Background
In 2011, the US national rate of smoking early in pregnancy was 11.5%. Unfortunately, our home state of Ohio had a rate twice as high at 23%. Smoking in pregnancy remains one of the most important modifiable risk factors for pregnancy complications, specifically preterm birth.
Objective
The objective of the study was to quantify the preterm birth risk to various trimester-specific smoking behaviors.
Study Design
The study was a population-based, retrospective cohort study of singleton non-anomalous live births, using Ohio birth records 2006 to 2012. Preterm birth rates were compared between non-smokers and women who smoked in the preconception period only, those who quit smoking after the 1st and 2nd trimesters, and those who smoked throughout pregnancy. Multivariate logistic regression quantified the risk of smoking with cessation at various times in pregnancy and preterm birth risk, adjusted for maternal race, education, age, Medicaid use, marital status, and parity. A stratified analysis was performed on the basis of preterm birth subtype: spontaneous preterm birth versus indicated preterm birth. We also performed an additional analysis stratifying for maternal race using the 2 largest categories of race (non-Hispanic white and non-Hispanic black).
Results
Of the 913,757 birth records analyzed, nearly 25% of the women reported some smoking behavior on the birth certificate data. Of smokers, less than half quit during pregnancy (38.8% vs 61.2% smoked throughout pregnancy). Early quitters had a similar preterm birth rate compared with non-smokers. Women who smoked through the 1st trimester only did not have a significant increase in their overall preterm birth odds ratio <37 weeks; however, it did increase the odds of extreme preterm birth <28 weeks by 20% (adjusted odds ratio, 1.20; 95% confidence interval [CI], 1.02, 1.40). Quitting late in pregnancy resulted in the highest odds ratio increase: 70% for preterm birth <37 weeks (adjusted odds ratio 1.70; CI, 1.60, 1.80), even after adjustment for the confounding influences. Quitting smoking early in pregnancy after the 1st trimester did not increase the overall risk of spontaneous or indicated preterm birth <37 weeks significantly. However, quitting after the 1st trimester was associated with a significant increase in risk of extreme spontaneous preterm birth <28 weeks, an effect not seen with indicated preterm birth <28 weeks. Delaying cessation until late in pregnancy—after the 2nd trimester—was associated with the highest risk increases, 65% increased odds of spontaneous and 78% increase in odds of indicated preterm births. The rate of preterm births to non-Hispanic black mothers was increased in all categories over those of non-Hispanic white mothers. The relative influence of smoking cessation in pregnancy was similar in black compared with white mothers. The effect modification in the regression model was analyzed and revealed no significant interaction between race and smoking patterns on preterm birth risk.
Conclusion
Smoking throughout pregnancy is associated with an increased risk of preterm birth. However, quitting early in pregnancy negates this risk. Widespread programs aimed at smoking cessation early in pregnancy could have a significant impact on reducing the rate of preterm birth nationally.
Both tobacco smoking and preterm birth are significant global health problems. Recent estimations in high-income countries suggest implementation of maternal smoking cessation along with other effective preventive approaches such as progesterone supplementation, cervical cerclage placement, decreasing non-medically indicated cesarean section and labor induction, and limiting multiple embryo transfer in assisted reproductive technology may reduce the rate of preterm birth by as much as 5% by the end of 2015. Preterm birth <37 weeks is a strong predictor of perinatal and infant mortality in the United States and also contributes to serious long-term morbidities, including neurological handicaps as well as financial burdens on families and healthcare systems.
Smoking is one of the most important modifiable risk factors for the reduction of pregnancy complications. In 2011, the prevalence of smoking early in pregnancy in Ohio was 23%, twice as high compared with the US national rate of 11.5%. This high rate has been attributed to a variety of factors; however, public health programs have been put in place to target pregnant smokers. Because of the high rate of smoking in pregnancy in our home state, we aim to quantify the influence of quitting smoking at various times in pregnancy on preterm birth risk. These data may be used to assist in smoking cessation counseling in pregnancy.
