Maternal treatment with opioid analgesics and risk for birth defects

Epidemic Intelligence Service, Office of Workforce and Career Development, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
American journal of obstetrics and gynecology (Impact Factor: 4.7). 02/2011; 204(4):314.e1-11. DOI: 10.1016/j.ajog.2010.12.039
Source: PubMed


We examined whether maternal opioid treatment between 1 month before pregnancy and the first trimester was associated with birth defects.
The National Birth Defects Prevention Study (1997 through 2005) is an ongoing population-based case-control study. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIS) for birth defects categories with at least 200 case infants or at least 4 exposed case infants.
Therapeutic opioid use was reported by 2.6% of 17,449 case mothers and 2.0% of 6701 control mothers. Treatment was statistically significantly associated with conoventricular septal defects (OR, 2.7; 95% CI, 1.1-6.3), atrioventricular septal defects (OR, 2.0; 95% CI, 1.2-3.6), hypoplastic left heart syndrome (OR, 2.4; 95% CI, 1.4-4.1), spina bifida (OR, 2.0; 95% CI, 1.3-3.2), or gastroschisis (OR, 1.8; 95% CI, 1.1-2.9) in infants.
Consistent with some previous investigations, our study shows an association between early pregnancy maternal opioid analgesic treatment and certain birth defects. This information should be considered by women and their physicians who are making treatment decisions during pregnancy.

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    • "Previous studies have demonstrated that opioid receptors are widely expressed in the reproductive system (Agirregoitia et al. 2012; Zhu and Pintar 1998) and involved in regulating various pregnancy events (Broussard et al. 2011; Epstein et al. 2013; McLaughlin et al. 2002). Our previous study revealed that opioid receptor subtypes are dynamically expressed in preimplantation embryos (Chen et al. 2014). "
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    ABSTRACT: Successful implantation requires intimate interactions between a competent blastocyst and a receptive uterus. We recently demonstrated that the aberrant activation of opioid signaling by exogenous ligands adversely affects preimplantation embryonic development and subsequent implantation in mice. However, the underlying machinery governing the dynamic homeostasis of the endogenous opioid system in the uterus during early pregnancy remains elusive. We now show that all three major endogenous opioid precursors are spatiotemporally expressed in the uterus during early pregnancy. Moreover, we observe the well-coordinated expression of the synthetic enzyme prohormone convertases 1/3 (PC1/3) at lower levels and of its inhibitor proprotein convertase subtilisin/kexin type 1 inhibitor (Pcsk1n) and the degrading enzyme membrane metallo-endopeptidase (MME) at higher levels in the receptive uterus. Both estrogen and progestin tend to reduce the uterine levels of opioid ligand precursors in the ovariectomized mouse model. This tight regulation of the endogenous opioid system by PC1/3, Pcsk1n and MME has been further confirmed in physiologically related pseudopregnancy and delayed implantation mouse models. The coordinated regulation of opioid precursor biosynthesis and metabolism helps to create appropriate opioid signaling ensuring uterine receptivity for implantation. Thus, endogenous uterine opioid levels are primarily determined by the coordinated expressions of PC1/3, Pcsk1n and MME under the influence of ovarian progestin and estrogen. Our findings raise an additional cautionary note regarding the effects of opioid abuse on early pregnancy events.
    Cell and Tissue Research 08/2015; DOI:10.1007/s00441-015-2259-8 · 3.57 Impact Factor
    • "These include interdisciplinary rehabilitation programmes [2], exercises [3] and manual therapy [4]. When these approaches are not effective, pharmacological interventions and other non-pharmacological therapies can be used after analysis of the potential risks to the mother and fetus [5] [6] [7]. "
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    ABSTRACT: Objective To evaluate the effects of application of transcutaneous electrical nerve stimulation (TENS) at low and high frequencies to the abdomens of Swiss mice throughout pregnancy. Design Experimental animal study. Setting Research laboratory. Participants Thirty Swiss mice received TENS throughout pregnancy. They were divided into three groups (n = 10): placebo, low-frequency TENS (LF group) and high-frequency TENS (HF group). Interventions In the placebo group, the electrodes were applied to the abdominal region without any electrical current. In the LF group, the frequency was 10 Hz, pulse duration was 200 μs and intensity started at 2 mA. In the HF group, the same parameters were applied and the frequency was 150 Hz. All stimulation protocols were applied for 20 min/day from Day 0 until Day 20. Main outcome measures The pregnant mice were weighed on Days 0, 7, 14 and 20 to verify weekly weight gain by two-way analysis of variance. The numbers of fetuses, placentas, implantations, resorptions and major external fetal malformations on Day 20 were analysed using the Kruskal–Wallis test. Results No significant differences were found between the placebo and TENS groups (P > 0.05). Conclusion Application of low- and high-frequency TENS to the abdomens of pregnant mice did not cause any deleterious or major teratogenic effects.
    Physiotherapy 10/2014; 101(2). DOI:10.1016/ · 1.91 Impact Factor
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    • "Ex vivo and animal studies suggest a possibility of teratogenic effects with early fetal exposure to some opioid analgesics [20e26]. A recent case control study using birth defect registry data demonstrated that early fetal exposure to prescription opioid analgesics was associated with 1.8-to 2.7-fold increased risk for specific cardiovascular and central nervous system defects [27]. The risk of neonatal abstinence syndrome with later fetal exposure is welldocumented [28e33]; evidence suggests that approximately half of all babies with later fetal opioid exposure are likely to develop some signs of neonatal abstinence syndrome [26] [34]. "
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    ABSTRACT: Purpose: To quantify the prevalence of prescribed opioid analgesics among pregnant women enrolled in Tennessee Medicaid from 1995 to 2009. Methods: Retrospective cohort study of 277,555 pregnancies identified from birth and fetal death certificates, and linked to previously validated, computerized pharmacy records. Poisson regression was used to estimate trends over time, rate ratios, and 95% confidence intervals (CI). Results: During the study period, 29% of pregnant women filled a prescription for an opioid analgesic. From 1995 to 2009, any pregnancy-related use increased 1.90-fold (95% CI, 1.83e1.98), first trimester use increased 2.27-fold (95% CI, 2.14e2.41), and second or third trimester use increased 2.02-fold (95% CI, 1.93e2.12), after adjusting for maternal characteristics. Any pregnancy-related, first trimester, and second or third trimester use were each more likely among mothers who were at least 21 years old, white, non-Hispanic, prima gravid, resided in nonurban areas, enrolled in Medicaid owing to disability, and who had less than a high school education. Conclusions: Opioid analgesic use by Tennessee Medicaid-insured pregnant women increased nearly 2-fold from 1995 to 2009. Additional study is warranted to understand the implications of this increased use.
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