0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Article |

Effect of Chorioamnionitis on Early Childhood Asthma FREE

Darios Getahun, MD, MPH; Daniel Strickland, PhD, MSPH; Robert S. Zeiger, MD, PhD; Michael J. Fassett, MD; Wansu Chen, MS; George G. Rhoads, MD, MPH; Steven J. Jacobsen, MD, PhD
[+] Author Affiliations

Author Affiliations: Departments of Research and Evaluation (Drs Getahun, Strickland, and Jacobsen, and Ms Chen), Allergy (Dr Zeiger), and Maternal-Fetal Medicine, West Los Angeles Medical Center (Dr Fassett), Kaiser Permanente Southern California Medical Group, Pasadena, California; and the Department of Epidemiology, University of Medicine and Dentistry of New Jersey School of Public Health, Piscataway (Dr Rhoads).


Arch Pediatr Adolesc Med. 2010;164(2):187-192. doi:10.1001/archpediatrics.2009.238.
Text Size: A A A
Published online

Objective  To examine the association between chorioamnionitis and childhood asthma based on gestational age at birth and race/ethnicity.

Design  A retrospective cohort study using the Kaiser Permanente Southern California (KPSC) Matched Perinatal records.

Setting  Kaiser Permanente Southern California, Pasadena, California.

Participants  All singleton children born in KPSC hospitals between 1991 and 2007 (N = 510 216).

Main Exposure  Clinically diagnosed chorioamnionitis.

Main Outcome Measures  Physician-diagnosed asthma in children aged 8 years or younger.

Results  The incidence rates of asthma among preterm- and full term–born children of pregnancies complicated by chorioamnionitis were 100.7 and 39.6 per 1000 person-years, respectively (incidence rate ratio, 2.9; 95% confidence interval [CI], 2.6-3.3). Children aged 8 years or younger with asthma were more likely to be born to women who were aged 35 years or older, African American, had 13 or more years of education, had maternal asthma, used antibiotics, had chorioamnionitis during the pregnancy, and had a male child. Multivariable Cox regression analysis revealed that children born at 23 to 28, 29 to 33, and 34 to 36 weeks' gestation after pregnancies complicated by chorioamnionitis had a 1.23-fold (95% CI, 1.02-1.49), 1.51-fold (95% CI, 1.26-1.80), and 1.20-fold (95% CI, 1.03-1.47), respectively, increased risk of asthma compared with children of similar gestational age born after pregnancies not complicated by chorioamnionitis. A preterm pregnancy complicated by chorioamnionitis was associated with increased risk of asthma among white (hazard ratio [HR], 1.66; 95% CI, 1.32-2.07), African American (HR, 1.98; 95% CI, 1.60-2.44), and Hispanic (HR, 1.70; 95% CI, 1.45-2.00), but not Asian/Pacific Islander (HR, 1.15; 95% CI, 0.83-1.58) women.

Conclusion  Findings suggest that chorioamnionitis at preterm gestation is independently associated with increased risk of childhood asthma.

Figures in this Article

Asthma is a heterogeneous disease of the airways that is characterized by increased responsiveness of the tracheobronchial tree to a variety of stimuli and airway obstruction that is partially or completely reversible.1,2 The underlying mechanism for the increased airway reactivity is unknown; however, there is a consensus that airway inflammation plays an important role. According to the US Department of Health and Human Services, in 2006, 9.9 million (14%) children younger than 18 years have been diagnosed with asthma, of which 6.8 million (9%) had current asthma,3 making it the most common chronic childhood disease. The prevalence is about 25% higher among American Indian, Alaskan Native, and African American children than among their white counterparts.4 The high rates of emergency department visits and hospitalizations,5 learning problems, school days missed, and disruption of daily activities4 clearly attest to childhood asthma's importance as a public health problem. In 1994, the annual costs of illness related to asthma in those younger than 18 years and of work lost for caretakers were estimated to be $3.2 billion and $956.7 million, respectively.68

Chorioamnionitis, an inflammation of the maternal-fetal interface, complicates approximately 8% of pregnancies. Ascending bacterial infections at the maternal-fetal interface9,10 as well as inflammatory processes at sites remote from the female genital tract1114 are potential pathoetiologic mechanisms of the condition. Chorioamnionitis is a major cause of maternal, fetal, and neonatal morbidity such as stillbirth,15 premature rupture of membranes,16 preterm birth,1719 bronchopulmonary dysplasia,20,21 and neonatal intensive care unit admissions.22 More than half of preterm births are thought to be associated with histological chorioamnionitis.17,18,23,24

There is persuasive evidence from studies based on animal models and human subjects that there is an association between chorioamnionitis and fetal lung injuries at an earlier gestational age.2529 Elevated umbilical vein and amniotic fluid interleukin 6 (IL-6) concentrations have been found in preterm neonates who were born with histological evidence of chorioamnionitis,30 and elevated levels of IL-6, IL-8, IL-1β, and tumor necrosis factor α in the amniotic fluid of preterm delivery may predict risk of bronchopulmonary dysplasia.28,30 While these important associations indicate lasting injury to the developing lung tissue, the relationship between chorioamnionitis and childhood asthma has not been examined in detail. Furthermore, whether gestational age at birth and race/ethnicity modify the magnitude of the association remains undetermined. Therefore, we undertook this study to test the hypotheses that (1) chorioamnionitis is associated with increased risk of asthma in children younger than 8 years and (2) gestational age at birth and race/ethnicity modify the magnitude of association.

DATA SOURCE

We conducted a retrospective cohort study to examine the association between chorioamnionitis and asthma in singleton children born alive in a large health maintenance organization (Kaiser Permanente Southern California [KPSC]). The study was approved by the KPSC institutional review board.

