Objective
Using 2 nationwide population-based datasets, this study aimed to assess the risk of adverse pregnancy outcomes, including low birthweight (LBW), preterm birth, small for gestational age (SGA), cesarean section (CS), lower Apgar score, and preeclampsia/eclampsia, between women with and without pneumonia.
Study Design
This study included 1462 women who had been hospitalized with pneumonia during pregnancy and used 7310 matched women without pneumonia as a comparison group.
Results
Compared to women without pneumonia, conditional logistic regression analyses showed that the adjusted odds ratios for LBW, preterm birth, SGA, CS, Apgar scores <7 at 5 minutes, and preeclampsia/eclampsia in women with pneumonia were 1.73 (95% confidence interval [CI], 1.41–2.12), 1.71 (95% CI, 1.42–2.05), 1.35 (95% CI, 1.17–1.56), 1.77 (95% CI, 1.58–1.98), 3.86 (95% CI, 1.64–9.06), and 3.05 (95% CI, 2.01–4.63), respectively.
Conclusion
Women with pneumonia during pregnancy had significantly higher risk of LBW, preterm birth, SGA, low Apgar scores infants, CS, and preeclampsia/eclampsia, compared to unaffected women.
Pneumonia is a common infection of the pulmonary parenchyma that is a significant cause of hospitalization for respiratory disorders during pregnancy, complicating 0.5-1.5 per 1000 pregnancies in the United States. Pneumonia is the most frequent cause of fatal nonobstetric maternal death in the United States. It is widely held that several physiologic and immunologic changes experienced during pregnancy may predispose pregnant women toward a more severe course of pneumonia, which may result in greater maternal and fetal morbidity and mortality.
The relationship between pneumonia and pregnancy outcome has long been a topic of interest among researchers. A growing number of studies have found that women with pneumonia were more likely to have preterm deliveries as well as lower average birthweight and small for gestational age (SGA) infants compared to women without pneumonia. Moreover, Romanyuk et al also found that pneumonia was significantly associated with placental abruption, intrauterine growth restriction, cesarean section (CS), low Apgar scores, and severe preeclampsia.
Even though several studies have explored the risk of adverse pregnancy outcomes among women with pneumonia, their studies generated inconsistent findings that remain to be resolved. A number of studies failed to observe any increased risk of preterm and low birthweight (LBW) infants among women with pneumonia. In addition, Shariatzadeh and Marrie and Jin et al suggested that pneumonia may not have any negative effects related to fetal outcome at all, and speculated that pneumonia may be very well tolerated during pregnancy. Therefore, the relationship between pneumonia and pregnancy outcomes remains unclear to date. Since prior studies dealing with the present topic have tended to be hospital-based studies often characterized by low case numbers or population subgroups, their inconsistent finding may have been due to the use of selective data, limited sample sizes, and inadequate control of confounding factors.
To fill this gap in the literature this study aimed to examine the risk of adverse pregnancy outcomes (LBW, preterm birth, SGA, CS, congenital anomalies, Apgar scores at 5 minutes, and preeclampsia/eclampsia) in pregnant women with pneumonia using a nationwide population-based dataset in Taiwan. To the best of our knowledge, this is the largest and most complete nationwide population-based study to investigate the relationship between pneumonia and adverse pregnancy outcomes.
Materials and Methods
Database
Two nationwide population-based datasets were used in this study: The Taiwan National Health Insurance (NHI) Research Dataset (NHIRD) and the Taiwan national birth certificate registry. The NHIRD includes all the registration files as well as original claims data for reimbursements covered by the Taiwan NHI program for about 25.68 million enrollees in Taiwan. Taiwan launched the NHI program in 1995 and has since maintained >95% enrollment rate, with the coverage >98.5% since 2007. The NHIRD thus allows researchers to follow up on all the medical service utilizations of every pregnant women in Taiwan. In addition, many studies have demonstrated the high validity of the Longitudinal Health Insurance Database 2000, with hundreds of papers employing the NHIRD having been published in internationally peer-reviewed journals.
The second dataset was the Taiwan national birth certificate registry, which included data on both infant and parental birth dates, gestational week at birth, birthweight, sex, parity, place of birth, parental educational level, and maternal marital status. Since it is mandatory that all births are registered in Taiwan, birth certificate data are considered to be very accurate and comprehensive.
With the assistance of the Bureau of Health Promotion, Department of Health, Taiwan, these 2 nationwide population-based datasets were linked. Since these 2 datasets consist of de-identified secondary data, this study was waived from full review by the Institutional Review Board of Taipei Medical University.
Study sample
This cross-sectional study features a study group and a comparison group. As for the selection of the study group, we first identified 218,776 women with live singleton births between Jan. 1, 2005, and Dec. 31, 2005. If a woman experienced >1 singleton birth during the study period, we only included the first birth in the study group. We also designated this delivery as the index delivery. Thereafter, we identified 1462 women who had been hospitalized with a diagnosis of pneumonia ( International Classification of Diseases, Ninth Revision, Clinical Modification codes 480–483.8, 485–486, and 487.0) during their pregnancies from the total 218,776 women who we selected above. In Taiwan, it is standardized practice that all pregnant women with pneumonia are hospitalized.
