Accepted Manuscript Outcomes in Pregnancies Complicated by Methamphetamine Use Margaret C. Gorman , MD Kaebah S. Orme , MD Nancy T. Nguyen , MD Edward J. Kent III, MD Aaron B. Caughey , MD PhD PII:

S0002-9378(14)00566-3

DOI:

10.1016/j.ajog.2014.06.005

Reference:

YMOB 9865

To appear in:

American Journal of Obstetrics and Gynecology

Received Date: 11 March 2014 Revised Date:

15 April 2014

Accepted Date: 2 June 2014

Please cite this article as: Gorman MC, Orme KS, Nguyen NT, Kent III EJ, Caughey AB, Outcomes in Pregnancies Complicated by Methamphetamine Use, American Journal of Obstetrics and Gynecology (2014), doi: 10.1016/j.ajog.2014.06.005. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Outcomes in Pregnancies Complicated by

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Methamphetamine Use

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Margaret C. Gorman, MD1, Kaebah S. Orme, MD1, Nancy T. Nguyen, MD1, Edward J. Kent III,

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MD1, Aaron B. Caughey, MD PhD1

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1. Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR

Corresponding author:

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Margaret C. Gorman Department of Obstetrics & Gynecology Oregon Health & Science University 3181 SW Sam Jackson Park Rd, Mail Code L466 Portland, OR 97239 Phone: (503) 789-8769 [email protected]

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Word Count, Abstract: 211 Word Count, Main Text: 3119

Conflict of interest: All authors declare no perceived or real conflict of interest.

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CONDENSATION:

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Use of methamphetamine during pregnancy is associated with numerous outcomes relating to

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maternal and neonatal morbidity and mortality.

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SHORT VERSION OF TITLE:

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Methamphetamine Use in Pregnancy

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ABSTRACT

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Objectives: Methamphetamine use is widespread. Our goal was to examine the effects of

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methamphetamine use on various maternal and neonatal outcomes.

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Study Design: We conducted a retrospective cohort study looking at all pregnancies between

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2005 and 2008 in the state of California associated with a diagnosis of methamphetamine use.

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Outcomes examined included: gestational hypertension, preeclampsia, preterm birth, small for

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gestational age, birth weight, abruption, IUFD, neonatal death, infant death, jaundice, and

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gestational diabetes. Statistical analysis included chi squared tests and multivariable logistic

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regression analyses.

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Results: After adjusting for multiple confounding variables on multivariable regression analysis,

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results indicated that compared with controls, methamphetamine users had greater odds of:

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gestational hypertension (OR 1.8, 95% CI 1.6-2.0), preeclampsia (OR 2.7, 95% CI 2.4-3.0),

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IUFD (OR 5.1, 95% CI 3.7-7.2), and abruption (OR 5.5, 95% CI 4.9-6.3). Additionally, these

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patients had a higher odds of preterm birth (OR 2.9, 95% CI 2.7-3.1), , neonatal death (OR 3.1,

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95% CI 2.3-4.2, and infant death (OR 2.5, 95% CI 1.7-3.7).

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Conclusion: Methamphetamine use in pregnancy was found to be associated with specific

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patterns of increased maternal and fetal morbidity and mortality. With these results in mind,

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further work can be done to improve the care of pregnancies complicated by methamphetamine

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use in hopes of reducing these complications.

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Key Words: methamphetamine, amphetamine, stimulant, substance abuse, pregnancy,

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maternal, neonatal

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Introduction

Methamphetamine use was once considered an illicit drug use phenomenon endemic to

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the West Coast. Unfortunately, this geographical divide no longer holds true. While many of the

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highest-use areas indeed remain in the Western states, use of methamphetamine has spread to

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reach all four corners of the country. According to the United States Drug Enforcement

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Administration’s National Clandestine Laboratory Register, there are known methamphetamine

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labs in all 50 states, implying production, sales, and use in each (1).

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According to the National Survey on Drug Use and Health 2012, women 12-44 years old reporting having ever used stimulants, including methamphetamine, was 7.2% among

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pregnant women versus 7.1% among non-pregnant women (2). In many western and

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Midwestern states, methamphetamine is now the third most commonly abused substance,

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following alcohol and marijuana, respectively, and an estimated 5.2% of pregnant women in the

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highest-use areas of the United States use the drug at some point during pregnancy (3).