The data for this study were derived from the 1991 through 2007 KPSC Matched Perinatal Records, which match birth certificate records for all KPSC births (Perinatal Services System) to maternal and infant hospitalizations in all KPSC hospitals, outpatient physician encounters, and pharmacy records. The Perinatal Services System records contain information on pregnancies and deliveries, maternal sociodemographic and behavioral characteristics, complications of pregnancy, labor, and delivery, and fetal and neonatal outcomes of all births in KPSC hospitals (more than 30 000 annual deliveries).

STUDY POPULATION

The cohort comprised singleton live and still births in all KPSC hospitals from 1991 through 2007 (N = 510 216). Of this group, we sequentially excluded stillbirths (n = 2023), spontaneous and induced abortions (n = 603), pregnancies delivered at fewer than 23 weeks' gestation (n = 2480), children with birth defect (n = 2676), and neonatal mortality cases (n = 956). The justification for restricting the analyses to pregnancies that lasted 23 or more weeks is to avoid errors in gestational age estimation and based on the fact that children who were born at this gestational age are less likely to survive. Furthermore, we excluded children who were born in the KPSC hospital but did not become a health plan member within 60 days of birth (19% of the total sample). This left us with a total of 397 852 singleton children born alive for analysis.

EXPOSURE AND OUTCOME VARIABLES

The exposure variable was clinically diagnosed chorioamnionitis, and the outcome variable was physician-diagnosed asthma in children younger than 8 years. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 762.7 and 658.4x were used to identify clinical diagnosis of chorioamnionitis, and ICD-9-CM code 493.x and presence of at least 2 prescriptions specific to asthma medication (β-agonists or asthma controller medications or their combination) were used to identify physician diagnosis of asthma.

Gestational age was defined as the time between the first day of the last normal menstrual period (LMP) and delivery of the fetus calculated in completed weeks of gestation. When data on last menstrual period were unavailable or when the last menstrual period–based gestational age estimate was not consistent with birthweight (<4% of records), a clinical estimate of gestational age was used as a substitute. Variables considered as potential confounders or mediators for the association between chorioamnionitis and childhood asthma included maternal race/ethnicity (grouped as non-Hispanic white, non-Hispanic African American, Hispanic, Asian/Pacific Islander, and other), maternal age (<20, 20-29, 30-34, and ≥35 years), maternal education (<12, 12, and ≥13 years of completed schooling), timing of prenatal care initiation (early or first trimester vs later/no prenatal care or second trimester), smoking during pregnancy (yes or no), antibiotic use during pregnancy (yes or no), maternal asthma (yes or no),31 and child's sex (male or female).

STATISTICAL METHODS

The distribution of maternal demographic and behavioral characteristics as well as child's characteristics were examined by the presence or absence of asthma diagnosis in children younger than 8 years. Categorical data were compared using the χ2 test. Follow-up of children started from the date of delivery and ended with an outcome (asthma diagnosis) or, when censoring occurred, on the earliest of the following dates: health plan disenrollment, eighth birthday, non–asthma-related death, or end of study (December 31, 2007). A Cox proportional hazards model was fit to examine the association between exposure to chorioamnionitis in utero and asthma at a later age after controlling for potential confounders (maternal age, race/ethnicity, education, initiation of prenatal care, smoking and antibiotic use during pregnancy, maternal asthma, and child's sex).32 Because preterm birth lies on the causal pathway between chorioamnionitis and childhood asthma, we examined the associations without adjustment for gestational age at delivery in the model. However, we examined the independent effect of chorioamnionitis on childhood asthma after stratifying the data set by gestational age categories. The categorization of gestational age into extreme (23-28 weeks), very (29-33 weeks), and moderate (34-36 weeks) preterm birth as well as birth at term (37-42 weeks) was based on an a priori decision.

The diagnosis of asthma in children younger than 3 years is challenging, as objective measurement of lung function in young children is difficult and not usually performed clinically. Including this group of children may, therefore, have affected our outcomes. Therefore, to verify whether our findings still hold, we performed a sensitivity analysis after excluding children younger than 3 years.

In all analyses, children who were not exposed to chorioamnionitis in utero served as the reference group. Because there are racial and ethnic disparities in the prevalence of childhood asthma,4 and because the incidence of chorioamnionitis among African American women is much higher than among their white counterparts,33 we repeated the analysis after stratifying the data by maternal race/ethnicity to assess whether race/ethnicity modifies the magnitude of association. Hazard ratios (HR) with 95% confidence intervals (CI) were used to quantify the associations. All analyses were performed using SAS 9.1 for Windows (SAS Institute, Cary, North Carolina).

The median follow-up times for children with and without exposure in utero to chorioamnionitis were 2.0 and 2.5 years, respectively. There was a statistically significant difference in asthma incidence rate among preterm children (60.2 per 1000 person-years) and those carried to term (40.0 per 1000 person-years), regardless of exposure status to chorioamnionitis (incidence rate ratio [IRR], 1.5; 95% CI, 1.4-1.6). However, the incidence rates of asthma in preterm children and those carried to term for pregnancies complicated by chorioamnionitis were 100.7 per 1000 person-years and 39.6 per 1000 person-years, respectively (IRR, 2.9; 95% CI, 2.6-3.3).

We present the distribution of maternal and infants characteristics among singleton children aged 8 years or younger with and without the diagnosis of asthma in Table 1. Compared with women who had a child without a history of asthma, women who had a child with a history of asthma were more likely to be African American, aged 35 years and older, have 13 years or more of formal education, and to have smoked during pregnancy. A history of chorioamnionitis, antibiotic use, and physician-diagnosed asthma during the pregnancy were more likely to occur among women whose children develop asthma later in life. There was a significant difference in the rate of asthma by gestational age at delivery.