Data on the gestational age and delivery date of each infant were also available in this study, which allowed us to calculate the period of pregnancy for each woman. In addition, we randomly retrieved 7310 comparison women (5 for every woman with pneumonia) to match the distribution of the study group in terms of age (<20, 20-24, 25-29, 30-34, and ≥35 years). As a result, 8772 women were included in this study.
Variables of interest
The selected variables for adverse pregnancy outcomes were LBW (<2500 g), preterm gestation (<37 completed weeks of gestation), SGA (birthweight <10th percentile for gestational age–specific birthweight distribution), major congenital anomalies (hydrocephaly, anencephaly, microcephaly, meningomyelocele, encephalocele, and spina bifida), Apgar scores at 5 minutes (<7), preeclampsia/eclampsia, and CS.
This study also took potential confounding factors into consideration in the regression models. These included factors consisting of maternal characteristics (highest educational level, gestational diabetes, gestational hypertension, coronary heart disease [CHD], anemia, hyperlipidemia, alcohol abuse/alcohol dependence syndrome, and obesity), infant sex and parity, and paternal age.
Statistical analysis
We performed all the analyses conducted in this study using a software package (SAS System for Windows, version 8.2; SAS Institute Inc, Cary, NC). We used χ 2 tests to explore the differences in maternal, paternal, and infant characteristics between women with and without pneumonia. We further used conditional logistic regression analyses (conditioned on maternal age) to calculate the odds of adverse pregnancy outcomes between women with and without pneumonia after adjusting for maternal, paternal, and infant characteristics. A 2-sided P value < .05 was considered statistically significant in this study.
Results
Of the 1462 women with pneumonia, 1363 (about 93%) were bacterial pneumonia. Table 1 presents the distributions of maternal, paternal, and infant characteristics between women with and without pneumonia. After matching for maternal age, we found that there was no significant difference in the distribution of infant sex, parity, maternal highest educational level, and geographic region. In addition, there was no significant difference in the prevalence of comorbidities of gestational diabetes, gestational hypertension, anemia, hyperlipidemia, alcohol abuse/alcohol dependence syndrome, and obesity between women with and without pneumonia. However, women with pneumonia were more likely to have CHD than women without pneumonia ( P = .002).
| Variable | Women with pneumonia (n = 1462) | Comparison women (n = 7310) | P value | ||
|---|---|---|---|---|---|
| No. | % | No. | % | ||
| Infant characteristics | |||||
| Sex | .068 | ||||
| Male | 788 | 53.9 | 3749 | 51.3 | |
| Female | 674 | 46.1 | 3561 | 48.7 | |
| Maternal characteristics | |||||
| Parity | .616 | ||||
| 1 | 744 | 50.9 | 3625 | 50.0 | |
| 2 | 554 | 37.9 | 2784 | 38.1 | |
| ≥3 | 164 | 11.2 | 874 | 11.9 | |
| Age, y | 1.000 | ||||
| <20 | 50 | 3.4 | 250 | 3.4 | |
| 20-24 | 352 | 24.1 | 1760 | 24.1 | |
| 25-29 | 454 | 31.1 | 2270 | 31.1 | |
| 30-34 | 427 | 29.2 | 2135 | 29.2 | |
| >34 | 179 | 12.2 | 895 | 12.2 | |
| Education level | .070 | ||||
| ≤Junior high school | 160 | 10.9 | 713 | 9.7 | |
| Senior high school | 1041 | 71.2 | 5121 | 70.1 | |
| ≥College | 261 | 17.9 | 1476 | 20.2 | |
| Alcohol abuse/alcohol dependence syndrome | 3 | 0.2 | 7 | 0.4 | .258 |
| Gestational diabetes | 48 | 3.3 | 227 | 3.1 | .722 |
| Gestational hypertension | 44 | 3.0 | 192 | 2.6 | .409 |
| Anemia | 158 | 10.8 | 723 | 9.9 | .287 |
| Coronary heart disease | 20 | 1.4 | 45 | 0.6 | .002 |
| Hyperlipidemia | 31 | 2.1 | 139 | 1.9 | .579 |
| Obesity | 9 | 0.6 | 36 | 0.5 | .548 |
| Geographic region | .604 | ||||
| North | 614 | 42.0 | 3105 | 42.5 | |
| Center | 393 | 26.9 | 1988 | 27.2 | |
| South | 412 | 28.2 | 2045 | 27.9 | |
| East | 43 | 2.9 | 172 | 2.4 | |
| Paternal age, y | .892 | ||||
| <30 | 518 | 35.4 | 2602 | 35.6 | |
| 30-34 | 466 | 31.9 | 2363 | 32.3 | |
| >34 | 478 | 31.7 | 2345 | 32.1 | |
The prevalence of adverse pregnancy outcomes is presented in Table 2 . It shows that women with pneumonia had a higher prevalence of LBW infants (9.8% vs 5.9%, P < .001), preterm births (12.3% vs 7.1%, P < .001), SGA infants (20.7% vs 16.2%, P < .001), CS (55.5% vs 40.6%, P < .001), preeclampsia/eclampsia (2.7% vs 0.8%, P < .001), and Apgar scores <7 at 5 minutes (0.7% vs 0.2%, P < .001) than women without pneumonia. There were no significant differences in the prevalence of major congenital anomalies (0.9% vs 0.7%, P = .396) between women with and without pneumonia. Moreover, the distributions of adverse pregnancy outcomes did not differ significantly for women with viral and with bacterial pneumonia (data not shown in table).