Materials and Methods
The Human Subjects Institutional Review Board of the Ohio Department of Health approved the protocol for this study and provided a de-identified set of data for analysis that included birth certificate data on 1,034,552 live births that occurred in Ohio over a 7-year period (2006–2012). This study was exempt from review by the Institutional Review Board at the University of Cincinnati, Cincinnati, Ohio. All Ohio birth records used the newest (2003) version of the national birth certificate beginning in 2006.
We performed a population-based, retrospective cohort study aimed to compare various trimester specific maternal self-reported smoking behaviors during pregnancy with preterm birth rates. The US birth certificate contains data on maternal tobacco smoking during 4 time periods: “3 months before pregnancy,” “first 3 months of pregnancy,” “second 3 months of pregnancy,” and “third trimester of pregnancy.” From this data, study subjects were categorized into 1 of 5 exposure groups, based on their smoking behaviors: “non-smokers,” “smoked preconception only” (smoked only in the 3 months prior to conception but not in any trimester), “smoked through 1st trimester” (smoked preconception and the 1st trimester but not in the 2nd or 3rd trimester), “smoked through 2nd trimester” (smoked preconception and the first 2 trimesters, but not the 3rd trimester), and “smoked throughout pregnancy” (smoked preconception and in all trimesters). Smoking ≥1 cigarette per day was considered a smoker for the purpose of this study. We performed additional sensitivity analyses defining smokers using a threshold of ≥5 cigarettes per day. Non-smokers comprised the referent group for exposure group comparisons.
Our analyses were limited to singleton, non-anomalous live births between 20 and 42 weeks of gestation with available data on maternal smoking during pregnancy. Gestational age was defined using the US Vital Statistics Birth Certificate variable gest_comb, which is the clinician’s best estimate of gestational age using a combination of the last menstrual period and earliest ultrasound measurement. The primary outcome of this study was preterm birth <37 weeks. We then stratified the outcomes into subcategories of preterm birth: extremely preterm (20–27 weeks) and preterm (28–36 weeks). Term births, 37 to 42 weeks, comprised the referent group for outcome comparisons.
We performed a stratified analysis based on preterm birth subtype: spontaneous preterm birth (SPTB) versus indicated preterm birth (IPTB). Indicated PTB included births at <37 weeks complicated by intrauterine growth restriction (IUGR), preeclampsia, eclampsia, or births that occurred <37 weeks following induction of labor as recorded in the birth certificate. IUGR was defined as birthweight less than the 10th percentile, based on a widely used US reference. Preterm births not categorized as indicated were considered spontaneous preterm births for the purposes of this study. We also performed an additional analysis stratifying for maternal race using the 2 largest categories of race (non-Hispanic white and non-Hispanic black). Additionally, we tested for effect modification and found no significant interaction between race and smoking patterns in preterm birth risk.
After exclusions of birth <20 or >42 weeks, missing gestational age, fetal anomalies, and twins or higher-order multiples, the cohort used for this analysis comprised 927,424 live births. Of the other variables that were analyzed (maternal age, race, educational attainment, and smoking habits), there was minimal missing data (<2%). Medicaid enrollment had slightly higher amounts of missing data (4%). Smoking behavior was largely reported; only 0.7% ( n = 6254) of birth records in Ohio had missing data on smoking, and 0.8% ( n = 7413) of the subjects had intermittent smoking habits that did not correspond with one of the 5 exposure categories defined for this study. Those cases were not included in this analysis.
Comparisons of dichotomous variables were performed with χ 2 tests and continuous variables were compared using ANOVA. Multivariate logistic regression quantified the odds of preterm birth among each of the smoking behavior groups compared with non-smokers (referent) after adjustment for the confounding influences of maternal race, maternal age, maternal education, marital status, Medicaid funded delivery, and parity. Covariates for the adjusted models were selected on the basis of significant differences noted among exposure groups as well as biologic plausibility. Analyses were performed using STATA 12.1 software (StataCorp, College Station, Texas). Comparisons were considered statistically significant if the P value was <.05.