Table Graphic Jump LocationTable 1. Distribution of Maternal and Infant Characteristics Among Children Aged 8 Years or Younger Who Had Ever Been Diagnosed With Asthmaa

Table 2 shows the association between exposure to chorioamnionitis in utero and physician-diagnosed asthma in children younger than 8 years stratified by gestational age categories at preterm and full-term gestations. After adjusting for important confounding variables, at preterm gestation, exposure to chorioamnionitis in utero was found to be associated with increased risk of asthma (HR, 1.68; 95% CI, 1.52-1.87) when compared with no exposure to chorioamnionitis. Further stratifying the analysis by gestational age categories has revealed an independent relationship between chorioamnionitis and childhood asthma. Compared with gestational age category–specific children who were not exposed to chorioamnionitis in utero, the risks of asthma were 1.23-fold (95% CI, 1.02-1.49), 1.51-fold (95% CI, 1.26-1.80), and 1.20-fold (95% CI, 1.03-1.47) among extremely (23-28 weeks), very (28-33 weeks), and moderately (34-36 weeks) preterm children who were exposed to chorioamnionitis in utero, respectively. The same analysis was repeated by maternal race/ethnicity groups. Of those born at less than 37 weeks' gestation, non-Hispanic white (HR, 1.66; 95% CI, 1.32-2.07), non-Hispanic African American (HR, 1.98; 95% CI, 1.60-2.44) and Hispanic (HR, 1.70; 95% CI, 1.45-2.00), but not Asian/Pacific Islander (HR, 1.15; 95% CI, 0.83-1.58) children aged 8 years or younger who were exposed to chorioamnionitis in utero were associated with increased risk of asthma compared with children of similar gestational age born after pregnancies not complicated by chorioamnionitis. Furthermore, compared with children of similar gestational age born after pregnancies not complicated by chorioamnionitis, the risk of childhood asthma seem to be elevated among non-Hispanic white, non-Hispanic African American, and Hispanic children born at 23 to 28, 29 to 33, and 34 to 36 weeks of gestation after pregnancies complicated by chorioamnionitis; however, for most part, these risks failed to reach statistical significance (data not shown).

Table Graphic Jump LocationTable 2. Association Between Chorioamnionitis and Childhood Asthma at Preterm and Term Gestations

One of the mechanisms through which preterm birth is presumably associated with respiratory problems in early childhood is bronchopulmonary dysplasia. Therefore, to assess whether our findings persist, we repeated the analysis after adjusting for the variables in the model. However, adjusting for the variable did not affect our results. Furthermore, we performed a sensitivity analysis after excluding children whose follow-up time was less than 3 years to evaluate whether our finding persist. Findings were virtually unchanged through these exclusions (data not shown).

Compared with children who were born between 37 and 38 weeks' gestation and who were not exposed to chorioamnionitis in utero, the risks of asthma in children who were born in all preterm subcategories and exposed to chorioamnionitis in utero were significantly higher (Figure), with a significant inverse gestational age at exposure–response relationship apparent in the magnitude of the association.

Place holder to copy figure label and caption
Figure.

Association between chorioamnionitis and asthma in children aged 8 years or younger, stratified by gestational age categories at birth. Adjustments were made for maternal age, education, smoking during pregnancy, prenatal care, maternal asthma, antibiotic use during pregnancy, and the child's sex. CI indicates confidence interval; * reference value.

Graphic Jump Location

In this large-scale cohort study, we showed that fetal exposure to chorioamnionitis combined with preterm delivery is associated with increased risk of physician-diagnosed asthma at 8 years of age or younger, and that the effects of chorioamnionitis on childhood asthma differ by race/ethnicity. Furthermore, we showed a significant inverse relationship between the gestational age at which the child was born and asthma, suggesting that early gestational exposure to chorioamnionitis may be much more detrimental to the developing lung of the fetus and/or may lead to heightened immune response following each subsequent antigen encounter and may predispose the child to asthma later in life. This effect could also be present if conservative management is planned to delay delivery in the presence of chorioamnionitis, leading to a higher bacterial load and fetal lung injury.

Although atopy plays an important role in the pathogenesis of asthma, fewer than half of childhood asthma cases are attributable to atopy.34 Other potential risk factors implicated in the association with childhood asthma include preterm birth,3537 low birth weight,3841 and cesarean delivery.42,43 Most previous studies that examined the associations between preterm birth and low birth weight and childhood asthma were in the setting of the delivery and postpartum period and, unfortunately, findings are often inconsistent regarding the direction and magnitude of associations. There are few studies, however, that specifically examine associations between the fetal environment and childhood respiratory conditions, including asthma.4447 Fetal exposure to cigarette smoke has been shown to be associated with increased risk of childhood wheezing and asthma.44,45 Nicotine readily passes across the placenta and can directly affect fetal lung development.48 In utero exposure to antibiotics, when much of the immune system develops, may also alter fetal microbial exposure and predispose the child to a higher risk of developing asthma and other atopic conditions later in life.46

The fetal lung is in constant contact with amniotic fluid. Consequently, in a pregnancy complicated by chorioamnionitis, the developing airway is exposed to microorganisms, toxic substances, and inflammation mediators released by stimulated cells at the maternal-fetal interface. Studies based on animal models clearly showed that exposure to chorioamnionitis in utero increases the risk of inflammation, injury, apoptosis, and remodeling of the fetal lung.25,26 Correspondingly, studies based on human subjects showed association between chorioamnionitis and fetal lung injury.2729,49 Elevated levels of IL-6, IL-8, IL-1β, and tumor necrosis factor α in the amniotic fluid of infants delivered preterm are associated with increased risk of bronchopulmonary dysplasia,28,30 suggesting a fetal origin of childhood respiratory disease.