| Variable | Women with pneumonia (n = 1462) | Comparison women (n = 7310) | P value | ||
|---|---|---|---|---|---|
| No. | % | No. | % | ||
| Low birthweight | 143 | 9.8 | 430 | 5.9 | < .001 |
| Preterm birth | 180 | 12.3 | 520 | 7.1 | < .001 |
| Small for gestational age | 303 | 20.7 | 1187 | 16.2 | < .001 |
| Cesarean section | 812 | 55.5 | 2965 | 40.6 | < .001 |
| Congenital anomalies | 13 | 0.9 | 50 | 0.7 | .396 |
| Low Apgar score at 5 min | 10 | 0.7 | 12 | 0.2 | < .001 |
| Preeclampsia/eclampsia | 39 | 2.7 | 60 | 0.8 | < .001 |
Table 3 presents the crude and adjusted odds ratios (ORs) for adverse pregnancy outcomes between women with and without pneumonia. Conditional logistic regression analyses (conditioned on maternal age group) revealed that compared to women without pneumonia, the OR for LBW, preterm birth, SGA, CS, Apgar scores <7 at 5 minutes, and preeclampsia/eclampsia in women with pneumonia were 1.73 (95% confidence interval [CI], 1.41–2.12), 1.71 (95% CI, 1.42–2.05), 1.35 (95% CI, 1.17–1.56), 1.77 (95% CI, 1.58–1.98), 3.86 (95% CI, 1.64–9.06), and 3.05 (95% CI, 2.01–4.63) respectively, after adjusting for highest maternal educational level, marital status, geographic region, gestational diabetes, gestational hypertension, CHD, anemia, hyperlipidemia, obesity, and alcohol abuse/alcohol dependence syndrome, as well as infant sex and parity, and paternal age. There was no increased OR for congenital anomalies for women with pneumonia.
| Variable | Women with pneumonia vs comparison women |
|---|---|
| Low birthweight | |
| OR a (95% CI) | 1.74 c (1.43–2.12) |
| Adjusted OR b (95% CI) | 1.73 c (1.41–2.12) |
| Preterm birth | |
| OR a (95% CI) | 1.84 c (1.53–2.20) |
| Adjusted OR b (95% CI) | 1.71 c (1.42–2.05) |
| Small for gestational age | |
| OR a (95% CI) | 1.35 c (1.17–1.56) |
| Adjusted OR b (95% CI) | 1.35 c (1.17–1.56) |
| Cesarean section | |
| OR a (95% CI) | 1.83 c (1.63–2.06) |
| Adjusted OR b (95% CI) | 1.77 c (1.58–1.98) |
| Congenital anomalies | |
| OR a (95% CI) | 1.30 (0.71–2.41) |
| Adjusted OR b (95% CI) | 1.15 (0.62–2.15) |
| Low Apgar score at 5 min | |
| OR a (95% CI) | 4.19 c (1.81–9.72) |
| Adjusted OR b (95% CI) | 3.86 d (1.64–9.06) |
| Preeclampsia/eclampsia | |
| OR a (95% CI) | 3.31 c (2.20–4.98) |
| Adjusted OR b (95% CI) | 3.05 c (2.01–4.63) |
a Calculated by conditional logistic regression (conditioned on maternal age group);
b Adjustment made for mother’s education, gestational diabetes, gestational hypertension, anemia, coronary heart disease, hyperlipidemia, obesity, alcohol abuse/alcohol dependence syndrome, geographic region, paternal age, and infant’s sex, and parity;
Furthermore, we analyzed the OR for adverse pregnancy outcomes according to pregnancy trimester. We found that the onset of pneumonia in about 93.6% of the women analyzed in this study occurred during the first trimester. Table 4 shows that when compared to comparison women, the adjusted OR for LBW, preterm birth, SGA, CS, Apgar scores <7 at 5 minutes, and preeclampsia/eclampsia in women with pneumonia during the first trimester of pregnancy were 1.73, 1.70, 1.35, 1.79, 3.74, and 3.17, respectively.
