Objective
Maternal smoking and preeclampsia independently increase the risk of adverse pregnancy outcomes; however, smoking decreases the risk of preeclampsia. We sought to estimate the risk of adverse pregnancy outcomes among preeclamptic women who smoke and hypothesized that this risk would be increased, compared with nonpreeclamptic women who smoke or preeclamptic women who do not smoke.
Study Design
With the use of the Niday Perinatal Database and multiple logistic regressions, we estimated the risk of adverse pregnancy outcomes in nonpreeclamptic women who smoke, preeclamptic women who do not smoke, and preeclamptic women who smoke in relation to nonpreeclamptic women who do not smoke.
Results
The incidence of adverse pregnancy outcomes was more than twice as high among preeclamptic women who smoke as among nonpreeclamptic women who do not smoke. The following data were observed: small-for-gestational-age infant (odds ratio [OR], 3.40; 95% CI, 2.27–4.89), preterm birth (OR, 5.77; 95% CI, 4.50–7.35), very preterm birth (OR, 5.44; 95% CI, 3.51–8.11), abruption (OR, 6.16; 95% CI, 3.05–11.01), Apgar <4 at 5 minutes (OR, 3.11; 95% CI, 1.48–5.72), and stillbirth (OR, 3.39; 95% CI, 1.33–6.99).
Conclusion
Smoking decreases the risk of preeclampsia, but smokers with preeclampsia have an increased risk for adverse pregnancy outcomes.
The prevalence of smoking among pregnant women is a major ongoing health concern, especially considering the number of adverse pregnancy outcomes that are associated with smoking during pregnancy. The related adverse outcomes include spontaneous abortion, stillbirth, preterm birth, and fetal growth restriction. Additional concerns include the possibility of long-term adverse effects on an infant, such as neurodevelopmental disorders and cancers. Although smoking generally is associated with increased perinatal morbidity and death, interestingly, it has been shown to have a protective effect on the risk of the development of preeclampsia. Indeed, smoking reduces the risk of preeclampsia and decreases its incidence in a dose-effect manner; it may “protect” against or “mask” its development. The risk of preeclampsia among pregnant women who smoke is 32% lower than that among nonsmoking pregnant women.
Preeclampsia is a disease of pregnancy that is characterized by increased maternal blood pressure and proteinurea. It is a major cause of maternal death and morbidity, and like smoking, it also causes perinatal deaths, preterm birth, and intrauterine growth restriction. Despite the apparent benefits of smoking on the risk of preeclampsia, the biologic linkage between smoking and preeclampsia is not well understood. Although it has been established that the risk of preeclampsia is decreased in pregnant smokers, the consequent risks that result when preeclampsia does develop in these women have not been characterized.
We undertook a study to estimate the interaction between the effects of smoking and preeclampsia on the risk of adverse pregnancy outcomes. Our objective was to determine the risk of the development of a wide range of adverse pregnancy outcomes among pregnant smokers who experience preeclampsia in relation to nonpreeclamptic nonsmoking pregnant women. We hypothesized that the risks of adverse pregnancy outcomes would be increased among smokers who are preeclamptic, compared with pregnant smokers who are not preeclamptic or nonsmokers who are preeclamptic.
Materials and Methods
This study was based on the 2004-2006 Niday Perinatal Database, which is part of the Ontario Perinatal Surveillance System and has included >95% of births in Ontario, Canada. There are 82 participating sites that include both hospitals and midwifery groups; 359,747 births were recorded between 2004 and 2006. Sites were permitted to enter data directly into the database (64 sites) or to upload data from their own databases (18 hospitals). The database includes information on the number of women who give birth and infants who are born in the province of Ontario and includes maternal demographic information, maternal behavior, maternal health problems, maternal complications, intrapartum complications and interventions, birth outcomes, and infant health. Ethical approval was obtained from The Ottawa Hospital Research Ethics Board to analyze the information from this database for our study.
