Objective
We sought to characterize complications of pregnancy, labor, and delivery associated with maternal asthma in a contemporary US cohort.
Study Design
We studied a retrospective cohort based on electronic medical record data from 223,512 singleton deliveries from 12 clinical centers across the United States from 2002 through 2008.
Results
Women with asthma had higher odds of preeclampsia (adjusted odds ratio [aOR], 1.14; 95% confidence interval [CI], 1.06−1.22), superimposed preeclampsia (aOR, 1.34; 95% CI, 1.15−1.56), gestational diabetes (aOR, 1.11; 95% CI, 1.03−1.19), placental abruption (aOR, 1.22; 95% CI, 1.09−1.36), and placenta previa (aOR, 1.30; 95% CI, 1.08−1.56). Asthmatic women had a higher odds of preterm birth overall (aOR, 1.17; 95% CI, 1.12−1.23) and of medically indicated preterm delivery (aOR, 1.14; 95% CI, 1.01−1.29). Asthmatics were less likely to have spontaneous labor (aOR, 0.87; 95% CI, 0.84−0.90) and vaginal delivery (aOR, 0.84; 95% CI, 0.80−0.87). Risks were higher for breech presentation (aOR, 1.13; 95% CI, 1.05−1.22), hemorrhage (aOR, 1.09; 95% CI, 1.03−1.16), pulmonary embolism (aOR, 1.71; 95% CI, 1.05−2.79), and maternal intensive care unit admission (aOR, 1.34; 95% CI, 1.04−1.72).
Conclusion
Maternal asthma increased risk for nearly all outcomes studied in a general obstetric population.
Asthma is the most common chronic disease in pregnancy, complicating 4-8% of pregnancies nearly 10 years ago and the rate of asthma continues to increase. Approximately 10% of US women of reproductive age had active asthma in 2008 through 2010 and 4.2% used a bronchodilator medication at least once during the past month during 2005 through 2008. In the National Hospital Discharge Survey, the rate of asthma reported during labor and delivery nearly doubled from 1993 through 1997 and from 2001 through 2005.
A recent metaanalysis concluded that maternal asthma increased the risk of low-birthweight and small-for-gestational-age infants, preterm delivery, and preeclampsia. Other conditions, such as gestational diabetes and serious obstetric complications (eg, hemorrhage, placental abruption, and placenta previa), are not consistently associated with maternal asthma, possibly due to underlying differences in patient populations, methodologic inadequacies (particularly for early studies), and relatively small numbers of women with asthma studied. Studies generally find that outcomes are more adverse when asthma is poorly controlled or when asthma is more severe, but few studies are large enough to examine specific risks for less common complications of pregnancy, labor, and delivery. The objectives of this study were to use a large, recent cohort of women in the United States to examine specific risks for complications of pregnancy, labor, and delivery including less frequent adverse outcomes and to explore the reasons for the increased risk of preterm delivery in women with asthma.
Materials and Methods
The Consortium on Safe Labor included 12 clinical centers (with 19 hospitals) across 9 American Congress of Obstetricians and Gynecologists (ACOG) US districts. Details of the study and data collection procedures are described elsewhere. Briefly, centers provided electronic medical records and International Classification of Diseases, Ninth Revision ( ICD-9 ) discharge codes from the intrapartum admission for 228,562 pregnancies among 208,695 women from 2002 through 2008. The majority of the cohort (87%) delivered from 2005 through 2007. This analysis is restricted to singleton pregnancies (n = 223,512) among 204,180 women. Most women (n = 185,785; 83.1%) contributed only 1 pregnancy. Institutional review board approval was obtained by all participating institutions.
