17-Hydroxyprogesterone caproate (17OHP-C) coverage among eligible women delivering at 2 North Carolina hospitals in 2012 and 2013: A retrospective cohort study

Background Although a weekly injection of 17-hydroxyprogestone caproate is recommended for preventing recurrent preterm birth, clinical experience in North Carolina suggested that many eligible patients were not receiving the intervention. Objective Our study sought to assess how well practices delivering at 2 major hospitals were doing in providing access to 17-hydroxyprogesterone caproate treatment for eligible patients. Study Design This retrospective cohort analysis studied all deliveries occurring between January 1, 2012, and December 31, 2013, at 2 large hospitals in North Carolina. Women were included if they had a singleton pregnancy and history of a prior spontaneous preterm birth. We extracted demographic, payer, and medical information on each pregnancy, including whether women had been offered, accepted, and received 17-hydroxyprogesterone caproate. Our outcome of 17-hydroxyprogesterone caproate coverage was defined as documentation of ≥1 injection of the drug. Results Over the 2-year study period, 1216 women with history of a prior preterm birth delivered at the 2 study hospitals, of which 627 were eligible for 17-hydroxyprogesterone caproate eligible after medical record review. Only 296 of the 627 eligible women (47%; 95% confidence interval, 43-51%) received ≥1 dose of the drug. In multivariable analysis, hospital of delivery, later presentation for prenatal care, fewer prenatal visits, later gestation of prior preterm birth, and having had a term delivery immediately before the index pregnancy were all associated with failed coverage. Among those women who were "covered," the median number of 17-hydroxyprogesterone caproate injections was 9 (interquartile range, 4-15), with 84 of 296 charts (28%) not having complete information on the number of doses. Conclusion Even under our liberal definition of coverage, less than half of eligible women received 17-hydroxyprogesterone caproate in this sample. Low overall use suggests that there is opportunity for improvement. Quality improvement strategies, including population-based measurement of 17-hydroxyprogesterone caproate coverage, are needed to fully implement this evidence-based intervention to decrease preterm birth

A WARNING ABOUT USING PREDICTED VALUES TO ESTIMATE DESCRIPTIVE MEASURES

In a recent article in the Journal, Ogburn et al. highlighted the issues with using predicted values when estimating associations or effects. While the authors cautioned against using predicted values to estimate associations or effects, they noted that predictions can be useful for descriptive purposes. In this work, we highlight the issues with using individual-level predicted values to estimate population-level descriptive parameter

Timing of Initiation of Antiretroviral Therapy and Risk of Preterm Birth in Studies of HIV-infected Pregnant Women: The Role of Selection Bias

Background: Women who initiate antiretroviral therapy (ART) during pregnancy are reported to have lower risk of preterm birth compared with those who enter pregnancy care already receiving ART. We hypothesize this association can be largely attributed to selection bias. Methods: We simulated a cohort of 1000 preconceptional, HIV-infected women, where half were randomly allocated to receive immediate ART and half to delay ART until their presentation for pregnancy care. Gestational age at delivery was drawn from population data unrelated to randomization group (i.e., the true effect of delayed ART was null). Outcomes of interest were preterm birth (<37 weeks), very preterm birth (<32 weeks), and extreme preterm birth (<28 weeks). We analyzed outcomes in 2 ways: (1) a prospectively enrolled clinical trial, where all women were considered (the intent-to-treat (ITT) analysis); and (2) an observational study, where women who deliver before initiating ART were excluded (the naïve analysis). We explored the impact of later ART initiation and gestational age measurement error on our findings. Results: Preconception ART initiation was not associated with preterm birth in ITT analyses. Risk ratios (RRs) for the effect of preconception ART initiation were RR = 1.10 (preterm), RR = 1.41 (very preterm), and RR = 5.01 (extreme preterm) in naïve analyses. Selection bias increased in the naïve analysis with advancing gestational age at ART initiation and with introduction of gestational age measurement error. Conclusions: Analyses of preterm birth that compare a preconception exposure to one that occurs in pregnancy are at risk of selection bias. See video abstract at, http://links.lww.com/EDE/B313

Preconception ART and preterm birth: real effect or selection bias?

In a recent systematic review and meta-analysis, Uthman and colleagues 1 examined the relation between timing of antiretroviral therapy (ART) initiation and adverse pregnancy outcomes. The researchers noted that women continuing preconception ART had a modestly higher risk of preterm birth (ie, birth before 37 weeks) compared with those initiating ART in pregnancy (RR 1·20, 95% CI 1·01–1·44)

Management of cryotherapy-ineligible women in a "screen-and-treat" cervical cancer prevention program targeting HIV-infected women in Zambia: Lessons from the field

Objective: We demonstrate the feasibility of implementing a referral and management system for cryotherapy-ineligible women in a "screen-and-treat" cervical cancer prevention program targeting HIV-infected women in Zambia. Methods: We established criteria for patient referral, developed a training program for loop electrosurgical excision procedure (LEEP) providers, and adapted LEEP to a resource-constrained setting. Results: We successfully trained 15 nurses to perform visual inspection with acetic acid (VIA) followed by immediate cryotherapy. Women with positive tests but ineligible for cryotherapy were referred for further evaluation. We trained four Zambian physicians to evaluate referrals, perform punch biopsy, LEEP, and manage intra-operative and post-operative complications. From January 2006 through October 2007, a total of 8823 women (41.5% HIV seropositive) were evaluated by nurses in outlying prevention clinics; of these, 1477 (16.7%) were referred for physician evaluation based on established criteria. Of the 875 (59.2% of 1147 referred) that presented for evaluation, 748 (8.4% of total screened) underwent histologic evaluation in the form of punch biopsy or LEEP. Complications associated with LEEP included anesthesia reaction (n = 2) which spontaneously resolved, intra-operative (n = 12) and post-operative (n = 2) bleeding managed by local measures, and post-operative infection (n = 12) managed with antibiotics. Conclusion: With adaptations for a resource-constrained environment, we have demonstrated that performing LEEP is feasible and safe, with low rates of complications that can be managed locally. It is important to establish referral and management systems using LEEP-based excisional evaluation for women with cryotherapy-ineligible lesions in VIA-based "screen-and-treat" protocols nested within HIV-care programs in resource-constrained settings

