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Using pharmacoepidemiologic methods to study pharmacotherapy in pregnancy: Application to opioid maintenance therapy and 17-OHPC for prevention of preterm birth

Siminerio Lemon, Lara (2017) Using pharmacoepidemiologic methods to study pharmacotherapy in pregnancy: Application to opioid maintenance therapy and 17-OHPC for prevention of preterm birth. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

We used pharmacoepidemiologic methods to overcome barriers innate to studying medication use in pregnancy. We applied these methods to two topics of high public health relevance: 1) optimal opioid maintenance therapy aimed at decreased neonatal abstinence syndrome (NAS), and 2) directing treatment with 17-OHPC for recurrent preterm delivery to women most likely to benefit.
Using a clinical dataset of women exposed to methadone or buprenorphine at Magee-Womens Hospital, Pittsburgh, PA (2013-2015, n=716), we performed a probabilistic bias analysis informed from an internal validation cohort to account for unmeasured confounding by maternal addiction severity. The historical increased risk of NAS associated with methadone compared with buprenorphine was not entirely attributable to maternal addiction severity [conventional adjRR: 1.3 (1.1, 1.5); bias adjRR: 1.2 (1.0, 1.4)]. Next, using an inverse probability weighted marginal structural model, we found that the association between treatment and NAS was mediated to a considerable degree through preterm birth (~25%). Because infants born preterm have lower rates of NAS, and methadone is associated with increased rates of preterm delivery, the increased risk of NAS associated with methadone was stronger among term births. For every 100 infants born to treated mothers, methadone was associated with 14 excess cases of NAS overall, which increased to 17 excess cases among term births [adjRD: 16.7 (9.3, 24.0)].
To study 17-OHPC, we built models inclusive of significant interactions between obstetric history factors to predict the risk of recurrent spontaneous preterm delivery (sptd) in a cohort derived from the NICHD MFM Omega-3 trial. This randomized controlled trial found no significant effect of omega-3 supplementation on recurrent sptd in addition to administration of 17-OHPC. Using the treated women in this trial (n=754) and an externally validated predictive model, we found that risk of recurrence increased with earliest gestational ages of prior delivery only in women with ≥2 previous spontaneous preterm deliveries. These findings support the argument that more information, beyond having one previous spontaneous preterm delivery, is needed to target therapy to those most likely to benefit. This is of utmost public health importance as preterm birth remains the primary contributor to neonatal morbidity and mortality.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Siminerio Lemon, Laralls47@pitt.edulls470000-0001-6806-7787
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBodnar, Lisabodnar@edc.pitt.edu
Committee MemberCaritis, Stevecarisn@mail.magee.edu
Committee MemberHaggerty, Catherinehaggertyc@edc.pitt.edu
Committee MemberVenkataramanan, Ramanrv@pitt.edu
Committee MemberYouk, AdaAYOUK@pitt.edu
Date: 30 August 2017
Date Type: Publication
Defense Date: 15 June 2017
Approval Date: 30 August 2017
Submission Date: 5 June 2017
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 135
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: pregnancy, pharmacoepidemiology, opioid maintenance therapy, buprenorphine, methadone, 17-OHPC, progesterone, preterm birth, neonatal abstinence syndrome
Date Deposited: 30 Aug 2017 21:45
Last Modified: 01 Jul 2018 05:15
URI: http://d-scholarship.pitt.edu/id/eprint/32361

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