Matern Child Health J (2014) 18:1779–1785 DOI 10.1007/s10995-014-1447-6
METHODOLOGICAL NOTES
The Association Between Contraceptive Use at the Time of Conception and Hypertensive Disorders During Pregnancy: A Retrospective Cohort Study of Prams Participants Katie E. Farley • Larissa R. Brunner Huber Jan Warren-Findlow • Jennifer L. Ersek
•
Published online: 18 February 2014 Ó Springer Science+Business Media New York 2014
Abstract Each year approximately 7 % of women experience hypertensive disorders during pregnancy which can result in adverse events for both the mother and child. Previous research suggests that contraception at the time of conception can also predispose one to hypertensive disorders during pregnancy. The objective of this study was to examine the association between contraceptive use at the time of conception and hypertensive complications during pregnancy. A total of 2,395 women aged 18–45 years participated in the 2007–2009 Michigan Pregnancy Risk Assessment Monitoring System. Contraception at the time of conception was self-reported by participants and classified as barrier, nonbarrier, or non-use. Information on hypertensive disorders during pregnancy was primarily from birth certificates. Logistic regression was used to obtain odds ratios (ORs) and 95 % confidence intervals (CIs) to model the contraception-hypertensive disorder association. After adjustment for age and race/ethnicity, there was no strong association between use of barrier contraception at the time of conception and hypertensive disorders during pregnancy as compared to non-users (OR 1.09, 95 % CI 0.62–1.92). After adjustment for the same variables, nonbarrier users had 1.22 times the odds of experiencing hypertensive disorders during pregnancy as
K. E. Farley (&) L. R. B. Huber J. Warren-Findlow J. L. Ersek Department of Public Health Sciences, UNC Charlotte, Charlotte, NC, USA e-mail:
[email protected] J. L. Ersek Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC, USA
compared to non-users (95 % CI 0.75–1.98). Although we did not find an association between contraceptive use at the time of conception and hypertensive disorders during pregnancy, additional studies with larger sample sizes and more explicit categorization of the outcome variable are needed to confirm these findings. Keywords Contraception Hypertensive disorders PRAMS Gestational hypertension Preeclampsia
Introduction Approximately 7 % of women experience hypertensive disorders such as chronic hypertension (existing prior and into pregnancy), gestational hypertension, or preeclampsia [1] during pregnancy each year in the United States [2]. Several risk factors have been established for hypertensive disorders during pregnancy including previously existing hypertension, diabetes, primigravida, and obesity [1, 3, 4]. Another possible risk factor for hypertensive disorders during pregnancy is maternal contraception prior to pregnancy. Previous research has suggested that oral contraceptive use could predispose one to preeclampsia [5, 6]. Although not well understood, it is thought that some women who use oral contraceptives at the time of conception may experience a combined effect of hypertension, increased insulin resistance, and elevated lipid levels that may continue into pregnancy even after the termination of oral contraceptive use [5]. Together, these combined biological reactions to oral contraceptive use (and perhaps other hormonal methods of contraception) at conception could possibly predispose the mother to preeclampsia [5]. Preeclampsia is the most severe form of hypertensive disorders during pregnancy and is the third leading cause of
123
1780
maternal morbidity [3, 4]. Possible treatments for preeclampsia are early delivery of the fetus, which increases the risk of preterm delivery, or termination of the pregnancy [3–5]. These treatments are not ideal or acceptable given the serious consequences of these treatments for the mother and baby. A possible association between oral contraceptive use and preeclampsia is particularly concerning given that oral contraceptives are the most widely-used method of reversible contraception with over 10 million women using oral contraceptives each year in the United States [7, 8]. Moreover, nearly half of women who intend to get pregnant or plan on having more children in the future use oral contraceptives for pregnancy prevention [8]. Other forms of contraception have also been investigated as risk factors for preeclampsia based on the maladaptation theory of preeclampsia [4, 9, 10]. The maladaptation theory states that frequent maternal contact with paternal sperm may have a protective effect on maternal immunology. Contraceptive methods that prevent sperm from contacting the maternal endometrium may predispose the mother to preeclampsia [4, 9, 10]. These barrier methods, including condoms, diaphragms, cervical caps, withdrawal, and sponges, inhibit the endometrium from coming in contact with sperm which in turn protects the mother from paternal antigens [4, 9, 10]. While some risk factors for hypertensive disorders during pregnancy have been established, previous literature on the association between contraceptive use at the time of conception and hypertensive disorders during pregnancy is limited, inconclusive, and dated [4–6, 9, 10]. Studies have had small sample sizes [4, 6] and many have been limited in their generalizability due to the lack of racial/ethnic diversity of the study participants [6, 10]. Additionally, studies have lacked consistent exposure measurements; some compared barrier method users to non-users while others compared nonbarrier method users to non-users [4– 6, 9, 10]. No study to our knowledge has compared the entire spectrum of contraceptive use (i.e. barrier, nonbarrier, and nonuse). Finally, prior studies have had inconsistent definitions of the outcome. The varying definitions of the outcomes and exposures in the current literature suggest that misclassification may be an issue, and these different definitions have made comparisons among studies difficult. This large, population-based study explored the association between contraception method (barrier, nonbarrier, and non-use) at the time of conception and hypertensive disorders during pregnancy. More specifically, we hypothesized that women who used barrier or nonbarrier contraceptive methods at the time of conception would have increased odds of hypertensive disorders during pregnancy compared to women who used no method of contraception at the time of conception.
