should receive counseling to optimize glycemic control prior to conception. This includes the adjustment of medications, dietary changes, and lifestyle modifications to achieve target blood glucose levels.

2. Regular Monitoring: Continuous monitoring of blood glucose levels throughout pregnancy is essential. This allows for timely interventions to manage hyperglycemia and prevent fluctuations that could harm fetal development.

3. Genetic Counseling: Women with a family history of NTDs or those identified with genetic mutations predisposing to NTDs should receive genetic counseling to assess risks and consider appropriate screening options.

4. Folic Acid Supplementation: All women of childbearing age should be advised to take folic acid supplements, particularly those with diabetes. This should begin before conception and continue through the first trimester.

5. Multidisciplinary Approach: Collaborative care involving endocrinologists, obstetricians, nutritionists, and genetic counselors can provide comprehensive support and management for pregnant women with diabetes.

FAQ

What are Neural Tube Defects (NTDs)?

NTDs are congenital defects that occur when the neural tube, which forms the brain and spinal cord, does not close completely during early fetal development. Common types of NTDs include spina bifida and anencephaly.

How does maternal diabetes affect the risk of NTDs?

Maternal diabetes, particularly when poorly controlled, can lead to elevated blood glucose levels, which increase oxidative stress and disrupt normal embryonic development, thereby raising the risk of NTDs.

What role does folic acid play in preventing NTDs?

Folic acid is essential for DNA synthesis and cell division. Adequate folic acid intake before and during early pregnancy can significantly reduce the risk of NTDs.

How can women with diabetes optimize their pregnancy outcomes?

Women with diabetes can optimize pregnancy outcomes by managing blood glucose levels, adhering to a healthy diet, taking folic acid supplements, and receiving regular prenatal care.

What is the significance of genetic counseling for pregnant women with diabetes?

Genetic counseling can help assess the risk of congenital anomalies, including NTDs, and guide screening and management options based on individual and family medical histories.

References

1. Cao, L., et al. (2025). Exploring Research Trends and Mechanisms: Maternal Diabetes and Neural Tube Defects (1991–2023). Journal of Multidisciplinary Healthcare. https://doi.org/10.2147/JMDH.S501402
2. Liu, Y., et al. (2025). Genetic landscape and ocular biometric correlations in microspherophakia: insights from a comprehensive patient cohort. Human Genomics. https://doi.org/10.1186/s40246-025-00729-6
3. El Aameri, M., et al. (2024). Chronic complications of type 2 diabetes and associated factors: a cross-sectional study at the Moulay Hassan Hospital in Kenitra, Morocco. Pan African Medical Journal. https://doi.org/10.11604/pamj.2024.49.84.42930