Narcotic Agonist Analgesic
PREGNANCY RECOMMENDATION: Human Data Suggest Risk
BREASTFEEDING RECOMMENDATION: Compatible
PREGNANCY SUMMARY
The National Birth Defects Prevention Study discussed below found evidence that opioid use during organogenesis is associated with a low absolute risk of congenital birth defects. As with all opioids, maternal and neonatal addiction is possible from inappropriate use. Neonatal depression, at times fatal, has historically been the primary concern following obstetric meperidine analgesia. Controversy has arisen over the potential long-term adverse effects resulting from this use.
FETAL RISK SUMMARY
The placental transfer of meperidine is very rapid, appearing in cord blood within 2 minutes following IV administration (1). It is detectable in amniotic fluid 30 minutes after IM injection (2). Cord blood concentrations average 70%–77% (range 45%–106%) of maternal plasma levels (3,4). The drug has been detected in the saliva of newborns for 48 hours following maternal administration during labor (5). Concentrations in pharyngeal aspirates were higher than in either arterial or venous cord blood.
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 62 newborns had been exposed to meperidine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Three (4.8%) major birth defects were observed (three expected), including (observed/expected) 1/0 polydactyly and 1/0 hypospadias. No malformations were observed in four other defect categories (cardiovascular defects, oral clefts, spina bifida, and limb reduction defects) for which specific data were available.
Respiratory depression in the newborn following use of the drug in labor is time- and dose-dependent. The incidence of depression increases markedly if delivery occurs 60 minutes or longer after injection, reaching a peak around 2–3 hours after injection (6,7). Whether this depression is caused by metabolites of meperidine (e.g., normeperidine) or the drug itself is not known (2,8–10). However, recent work suggests that these effects are related to unmetabolized meperidine and not to normeperidine (7).
Impaired behavioral response and electroencephalographic changes persisting for several days have been observed (11,12). These persistent effects may be partially explained by the slow elimination of meperidine and normeperidine from the neonate over several days (13,14). One group of investigators related depressed attention and social responsiveness during the first 6 weeks of life to high cord blood levels of meperidine (15). An earlier study reported long-term follow-up of 70 healthy neonates born to mothers who had received meperidine within 2 hours of birth (16,17). Psychologic and physical parameters at 5 years of age were similar in both exposed and control groups. Academic progress and behavior during the 3rd and 4th years in school were also similar.
The Collaborative Perinatal Project monitored 50,282 mother–child pairs, 268 of whom had 1st trimester exposure to meperidine (18, pp. 287–295). For use anytime during pregnancy, 1100 exposures were recorded (18, p. 434). No evidence was found to suggest a relationship to large categories of major or minor malformations. A possible association between the use of meperidine in the 1st trimester and inguinal hernia was found based on six cases (18, p. 471). The statistical significance of this association is unknown and independent confirmation is required.
Results of a National Birth Defects Prevention Study (1997–2005) were published in 2011 (19). This population-based case–control study examined the association between maternal use of opioid analgesics and >30 types of major structural birth defects. In 17,449 case mothers, therapeutic opioid use was reported by 454 (2.6%) compared with 134 (2.0%) of 6701 control mothers. Indications for use of opioid analgesics were surgical procedures (41%), infections (34%), chronic diseases (20%), and injuries (18%). Dose, duration, or frequency were not evaluated. The exposure period evaluated was from 1 month before to 3 months after conception. Limiting the exposure period to the first 2 months after conception produced similar results. Infants with >1 defect were included in multiple birth defect categories. The following opioids were included (number of cases for each agent not specified): codeine, hydrocodone, hydromorphone, fentanyl, meperidine, methadone, morphine, oxycodone, pentazocine, propoxyphene, and tramadol. The birth defect, total number, number exposed, and the adjusted odds ratio (aOR) with 95% confidence interval (CI) were as follows:
The authors speculated that the activity of opioids and their receptors as growth regulators during development of the embryo might be a mechanism to explain the above findings. The exposure data were obtained by retrospective maternal self-report; the authors acknowledged that recall bias and misclassification might have affected their results. They concluded that the absolute risk was a modest absolute increase above the baseline risk for birth defects (19).
BREASTFEEDING SUMMARY
Meperidine is excreted into breast milk (20,21). In a group of mothers who had received meperidine during labor, the breastfed infants had higher saliva levels of the drug for up to 48 hours after birth than a similar group that was bottle-fed (5). In nine nursing mothers, a single 50-mg IM dose produced peak levels of 0.13 mcg/mL at 2 hours (21). After 24 hours, the concentrations decreased to 0.02 mcg/mL. Average milk:plasma ratios for the nine patients were greater than 1.0. No adverse effects in nursing infants were reported in any of the above studies.
The American Academy of Pediatrics classifies meperidine as compatible with breastfeeding (22).
References
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