Most complications of pregnancy, labor, and delivery as well as the diagnosis of asthma were derived from medical record data supplemented with ICD-9 codes where available ( Table 1 ). The source of case ascertainment (medical record or ICD-9 codes) varied by site. Overall, only 10.7% of asthma cases were reported in ICD-9 discharge codes alone while the remaining cases were noted in the medical record or both sources. We examined various obstetric outcomes including gestational hypertension, preeclampsia, superimposed preeclampsia, maternal seizure (with or without mention of hypertension), gestational diabetes, chorioamnionitis, placenta previa, placental abruption, hemorrhage, pulmonary embolism, postpartum fever, premature rupture of membranes (PROM), preterm PROM (PPROM) (defined as PROM <37 gestational weeks), and breech presentation.
| Definition in current study | Collected ICD-9 codes | Definition |
|---|---|---|
| Asthma | 493-493.9 | Asthma |
| Other chronic diseases | ||
| Diabetes | 250-250.9 | Diabetes mellitus |
| 648.0 | Other current conditions in mothers classifiable elsewhere but complicating pregnancy, childbirth, or puerperium–diabetes mellitus | |
| Hypertension | 401 | Essential hypertension |
| 402 | Hypertensive heart disease | |
| 403 | Hypertensive renal disease | |
| 404 | Hypertensive heart and renal disease | |
| 405 | Secondary hypertension | |
| 642.0 | Benign essential hypertension complicating pregnancy, childbirth, and puerperium | |
| 642.1 | Hypertension secondary to renal disease complicating pregnancy childbirth and puerperium | |
| 642.2 | Other preexisting hypertension complicating pregnancy, childbirth, and puerperium | |
| Thyroid diseases | 193 | Malignant neoplasm of thyroid gland |
| 226 | Benign neoplasm of thyroid glands | |
| 240-240.9 | Simple and unspecified goiter | |
| 241-241.9 | Nontoxic nodular goiter | |
| 242-242.9 | Thyrotoxicosis with or without goiter | |
| 243 | Congenital hypothyroidism | |
| 244.0-244.9 | Acquired hypothyroidism | |
| 245-245.9 | Thyroiditis | |
| 246-246.9 | Other disorders of thyroid | |
| 648.1 | Other current conditions in mothers classifiable elsewhere but complicating pregnancy, childbirth, or puerperium–thyroid dysfunction | |
| HIV | 42 | HIV disease |
| Outcomes | ||
| Gestational diabetes | 648.8 | Other current conditions in mothers classifiable elsewhere but complicating pregnancy, childbirth, or puerperium–abnormal glucose tolerance |
| Gestational hypertension | 642.3 | Transient hypertension of pregnancy |
| Preeclampsia | 642.4 | Mild or unspecified preeclampsia |
| 642.5 | Severe preeclampsia | |
| Superimposed preeclampsia | 642.7 | Preeclampsia or eclampsia superimposed on preexisting hypertension |
| Placental abruption | 641.2 | Premature separation of placenta |
| Placenta previa | 641.0 | Placenta previa without hemorrhage |
| 641.1 | Hemorrhage from placenta previa | |
| Pulmonary embolism | 415.1 | Pulmonary embolism and infarction |
| 673 | Obstetrical pulmonary embolism | |
| Hemorrhage | 666-666.3 | Postpartum hemorrhage |
| Chorioamnionitis | 658.4 | Infection of amniotic cavity |
| 762.7 | Chorioamnionitis | |
| Preterm rupture of membranes | 658.1 | Premature rupture of membranes |
| Breech presentation | 652.2 | Breech presentation without mention of version |
| Fever | 672 | Pyrexia of unknown origin during puerperium |
Outcomes derived solely from medical records include prelabor cesarean delivery (defined as a cesarean delivery without any indication of labor and <2 vaginal examinations after admission to hospital), induction, spontaneous labor, route of delivery (vaginal or cesarean), preterm birth (<37 gestational weeks), low birthweight (<2500 g), intrauterine fetal death, maternal intensive care unit (ICU) admission, and maternal death.
