Researchers studied the genes and body chemicals that might cause cleft lip and palate, a condition where a baby’s lip or mouth doesn’t form completely before birth. Using advanced genetic analysis on nearly 2,800 people, they discovered that certain minerals in the blood—especially calcium—appear to protect against cleft lip, while high sodium levels increase risk. They also found that vitamin D and specific genes play important roles. This research suggests that both our genes and what we’re exposed to in the environment work together to influence whether someone develops a cleft.

The Quick Take

  • What they studied: What genetic and body chemistry factors cause cleft lip and palate, a birth condition where the lip or mouth doesn’t form properly
  • Who participated: The study analyzed genetic information from 1,069 people with cleft lip/palate and 1,724 people without it, all from Asian populations
  • Key finding: Higher calcium and good cholesterol levels appear to protect against cleft lip, while higher sodium levels increase risk. Vitamin D and specific genes also play important roles in whether someone develops this condition
  • What it means for you: This research suggests that nutrition—especially calcium and vitamin D—may be important during pregnancy, though more research is needed before making specific recommendations. If you’re pregnant or planning to be, talk to your doctor about proper nutrition

The Research Details

Scientists used a special type of genetic analysis called Mendelian randomization, which helps determine whether something actually causes a disease rather than just being associated with it. They looked at genetic data from over 2,100 different body measurements and health factors in Asian populations. They used multiple statistical methods to check their findings and make sure the results were reliable. They also looked for genes that affect multiple traits at once, which helped them understand the biological pathways involved.

This approach is important because it helps separate cause from correlation. Just because two things happen together doesn’t mean one causes the other. By using genetic information, researchers can better understand what actually causes cleft lip and palate, which is important for prevention and treatment. Understanding the role of minerals like calcium and vitamin D could eventually lead to better nutritional guidance for pregnant people.

The study used well-established genetic databases and multiple statistical methods to verify results. They performed sensitivity tests to ensure findings were robust. However, the study was observational based on genetic data, not a controlled experiment. The findings are from Asian populations, so results may not apply equally to other ethnic groups. More research is needed to confirm these findings and understand exactly how these factors work.

What the Results Show

The research identified four key factors related to cleft lip and palate risk. Higher blood calcium levels were strongly protective—people with higher calcium had about 88% lower odds of cleft lip. Higher HDL cholesterol (the ‘good’ kind) and higher hemoglobin concentration in red blood cells also appeared protective. In contrast, higher sodium levels in the blood were associated with significantly increased risk—about 21 times higher odds. These findings suggest that mineral balance in the body is important for proper mouth and lip development. The strongest connection was between calcium levels and cleft lip risk, suggesting calcium plays a particularly important role.

The researchers also discovered that vitamin D response pathways are involved in cleft development. They identified specific genes (CASR and CSTA) on chromosomes 16 and 3 that appear to influence both calcium regulation and cleft lip risk. These genes work together in ways that affect how the body handles calcium and responds to vitamin D. This suggests that the biological mechanism involves how the body processes and uses calcium during fetal development, particularly during the critical period when the lip and palate are forming.

Previous research has suggested that nutritional factors during pregnancy matter for cleft prevention, but this study provides stronger evidence for specific minerals. Earlier studies hinted at calcium and vitamin D importance, but this genetic analysis provides more direct evidence of causation rather than just association. The findings align with biological knowledge that calcium is crucial for cell development and that vitamin D helps the body absorb calcium. This research builds on and strengthens previous observations about nutrition’s role in cleft prevention.

The study analyzed genetic data rather than directly studying pregnant people, so the findings suggest associations but don’t prove cause-and-effect in real life. The research focused on Asian populations, so results may differ in other ethnic groups. The study couldn’t account for all possible environmental factors that might influence cleft development. While the findings are promising, they represent early-stage research that needs confirmation through additional studies before changing medical recommendations.

The Bottom Line

Based on this research (moderate confidence level), pregnant people should ensure adequate calcium and vitamin D intake, as recommended by their healthcare provider. This is especially important during the first trimester when the lip and palate develop. Avoid excessive sodium intake. However, these findings are preliminary, and pregnant people should follow their doctor’s nutritional guidance rather than making changes based solely on this study. This research suggests future prevention strategies but doesn’t yet change standard medical care.

This research is most relevant to pregnant people, people planning pregnancy, and healthcare providers who advise them. It’s particularly important for those with family history of cleft lip and palate. The findings may eventually help develop prevention strategies. However, the research is still preliminary and shouldn’t replace standard prenatal care and medical advice.

If nutritional factors do play a role, the critical period would be during pregnancy, particularly the first three months when the lip and palate form. Any protective effects would need to be present during this developmental window. It typically takes several years of follow-up research before findings like these translate into changed medical recommendations.

Want to Apply This Research?

  • Track daily calcium and vitamin D intake during pregnancy using a nutrition app, aiming for recommended daily amounts (1,000 mg calcium and 600-800 IU vitamin D for pregnant adults). Also monitor sodium intake to stay below recommended limits (less than 2,300 mg daily).
  • Add calcium-rich foods (dairy, leafy greens, fortified foods) and vitamin D sources (fatty fish, egg yolks, fortified milk) to daily meals. Reduce processed foods high in sodium. Log these foods in the app to track patterns and ensure adequate intake throughout pregnancy.
  • Create a weekly nutrition summary showing calcium, vitamin D, and sodium intake trends. Set reminders for prenatal vitamin intake if recommended by your doctor. Share reports with your healthcare provider during prenatal visits to ensure nutritional goals are being met.

This research is preliminary and based on genetic analysis rather than direct clinical trials. The findings suggest associations but do not prove that specific nutritional changes will prevent cleft lip and palate. Pregnant people should not make dietary changes based solely on this study. Always consult with your obstetrician or healthcare provider about proper nutrition during pregnancy and any concerns about cleft lip and palate risk. This information is for educational purposes only and should not replace professional medical advice.