Mothers who used macrolides or prescription opioids in early pregnancy did not seem to have an increased risk of having a baby with a birth defect, according to a pair of observational studies.
Compared with those who took penicillin, expectant mothers who took macrolides — such as azithromycin, clarithromycin, erythromycin, and others — in the first trimester did not have a higher chance of having a baby with a malformation (relative risk ratio 0.95, 95% CI 0.84-1.08), reported Niklas W. Andersson, MD, of the Copenhagen University Hospital Bispebjerg and Frederiksberg, and colleagues, in The BMJ.
Andersson’s group also reported no significantly increased risk of malformation in any specific defect group, including cardiovascular defects.
In a separate BMJ study, mothers who used prescription opioids in the first trimester had no increased risk of having a child with a birth defect, reported Brian Bateman, MD, of Brigham and Women’s Hospital in Boston, and colleagues.
“This nationwide cohort study found no association between the use of macrolide antibiotics during pregnancy and risk of major birth defects overall, or in the 12 organ-specific subgroups of birth defects examined,” Andersson said in an email to MedPage Today.
The results of this study contradict those of a cohort study published last year, which found a 55% increased risk of major malformations for pregnant macrolide-users versus penicillin-users. The previous study specifically found an increased risk of heart defects. Given the larger sample size of the current study, Andersson stated that this “data provides reassurance about the risk of major birth defects when treatment with macrolide antibiotics is needed during pregnancy.”
Andersson and colleagues conducted a nationwide cohort study of 1.2 million pregnancies based in Denmark that occurred between 1997 and 2016. They compared the risk of birth defects in mothers who were prescribed macrolides during the first trimester to those who were prescribed penicillin, including two other comparison groups of mothers who received a prescription for macrolides before pregnancy and those whose pregnancies were unexposed to any antibiotic.
The risk of major birth defects in patients who took macrolides in early pregnancy was around 35 per 1,000 pregnancies versus 37 per 1,000 pregnancies in the penicillin cohort. There also were no significant risk differences between pregnant macrolide-users and those who took the antibiotics before pregnancy, as well as those who took no medications at all.
In the second study on the use of prescription opioids during early pregnancy, Bateman and colleagues found no increased risk of any specific malformation, except for oral clefts (relative risk 1.21, 95% CI 0.98-1.50), which was driven by a greater risk of cleft palate (RR 1.62, 95% CI 1.23-2.14),
“Our results, in general, are reassuring,” Bateman told MedPage Today. “But they do point to this increase in risk for oral clefts, which physicians should communicate to their patients.”
He added that several risks associated with opioid exposure during pregnancy were not evaluated in this study, such as fetal growth issues and neonatal abstinence syndrome. Similar to opioid use outside of pregnancy, Bateman said that opioids should only be used during pregnancy when clearly indicated, at the lowest dose and for the shortest duration possible.
Bateman and colleagues conducted a population cohort study of pregnancies in the U.S. occurring between 2000 and 2015. The researchers obtained patient data from two separate databases analyzing both publicly and commercially insured patients. Pregnancies were considered to have an opioid exposure if mothers filled two or more prescriptions during the first trimester. The researchers measured covariates including indication for opioids, maternal demographics, chronic comorbidities, concomitant medications, and general markers for burden of illness.
Of the more than 2.7 million pregnancies included in the analysis, 82,000 were exposed to opioids. Around 70,000 of pregnancies exposed to opioids were in the Medicaid-insured cohort, and the majority of patients in both groups received a prescription for hydrocodone.
In both insurance cohorts, mothers who were prescribed opioids were more likely to have a pain condition, comorbid psychiatric or medical conditions, and higher measures of general comorbidity. They were also more likely receive prescriptions for other medications besides opioids in the first trimester.
Both observational studies were limited by the potential for uncontrolled confounding, and both relied on the assumption that a filled prescription was equivalent to the use of a drug, as the researchers did not have access to adherence information.
Andersson and co-authors disclosed no relevant relationships with industry.
The study by Bateman’s group was funded by the National Institute on Drug Abuse. Bateman and co-authors disclosed relevant relationships with Aetion, the Alosa Foundation, Novartis, Bayer, Vertex, BillionToOne, Quest Diagnostics, and Illumina.