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Furthermore, in 2006 based on data from the Treatment Episode Data Set (TEDS), a nationwide

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data system maintained by the University of Michigan that tracks admissions into substance

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treatment facilities that receive federal funding in all 50 states, it was reported that among

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pregnant women seeking drug abuse treatment, one in four report methamphetamine as their

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primary drug of abuse (4).

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Effects of the drug on the user are well established. Furthermore, amphetamines cross the placenta and have been found in fetal organs following in-utero exposure (5-7). Early reports

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suggested an association with an increase in various fetal anomalies (8-10), however case control

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and prospective analyses have not confirmed these associations (11-13). Moreover, in assessing

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the risk of fetal anomalies after exposure to methamphetamine, the Teratogen Information

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System database has deemed this unlikely based on fair to good data (14). Existing research has

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demonstrated an association between maternal methamphetamine use and an increased risk for

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intrauterine growth restriction (IUGR), low birth weight (LBW) or small for gestational age

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(SGA) neonates (13,15-22). Two small studies evaluating the effects of methamphetamine use

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among pregnant women have found a statistically significant decrease in birth weight and head

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circumference among neonates born to methamphetamine abusing mothers compared to controls

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after adjusting for gestational age at birth (13, 23). However, many of these studies were small

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and evaluated limited outcomes. The largest study to date was published in 2010, and examined

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276 pregnant methamphetamine users, reporting a positive association with preterm delivery,

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low APGAR scores, cesarean delivery, and neonatal mortality (24).

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Given this background including the wide use of methamphetamines in pregnancy and

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the relatively small number of studies, we sought to better characterize the associations between

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methamphetamine use in pregnancy and adverse maternal and neonatal outcomes.

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Materials and Methods We conducted a retrospective cohort study including all pregnancies from 2005 through

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2008 in the state of California. The data for these calculations was derived from linked mother-

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infant datasets from the California Vital Statistics Birth Certificate Data, Vital Statistics Death

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Certificate Data, California Patient Discharge Data and Vital Statistics Fetal Death File. Data

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linkage is performed by the California Office of Statewide Health Planning and Development

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(OSHPD) Healthcare Information Resource Center, under the California Health and Human

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Services Agency (CHHS) using a unique “record linkage number” specific to the mother-infant

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pair. The state of California maintains these linked datasets that include health information from

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maternal antepartum and postpartum hospital records for the nine months prior to delivery and

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one year after delivery, as well as birth records and all infant admissions occurring within the

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first year of life. We obtained human subjects approval from the Institutional Review Board at

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Oregon Health & Science University, the California Office of Statewide Health Planning and

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Development (OSHPD) and the Committee for the Protection of Human Subjects. The linked

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dataset did not contain potential patient privacy/identification information, so informed consent

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was exempted.

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Our primary exposure of interest was a diagnosis of methamphetamine use during the pregnancy and we identified 8,542 women with pregnancies associated with methamphetamine

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use using the following International Classification of Diseases, 9th Revision [ICD-9] codes:

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304.4, 304.40 (Dependence, Unspecified Use), 304.41 (Dependence, Continuous Use), 304.42

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(Dependence, Episodic Use), 305.70 (Nondependent Abuse, Unspecified Use), 305.71

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(Nondependent Abuse, Continuous Use), 305.72 (Nondependent Abuse, Episodic Use), and

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969.72 (Poisoning by Amphetamines). These 8,542 cases were compared with 2,031,328 control

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ACCEPTED MANUSCRIPT 7 pregnancies. In order to avoid the confounding of complications linked to multi-fetal gestations

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and congenital anomalies, we excluded these pregnancies for both the case group and the control

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group. Analyses were conducted using Stata (version 12, StataCorp; College Station, TX) and R

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(version 2.13.1, R Foundation for Statistical Computing; Vienna, Austria).

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Outcomes of interest examined were also determined retrospectively through the use of ICD 9 codes and included: gestational hypertension, preeclampsia, pregnancy-associated

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hypertension (PAH, defined as gestational hypertension or preeclampsia), severe preeclampsia,

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severe preeclampsia among those with pregnancy-associated hypertension, eclampsia, abruption,

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intrauterine fetal demise, preterm delivery (

Outcomes in pregnancies complicated by methamphetamine use.

Methamphetamine use is widespread. Our goal was to examine the effects of methamphetamine use on various maternal and neonatal outcomes...
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