The chosen sample size was based on the entire data of the large convenience sample of the 3-year Ontario database for the years 2004-2006. For the analysis, we first compared the demographic information between the smoking and nonsmoking groups, for which smoking was defined as any smoking during pregnancy (regardless of the amount). Second, we compared the demographic information between the preeclamptic and nonpreeclamptic groups, for which preeclampsia was defined (by the Niday Perinatal Database) as the development of hypertension ([1] a rise in systolic pressure of at least 30 mm Hg, a rise in diastolic pressure of at least 15 mm Hg, or a diastolic pressure of at least 90 mm Hg; [2] a blood pressure of 140/90 mm Hg on at least 2 occasions at least 6 hours apart; [3] a mean arterial pressure of 105 mm Hg) with proteinuria (determined by either urine dipstick analysis or protein concentration >0.3 g in a 24-hour urine collection) that occurred after 20 weeks of gestation. In all cases, we used chi-squared statistical tests. Third, we compared the incidences of selected fetal outcomes that were associated with maternal smoking or preeclampsia, compared with either all nonsmoking or nonpreeclamptic pregnancies, respectively, using chi-squared statistical tests. With the use of multiple logistic regression, the adjusted odds ratios were determined. Fourth, using chi-squared statistical tests and multiple logistic regression, we estimated the effect on adverse pregnancy outcomes when smoking and preeclampsia both occurred, in comparison to nonsmoking nonpreeclamptic pregnancies. As a control, we performed the same analyses for the group of smoking nonpreeclamptic women and nonsmoking preeclamptic women. The outcomes that were assessed in this study included small-for-gestational-age births (<3rd percentile), preterm birth (delivery at <37 weeks of gestation), very preterm birth (<32 weeks of gestation), placental abruption (premature separation of a normally implanted placenta that resulted in retroplacental bleeding after week 20 of gestation and before the fetus was delivered), venous cord pH (<7.0), Apgar reading (<4 at 5 minutes), and stillbirth (death of fetus at >20 weeks of gestation). Potential confounding variables included maternal age, parity, and multiple gestation. All analyses were performed with SAS-PC statistical software (version 9.1; SAS Institute Inc, Cary, NC).
Results
Women who smoked during pregnancy tended to be young (<25 years old) and were less likely to have had a prenatal visit during their first trimester, to have used reproductive technologies, to have had a multiple pregnancy, or to have been diabetic ( Table 1 ). Preeclampsia was more likely in women <25 and >35 years old, nulliparous women and women who had a prenatal visit during their first trimester, women who used assisted reproductive technologies, women with multiple gestation, and women who had either diabetes mellitus or high blood pressure ( Table 2 ).
| Variable | Nonsmoker, n (%) a | Smoker, n (%) a |
|---|---|---|
| Age, y | ||
| <19 | 3838 (1.40) | 2456 (7.12) |
| 19-25 | 33,674 (12.30) | 12,006 (34.79) |
| 26-30 | 77,533 (28.33) | 9547 (27.67) |
| 31-35 | 98,834 (36.11) | 6526 (18.91) |
| >35 | 59,810 (21.85) | 3973 (11.51) |
| Parity | ||
| 0 | 121,889 (45.19) | 15,712 (45.91) |
| ≥1 | 147,865 (54.81) | 18,511 (54.09) |
| First prenatal visit | 108,965 (83.28) | 15,805 (77.43) |
| Assisted reproductive technologies | 3393 (2.29) | 184 (0.79) |
| Multiple gestation (twins) | 9679 (3.54) | 1083 (3.14) |
| Medical problems | ||
| Diabetes mellitus b | 9529 (4.84) | 1078 (4.08) |
| Chronic hypertension | 7649 (4.00) | 1056 (3.99) |
a χ 2 statistical tests were used to calculate numbers and percentages;
b Represents insulin-dependent, noninsulin-dependent, and gestational diabetes mellitus.