Pregnancy was the unit of analysis for all statistical testing. Descriptive statistics were calculated for all study variables and significance testing was based on either linear or logistic regression using generalized estimating equations (GEE) to account for correlations between pregnancies contributed by the same woman. Odds ratios (ORs) and 95% confidence limits were calculated using logistic regression with GEE using a first-order autoregressive covariance structure. Pregnancies among women without asthma were the reference group in all analyses. All reported odds are adjusted for site and fully adjusted models included site, maternal age, race/ethnicity, marital status, prepregnancy body mass index (weight in kg/height in m 2 ), insurance status, smoking and alcohol use during pregnancy, presence of chronic disease (preexisting diabetes, chronic hypertension, thyroid disease, or human immunodeficiency virus), and parity. Women with chronic hypertension were excluded from the analyses of gestational hypertension and preeclampsia. Women with preexisting diabetes were excluded from the analyses of gestational diabetes. In the analyses of superimposed preeclampsia, women with chronic hypertension were not categorized as having a chronic disease unless they had another chronic condition. Analyses regarding labor and route of delivery were also adjusted for prior cesarean delivery.
Multiple sensitivity analyses were conducted, first to test the robustness of our findings given potential bias or error in medical record ascertainment, including restriction to women with ICD-9 -coded asthma as these women may be more likely to have active asthma (as opposed to a history); removing sites with asthma rates at the tails of the distribution (2 sites each at the high and the low end); restriction to sites with complete data; and finally, restriction to patients with no missing data. Results from these logistic regression with GEE analyses yielded similar findings, so only the full sample analysis is presented. We also ran 2 subgroup analyses: (1) restricted to nulliparas to explore the potential for residual confounding by history of preterm delivery, cesarean delivery, or other prior complications in multiparas, and (2) restricted to preterm deliveries to determine if the precursors of preterm delivery were different for women with asthma.
All statistical analyses were performed using PROC GENMOD in SAS software (version 9.2; SAS Institute Inc, Cary, NC).
Results
Maternal asthma complicated 7.6% of singleton pregnancies. Mothers with asthma were younger (26.2 vs 27.5 years, P < .0001) and more likely to be non-Hispanic black, be unmarried, and have public insurance than their counterparts without asthma ( Table 2 ). Women with asthma were more likely to be obese prior to pregnancy and more likely to have smoking (12.2% vs 6.2%, P < .0001) or alcohol use (3.1% vs 1.7%, P < .0001) during pregnancy recorded in their medical records. Pregnancies complicated by asthma had a significantly greater burden of other chronic diseases as well (8.2% vs 6.2%, P < .0001). Parity was similar among pregnancies with and without asthma but among multiparas, women with asthma had more prior cesarean deliveries (15.3% vs 14.0%, P < .0001).