123
Matern Child Health J (2014) 18:1779–1785
Methods Study Design and Population This study used data from the 2007–2009 Michigan Pregnancy Risk Assessment Monitoring System (PRAMS). PRAMS is a large, national survey initiated in 1987 by the centers for disease control and prevention (CDC) to examine state-specific and population-based information on maternal experiences before, during, and after pregnancy [22]. PRAMS is a surveillance system which allows state health professionals to monitor and compare trends in maternal and child health indicators. PRAMS uses a multi-stage, complex sampling strategy [11]. Every month, a list of mothers who recently delivered a live-born infant in the past 2–4 months is randomly generated from a file of birth certificate records [12]. The randomly selected mothers are then sent a letter in the mail that introduces them to PRAMS. Following the introductory letter, the mothers are sent a 14 page self-administered questionnaire. In addition to the information provided on the PRAMS questionnaire, the birth certificate records are also available for data analysis and include birth outcomes such as gestational age, APGAR score, maternal and child outcomes, and whether or not there were any labor abnormalities. Nonrespondents are followed up with telephone interviews. Spanish speaking respondents have access to Spanish translated questionnaires. A total of 1,300–3,400 women are sampled from each state annually [11]. The current study used data from a single state. While there are nationwide core PRAMS questions that are universal to each state, individual states can ask state-specific questions in addition to the core questions on the selfadministered questionnaire. Michigan PRAMS was the only state that explicitly asked about the particular type of contraceptive methods used at the time of conception during these years. In addition to the human subjects protection used by PRAMS, this secondary data analysis was also approved by the local institutional review board. Description of Variables The main exposure in this study was contraceptive use at the time of conception. In the PRAMS questionnaire, contraceptive use at the time of conception was measured by the following question: ‘‘When you got pregnant with your new baby, what were you or your husband or partner using to keep from getting pregnant?’’. Participants were able to choose from a selection of options. These responses were further categorized into the following: barrier method user (i.e. condoms, diaphragm, cervical cap, sponge, or withdrawal), nonbarrier method user (i.e. oral contraceptives,
Matern Child Health J (2014) 18:1779–1785
shot once a month, shot once every 3 months, contraceptive patch, contraceptive implant, vaginal ring, intrauterine devices (IUD), or rhythm method), and non-user (i.e. did not report using any method of contraception at the time of conception). The previously listed categorizations have been used in prior studies of the association between contraceptive use at the time of conception and hypertensive disorders during pregnancy [4, 9, 10]. As with prior studies, non-users were considered to be the referent in order to allow for better comparison with these past studies [9, 10]. The main outcome of interest was the presence of hypertensive disorders during pregnancy. Information on hypertensive disorders was collected on the birth certificate records and in the PRAMS questionnaire. In the birth certificate records, hypertensive disorders during pregnancy is labeled as ‘‘Hypertension?’’. This variable is a combination of two checkboxes: pregnancy (chronic) and gestational (i.e. pregnancy-induced hypertension, preeclampsia, and eclampsia). If either of the boxes was checked on the birth certificate, PRAMS personnel further collapsed the information to just be a ‘‘yes’’ for hypertension. If outcome information was missing from the birth certificate data, it was augmented from the questionnaire. In the PRAMS questionnaire, hypertensive disorders during pregnancy is measured with the question: ‘‘Did you have any of these problems during your most recent pregnancy?’’. Included within this question is a statement about ‘‘high blood pressure, hypertension (including pregnancy-induced hypertension (PIH), preeclampsia, or toxemia).’’ For the outcome measurement, if the birth certificate variable or the survey question (for those missing birth certificate data) was marked as ‘‘yes’’, the person was considered to have the outcome. Statistical Analysis Information on demographic, lifestyle, and pregnancy characteristics collected through PRAMS were considered as potential confounding factors. The confounders that were considered are based on the literature [4, 5, 9, 10] and other factors that are not believed to be on the causal pathway between the exposure and the outcome. The potential confounders that were considered include: marital status, age, race/ethnicity, education, number of prenatal care visits, maternal weight gain, pre-pregnancy BMI, smoking before or during pregnancy, alcohol consumption during pregnancy, and diabetes. All information on the potential confounding factors was obtained from the birth certificate records. A total of 4,807 women participated in the 2007–2009 Michigan PRAMS. Women were excluded from this study if they were not between the ages of 18 to 45 years (n = 235) or if they did not answer the question about
1781
contraceptive use at the time of conception (n = 1,987). Women were further excluded if they selected ‘‘other’’, ‘‘abstinence’’, ‘‘tubes tied’’, or ‘‘vasectomy’’ as a contraceptive choice (n = 145) or if they were missing information on any of the following variables: hypertensive disorders during pregnancy (n = 4), education (n = 30), smoking (n = 3), alcohol use (n = 2), or race/ethnicity (n = 6). Thus, 2,395 women were available for analysis. The frequencies and percentages of all demographic, lifestyle, and pregnancy characteristics were summarized for the participants in the study. Logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CIs) to provide a crude association between contraceptive use at the time of conception and hypertensive disorders during pregnancy. In addition, other risk factors for hypertensive disorders during pregnancy were identified. Multivariate logistic regression was used to model the association between contraceptive use at the time of conception and hypertensive disorders during pregnancy while controlling for confounders. A variable was considered to be a confounder if it changed the magnitude of the exposure-disease relationship by at least 10 % [13]. Ultimately, no variables met the criteria for being a confounder. However, age and race/ethnicity were retained in the final model due to their strong associations with hypertensive complications [14]. Due to the complex sampling design used by PRAMS, SAS-callable SUDAAN was used in all analyses.
Results The majority of women were between the ages of 18–25 years (48.42 %) and non-Hispanic white (66.32 %, Table 1). Over half of the women reported using no method of contraception at the time of conception (59.14 %). Of the women who did report using contraception at the time of conception, 19.59 % used barrier methods and 21.27 % used nonbarrier methods. Condoms were the most widely used method among barrier method users (72.8 %), followed by withdrawal (26.3 %), and diaphragms (0.8 %); alternatively, among nonbarrier method users, oral contraceptives were most popular (55.0 %), followed by the rhythm method (21.3 %), injectables (11.2 %), vaginal ring (6.9 %), transdermal patch (3.7 %), and IUD (1.8 %). Additionally, 5.10 % of the sample experienced some type of hypertensive disorder during their pregnancy. Women who were 36 years or older had 2.41 times the odds of experiencing hypertensive disorders during pregnancy as compared to women who were 18–25 years (95 % CI 1.33–4.36; Table 2) while there was no association between being 26–35 years and experiencing
123
1782
Matern Child Health J (2014) 18:1779–1785
Table 1 Characteristics of study sample, 2007–2009 Michigan PRAMS Variables
Number (N)
1,417
59.14
Barrier
471
19.59
Non-barrier
507
21.27
151
5.41
2,244
94.59
Hypertensive complications Yes No Age 18–25
1,238
48.42
26–35
962
42.82
C36
195
8.76
Race/ethnicity Hispanic
87
5.41
Non-Hispanic White
1,051
66.32
Non-Hispanic Black
1,184
24.05
73
4.22
Other Education Less than high school
533
23.51
High school
837
34.11
Some college
698
26.47
College or more
327
15.91
839
42.25
1,556
57.75
Marital status Married Other BMI \18.5
82
3.18
18.5–24.9
1,000
44.05
25.0–29.9
602
25.39
C30.0
640
24.63
71
2.75
Low
622
27.66
Normal
595
23.05
1,107
46.54
71
2.75
542
24.72
1,853
75.28
Missing
Variables
Number (N)
Weighted percent
Weighted percent
Contraceptive use Non-user
Table 1 continued
1–5
107
3.23
C6
2,183
93.00
70
2.66
Missing