Results
Of the 913,757 birth records included in this study, nearly 25% ( n = 216,491, 23.7%) of the women in our study population reported some smoking behavior on the birth certificate data. Women who smoked preconception only comprised 5.8% ( n = 53,355) of the study cohort; 2.4% ( n = 21,803) smoked through the 1st trimester, 1.0% ( n = 8797) smoked through the 2nd trimester, and 14.3% ( n = 132,536) smoked throughout pregnancy. Of women who smoked, less than half quit smoking during pregnancy ( n = 83,955; 38.8% vs 132,536 who smoked throughout pregnancy; 61.2%). Of quitters, more women quit early in pregnancy compared with quitting in the 2nd or 3rd trimester ( P < .01). Summary statistics regarding quantity of smoking among this population are reported elsewhere.
Women who smoked throughout pregnancy were more likely of non-Hispanic white race, maternal age <20 years, low educational attainment, were unmarried, and had Medicaid funded medical care. Women who smoked through the 2nd trimester had significant increases in rates of preterm birth, most notably among the following high risk groups: non-Hispanic black race (23.9%), maternal age >35 years (29.4%), and low educational attainment (21.8%); where the percentage equals the percent of preterm birth rates for the corresponding high-risk group. Women of advanced maternal age (>35 years) had nearly a 3-fold increased risk of preterm birth if they smoked through the 2nd trimester compared with non-smoking women of the same age group ( Table 1 ).
| Non-smokers n = 697,266 | Smoked preconception only n = 53,355 | Smoked through 1st trimester n = 21,803 | Smoked through 2nd trimester n = 8797 | Smoked throughout pregnancy n = 132,536 | |
|---|---|---|---|---|---|
| Demographic factors | |||||
| Maternal race | |||||
| Non-Hispanic white | 517,166 (8.7%) | 44,435 (8.8%) | 17,728 (10.4%) | 7130 (17.0%) | 114,230 (13.0%) |
| Non-Hispanic black | 120,430 (15.3%) | 6534 (14.9%) | 3123 (16.9%) | 1355 (23.9%) | 14,920 (18.6%) |
| Hispanic | 36,657 (11.7%) | 1858 (9.0%) | 753 (10.5%) | 249 (18.1%) | 2564 (13.8%) |
| Other | 21,805 (9.1%) | 471 (10.6%) | 169 (9.5%) | 48 (12.5%) | 651 (12.4%) |
| Age group, years | |||||
| <20 | 63,110 (14.1%) | 6163 (10.3%) | 3580 (11.4%) | 1524 (17.7%) | 16,883 (12.9%) |
| 20–34 | 538,815 (9.4%) | 43,783 (9.2%) | 17,068 (11.0%) | 6777 (17.3%) | 106,755 (13.3%) |
| ≥35 | 95,341 (10.7%) | 3409 (12.5%) | 1155 (17.1%) | 496 (29.4%) | 8898 (18.3%) |
| Socioeconomic factors | |||||
| Less than high school diploma | 94,378 (13.2%) | 7171 (11.3%) | 4243 (12.6%) | 2192 (21.8%) | 42,280 (15.3%) |
| Unmarried | 238,063 (13.4%) | 29,475 (10.3%) | 15,005 (11.9%) | 6533 (18.2%) | 94,084 (14.1%) |
| Medicaid | 239,827 (10.8%) | 26,265 (9.1%) | 13,141 (11.1%) | 5709 (18.1%) | 90,035 (13.8%) |
The preterm birth (PTB) rate in non-smokers among our study cohort of singleton non-anomalous births was 10%. Early quitters (smoked preconception only) had a similar PTB rate compared with non-smokers (9.6%), although statistically significant at P < .01. Women who smoked through the 1st trimester only then quit did not have a significant increase in their overall PTB risk <37 weeks (11.4%) compared with non-smokers (adjusted odds ratio [adj OR], 1.02 [0.98, 1.07]); however, it did increase the risk of extreme preterm birth <28 weeks by 20% (adj OR, 1.20 [1.02, 1.40]). Smoking through the 2nd trimester, then quitting late in pregnancy, resulted in the highest risk increase (70% for PTB <37 weeks [adj OR, 1.70; 95% CI, 1.60, 1.80]) compared with non-smokers, even after adjustment for the confounding influences of maternal race, maternal age, maternal education, Medicaid-funded medical care, marital status, and parity ( Table 2 ).
