Hooman Mirzakhani1, Vincent J Carey1, Thomas F McElrath2, Weiliang Qiu1, Bruce W Hollis3, George T O'Connor4, Robert S Zeiger5, Leonard Bacharier6, Augusto A Litonjua7, Scott T Weiss1,8. 1. 1 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 2. 2 Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts. 3. 3 Department of Pediatrics, Medical College of South Carolina, Charleston, South Carolina. 4. 4 Pulmonary Center, Department of Medicine, Boston Medical Center, Boston University, Boston, Massachusetts. 5. 5 Department of Allergy and Research and Evaluation, Kaiser Permanente Southern California, Region, San Diego and Pasadena, California. 6. 6 Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington University, St. Louis, Missouri. 7. 7 Division of Pediatric Pulmonary Medicine, Department of Pediatrics, Golisano Children's Hospital at Strong, University of Rochester Medical Center, Rochester, New York; and. 8. 8 Partners Center for Personalized Medicine, Partners Health Care, Boston, Massachusetts.
Abstract
RATIONALE: Maternal asthma and preeclampsia have independently been reported to be associated with increased asthma incidence in children of affected mothers. Maternal asthma is also associated with increased risk of preeclampsia development. However, the joint effect of these maternal conditions on child asthma risk is unknown. OBJECTIVES: To study whether development of preeclampsia among pregnant women with asthma was associated with higher risk of childhood asthma in the VDAART (Vitamin D Antenatal Asthma Reduction Trial). METHODS: A total of 806 pregnant women and their offspring at high risk of asthma or atopy, who were followed from VDAART enrollment (10-18 wk of gestation) through the child's third birthday, were included in this cohort analysis. Preeclampsia status was determined by chart review, obstetrician diagnosis, and adjudication by a panel of obstetricians. Child asthma was the main outcome as determined by parental report of a physician diagnosis, and the risk of child asthma was also examined if accompanied by recurrent wheeze. The main risk variable of interest was a four-level ordered variable defined for each mother, with values without asthma without preeclampsia, without asthma with preeclampsia, with asthma without preeclampsia, and with asthma with preeclampsia during their pregnancy. We examined the trend of outcome proportions across these categories. To account for differences in maternal and child characteristics, we used a Weibull regression model for interval-censored data to compare the incidence of child asthma by age of 3 years across the maternal variable categories. MEASUREMENTS AND MAIN RESULTS: The incidence of asthma in 3-year-old children was 9.90% (44/445), 17.95% (7/39), 22.11% (65/294), and 32.14% (9/28) among those born to mothers without asthma and without preeclampsia, mothers without asthma with preeclampsia, mothers with asthma without preeclampsia, and mothers with asthma with preeclampsia, respectively. The incidences demonstrated an increasing trend in risk of child asthma across the maternal groups (P for trend <0.001). After accounting for potential confounders and using time to report of childhood asthma as analysis outcome, risk of asthma was greater among children born to mothers with asthma without preeclampsia, compared with mothers without asthma without preeclampsia (adjusted hazard ratio, 2.18; 95% confidence interval, 1.46-3.26). This risk was 50% greater for children born to mothers with asthma who developed preeclampsia during pregnancy (adjusted hazard ratio, 2.68; 95% confidence interval, 1.30-5.61). The trend in asthma and recurrent wheeze proportions across the maternal groups' children also indicated a higher risk for children born to mothers with asthma with preeclampsia (adjusted hazard ratio, 4.73; 95% confidence interval, 2.20-10.07; P for trend <0.001). CONCLUSIONS: Preeclampsia is associated with increased risk of early life childhood asthma in children less than 3 years old over and above that associated with maternal asthma alone. The results implicate the interplay between maternal factors as strong predictors of offspring asthma and in utero maternal-fetal immune perturbations and developmental dysregulations associated with preeclampsia.
