Pregnant women whose bodies contain higher amounts of the trace mineral copper—which is especially important during pregnancy and found in many foods and prenatal vitamins—are at an increased risk of preterm birth, investigators at the March of Dimes Ohio Collaborative Prematurity Research Center (PRC) have discovered.
In a study published earlier this year in The American Journal of Clinical Nutrition, senior authors and PRC investigators Dr. Louis J. Muglia and Dr. Ge Zhang found that for every 1 microgram/ml increase in blood copper levels, pregnant women saw their preterm birth risk jump by 30% and their gestational duration shorten by 1.6 days.
The study, which analyzed more than 10,000 maternal blood samples from 18 different studies spanning 13 countries on nearly every continent, found an average maternal copper concentration of 1.92 micrograms/mL.
The vast majority of study samples, nearly 70%, landed between 1.49 to 2.35 micrograms/ml. Women with excess copper (the 90th percentile) had a 2.92 microgram/ml concentration in their blood—a significant increase that resulted in a 30% spike in preterm birth risk.
Dr. Sing Sing Way, an infectious disease pediatrician at Cincinnati Children’s Hospital and the coordinating principal investigator of the Ohio PRC, said that it was premature to caution pregnant women on the potential dangers of excess copper, and that more study was needed into the associative link, which was strong.
“We can say that excess maternal copper appears to be an additional risk factor for poor birth outcomes like preterm birth,” said Dr. Way, who was not directly involved in the study. The study was authored by Dr. Nagendra K. Monangi, a neonatologist from the University of Cincinnati, and funded by the Bill and Melinda Gates Foundation. March of Dimes supports the study’s investigators and supported components of the study.
Dr. Way added that there “is still a lot to be uncovered” on the topic. He is referring to the important differences in the three ways copper can be measured in the body. First, there is ‘absolute,’ copper, or the total amount of copper in a person’s body. That is the type of copper measured in the study. But that ‘absolute’ umbrella term contains two important copper subtypes: ‘bound’ and ‘unbound’ copper. Bound copper, which represents about 90% of copper in the body, is copper that is bound to a protein called ceruloplasmin. Unbound copper is copper that is not protein associated and is free flowing in the body.
“Right now, we don’t know which type of copper is associated with preterm birth,” Dr. Way said, “and important areas for future research include further defining whether preterm birth is associated with elevated bound or unbound copper.”
Because levels of the copper binding protein ceruloplasmin increase with inflammation, such as with infection or an impending birth, ceruloplasmin, and by extension bound copper levels, have piqued the interest of the PRC team. What is not clear, however, is whether high levels of bound copper cause inflammation that can lead to preterm birth, or whether inflammation is causing high levels of bound copper.
“What we can say is that too much copper is linked with preterm birth risk,” said Dr. Way, “and that copper levels may in the future be used, along with other markers for inflammation, to investigate preterm birth risk.”
“Ultimately, we need more research on how pregnancy may change the metabolism of copper and how it binds to proteins.”
Copper, which is found in a wide range of foods including meat, fish, nuts, organ meat, and whole grains and vegetables, is an important trace mineral because it plays crucial roles in the function of proteins in the body. Like the birth-defect-fighting trace compound folic acid, copper is almost certainly important for healthy pregnancy.
“But we need more research into whether too much of a good thing, in the form of this trace mineral, may be harmful, or alternatively a marker of maternal inflammation, during pregnancy,” Dr. Way said.