Cleft lip is a birth difference where the upper lip does not fully close during early development, resulting in a gap or opening. This opening can vary in size, from a small notch to a split extending into the nose, and can occur on one or both sides of the lip. Globally, it affects approximately 1 in 700 to 1,000 live births. While surgical repair is often successful, cleft lip can lead to challenges with feeding, speech, and hearing for affected individuals. Many factors can influence its development, and certain medications taken during pregnancy have been identified as contributors.
How Cleft Lip Develops
A baby’s face, including the lips and mouth, forms very early in pregnancy. The tissues forming the upper lip typically fuse between the fourth and seventh weeks of gestation. During this critical window, specialized cells and tissues grow towards the center and join. A cleft lip develops if these tissues do not properly merge or if the fusion process is interrupted. The precise timing and nature of any disruption during these initial weeks determine the type and extent of the cleft.
Medications Linked to Cleft Lip
Several medications are associated with increased cleft lip risk when taken during early pregnancy. Anti-epileptic drugs (AEDs) are a notable category, with varying levels of association. For instance, topiramate, used for epilepsy and migraine prevention, has been linked to an elevated risk. Data from the North American Antiepileptic Drug Pregnancy Registry indicate that infants exposed to topiramate monotherapy in the first trimester had a 1.4% prevalence of oral clefts, a 21-fold increase compared to unexposed infants. Risk is higher when topiramate is used for epilepsy, likely due to higher dosages for seizure control.
Other AEDs also carry risks. Phenytoin has been associated with birth differences, including cleft lip. Valproic acid is another AED linked to various birth variations, including cleft lip and palate. While carbamazepine has also been associated with cleft lip in some studies, other research suggests a lower risk compared to certain other AEDs. Lamotrigine has also been noted in studies as having an association with cleft lip and palate.
Beyond AEDs, other medication classes connect to cleft lip. Certain retinoids, such as isotretinoin for severe acne, are recognized for their potential to cause birth differences, including clefts. Methotrexate, used for cancer, arthritis, and psoriasis, has also been linked to increased cleft lip risk. Some antiviral drugs for HIV, including efavirenz, nelfinavir, nevirapine, and lamivudine, have been connected to oral clefts in infants exposed during pregnancy.
The evidence regarding corticosteroids and cleft lip risk is less clear and has shown inconsistent results across studies. While some earlier reports suggested a possible association, more recent studies have generally not found a significant increased risk, or only a small potential increase. These associations do not guarantee a cleft will develop with every exposure, and risk can sometimes be influenced by dosage. This information is for general awareness and should not replace medical guidance.
Other Risk Factors
Cleft lip development is often influenced by genetic and environmental factors, rather than a single cause. Genetic predispositions play a role, with multiple genes inherited from parents contributing to the overall likelihood. A family history of clefts increases the chance of a child being born with the condition; if parents without clefts have an affected child, risk for subsequent children can range from 2% to 8%.
Environmental factors during pregnancy can also increase risk. Maternal smoking, especially during the first trimester, is consistently linked to a higher cleft lip chance. Studies indicate mothers who smoke during pregnancy have approximately a 1.3-fold increased risk of having a baby with cleft lip, with heavier smoking potentially increasing this risk to nearly two-fold. Paternal smoking before conception has also been associated with increased birth differences due to potential DNA changes.
Maternal alcohol consumption during pregnancy has been connected to cleft lip. Nutritional deficiencies, such as inadequate folate intake before and during early pregnancy, are recognized as potential contributing factors. Other maternal health conditions and exposures, including diabetes, obesity, and certain infections, have also been identified as possible risk factors.
Important Considerations During Pregnancy
Given the various factors influencing cleft lip development, careful planning and communication with healthcare providers are important during pregnancy. Individuals who are pregnant or considering pregnancy should always discuss all medications they are taking, including prescription drugs, over-the-counter remedies, and supplements, with their doctor. This dialogue allows for an assessment of potential risks and benefits.
It is important to avoid discontinuing any prescribed medication without consulting a healthcare professional. For some conditions, risks associated with stopping a necessary medication, such as uncontrolled seizures, might outweigh potential risks to the developing fetus. Healthcare providers can help evaluate alternative treatment options or adjust dosages to minimize risks while managing the mother’s health.
Pre-conception counseling is also beneficial for women of childbearing age, especially with underlying health conditions requiring medication. This allows for thoughtful medication management and planning before pregnancy, supporting the best possible outcomes for both mother and baby. By proactively engaging with medical professionals, individuals can navigate medication use during pregnancy with informed decisions.