RATIONALE: Maternal asthma and preeclampsia have independently been reported to be associated with increased asthma incidence in children of affected mothers. Maternal asthma is also associated with increased risk of preeclampsia development. However, the joint effect of these maternal conditions on child asthma risk is unknown. OBJECTIVES: To study whether development of preeclampsia among pregnant women with asthma was associated with higher risk of childhood asthma in the VDAART (Vitamin D Antenatal Asthma Reduction Trial). METHODS: A total of 806 pregnant women and their offspring at high risk of asthma or atopy, who were followed from VDAART enrollment (10-18 wk of gestation) through the child's third birthday, were included in this cohort analysis. Preeclampsia status was determined by chart review, obstetrician diagnosis, and adjudication by a panel of obstetricians. Child asthma was the main outcome as determined by parental report of a physician diagnosis, and the risk of child asthma was also examined if accompanied by recurrent wheeze. The main risk variable of interest was a four-level ordered variable defined for each mother, with values without asthma without preeclampsia, without asthma with preeclampsia, with asthma without preeclampsia, and with asthma with preeclampsia during their pregnancy. We examined the trend of outcome proportions across these categories. To account for differences in maternal and child characteristics, we used a Weibull regression model for interval-censored data to compare the incidence of child asthma by age of 3 years across the maternal variable categories. MEASUREMENTS AND MAIN RESULTS: The incidence of asthma in 3-year-old children was 9.90% (44/445), 17.95% (7/39), 22.11% (65/294), and 32.14% (9/28) among those born to mothers without asthma and without preeclampsia, mothers without asthma with preeclampsia, mothers with asthma without preeclampsia, and mothers with asthma with preeclampsia, respectively. The incidences demonstrated an increasing trend in risk of child asthma across the maternal groups (P for trend <0.001). After accounting for potential confounders and using time to report of childhood asthma as analysis outcome, risk of asthma was greater among children born to mothers with asthma without preeclampsia, compared with mothers without asthma without preeclampsia (adjusted hazard ratio, 2.18; 95% confidence interval, 1.46-3.26). This risk was 50% greater for children born to mothers with asthma who developed preeclampsia during pregnancy (adjusted hazard ratio, 2.68; 95% confidence interval, 1.30-5.61). The trend in asthma and recurrent wheeze proportions across the maternal groups' children also indicated a higher risk for children born to mothers with asthma with preeclampsia (adjusted hazard ratio, 4.73; 95% confidence interval, 2.20-10.07; P for trend <0.001). CONCLUSIONS: Preeclampsia is associated with increased risk of early life childhood asthma in children less than 3 years old over and above that associated with maternal asthma alone. The results implicate the interplay between maternal factors as strong predictors of offspring asthma and in utero maternal-fetal immune perturbations and developmental dysregulations associated with preeclampsia.
Authors: Hooman Mirzakhani; Augusto A Litonjua; Thomas F McElrath; George O'Connor; Aviva Lee-Parritz; Ronald Iverson; George Macones; Robert C Strunk; Leonard B Bacharier; Robert Zeiger; Bruce W Hollis; Diane E Handy; Amitabh Sharma; Nancy Laranjo; Vincent Carey; Weilliang Qiu; Marc Santolini; Shikang Liu; Divya Chhabra; Daniel A Enquobahrie; Michelle A Williams; Joseph Loscalzo; Scott T Weiss Journal: J Clin Invest Date: 2016-11-14 Impact factor: 14.808
Authors: M Leusink; S J H Vijverberg; L Koenderman; J A M Raaijmakers; J C de Jongste; P J Sterk; E J Duiverman; N C Onland-Moret; D S Postma; A de Boer; P I W de Bakker; G H Koppelman; A H Maitland-van der Zee Journal: Pharmacogenomics J Date: 2015-05-12 Impact factor: 3.550
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Authors: Hooman Mirzakhani; Vincent J Carey; Thomas F McElrath; Bruce W Hollis; George T O'Connor; Robert S Zeiger; Leonard Bacharier; Augusto A Litonjua; Scott T Weiss Journal: Am J Respir Crit Care Med Date: 2019-09-01 Impact factor: 21.405
Authors: Clement L Ren; James E Slaven; David M Haas; Laura S Haneline; Christina Tiller; Graham Hogg; Jeffrey Bjerregaard; Robert S Tepper Journal: Pediatr Pulmonol Date: 2022-07-14
Authors: Aishwarya P Yadama; Enrico Maiorino; Vincent J Carey; Thomas F McElrath; Augusto A Litonjua; Joseph Loscalzo; Scott T Weiss; Hooman Mirzakhani Journal: Sci Rep Date: 2020-10-12 Impact factor: 4.379