hypertensive disorders during pregnancy (OR 0.96, 95 % CI 0.61–1.50). Obese women had three-fold increased odds of hypertensive disorders during pregnancy (OR 3.02, 95 % CI 1.81–5.03) while overweight women had 1.60 times the odds of experiencing hypertensive disorders during pregnancy (95 % CI 0.90–2.83). Women who had ever been diagnosed with diabetes had 5.37 times the odds of experiencing hypertensive disorders during pregnancy as compared to women who did not have diabetes, and this result was statistically significant (95 % CI 2.48–11.66). Compared to non-users, there was no association between barrier or nonbarrier method use at the time of conception and hypertensive disorders during pregnancy (OR 1.07, 95 % CI 0.61–1.85; OR 1.21, 95 % CI 0.75–1.95, respectively; Table 2). After adjusting for age and race/ethnicity, the magnitude of the contraceptive use at the time of conception-hypertensive disorders during pregnancy associations remained largely unchanged (Table 3). Specifically, women who used nonbarrier methods of contraception at the time of conception had 1.22 times the odds of experiencing hypertensive disorders during pregnancy (95 % CI 0.75–1.98) and women who used barrier methods had 1.09 times the odds of experiencing hypertensive disorders during pregnancy as compared to non-users (95 % CI 0.62–1.92).
Pregnancy weight gain
High Missing Smoking status Smoker Nonsmoker Alcohol during pregnancy Yes No
9
0.29
2,386
99.71
71
3.06
2,153
88.71
171
8.23
35
1.11
Diabetes Yes No Missing Prenatal care visits 0
123
Discussion In this population-based study of women who recently had a live birth, neither barrier nor nonbarrier use at the time of conception was strongly associated with hypertensive disorders during pregnancy in unadjusted or adjusted models. The current study’s findings on the use of nonbarrier methods of conception and hypertensive disorders during pregnancy are consistent with previous results of oral contraceptive use and development of gestational hypertension or preeclampsia. Bracken and Srisuphan examined recent oral contraceptive use (\3 months prior to conception) and later development of hypertensive disorders in 341 women, and found no association between recent oral contraceptive use and development of gestational hypertension (OR 1.01, 95 % CI 0.46, 2.20) [6]. Conversely, Thadhani and colleagues, who also moderated for duration
Matern Child Health J (2014) 18:1779–1785
1783
Table 2 Unadjusted OR and 95 % CI for the association between demographic and medical characteristics and hypertensive disorders during pregnancy, Michigan PRAMS Variables
OR
95 % CI
Non-user
1.00
Referent
Barrier Non-barrier
1.07 1.21
0.61–1.85 0.75–1.95
18–25
1.00
Referent
26–35
0.96
0.61–1.50
C36
2.41
1.33–4.36
Hispanic
0.41
0.09–1.97
Non-hispanic white
1.00
Referent
Non-hispanic black
1.06
0.73–1.55
Other
1.12
0.41–3.09
Contraceptive use
OR
95 % CI
Non-user
1.00
Referent
Barrier Non-barrier
1.09 1.22
0.62–1.92 0.75–1.98
Contraceptive use
Age
Model adjusted for age and race/ethnicity
Race/ethnicity
Education Less than high school
0.77
0.42–1.43
High school
0.73
0.41–1.30
Some college
0.70
0.39–1.24
College or more Marital status
1.00
Referent
Married
1.00
Referent
Other
0.69
0.46–1.03
BMI \18.5
0.42
0.10–1.79
18.5–24.9
1.00
Referent
25.0–29.9
1.60
0.90–2.83
C30.0
3.02
1.81–5.03
Missing
3.41
1.09–10.61
Low
1.03
0.57–1.86
Normal
1.00
Referent
High
1.21
0.72–2.03
Missing
2.32
0.74–7.28
0.63 1.00
0.37–1.06 Referent
Pregnancy weight gain
Smoking status Smoker Nonsmoker
Table 3 Adjusted OR and 95 % CI for the association between contraceptive use at the time of conception and hypertensive complications during pregnancy, Michigan PRAMS
Alcohol during pregnancy Yes
1.17
0.13–10.12
No
1.00
Referent
Diabetes Yes
5.37
2.48–11.66
No
1.00
Referent
Missing
3.66
2.08–6.44
Prenatal care visits 0
2.69
0.67–10.85
1–5
1.67
0.634–46
C6
1.00
Referent
Missing
1.80
0.71–4.57
of use in their prospective cohort study of 4,308 women, did find that women who used oral contraceptives for greater than 8 years had two times the risk of experiencing preeclampsia compared to users of shorter duration (OR 2.1, 95 % CI 1.10, 4.20) [5]. In the current study, duration of use of contraceptive methods was not available and the sample size did not permit investigating how individual contraceptive methods were associated with hypertensive disorders during pregnancy which may explain the inconsistencies with these findings. The findings on the use of barrier methods at the time of conception and hypertensive disorders during pregnancy are inconsistent with the major findings of a case–control study of 244 women conducted by Klonoff-Cohen et al. [4] They concluded that barrier methods of contraception at the time of conception increased a woman’s