| Maternal characteristics | No asthma n = 206,468 | Asthma n = 17,044 | Site-adjusted P value a |
|---|---|---|---|
| Demographic factors | |||
| Maternal age, y mean (SD) | 27.5 (6.2) | 26.6 (6.2) | < .0001 |
| Race, n (%) | |||
| Non-Hispanic white | 102,447 (49.6) | 8156 (47.9) | < .0001 |
| Non-Hispanic black | 44,840 (21.7) | 5444 (31.9) | |
| Hispanic | 36,543 (17.7) | 2288 (13.4) | |
| Asian | 8970 (4.3) | 211 (1.2) | |
| Other | 4966 (2.4) | 265 (1.6) | |
| Missing | 8702 (4.2) | 680 (4.0) | |
| Marital status, n (%) | |||
| Not married | 76,248 (36.9) | 8765 (51.4) | < .0001 |
| Married | 123,800 (60.0) | 7461 (43.8) | |
| Missing | 6420 (3.1) | 818 (4.8) | |
| Insurance, n (%) | |||
| Private | 116,084 (56.2) | 8883 (52.1) | < .0001 |
| Public | 65,097 (31.5) | 7105 (41.7) | |
| Other | 2774 (1.3) | 208 (1.2) | |
| Missing | 22,513 (10.9) | 848 (5.0) | |
| Pregnancies per woman, n (%) | |||
| 1 | 172,355 (91.2) | 14,074 (90.7) | |
| 2 | 15,878 (8.4) | 1355 (8.7) | |
| 3 | 724 (0.4) | 80 (0.5) | |
| 4 | 45 (0.02) | 5 (0.03) | |
| 5 | 1 (< .01) | 0 (0.0) | |
| Clinical factors | |||
| Prepregnancy BMI, kg/m 2 , n (%) | |||
| Underweight, <18.5 | 7517 (3.6) | 463 (2.7) | < .0001 |
| Normal weight, 18.5–<25 | 74,442 (36.1) | 4641 (27.2) | |
| Overweight, 25–<30 | 30,909 (15.0) | 2614 (15.3) | |
| Obese, 30–<35 | 14,212 (6.9) | 1530 (9.0) | |
| Severely obese, ≥35 | 10,553 (5.1) | 1605 (9.4) | |
| Unknown | 68,835 (33.3) | 6191 (36.3) | |
| Smoking during pregnancy, n (%) | 12,858 (6.2) | 2075 (12.2) | < .0001 |
| Alcohol during pregnancy, n (%) | 3559 (1.7) | 532 (3.1) | < .0001 |
| Preexisting diabetes, n (%) | 2931 (1.4) | 381 (2.2) | < .0001 |
| Chronic hypertension, n (%) | 3733 (1.8) | 480 (2.8) | < .0001 |
| Thyroid disease, n (%) | 6043 (2.9) | 568 (3.3) | .003 |
| HIV/AIDS, n (%) | 778 (0.4) | 107 (0.6) | < .0001 |
| Any chronic disease (diabetes, hypertension, thyroid, HIV), n (%) | 12,722 (6.2) | 1404 (8.2) | < .0001 |
| Parity, n (%) | |||
| Nulliparous | 82,417 (39.9) | 6824 (40.0) | .84 |
| Multiparous | 124,051 (60.1) | 10,220 (60.0) | |
| Prior cesarean section, n (%) | |||
| Nullipara | 82,417 (39.9) | 6824 (40.0) | < .0001 |
| Multipara–no | 95,123 (46.1) | 7608 (44.6) | |
| Multipara–yes | 28,928 (14.0) | 2612 (15.3) | |
a P values are based on generalized estimating equations that account for multiple pregnancies to same woman.
Analyses of the complications of pregnancy, labor, and delivery encountered by women with and without asthma ( Table 3 ) demonstrate a general pattern of increased risk for asthmatic pregnancies.
| Outcomes | No asthma n = 206,468 n (%) | Asthma n = 17,044 n (%) | Site-adjusted P value a | Site-adjusted odds ratio (95% CI) a | Fully adjusted odds ratio (95% CI) a , b |