Kumar et al47 showed an association between preterm birth and chorioamnionitis and increased risk of asthma. Our results and those of Kumar et al suggest that there is probably a shared effect of chorioamnionitis and preterm birth in the risk of asthma. However, because their study was limited by its small sample, they were not able to show the effect of chorioamnionitis on childhood asthma in moderately preterm infants. One important contribution of the current study is that it shows an independent association between chorioamnionitis and childhood asthma at preterm gestation. Furthermore, unlike our study, Kumar et al47 only presented data on African American children, once again owing to small sample size. Our findings indicate that, compared with the preterm children of women who did not develop chorioamnionitis during a pregnancy, preterm children of non-Hispanic white, non-Hispanic African American, and Hispanic, but not Asian/Pacific Islander women whose pregnancy was complicated by chorioamnionitis were at significantly increased risk of asthma later in life.

There are some potential limitations that need to be considered when interpreting our findings. For this study, subjects were selected through stringent exclusion criteria that resulted in a lower rate of chorioamnionitis than other studies. In this study, the diagnosis of chorioamnionitis was based on clinical examination of subjects (ICD-9-CM codes), which is less likely to be influenced by variation owing to self-reporting. However, the clinical diagnosis of chorioamnionitis is likely to miss most cases of asymptomatic chorioamnionitis. This subsequently may affect our estimates. Furthermore, subjects could have a wide range of exposure to microbials and/or inflammation mediators. Because we did not obtain data on the level of exposure to microbials and/or inflammation mediators, we could not investigate whether the level of exposure to microbial burden and/or inflammation mediators modulated the observed association between chorioamnionitis and childhood asthma. Thus, the association could be even stronger in children exposed to high levels of microbial and/or inflammation products in utero and in those whose infants mounted an exuberant inflammatory response.

Making a definite diagnosis of asthma in children younger than 3 years is challenging because respiratory tract infections are common in this age group and their symptoms closely resemble those of asthma. Furthermore, objective measurement of lung function is difficult and not usually performed clinically in those younger than 3 years. However, in the current study, limiting the analysis to children older than 3 years did not change the overall and race/ethnicity-specific results. Although there is clear evidence that both maternal and paternal history of atopy and asthma50 and maternal smoking during pregnancy51,52 are associated with increased risk of childhood asthma, the findings are inconsistent regarding the effects of paternal smoking on childhood asthma.5355 Because the data set used in this study lacks information on parental atopy and smoking, we were unable to adjust for these potential confounders. In the medical records used for this study, information on maternal smoking during pregnancy was self-reported and severely underreported, which may have influenced our estimates. However, Buka et al56 reported that there is significant agreement between self-reported smoking and serum levels of the nicotine metabolite cotinine. Although we adjusted for several potential confounding factors, the potential for residual confounding remains.

Our findings may provide clues to the role of a heretofore unrecognized component of the complex etiology of childhood asthma. This risk factor, intrauterine exposure to chorioamnionitis, is well supported by animal models,25,26 biologically plausible, and readily amenable to a variety of preventive interventions. Further research seems warranted to confirm the findings. If confirmed, they could lead to a better understanding of the pathoetiologic mechanism of the disease and its prevention.

In conclusion, the findings of this study on the association between chorioamnionitis and childhood asthma have important implications. Chorioamnionitis and preterm gestation may result in increased risk of childhood asthma, presumably in response to inflammation-mediated fetal lung injury and/or heightened immune response against subsequent encounters with pathogens.

Correspondence: Darios Getahun, MD, MPH, Department of Research and Evaluation, Kaiser Permanente Southern California Medical Group, 100 Los Robles Ave, 2nd Floor, Pasadena, CA 91101 (darios.t.getahun@kp.org).

Accepted for Publication: July 9, 2009.

Author Contributions:Study concept and design: Getahun. Acquisition of data: Getahun. Analysis and interpretation of data: Getahun, Strickland, Zeiger, Fassett, Rhoads, Chen, and Jacobsen. Drafting of the manuscript: Getahun. Critical revision of the manuscript for important intellectual content: Getahun, Strickland, Zeiger, Fassett, Chen, Rhoads, and Jacobsen. Statistical analysis: Getahun and Chen. Administrative, technical, and material support: Strickland and Zeiger. Study supervision: Getahun, Strickland, Rhoads, and Jacobsen.

Financial Disclosure: None reported.

Funding/Support: This study was supported by Kaiser Permanente Direct Community Benefit funds.

Disclaimer: The funding body did not influence the design or conduct of the study; analysis or interpretation of the data; or the preparation, review, or approval of the manuscript.