Effect of weekly 17-hydroxyprogesterone caproate on small for gestational age among pregnant women with HIV in Zambia

The IPOP trial demonstrated a reduced risk of severe small for gestational age among infants born to women with HIV who received weekly intramuscular 17 alpha-hydroxyprogesterone caproate. This secondary analysis examined the 17P treatment effect in subgroups of maternal body mass index, parity, timing of ART initiation, and ART regimen. We found 17P was more effective among nulliparous women, women who started ART before pregnancy, and those taking protease inhibitors

Missing Outcome Data in Epidemiologic Studies

Missing data are pandemic and a central problem for epidemiology. Missing data reduce precision and can cause notable bias. There remain too few simple published examples detailing types of missing data and illustrating their possible impact on results. Here we take an example randomized trial that was not subject to missing data and induce missing data to illustrate 4 scenarios in which outcomes are 1) missing completely at random, 2) missing at random with positivity, 3) missing at random without positivity, and 4) missing not at random. We demonstrate that accounting for missing data is generally a better strategy than ignoring missing data, which unfortunately remains a standard approach in epidemiology

Implementation of 'see-and-treat' cervical cancer prevention services linked to HIV care in Zambia

Greater than 80% of the world's new cases and deaths due to cervical cancer occur in the developing world. No more than 5% of women in these settings are screened for cervical cancer even once in their lifetimes. Earlier attempts to establish population-based cervical cancer prevention programs using cytology screening in resource-limited settings have inevitably fallen short or failed. Although many of the reasons for failure can be attributed to lack of resources and trained manpower, the multiple visit requirements of cytology-based screening programs jeopardizes success and sustainability

Quantifying bias between reported last menstrual period and ultrasonography estimates of gestational age in Lusaka, Zambia

Objective To quantify differences in assessing preterm delivery when calculating gestational age from last menstrual period (LMP) versus ultrasonography biometry. Methods The Zambian Preterm Birth Prevention Study is an ongoing prospective cohort study that commenced enrolment in August 2015 at Women and Newborn Hospital of University Teaching Hospital in Lusaka, Zambia. Women at less than 20 weeks of pregnancy who were enrolled between August 17, 2015, and August 31, 2017, and underwent ultrasonography examination were included in the present analysis. The primary outcome was the difference between ultrasonography‐ and LMP‐based estimated gestational age. Associations between baseline predictors and outcomes were assessed using simple regression. The proportion of preterm deliveries using LMP‐ and ultrasonography‐derived gestational dating was calculated using Kaplan–Meier analysis. Results The analysis included 942 women. The discrepancy between estimating gestational age using ultrasonography and LMP increased with greater gestational age at presentation and among patients with no history of preterm delivery. In a Kaplan‐Meier analysis of 692 deliveries, 140 (20.2%, 95% confidence interval [CI] 17.7–23.0) and 79 (11.4%, 95% CI 9.6–13.6) deliveries were classified as preterm by LMP and ultrasonography estimates, respectively. Conclusion Taking ultrasonography as a standard, a bias was observed in LMP‐based gestational age estimates, which increased with advancing gestation at presentation. This resulted in misclassification of term deliveries as preterm

Maternal HIV Infection and Spontaneous Versus Provider-Initiated Preterm Birth in an Urban Zambian Cohort

Objective: We investigated the effect of maternal HIV and its treatment on spontaneous and provider-initiated preterm birth (PTB) in an urban African cohort. Methods: The Zambian Preterm Birth Prevention Study enrolled pregnant women at their first antenatal visit in Lusaka. Participants underwent ultrasound, laboratory testing, and clinical phenotyping of delivery outcomes. Key exposures were maternal HIV serostatus and timing of antiretroviral therapy initiation. We defined the primary outcome, PTB, as delivery between 16 and 37 weeks’ gestational age, and differentiated spontaneous from provider-initiated parturition. Results: Of 1450 pregnant women enrolled, 350 (24%) had HIV. About 1216 (84%) were retained at delivery, 3 of whom delivered,16 weeks. Of 181 (15%) preterm deliveries, 120 (66%) were spontaneous, 56 (31%) were provider-initiated, and 5 (3%) were unclassified. In standardized analyses using inverse probability weighting, maternal HIV increased the risk of spontaneous PTB [RR 1.68; 95% confidence interval (CI): 1.12 to 2.52], but this effect was mitigated on overall PTB [risk ratio (RR) 1.31; 95% CI: 0.92 to 1.86] owing to a protective effect against provider-initiated PTB. HIV reduced the risk of preeclampsia (RR 0.32; 95% CI: 0.11 to 0.91), which strongly predicted provider-initiated PTB (RR 17.92; 95% CI: 8.13 to 39.53). The timing of antiretroviral therapy start did not affect the relationship between HIV and PTB. Conclusion: The risk of HIV on spontaneous PTB seems to be opposed by a protective effect of HIV on provider-initiated PTB. These findings support an inflammatory mechanism underlying HIV-related PTB and suggest that published estimates of PTB risk overall underestimate the risk of spontaneous PTB