| Preterm birth | Never-smokers | Smoked Preconception only | Adj OR a (95%CI) | Quit after 1 st Trimester | Adj OR a (95%CI) | Quit after 2 nd Trimester | Adj OR a (95%CI) | Smoked throughout pregnancy | Adj OR a (95%CI) |
|---|---|---|---|---|---|---|---|---|---|
| Overall PTB <37 weeks | |||||||||
| <37 weeks, n (%) | 69,794 (10.01) | 5096 (9.55) | 0.91 (0.88, 0.94) | 2477 (11.36) | 1.02 (0.98, 1.07) | 1590 (18.07) | 1.70 (1.60, 1.80) | 18,053 (13.62) | 1.21 (1.19, 1.24) |
| Subcategories of PTB | |||||||||
| 20–27 weeks, n (%) | 4230 (0.61) | 312 (0.58) | 0.87 (0.77, 0.98) | 202 (0.93) | 1.20 (1.03, 1.40) | n/a | 870 (0.66) | 0.90 (0.83, 0.97) | |
| 28–36 weeks, n (%) | 65, 564 (9.40) | 4784 (8.97) | 0.91 (0.88, 0.94) | 2275 (10.43) | 1.01 (0.96, 1.05) | 1268 (14.41) | 1.46 (1.37, 1.55) | 17,183 (12.96) | 1.24 (1.21, 1.26) |
a Adjusted for mother’s race, mother’s education, mother’s age, Medicaid, marital status, and parity. Anomalies and multiples excluded.
After redefining smokers as those who reported using 5 cigarettes or more per day, we performed a sensitivity analysis that generated similar results. With the use of this new definition, the rate of PTB in early quitters and those who quit after the 1st trimester were nearly identical to the original analysis (9.4% and 11.5%, respectively), which did not significantly increase their PTB risk from the non-smokers (adj OR, 1.03; CI, 0.98, 1.09). Women who smoked ≥5 cigarettes per day and did not quit smoking until after the 2nd trimester had an increased risk of PTB <37 weeks of 90% (adj OR, 1.90; CI, 1.76, 2.04), again similar to our initial analysis defining smokers as ≥1 cigarette per day.
Preterm birth rates related to each smoking behavior were stratified by maternal race (non-Hispanic black race and non-Hispanic white race). The rate of PTB to non-Hispanic black mothers was increased in all categories over those of non-Hispanic white mothers. In fact, the rate of PTB in non-Hispanic black mothers was nearly double (15.3% vs 8.7%) compared with that of non-Hispanic white mothers. The relative influence of smoking cessation in pregnancy was similar in black compared with white mothers, respectively (for cessation after the 1st trimester: adj OR, 1.10 [0.99, 1.21] vs adj OR, 1.06 [1.01, 1.12]; cessation after 2nd trimester: adj OR, 1.59 [1.40, 1.82] vs adj OR, 1.81 [1.70, 1.94]; and smoked throughout pregnancy: adj OR, 1.15 [1.10, 1.21] vs adj OR, 1.28 [1.26, 1.32]) (data not shown in Table 2 ).
When stratified by preterm birth subtype, smoking had a similar influence on risk of both indicated and spontaneous preterm births. Quitting smoking early in pregnancy after the 1st trimester did not increase the overall risk of spontaneous or indicated preterm birth <37 weeks significantly, Table 3 . However, quitting after the 1st trimester was associated with a significant increase in risk of extreme spontaneous PTB <28 weeks, an effect not seen with indicated PTB <28 weeks. Delaying cessation until late in pregnancy—after the 2nd trimester—was associated with the highest risk increases (65% increased odds of spontaneous and 78% increase in odds of indicated preterm birth).