 National asthma education and prevention program expert panel report 3: guidelines for the diagnosis and management of asthma, 2007. National Heart, Lung, and Blood Institute Web site. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. Accessed June 20, 2009
Kasper  DBraunwald  EFauci  AHauser  SLongo  DJameson  JHarrison's Principles of Internal Medicine. 16th ed. New York, NY McGraw-Hill Professional2008;
Bloom  BCohen  RA Summary health statistics for US children: National Health Interview Survey, 2006. Vital Health Stat 10 2007; (234) 1- 79
PubMed
Moorman  JERudd  RAJohnson  CA  et al. Centers for Disease Control and Prevention (CDC), National surveillance for asthma: United States, 1980-2004. MMWR Surveill Summ 2007;56 (8) 1- 54
PubMed
Getahun  DDemissie  KRhoads  GG Recent trends in asthma hospitalization and mortality in the United States. J Asthma 2005;42 (5) 373- 378
PubMed
Weiss  KBSullivan  SD The health economics of asthma and rhinitis I: assessing the economic impact. J Allergy Clin Immunol 2001;107 (1) 3- 8
PubMed
Weiss  KBSullivan  SDLyttle  CS Trends in the cost of illness for asthma in the United States, 1985-1994. J Allergy Clin Immunol 2000;106 (3) 493- 499
PubMed
Department of Health and Human Services, Centers for Disease Control and Prevention, Asthma's Impact on Children and Adolescents. http://www.cdc.gov/asthma/children.htm. Accessed December 19, 2008
Krohn  MAHillier  SLNugent  RP  et al. Vaginal Infection and Prematurity Study Group, The genital flora of women with intraamniotic infection. J Infect Dis 1995;171 (6) 1475- 1480
PubMed
Abele-Horn  MScholz  MWolff  CKolben  M High-density vaginal Ureaplasma urealyticum colonization as a risk factor for chorioamnionitis and preterm delivery. Acta Obstet Gynecol Scand 2000;79 (11) 973- 978
PubMed
Offenbacher  SLieff  SBoggess  KA  et al.  Maternal periodontitis and prematurity part I: obstetric outcome of prematurity and growth restriction. Ann Periodontol 2001;6 (1) 164- 174
PubMed
Madianos  PNLieff  SMurtha  AP  et al.  Maternal periodontitis and prematurity part II: maternal infection and fetal exposure. Ann Periodontol 2001;6 (1) 175- 182
PubMed
Offenbacher  SBoggess  KAMurtha  AP  et al.  Progressive periodontal disease and risk of very preterm delivery. Obstet Gynecol 2006;107 (1) 29- 36
PubMed
Getahun  DAnanth  CVOyelese  YPeltier  MRSmulian  JCVintzileos  AM Acute and chronic respiratory diseases in pregnancy: associations with spontaneous premature rupture of membranes. J Matern Fetal Neonatal Med 2007;20 (9) 669- 675
PubMed
Getahun  DAnanth  CVKinzler  WL Risk factors for antepartum and intrapartum stillbirth: a population-based study. Am J Obstet Gynecol 2007;196 (6) 499- 507
PubMed
Tasci  YDilbaz  BUzmez Onal  B  et al.  The value of cord blood interleukin-6 levels for predicting chorioamnionitis, funisitis and neonatal infection in term premature rupture of membranes. Eur J Obstet Gynecol Reprod Biol 2006;128 (1-2) 34- 39
PubMed
Goldenberg  RLHauth  JCAndrews  WW Intrauterine infection and preterm delivery. N Engl J Med 2000;342 (20) 1500- 1507
PubMed
Gibbs  RSRomero  RHillier  SLEschenbach  DASweet  RL A review of premature birth and subclinical infection. Am J Obstet Gynecol 1992;166 (5) 1515- 1528
PubMed
Romero  RGomez  RGhezzi  F  et al.  A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition. Am J Obstet Gynecol 1998;179 (1) 186- 193
PubMed
Groneck  PGotze-Speer  BOppermann  MEiffert  HSpeer  CP Association of pulmonary inflammation and increased microvascular permeability during the development of bronchopulmonary dysplasia: a sequential analysis of inflammatory mediators in respiratory fluids of high-risk preterm neonates. Pediatrics 1994;93 (5) 712- 718
PubMed
Speer  CP Inflammation and bronchopulmonary dysplasia. Semin Neonatol 2003;8 (1) 29- 38
PubMed
Marret  SAncel  PYMarpeau  L  et al. Epipage Study Group, Neonatal and 5-year outcomes after birth at 30-34 weeks of gestation. Obstet Gynecol 2007;110 (1) 72- 80
PubMed
Garland  SMNi Chuileannain  FSatzke  CRobins-Browne  R Mechanisms, organisms and markers of infection in pregnancy. J Reprod Immunol 2002;57 (1-2) 169- 183
PubMed
Goldenberg  RLRouse  DJ Prevention of premature birth. N Engl J Med 1998;339 (5) 313- 320
PubMed
Kramer  BWKramer  SIkegami  MJobe  AH Injury, inflammation, and remodeling in fetal sheep lung after intra-amniotic endotoxin. Am J Physiol Lung Cell Mol Physiol 2002;283 (2) L452- L459
PubMed
Coalson  JJWinter  VTSiler-Khodr  TYoder  BA Neonatal chronic lung disease in extremely immature baboons. Am J Respir Crit Care Med 1999;160 (4) 1333- 1346
PubMed
Watterberg  KLDemers  LMScott  SMMurphy  S Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics 1996;97 (2) 210- 215
PubMed
Yoon  BHRomero  RKim  KS  et al.  A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia. Am J Obstet Gynecol 1999;181 (4) 773- 779
PubMed