odds of experiencing preeclampsia after adjusting for confounders (OR 2.37, 95 % CI 1.01, 5.58). It is possible that selection bias occurred in the Klonoff-Cohen [4] study because cases and controls were recruited from an obstetric hospital inferring that they may have been women with at-risk pregnancies. The current results on the use of barrier methods at the time of conception and hypertensive disorders during pregnancy, however, did support further findings on the topic by Mills et al. [9] who examined barrier and nonbarrier methods of contraception and development of preeclampsia. In their study which used preexisting data from The Kaiser permanente birth defects study and the Vaginal infection and prematurity study, they also found no association between barrier or nonbarrier methods of contraception and preeclampsia . The present study did have several limitations. The outcome variable, hypertensive disorders during pregnancy, was obtained primarily from birth certificate records. A recent review article identified birth certificates as a reliable source of information for pre- and perinatal surveillance, including maternal demographic and birth outcome variables [15], thus limiting the possibility for nondifferential misclassification of the outcome. In some cases, the birth certificate data was incomplete, and outcome information was supplemented with responses from the PRAMS questionnaire. As a result, there is the
123
1784
possibility for nondifferential misclassification of the outcome since some of the responses were self-reported; however, only 7.1 % of the outcome data were supplemented with responses from the PRAMS questionnaire. Another possible source of nondifferential misclassification of the outcome is the collapsing of the different types of hypertensive disorders of pregnancy into one variable by PRAMS personnel when recording information from both the questionnaire and birth certificate data. Presumably most of the women who were coded as experiencing hypertensive disorders during pregnancy had a gestational form of hypertension rather than chronic hypertension [16]. However, collapsing the different variables into one made it impossible to further investigate specific outcomes like PIH or preeclampsia. Furthermore, nondifferential misclassification of the exposure variable, contraceptive use at the time of conception, is also possible since this information was self-reported. If nondifferential misclassification of the exposure or outcome occurred, it would likely bias the results towards the null. In general, selection bias is less likely due to the relatively high response rate of PRAMS. Response rates for Michigan PRAMS were [65 % for the years studied. However, it is still possible that selection bias occurred since women who agreed to participate in PRAMS may be different from women who declined to participate, and since a number of participants did not answer the question regarding contraceptive use at the time of conception. We compared women who responded to the contraception question to women who did not with respect to a number of sociodemographic variables. Respondents and nonrespondents of the exposure differed with regards to age, race/ ethnicity, education, and marital status. Specifically, women who did not respond to the question about contraceptive use at the time of conception were more likely to be Non-Hispanic white, older, college educated, and married. Thus, selection bias cannot be ruled out. The current study did have some notable strengths. Compared to previous studies, our study population was more diverse with respect to race/ethnicity, education, and marital status [6, 10]. The complex sampling design employed by PRAMS helps to ensure that results are generalizable to women residing in Michigan; however, it is possible that regional differences may limit further generalizing these results to all women in the United States. It is also important to note that the current study had a larger sample size (n = 2,395) compared to previous studies examining contraceptive use at the time of conception and hypertensive disorders during pregnancy (n = 300–2,200) [4, 6, 10]. Additionally, unlike prior studies, this study considered barrier and nonbarrier methods users as well as non-users of contraception. This complete classification allowed for a more rigorous examination of how
123
Matern Child Health J (2014) 18:1779–1785
contraceptive use at the time of conception potentially impacts the development of hypertensive disorders during pregnancy.