| Variable | Nonpreeclampsia, n (%) a | Preeclampsia, n (%) |
|---|---|---|
| Age, y | ||
| <19 | 5124 (2.15) | 103 (3.03) |
| 19-25 | 36,265 (15.20) | 526 (15.45) |
| 26-30 | 67,072 (28.11) | 915 (26.88) |
| 31-35 | 80,597 (33.78) | 1077 (31.64) |
| >35 | 49,564 (20.77) | 783 (23.00) |
| Parity | ||
| 0 | 105,595 (45.05) | 2234 (66.33) |
| ≥1 | 128,822 (54.95) | 1134 (33.67) |
| First prenatal visit | 117,986 (81.03) | 1305 (85.24) |
| Assisted reproductive technologies | 3562 (2.07) | 106 (4.73) |
| Multiple gestation (twins) | 8776 (3.68) | 357 (10.49) |
| Medical problems | ||
| Diabetes mellitus b | 11,048 (4.70) | 256 (7.80) |
| Chronic hypertension | 8957 (3.81) | 443 (13.50) |
a χ 2 statistical tests were used to calculate numbers and percentages;
b Represents insulin-dependent, noninsulin-dependent, and gestational diabetes mellitus.
To consider which outcomes were associated with smoking and preeclampsia, we studied the groups of all women who smoked during pregnancy and all women who experienced preeclampsia. The incidence of adverse pregnancy outcomes that were studied was higher among smokers, compared with nonsmoking pregnant women ( Table 3 ). One exception was the incidence of preeclampsia, which was reduced among smokers compared with nonsmokers (adjusted odds ratio, 0.83; 95% confidence interval, 0.74–0.94). Additionally, the incidences of adverse pregnancy outcomes that were studied were increased among women with preeclampsia, compared with nonpreeclamptic women ( Table 4 ). The incidence of venous cord pH <7.0 was similar among the smoking and preeclamptic groups, compared with the nonsmoking and nonpreeclamptic groups, respectively. The incidence of stillbirth was not increased in the preeclamptic group.
| Outcome | Smoker, n (%) | Nonsmoker, n (%) | Adjusted OR (95% CI) a |
|---|---|---|---|
| Small-for-gestational-age <3 | 1521 (4.42) | 7038 (2.58) | 1.73 (1.63–1.84) |
| Preterm birth | |||
| <37 | 3741 (10.87) | 22603 (8.27) | 1.26 (1.22–1.31) |
| <32 | 828 (2.41) | 4156 (1.52) | 1.63 (1.51–1.77) |
| Abruption | 247 (0.92) | 1007 (0.52) | 1.82 (1.57–2.11) |
| Preeclampsia | 324 (1.21) | 2888 (1.49) | 0.83 (0.74–0.94) |
| pH <7.0 | 84 (0.42) | 589 (0.43) | 1.10 (0.87–1.39) |
| Apgar <4 at 5 mins | 404 (1.18) | 2144 (0.79) | 1.47 (1.31–1.64) |
| Admission to NICU | 1600 (7.11) | 8178 (5.74) | 1.31 (1.24–1.39) |
| Stillbirth | 269 (0.78) | 1343 (0.49) | 1.58 (1.38–1.81) |
a Adjusted for maternal age, parity, and multiple gestation.
| Outcome | Preeclampsia, n (%) a | Nonpreeclampsia, n (%) a | Adjusted odds ratio (95% CI) b |
|---|---|---|---|
| Small-for-gestational-age <3rd percentile | 190 (5.59) | 6610 (2.78) | 1.62 (1.39–1.88) |
| Preterm birth, wk | |||
| <37 | 1314 (38.65) | 21,003 (8.84) | 6.16 (5.71–6.65) |
| <32 | 303 (8.91) | 4141 (1.74) | 4.06 (3.55–4.62) |
| Abruption | 33 (0.97) | 1347 (0.56) | 1.60 (1.09–2.25) |
| pH <7.0 | 16 (0.81) | 640 (0.44) | 1.67 (0.97–2.66) |
| Apgar score <4 at 5 min | 59 (1.74) | 2137 (0.90) | 1.57 (1.19–2.03) |
| Admission to neonatal intensive care unit | 428 (20.91) | 9712 (6.27) | 3.39 (3.02–3.81) |
| Stillbirth | 31 (0.91) | 1369 (0.57) | 1.39 (0.95–1.96) |
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