Fujimura  MKitajima  HNakayama  M Increased leukocyte elastase of the tracheal aspirate at birth and neonatal pulmonary emphysema. Pediatrics 1993;92 (4) 564- 569
PubMed
Goepfert  ARAndrews  WWCarlo  W  et al.  Umbilical cord plasma interleukin-6 concentrations in preterm infants and risk of neonatal morbidity. Am J Obstet Gynecol 2004;191 (4) 1375- 1381
PubMed
Schatz  MZeiger  RSHoffman  CPSaunders  BSHarden  KMForsythe  AB Increased transient tachypnea of the newborn in infants of asthmatic mothers. Am J Dis Child 1991;145 (2) 156- 158
PubMed
Kleinbaum  DGSurvival Analysis: a Self-learning Text. New York, NY Springer-Verlag1996;
Holzman  CLin  XSenagore  PChung  H Histologic chorioamnionitis and preterm delivery. Am J Epidemiol 2007;166 (7) 786- 794
PubMed
Pearce  NPekkanen  JBeasley  R How much asthma is really attributable to atopy? Thorax 1999;54 (3) 268- 272
PubMed
Gessner  BDChimonas  MA Asthma is associated with preterm birth but not with small for gestational age status among a population-based cohort of Medicaid-enrolled children <10 years of age. Thorax 2007;62 (3) 231- 236
PubMed
Dombkowski  KJLeung  SWGurney  JG Prematurity as a predictor of childhood asthma among low-income children. Ann Epidemiol 2008;18 (4) 290- 297
PubMed
Steffensen  FHSorensen  HTGillman  MW  et al.  Low birth weight and preterm delivery as risk factors for asthma and atopic dermatitis in young adult males. Epidemiology 2000;11 (2) 185- 188
PubMed
Nepomnyaschy  LReichman  NE Low birthweight and asthma among young urban children. Am J Public Health 2006;96 (9) 1604- 1610
PubMed
Darlow  BAHorwood  LJMogridge  N Very low birthweight and asthma by age seven years in a national cohort. Pediatr Pulmonol 2000;30 (4) 291- 296
PubMed
Matthes  JWLewis  PADavies  DPBethel  JA Birth weight at term and lung function in adolescence: no evidence for a programmed effect. Arch Dis Child 1995;73 (3) 231- 234
PubMed
Taveras  EMCamargo  CA  JrRifas-Shiman  SL  et al.  Association of birth weight with asthma-related outcomes at age 2 years. Pediatr Pulmonol 2006;41 (7) 643- 648
PubMed
Gerten  KACoonrod  DVBay  RCChambliss  LR Cesarean delivery and respiratory distress syndrome: does labor make a difference? Am J Obstet Gynecol 2005;193 (3 pt 2) 1061- 1064
PubMed
Debley  JSSmith  JMRedding  GJCritchlow  CW Childhood asthma hospitalization risk after cesarean delivery in former term and premature infants. Ann Allergy Asthma Immunol 2005;94 (2) 228- 233
PubMed
Jaakkola  JJGissler  M Maternal smoking in pregnancy, fetal development, and childhood asthma. Am J Public Health 2004;94 (1) 136- 140
PubMed
Gilliland  FDBerhane  K McConnell  R  et al.  Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function. Thorax 2000;55 (4) 271- 276
PubMed
McKeever  TMLewis  SASmith  CHubbard  R The importance of prenatal exposures on the development of allergic disease: a birth cohort study using the West Midlands General Practice Database. Am J Respir Crit Care Med 2002;166 (6) 827- 832
PubMed
Kumar  RYu  YStory  RE  et al.  Prematurity, chorioamnionitis, and the development of recurrent wheezing: a prospective birth cohort study. J Allergy Clin Immunol 2008;121 (4) 878- 884, e6
PubMed
Rehan  VKWang  YSugano  S  et al.  In utero nicotine exposure alters fetal rat lung alveolar type II cell proliferation, differentiation, and metabolism [corrected in Am J Physiol Lung Cell Mol Physiol. 2007;293(3):L820]. Am J Physiol Lung Cell Mol Physiol 2007;292 (1) L323- L333
PubMed
Burri  PH Structural aspects of prenatal and postnatal development and growth of the lung. McDonald  JALung Growth and Development. New York, NY Marcel Dekker Inc1997;1- 35
Litonjua  AACarey  VJBurge  HAWeiss  STGold  DR Parental history and the risk for childhood asthma: does mother confer more risk than father? Am J Respir Crit Care Med 1998;158 (1) 176- 181
PubMed
Gilliland  FDLi  YFPeters  JM Effects of maternal smoking during pregnancy and environmental tobacco smoke on asthma and wheezing in children. Am J Respir Crit Care Med 2001;163 (2) 429- 436
PubMed
Weitzman  MGortmaker  SWalker  DKSobol  A Maternal smoking and childhood asthma. Pediatrics 1990;85 (4) 505- 511
PubMed
Strachan  DPCook  DG Health effects of passive smoking 6: parental smoking and childhood asthma: longitudinal and case-control studies. Thorax 1998;53 (3) 204- 212
PubMed
Kay  JMortimer  MJJaron  AG Do both paternal and maternal smoking influence the prevalence of childhood asthma? a study into the prevalence of asthma in children and the effects of parental smoking. J Asthma 1995;32 (1) 47- 55
PubMed
Gortmaker  SLWalker  DKJacobs  FHRuch-Ross  H Parental smoking and the risk of childhood asthma. Am J Public Health 1982;72 (6) 574- 579
PubMed
Buka  SLShenassa  EDNiaura  R Elevated risk of tobacco dependence among offspring of mothers who smoked during pregnancy: a 30-year prospective study. Am J Psychiatry 2003;160 (11) 1978- 1984
PubMed