Conclusion The current study is one of the few to examine barrier and nonbarrier methods of contraception at the time of conception as possible risk factors for hypertensive disorders during pregnancy. As previously noted, this study had several methodological improvements compared to prior studies specifically as it relates to selection of the study population and exposure assessment. Based on this study’s results, it does not appear that contraceptive use at the time of conception is associated with experiencing hypertensive disorders during pregnancy. Still, it is important to note that findings related to the potential association between contraceptive use at the time of conception and hypertensive disorders during pregnancy are limited and inconclusive. Future research should focus on examining the outcome more specifically and independently. In this study, the outcome variable, hypertensive disorders during pregnancy, was collapsed into one variable but included four different diagnoses. It may be helpful to examine each hypertensive diagnosis independently of the others. Furthermore, to limit nondifferential misclassification, the outcome variable should be exclusively measured from medical records. Future studies should also try to have a more diverse study population. While the current study was more racially/ethnically diverse than previous studies, the population was still over 66 % non-Hispanic white. Finally, more detailed information on the exposure should be collected including duration of use of contraceptives. In summary, while the current study did not find any association between contraception at the time of conception and hypertensive disorders during pregnancy, more research is needed, especially due to the current lack of acceptable treatments for women who experience hypertensive disorders during pregnancy. References 1. Marik, P. E. (2009). Hypertensive disorders of pregnancy. Postgraduate Medicine, 121(2), 69–76. 2. Centers for Disease Control and Prevention. (2011). Summary of health indicators. Pediatric and Pregnancy Nutrition Surveillance System. 3. Wallis, A. B., Saftlas, A. F., Hsia, J., & Atrash, H. K. (2008). Secular trends in the rates of preeclampsia, eclampsia, and gestational hypertension, United States, 1987–2004. American Journal of Hypertension, 21(5), 521–526. 4. Klonoff-Cohen, H. S., Savitz, D. A., Cefalo, R. C., & McCann, M. F. (1989). An epidemiologic study of contraception and preeclampsia. JAMA, 262(22), 3143–3147.
Matern Child Health J (2014) 18:1779–1785 5. Thadhani, R., Stampfer, M. J., Chasan-Taber, L., Willett, W. C., & Curhan, G. C. (1999). A prospective study of pregravid oral contraceptive use and risk of hypertensive disorders of pregnancy. Contraception, 60(3), 145–150. 6. Bracken, M. B., & Srisuphan, W. (1982). Oral contraception as a risk factor for preeclampsia. American Journal of Obstetric Gynecology, 142(2), 191–196. 7. Chen, X. K., Wen, S. W., Sun, L. M., Yang, Q., Walker, M. C., et al. (2009). Recent oral contraceptive use and adverse birth outcomes. European Journal of Obstetrics & Gynecology and Reproductive Biology, 144(1), 40–43. 8. Mosher, W. D, Jones, J. & National Center for Health Statistics (U.S.). (2010) Use of contraception in the United States : 1982–2008. Hyattsville, Md: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics. 9. Mills, J. L., Klebanoff, M. A., Graubard, B. I., Carey, J. C., & Berendes, H. W. (1991). Barrier contraceptive methods and preeclampsia. JAMA, 265(1), 70–73. 10. Ness, R. B., Markovic, N., Harger, G., & Day, R. (2004). Barrier methods, length of preconception intercourse, and preeclampsia. Hypertensive Pregnancy, 23(3), 227–235.
1785 11. Centers for Disease Control and Prevention. (2011). Pregnancy risk assessment monitoring system (PRAMS). http://www.cdc. gov/prams/. 12. Centers for Disease Control and Prevention. Michigan PRAMS. Michigan Department of Community Health. http://www.michi gan.gov/mdch/0,4612,7-132-2942_4911_21428—,00.html. 13. Maldonado, G., & Greenland, S. (1993). Simulation study of confounder-selection strategies. American Journal of Epidemiology, 138(11), 923–936. 14. Chasan-Taber, L., Willet, W. C., Manson, J. E., Spiegelman, D., Hunter, D. J., et al. (1996). Prospective study of oral contraceptives and hypertension among women in the United States. Circulation, 94, 483–489. 15. Vinikoor, L.C., Messer, L.C., Laraia, B.A., Kaufman, J.S. (2010) Reliability of variables on the North Carolina birth certificate: a comparison with directly queried values from a cohort study. Paediatric and Perinatal Epidemilogy , 24. 102–112. 16. Sibai, B. M. (2002). Chronic hypertension in pregnancy. Management of Chronic Hypertension in Pregnancy, 100(2), 369–377.
123