|---|---|---|---|---|---|
| Hypertensive disorders of pregnancy | |||||
| Superimposed preeclampsia | 1680 (0.8) | 213 (1.3) | < .0001 | 1.54 (1.33–1.79) | 1.34 (1.15–1.56) |
| Eclampsia | 207 (0.1) | 33 (0.2) | .01 | 1.61 (1.10–2.36) | 1.41 (0.96–2.07) |
| Preeclampsia | 9628 (4.7) | 924 (5.4) | < .0001 | 1.24 (1.16–1.33) | 1.14 (1.06–1.22) |
| Gestational hypertension | 5523 (2.7) | 557 (3.3) | .0003 | 1.18 (1.08–1.30) | 1.08 (0.98–1.19) |
| Maternal seizure | |||||
| All maternal seizures | 176 (0.1) | 33 (0.2) | .0008 | 1.93 (1.32–2.83) | 1.79 (1.21–2.63) |
| Maternal seizure without hypertension noted | 93 (0.05) | 14 (0.09) | .19 | 1.45 (0.83–2.55) | 1.35 (0.77–2.37) |
| Maternal seizure with hypertension noted | 83 (0.05) | 19 (0.12) | .0006 | 2.51 (1.48–4.25) | 2.37 (1.40–4.02) |
| Other pregnancy complications | |||||
| Gestational diabetes | 10,420 (5.1) | 927 (5.4) | .06 | 1.07 (1.00–1.15) | 1.11 (1.03–1.19) |
| Chorioamnionitis | 6415 (3.1) | 504 (3.0) | .32 | 1.05 (0.95–1.16) | 1.06 (0.96–1.17) |
| Placenta previa | 1444 (0.7) | 141 (0.8) | .06 | 1.19 (0.99–1.42) | 1.30 (1.08–1.56) |
| Complications of labor and delivery | |||||
| Prelabor cesarean delivery | 23,688 (11.5) | 2193 (12.9) | < .0001 | 1.15 (1.10–1.21) | 1.16 (1.09–1.23) |
| Spontaneous labor | 111,523 (54.0) | 8921 (52.3) | < .0001 | 0.86 (0.84–0.89) | 0.87 (0.84–0.90) |
| Cesarean delivery after spontaneous labor | 18,835 (9.1) | 1749 (10.3) | .0003 | 1.10 (1.05–1.16) | 1.06 (1.00–1.12) |
| Induction | 71,257 (34.5) | 5930 (34.8) | < .0001 | 1.10 (1.06–1.13) | 1.10 (1.06–1.14) |
| Cesarean delivery after induction | 14,746 (7.1) | 1381 (8.1) | < .0001 | 1.22 (1.15–1.29) | 1.17 (1.10–1.24) |
| All vaginal delivery | 149,199 (72.3) | 11,721 (68.8) | < .0001 | 0.84 (0.81–0.87) | 0.84 (0.80–0.87) |
| PPROM | 4596 (2.2) | 516 (3.0) | < .0001 | 1.23 (1.12–1.36) | 1.18 (1.07–1.30) |
| PROM | 14,379 (7.0) | 1212 (7.1) | .98 | 1.00 (0.94–1.07) | 0.99 (0.93–1.05) |
| Breech presentation | 8785 (4.3) | 811 (4.8) | .01 | 1.10 (1.02–1.19) | 1.13 (1.05–1.22) |
| Placental abruption | 3242 (1.6) | 380 (2.2) | < .0001 | 1.27 (1.14–1.42) | 1.22 (1.09–1.36) |
| Maternal hemorrhage | 13,423 (6.5) | 1292 (7.6) | .001 | 1.11 (1.04–1.18) | 1.09 (1.03–1.16) |
| Maternal pulmonary embolism | 114 (0.06) | 20 (0.12) | .008 | 1.90 (1.18–3.07) | 1.71 (1.05–2.79) |
| Maternal postpartum fever | 5531 (2.7) | 532 (3.1) | .35 | 1.05 (0.95–1.15) | 0.99 (0.90–1.09) |
| Maternal ICU admission | 902 (0.6) | 73 (0.6) | .01 | 1.38 (1.08–1.76) | 1.34 (1.04–1.72) |
| Maternal death | 18 (0.01) | 1 (0.01) | .70 | Not calculated | Not calculated |
| Low birthweight, <2500 g | 16,551 (8.1) | 1815 (10.7) | < .0001 | 1.26 (1.19–1.33) | 1.16 (1.10–1.23) |
| Preterm birth, <37 wk | 23,618 (11.4) | 2526 (14.8) | < .0001 | 1.25 (1.19–1.31) | 1.17 (1.12–1.23) |
| Intrauterine fetal death | 1148 (0.6) | 110 (0.7) | .26 | 1.12 (0.92–1.38) | 1.07 (0.87–1.32) |
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