Figures

Place holder to copy figure label and caption
Figure.

Association between chorioamnionitis and asthma in children aged 8 years or younger, stratified by gestational age categories at birth. Adjustments were made for maternal age, education, smoking during pregnancy, prenatal care, maternal asthma, antibiotic use during pregnancy, and the child's sex. CI indicates confidence interval; * reference value.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Distribution of Maternal and Infant Characteristics Among Children Aged 8 Years or Younger Who Had Ever Been Diagnosed With Asthmaa
Table Graphic Jump LocationTable 2. Association Between Chorioamnionitis and Childhood Asthma at Preterm and Term Gestations

References

 National asthma education and prevention program expert panel report 3: guidelines for the diagnosis and management of asthma, 2007. National Heart, Lung, and Blood Institute Web site. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. Accessed June 20, 2009
Kasper  DBraunwald  EFauci  AHauser  SLongo  DJameson  JHarrison's Principles of Internal Medicine. 16th ed. New York, NY McGraw-Hill Professional2008;
Bloom  BCohen  RA Summary health statistics for US children: National Health Interview Survey, 2006. Vital Health Stat 10 2007; (234) 1- 79
PubMed
Moorman  JERudd  RAJohnson  CA  et al. Centers for Disease Control and Prevention (CDC), National surveillance for asthma: United States, 1980-2004. MMWR Surveill Summ 2007;56 (8) 1- 54
PubMed
Getahun  DDemissie  KRhoads  GG Recent trends in asthma hospitalization and mortality in the United States. J Asthma 2005;42 (5) 373- 378
PubMed
Weiss  KBSullivan  SD The health economics of asthma and rhinitis I: assessing the economic impact. J Allergy Clin Immunol 2001;107 (1) 3- 8
PubMed
Weiss  KBSullivan  SDLyttle  CS Trends in the cost of illness for asthma in the United States, 1985-1994. J Allergy Clin Immunol 2000;106 (3) 493- 499
PubMed
Department of Health and Human Services, Centers for Disease Control and Prevention, Asthma's Impact on Children and Adolescents. http://www.cdc.gov/asthma/children.htm. Accessed December 19, 2008
Krohn  MAHillier  SLNugent  RP  et al. Vaginal Infection and Prematurity Study Group, The genital flora of women with intraamniotic infection. J Infect Dis 1995;171 (6) 1475- 1480
PubMed
Abele-Horn  MScholz  MWolff  CKolben  M High-density vaginal Ureaplasma urealyticum colonization as a risk factor for chorioamnionitis and preterm delivery. Acta Obstet Gynecol Scand 2000;79 (11) 973- 978
PubMed
Offenbacher  SLieff  SBoggess  KA  et al.  Maternal periodontitis and prematurity part I: obstetric outcome of prematurity and growth restriction. Ann Periodontol 2001;6 (1) 164- 174
PubMed
Madianos  PNLieff  SMurtha  AP  et al.  Maternal periodontitis and prematurity part II: maternal infection and fetal exposure. Ann Periodontol 2001;6 (1) 175- 182
PubMed
Offenbacher  SBoggess  KAMurtha  AP  et al.  Progressive periodontal disease and risk of very preterm delivery. Obstet Gynecol 2006;107 (1) 29- 36
PubMed
Getahun  DAnanth  CVOyelese  YPeltier  MRSmulian  JCVintzileos  AM Acute and chronic respiratory diseases in pregnancy: associations with spontaneous premature rupture of membranes. J Matern Fetal Neonatal Med 2007;20 (9) 669- 675
PubMed
Getahun  DAnanth  CVKinzler  WL Risk factors for antepartum and intrapartum stillbirth: a population-based study. Am J Obstet Gynecol 2007;196 (6) 499- 507
PubMed
Tasci  YDilbaz  BUzmez Onal  B  et al.  The value of cord blood interleukin-6 levels for predicting chorioamnionitis, funisitis and neonatal infection in term premature rupture of membranes. Eur J Obstet Gynecol Reprod Biol 2006;128 (1-2) 34- 39
PubMed
Goldenberg  RLHauth  JCAndrews  WW Intrauterine infection and preterm delivery. N Engl J Med 2000;342 (20) 1500- 1507
PubMed
Gibbs  RSRomero  RHillier  SLEschenbach  DASweet  RL A review of premature birth and subclinical infection. Am J Obstet Gynecol 1992;166 (5) 1515- 1528
PubMed
Romero  RGomez  RGhezzi  F  et al.  A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition. Am J Obstet Gynecol 1998;179 (1) 186- 193
PubMed
Groneck  PGotze-Speer  BOppermann  MEiffert  HSpeer  CP Association of pulmonary inflammation and increased microvascular permeability during the development of bronchopulmonary dysplasia: a sequential analysis of inflammatory mediators in respiratory fluids of high-risk preterm neonates. Pediatrics 1994;93 (5) 712- 718
PubMed
Speer  CP Inflammation and bronchopulmonary dysplasia. Semin Neonatol 2003;8 (1) 29- 38
PubMed
Marret  SAncel  PYMarpeau  L  et al. Epipage Study Group, Neonatal and 5-year outcomes after birth at 30-34 weeks of gestation. Obstet Gynecol 2007;110 (1) 72- 80
PubMed
Garland  SMNi Chuileannain  FSatzke  CRobins-Browne  R Mechanisms, organisms and markers of infection in pregnancy. J Reprod Immunol 2002;57 (1-2) 169- 183
PubMed
Goldenberg  RLRouse  DJ Prevention of premature birth. N Engl J Med 1998;339 (5) 313- 320
PubMed
Kramer  BWKramer  SIkegami  MJobe  AH Injury, inflammation, and remodeling in fetal sheep lung after intra-amniotic endotoxin. Am J Physiol Lung Cell Mol Physiol 2002;283 (2) L452- L459
PubMed
Coalson  JJWinter  VTSiler-Khodr  TYoder  BA Neonatal chronic lung disease in extremely immature baboons. Am J Respir Crit Care Med 1999;160 (4) 1333- 1346
