Association of Gestational Opioid Exposure and Risk of Major and Minor Congenital Malformations

Importance: The rapid increase of opioid-related overdoses and deaths has become a public health concern in the US. Use of prescription opioids in pregnant women has increased; results from teratogenicity studies remain controversial. Objective: To evaluate the association between maternal prescription opioid use (excluding opioid use disorders) during pregnancy and the incidence of congenital malformations. Design, Setting, and Participants: This retrospective population-based cohort study evaluated linked Rhode Island Medicaid claims and vital statistics data of live births from January 1, 2008, to December 31, 2016. Data analysis was conducted from May 1, 2019, to May 31, 2020. Women who had a live birth during the study period, but no cancer or opioid use disorder, were followed up from 3 months before pregnancy to the end of pregnancy. Exposures: Data on the mother’s prescription opioid exposure were obtained through pharmacy claims and exposure was defined as dispensing of at least 1 prescription opioid during the first, second, or third trimester. Main Outcomes and Measures: The primary outcome was overall major or minor congenital malformations, defined as 1 or more major or minor congenital malformation. Secondary outcomes were defined as 10 specific categories of congenital malformations classified by organ systems using International Classification of Diseases diagnosis codes. Results: Of 12 424 included pregnancies, 891 mothers (7.2%) received prescription opioids during pregnancy and 3153 infants (25.4%) were diagnosed with major or minor congenital malformations. Comparing prescription opioid exposure vs nonexposure, no excess risk was observed for major birth defects in infants with opioid exposure in trimester 1 (adjusted relative risk [aRR], 1.40; 95% CI, 0.84-2.34), and higher risks were found for overall minor birth defects in trimester 3 (aRR, 1.26; 95% CI, 1.04-1.53) and minor birth defects in the musculoskeletal system in trimester 2 (aRR, 1.50; 95% CI, 1.10-2.03) and trimester 3 (aRR, 1.65; 95% CI, 1.23-2.22). Significant dose responses in selected minor malformations and effects of specific opioids were also identified. Hydrocodone in trimester 2 (aRR, 3.01; 95% CI, 1.80-5.03) and oxycodone in trimester 3 (aRR, 2.43; 95% CI, 1.37-4.02) were associated with plagiocephaly, polydactyly, and other specified congenital deformities of the hip. Conclusions and Relevance: The findings of this study suggest a higher risk of minor congenital malformations associated with use of prenatal prescription opioids in trimester 3, which seems to be dose-dependent. Further investigation is needed to establish causality and explore the physiologic plausibility of the association

Comparative Safety Analysis of Opioid Agonist Treatment in Pregnant Women with Opioid Use Disorder: A Population-Based Study

Introduction and Objective: Receipt of opioid agonist treatment during early and late pregnancy for opioid use disorder may relate to varying perinatal risks. We aimed to assess the effect of time-varying prenatal exposure to opioid agonist treatment using buprenorphine or methadone on adverse neonatal and pregnancy outcomes. Methods: We conducted a retrospective cohort study of pregnant women with opioid use disorder using Rhode Island Medicaid claims data and vital statistics during 2008–16. Time-varying exposure was evaluated in early (0–20 weeks) and late (≥ 21 weeks) pregnancy. Marginal structural models with inverse probability of treatment weighting were applied. Results: Of 400 eligible pregnancies, 85 and 137 individuals received buprenorphine and methadone, respectively, during early pregnancy. Compared with 152 untreated pregnancies with opioid use disorders, methadone exposure in both periods was associated with an increased risk of preterm birth (adjusted odds ratio [aOR]: 2.52; 95% confidence interval [CI] 1.07–5.95), low birth weight (aOR: 2.99; 95% CI 1.34–6.66), neonatal intensive care unit admission (aOR, 5.04; 95% CI 2.49–10.21), neonatal abstinence syndrome (aOR: 11.36; 95% CI 5.65–22.82), respiratory symptoms (aOR, 2.71; 95% CI 1.17–6.24), and maternal hospital stay \u3e 7 days (aOR, 14.51; 95% CI 7.23–29.12). Similar patterns emerged for buprenorphine regarding neonatal abstinence syndrome (aOR: 10.27; 95% CI 4.91–21.47) and extended maternal hospital stay (aOR: 3.84; 95% CI 1.83–8.07). However, differences were found favoring the use of buprenorphine for preterm birth versus untreated pregnancies (aOR: 0.17; 95% CI 0.04–0.77), and for several outcomes versus methadone. Conclusions: Methadone and buprenorphine prescribed for the treatment of opioid use disorder during pregnancy are associated with varying perinatal risks. However, buprenorphine may be preferred in the setting of pregnancy opioid agonist treatment. Further research is necessary to confirm our findings and minimize residual confounding

Pooled Analysis of a Self-Sampling HPV DNA Test as a Cervical Cancer Primary Screening Method

BackgroundWorldwide, one-seventh of cervical cancers occur in China, which lacks a national screening program. By evaluating the diagnostic accuracy of self-collected cervicovaginal specimens tested for human papillomavirus (HPV) DNA (Self-HPV testing) in China, we sought to determine whether Self-HPV testing may serve as a primary cervical cancer screening method in low-resource settings.MethodsWe compiled individual patient data from five population-based cervical cancer–screening studies in China. Participants (n = 13 140) received Self-HPV testing, physician-collected cervical specimens for HPV testing (Physician-HPV testing), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Screen-positive women underwent colposcopy and confirmatory biopsy. We analyzed the accuracies of pooled Self-HPV testing, Physician-HPV testing, VIA, and LBC to detect biopsy-confirmed cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and CIN3+. All statistical tests were two-sided.ResultsOf 13 004 women included in the analysis, 507 (3.9%) were diagnosed as CIN2+, 273 (2.1%) as CIN3+, and 37 (0.3%) with cervical cancer. Self-HPV testing had 86.2% sensitivity and 80.7% specificity for detecting CIN2+ and 86.1% sensitivity and 79.5% specificity for detecting CIN3+. VIA had statistically significantly lower sensitivity for detecting CIN2+ (50.3%) and CIN3+ (55.7%) and higher specificity for detecting CIN2+ (87.4%) and CIN3+ (86.9%) (all P values < .001) than Self-HPV testing, LBC had lower sensitivity for detecting CIN2+ (80.7%, P = .015), similar sensitivity for detecting CIN3+ (89.0%, P = .341), and higher specificity for detecting CIN2+ (94.0%, P < .001) and CIN3+ (92.8%, P < .001) than Self-HPV testing. Physician-HPV testing was more sensitive for detecting CIN2+ (97.0%) and CIN3+ (97.8%) but similarly specific for detecting CIN2+ (82.7%) and CIN3+ (81.3%) (all P values <.001) than Self-HPV testing.ConclusionsThe sensitivity of Self-HPV testing compared favorably with that of LBC and was superior to the sensitivity of VIA. Self-HPV testing may complement current screening programs by increasing population coverage in settings that do not have easy access to comprehensive cytology-based screening

Prevalence of human papillomavirus and cervical intraepithelial neoplasia in China: A pooled analysis of 17 population-based studies

High-risk (HR) human papillomavirus (HPV) prevalence has been shown to correlate well with cervical cancer incidence rates. Our study aimed to estimate the prevalence of HR-HPV and cervical intraepithelial neoplasia (CIN) in China and indirectly inform on the cervical cancer burden in the country. 30,207 women from 17 population-based studies throughout China were included. All women received HPV DNA testing (HC2, Qiagen), visual inspection with acetic acid, and liquid-based cytology. Women positive for any test received colposcopy-directed or 4-quadrant biopsies. 29,579 women had HR-HPV testing results, of whom 28,761 had biopsy-confirmed (9019, 31.4%) or assumed (19,742, 68.6%) final diagnosis. Overall crude HR-HPV prevalence was 17.7%. HR-HPV prevalence was similar in rural and urban areas but showed dips in different age groups: at age 25–29 years (11.3%) in rural and at age 35–39 (11.3%) in urban women. In rural and urban women, age-standardized CIN2 prevalence was 1.5% (95%CI: 1.4%–1.6%) and 0.7% (95%CI: 0.7%–0.8%), and CIN3+ prevalence was 1.2% (95%CI: 1.2%–1.3%) and 0.6% (95%CI: 0.5%–0.7%), respectively. Prevalence of CIN3+ as a percentage of either all women or HR-HPV positive women steadily increased with age, peaking in 45–49 year-old women. High prevalence of HR-HPV and CIN3+ was detected in both rural and urban China. The steady rise of CIN3+ up to the age group 45–49 is attributable to lack of lesion removal through screening. Our findings document the inadequacy of current screening in China while indirectly raising the possibility that the cervical cancer burden in China is under-reported

Sociodemographic and attitudinal predictors of simultaneous and redundant multiple marker and cell-free DNA screening among women aged ⩾35 years

ObjectiveTo identify characteristics associated with undergoing cell-free DNA (cfDNA) and multiple marker screening (MMS) simultaneously or redundantly (after receiving negative results from the first screening test) among women aged ⩾35 years.Study designParticipants presenting for prenatal testing completed a questionnaire that included measures of pregnancy worry and attitudes toward potential testing outcomes; data on prenatal test use was obtained via medical record review. We used multivariable logistic regression to identify factors associated with redundant or simultaneous screening.ResultsAmong 164 participants, 69 (42.1%) had cfDNA redundantly (n=51) to, or simultaneously (n=18) with, MMS. Compared with the 46 MMS-negative women who did not undergo further testing, those who underwent redundant or simultaneous cfDNA/MMS screening were more likely to have annual family incomes &gt;$150 000, to feel having a miscarriage would be worse than having an intellectually disabled child, to desire comprehensive testing for intellectual disability and to have more pregnancy worry.ConclusionProviders who counsel patients on prenatal aneuploidy screening tests should explain the appropriate utilization of these screening tests to avoid unnecessary or minimally informative use of multiple tests