How often are opioids dispensed to women after vaginal delivery?

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Given the country’s opioid epidemic, physicians are looking for ways to reduce unnecessary prescribing of the drugs. A recent study published in Obstetrics and Gynecology found that opioid dispensing after vaginal delivery is common and often occurs at high doses and may represent a source of over-prescription in the United States.

Using the Truven Health Analytics MarketScan database, the authors performed a nationwide retrospective cohort study of commercially insured beneficiaries who underwent vaginal delivery between 2003 and 2015 and were also opioid-naive for 12 weeks before delivery. They examined the ratio of women who were prescribed an oral opioid within 1 week of discharge, the median oral morphine milligram equivalent dose dispensed, and the frequency of opioid refills by the patient during the 6 weeks of discharge.

The researchers found that of the more than 1.3 million women included in the study, 28.5% were dispensed an opioid with 1 week of discharge. Hydrocodone (44.7%), oxycodone (34.6%) and codeine (13.1%) were the most commonly prescribed opioids among the study population. In addition, codeine accounted for 15.2% of opioids dispensed, which the authors note as worrisome given the US Food and Drug Administration’s warning against use of the drug in breastfeeding women because of variability in metabolism and risk to the infant.

In multivariable regression analysis, the adjusted odds ratio (OR) for dispensing an opioid prescription was 4.70 (95% CI, 4.63-4.77) among women in the south, adjusted OR 2.94 (95% CI, 2.90-2.99) among women from the west, and adjusted OR 2.77 (95% CI 2.72-2.81) among women from the midwest as compared to women from the northeast. The odds for dispensing the prescription were also higher for those using benzodiazepines (adjusted OR 1.87; 95% CI 1.73-2.02) and antidepressants (adjusted OR 1.63; 95% CI 1.59-1.66) and smokers (adjusted OR 1.44; 95% CI 1.38-1.51). Patients who had undergone tubal ligation, operative vaginal delivery and who had higher-order perineal lacerations also had increased rates of receiving an opioid prescription.

The median dose of opioids dispensed was 150 morphine milligram equivalents (approximately 20 tablets of 5- mg oxycodone). Among the 366,691 women with at least 6 weeks’ follow-up, 8.5% (95% CI 8.4-8.6%) had at least one refill during that time period.

The authors highlighted a few limitations of their study. Because the analysis focused just on opioid dispensing, it did not capture the number of prescriptions that were not filled or were filled and paid for out of pocket. Nor can the quantity of opioids consumed be determined from the data. They also noted that the procedure and diagnostic codes used to define deliveries favored specificity over sensitivity because a linkage to infants, which can be used in insurance claims to confirm that the encounter resulted in a birth, was not used. However, the authors point out that when their data are generalized to all women delivering vaginally in the United States, the results suggest that 850,000 women are given an opioid prescription per year. So, limiting unnecessary opioid prescribing in this clinical setting could have a significant effect on public health and the opioid epidemic.

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Can marijuana pass into mother's milk?

A new study shows that women who use marijuana and breastfeed may be passing along to their babies more than just nutrients with their breastmilk. The findings, published in Pediatrics, suggest that one cannabinoid may be present in breastmilk for days after drug use.

For the research, the authors sought to quantify cannabinoids in human milk after maternal marijuana use by studying breast milk samples from 50 breastfeeding women who reported using the drug. The mothers provided 54 samples to a research repository, Mommy’s Milk, between 2014 and 2017. Of the women, 64% exclusively smoked the drug and 88% said they used is daily. Two-thirds of them were breastfeeding a child < 1 year of age.

The researchers measured concentrations of Δ-9-tetrahydrocannabinol (Δ9-THC), 11-hydroxy-Δ-9-tetrahydrocannabinol, cannabidiol, and cannabinol in the breastmilk using liquid chromatography mass spectrometry electrospray ionization. Δ9-THC is the primary psychoactive constituent of cannabis. 11-hydroxy-Δ-9-tetrahydrocannabinol is the main active metabolite of THC formed in the body after cannabis consumption. Cannabidiol has anticonvulsant and not psychoactive action. Cannabinol is less powerful than Δ9-THC.  

In 34 (63%) of the 54 samples from the mothers, Δ9-THC was detected up to approximately 6 days after their last reported use of marijuana. The median concentration of Δ9-THC was 9.47 ng/mL (range: 1.01 to 3.23.00). In five samples, 11-hydroxy-Δ-9-tetrahydrocannabinol or cannabidiol was detectable (ranges 1.33-12.80 ng/mL and 1.32-8.56 ng/mL, respectively). The sample with the highest concentration of cannabidiol (8.56 ng/mL) did not have measurable Δ9-THC. The majority of women (76.5%) whose breastmilk contained quantifiable levels of Δ9-THC used marijuana exclusively by smoking it.

The number of hours since a woman’s last use of marijuana was a significant predictor of log Δ9-THC concentrations (-0.03; 95% confidence interval [CI] -0.04 to -0.01; P = .005). Adjusted for time since last use, the number of daily uses and time from sample collection to analysis were also significant predictors of log Δ9-THC concentrations (0.51; 95% CI 0.03 to 0.99; P = .039; 0.08; 95% CI 0.00 to 0.15; P = 0.38, respectively).

The authors said that it is “reasonable to speculate that Δ9-THC, 11-OH-THC, or cannabidiol exposure during breastfeeding, depending on the dose and timing, could influence normal brain development in a child.” Their findings underscore a “critical need for further research on neurodevelopmental outcomes in infants breastfed by mothers using marijuana.”

Commenting on the results, they noted several limitations of the study. Samples were not collected under uniform conditions nor always directly observed and the authors relied on reports from the women about their drug exposure. The authors also said that to determine the extent to which cannabinoids accumulate in infants being breastfed, longitudinal sampling of plasma from the infants is necessary.

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How do race and ethnicity impact HPV vaccine completion rates?

The human papillomavirus (HPV) vaccine has been shown to be safe and highly effective, but vaccine coverage in the United States remains low. A recent study in Obstetrics and Gynecology looked at the role race and ethnicity play in HPV completion rates in an integrated health care system.

The retrospective cohort study included female adolescents and young women who initiated the HPV vaccine series in the Kaiser Permanente Northern California system between January 1, 2008 and December 31, 2012. Women were included if they were continuously enrolled in the Kaiser Permanente healthcare plan 1 year before and 1 year after administration of the index vaccination dose and had been given the vaccine at a Kaiser Permanente Northern California facility. Exclusion criteria were history of cervical dysplasia or neoplasia at the time of vaccine initiation as well as insufficient or lapsed health plan enrollment.

All cohort members were HPV-4 initiators. The prevalence of vaccine completion was determined for each race and ethnicity (Hispanic, black, Asian or Pacific Islander, Native American, white, or unknown) and predetermined age categories: younger adolescents (11-14 years), teens (15-17 years), and young adults (18-26 years). The researchers defined vaccine completion as receipt of at least three vaccine injections for all age groups.

After exclusions, the final study cohort consisted of 102,052 women who initiated HPV vaccination in the Kaiser Permanente Northern California system during the 4-year period of the study. The mean age at vaccine initiation was 14.5 years (SD 3.4) and the majority of females who initiated vaccination were younger adolescents (n=60,032 [58.8%]), followed by teens (n=27,668 [27.1%]), and young adults (n=14,349 [14.1%]).

A total of 41.0% of the cohort (41,847) who initiated the HPV-4 vaccine during the study period completed the series. Younger adolescents had the highest completion rates (43.4%, P = .001), followed by young adults (38.0%) and teens (37.4%). By race and ethnicity, the highest prevalence for vaccine series completion was seen among Asian and Pacific Islander patients (49.5%) and lowest among black patients (28.7%). Among Hispanic patients, 38.9% completed the vaccine series but prevalence of vaccine completion varied by level of acculturation, the process by which certain groups adopt the attitudes, values, and practice of a host society. The researchers found an inverse relationship between acculturation and vaccine completion rates, with the highest rate of vaccine completion seen in the lowest acculturated group (44.2%), compared to the moderate acculturation group (40.6%) and the high acculturation group (37.2%).

The authors believe their findings are consistent with previous investigations on HPV vaccine coverage across all racial and ethnic groups, as are their findings regarding acculturation levels. They noted that previous studies have shown improved rates of infant morbidity and mortality among low acculturated Hispanics. The authors suggest that low acculturated groups might exhibit higher adherence to medical recommendations or have social networks that encourage healthy behaviors. Earlier studies also showed that Latina women were more likely to receive an HPV vaccine recommendation from a Latin health care provider, indicating that increasing diversity and cultural awareness of health providers may decrease medial mistrust and increase HPV vaccination adherence.

The authors also noted a few strengths and limitations of their study. Among the strengths were the large, diverse cohort of females in an integrated health system and the diverse economic backgrounds of the population. Noted limitations included the retrospective design, a limited definition of Hispanic acculturation, and a lack of completion rates among boys.