PubMed
Watterberg  KLDemers  LMScott  SMMurphy  S Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops. Pediatrics 1996;97 (2) 210- 215
PubMed
Yoon  BHRomero  RKim  KS  et al.  A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia. Am J Obstet Gynecol 1999;181 (4) 773- 779
PubMed
Fujimura  MKitajima  HNakayama  M Increased leukocyte elastase of the tracheal aspirate at birth and neonatal pulmonary emphysema. Pediatrics 1993;92 (4) 564- 569
PubMed
Goepfert  ARAndrews  WWCarlo  W  et al.  Umbilical cord plasma interleukin-6 concentrations in preterm infants and risk of neonatal morbidity. Am J Obstet Gynecol 2004;191 (4) 1375- 1381
PubMed
Schatz  MZeiger  RSHoffman  CPSaunders  BSHarden  KMForsythe  AB Increased transient tachypnea of the newborn in infants of asthmatic mothers. Am J Dis Child 1991;145 (2) 156- 158
PubMed
Kleinbaum  DGSurvival Analysis: a Self-learning Text. New York, NY Springer-Verlag1996;
Holzman  CLin  XSenagore  PChung  H Histologic chorioamnionitis and preterm delivery. Am J Epidemiol 2007;166 (7) 786- 794
PubMed
Pearce  NPekkanen  JBeasley  R How much asthma is really attributable to atopy? Thorax 1999;54 (3) 268- 272
PubMed
Gessner  BDChimonas  MA Asthma is associated with preterm birth but not with small for gestational age status among a population-based cohort of Medicaid-enrolled children <10 years of age. Thorax 2007;62 (3) 231- 236
PubMed
Dombkowski  KJLeung  SWGurney  JG Prematurity as a predictor of childhood asthma among low-income children. Ann Epidemiol 2008;18 (4) 290- 297
PubMed
Steffensen  FHSorensen  HTGillman  MW  et al.  Low birth weight and preterm delivery as risk factors for asthma and atopic dermatitis in young adult males. Epidemiology 2000;11 (2) 185- 188
PubMed
Nepomnyaschy  LReichman  NE Low birthweight and asthma among young urban children. Am J Public Health 2006;96 (9) 1604- 1610
PubMed
Darlow  BAHorwood  LJMogridge  N Very low birthweight and asthma by age seven years in a national cohort. Pediatr Pulmonol 2000;30 (4) 291- 296
PubMed
Matthes  JWLewis  PADavies  DPBethel  JA Birth weight at term and lung function in adolescence: no evidence for a programmed effect. Arch Dis Child 1995;73 (3) 231- 234
PubMed
Taveras  EMCamargo  CA  JrRifas-Shiman  SL  et al.  Association of birth weight with asthma-related outcomes at age 2 years. Pediatr Pulmonol 2006;41 (7) 643- 648
PubMed
Gerten  KACoonrod  DVBay  RCChambliss  LR Cesarean delivery and respiratory distress syndrome: does labor make a difference? Am J Obstet Gynecol 2005;193 (3 pt 2) 1061- 1064
PubMed
Debley  JSSmith  JMRedding  GJCritchlow  CW Childhood asthma hospitalization risk after cesarean delivery in former term and premature infants. Ann Allergy Asthma Immunol 2005;94 (2) 228- 233
PubMed
Jaakkola  JJGissler  M Maternal smoking in pregnancy, fetal development, and childhood asthma. Am J Public Health 2004;94 (1) 136- 140
PubMed
Gilliland  FDBerhane  K McConnell  R  et al.  Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function. Thorax 2000;55 (4) 271- 276
PubMed
McKeever  TMLewis  SASmith  CHubbard  R The importance of prenatal exposures on the development of allergic disease: a birth cohort study using the West Midlands General Practice Database. Am J Respir Crit Care Med 2002;166 (6) 827- 832
PubMed
Kumar  RYu  YStory  RE  et al.  Prematurity, chorioamnionitis, and the development of recurrent wheezing: a prospective birth cohort study. J Allergy Clin Immunol 2008;121 (4) 878- 884, e6
PubMed
Rehan  VKWang  YSugano  S  et al.  In utero nicotine exposure alters fetal rat lung alveolar type II cell proliferation, differentiation, and metabolism [corrected in Am J Physiol Lung Cell Mol Physiol. 2007;293(3):L820]. Am J Physiol Lung Cell Mol Physiol 2007;292 (1) L323- L333
PubMed
Burri  PH Structural aspects of prenatal and postnatal development and growth of the lung. McDonald  JALung Growth and Development. New York, NY Marcel Dekker Inc1997;1- 35
Litonjua  AACarey  VJBurge  HAWeiss  STGold  DR Parental history and the risk for childhood asthma: does mother confer more risk than father? Am J Respir Crit Care Med 1998;158 (1) 176- 181
PubMed
Gilliland  FDLi  YFPeters  JM Effects of maternal smoking during pregnancy and environmental tobacco smoke on asthma and wheezing in children. Am J Respir Crit Care Med 2001;163 (2) 429- 436
PubMed
Weitzman  MGortmaker  SWalker  DKSobol  A Maternal smoking and childhood asthma. Pediatrics 1990;85 (4) 505- 511
PubMed
Strachan  DPCook  DG Health effects of passive smoking 6: parental smoking and childhood asthma: longitudinal and case-control studies. Thorax 1998;53 (3) 204- 212
PubMed
Kay  JMortimer  MJJaron  AG Do both paternal and maternal smoking influence the prevalence of childhood asthma? a study into the prevalence of asthma in children and the effects of parental smoking. J Asthma 1995;32 (1) 47- 55
PubMed
Gortmaker  SLWalker  DKJacobs  FHRuch-Ross  H Parental smoking and the risk of childhood asthma. Am J Public Health 1982;72 (6) 574- 579
PubMed
Buka  SLShenassa  EDNiaura  R Elevated risk of tobacco dependence among offspring of mothers who smoked during pregnancy: a 30-year prospective study. Am J Psychiatry 2003;160 (11) 1978- 1984
PubMed

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics