Maternal Hypocalcemia May Be Associated with Idiopathic Clubfoot

A retrospective cohort study that sought to identify both maternal and pediatric risk factors for presentation of clubfoot found that race, oligohydramnios, maternal hypocalcemia, maternal tobacco use, and maternal infectious disease were risk factors for presentation of idiopathic clubfoot. A novel finding of the study was that maternal hypocalcemia imparted a relative risk for clubfoot. The findings were presented as an ePoster at the AAOS 2024 Annual Meeting.

The authors queried the 2016 Kids’ Inpatient Database (KID) for newborns (International Classification of Diseases, Tenth Revision code Z38) diagnosed with clubfoot. They identified patient and hospital demographics and risk factors in the mother and neonate. Of the 1,323,148 newborns identified, 1,590 (0.12 percent) had clubfoot. There were differences in sex, race, hospital teaching status, perinatal and postpartum factors, and perinatal complications between newborns with clubfoot and those without clubfoot. Males were 1.388 times more likely to have clubfoot than females. White patients were 1.253 times more likely to have clubfoot than Black patients. Patients who had oligohydramnios were 2.677 times more likely to have clubfoot than those with normal amniotic fluid levels. Newborns with transitory hypocalcemia of the mother—hypocalcemia for less than 6 months during the pregnancy—were 1.559 times more likely to have clubfoot than those in mothers with normal calcium levels. Maternal tobacco use and maternal infectious disease were associated with a 1.517 times higher likelihood and a 1.202 times higher likelihood of clubfoot, respectively (Fig. 1).

The first author of the study, Dhruv Mendiratta, a medical student at Rutgers New Jersey Medical School, told AAOS Now that he and his colleagues undertook the investigation in light of the conflicting literature on various risk factors that contribute to the development of certain orthopaedic conditions in the perinatal period. “It is well known that smoking, oligohydramnios, and maternal substance use can contribute to a number of conditions,” Mr. Mendiratta said. “However, we wanted to tease out some more specific etiologies, and we are granted that liberty due to the ubiquitousness of these large datasets, such as KID.”

He said that major findings of their study largely confirmed previous publications—i.e., that maternal tobacco use and infectious disease are associated with increased incidence of clubfoot. The novel finding the study yielded was that transitory hypocalcemia was associated with approximately a twofold incidence in clubfoot. “Intuitively, this is not a surprising finding, but it is surprising that it is somewhat underreported,” Mr. Mendiratta said. The investigators proceeded to check for a similar association in another congenital orthopaedic condition, developmental dysplasia of the hip, but they did not detect one, making this finding apparently unique to clubfoot.

The authors noted, “Preventive strategies targeted at these risk factors can be developed by the healthcare team to decrease incidence of clubfoot.” Clinically, Mr. Mendiratta said, “This information can be used as a preventive measure to recommend monitoring calcium levels in the mother or as a potential tool for early detection, but this would require some more evidence-based studies.” In light of these findings, he added that future directions for research would include a randomized, controlled study that evaluates the impact of supplements during the prenatal period on pregnancy outcomes, specifically pertaining to clubfoot.

Limitations of the study, Mr. Mendiratta said, are those inherent to the use of a large database, which may include bias, and its retrospective nature.

Dr. Mendiratta’s coauthors of “Perinatal and Infant Risk Factors for Incidence of Idiopathic Clubfoot” are Isabel Herzog, BA, and Alice Chu, MD.