TY - JOUR
T1 - Phthalate exposure in the neonatal intensive care unit is associated with development of bronchopulmonary dysplasia
AU - Stroustrup, Annemarie
AU - Zhang, Xueying
AU - Spear, Emily
AU - Bandyopadhyay, Sanjukta
AU - Narasimhan, Srinivasan
AU - Meher, Anil K.
AU - Choi, Jaeun
AU - Qi, Gao
AU - Poindexter, Brenda B.
AU - Teitelbaum, Susan L.
AU - Andra, Syam S.
AU - Gennings, Chris
AU - Aschner, Judy L.
N1 - Publisher Copyright:
© 2023
PY - 2023/8
Y1 - 2023/8
N2 - Objective: Bronchopulmonary dysplasia (BPD) is a serious yet common morbidity of preterm birth. Although prior work suggests a possible role for phthalate exposure in the development of BPD, no study has rigorously evaluated this. Our objective was to determine whether hospital-based phthalate exposure is associated with the development of BPD and to identify developmental windows sensitive to exposure. Study Design: This is a prospective multicenter cohort study of 360 preterm infants born at 23–33 weeks gestation participating in the Developmental Impact of NICU Exposures (DINE) cohort. 939 urine specimens collected during the NICU stay were analyzed for biomarkers of phthalate exposure by liquid chromatography with tandem mass spectrometry. The modified Shennan definition was used to diagnose bronchopulmonary dysplasia. Reverse distributed-lag modeling identified developmental windows sensitive to specific phthalate exposure, controlling for relevant covariates including sex and respiratory support. Results: Thirty-five percent of participants were diagnosed with BPD. Exposure to specific phthalate mixtures at susceptible points in preterm infant development are associated with later diagnosis of BPD in models adjusted for use of respiratory support. The weighted influence of specific phthalate metabolites in the mixtures varied by sex. Metabolites of di(2-ethylhexyl) phthalate, a phthalate previously linked to neonatal respiratory support equipment, drove this association, particularly among female infants, at 26- to 30-weeks post-menstrual age. Conclusions: This is the largest and only multi-site study of NICU-based phthalate exposure and clinical impact yet reported. In well-constructed models accounting for infant sex and respiratory support, we found a significant positive association between ultimate diagnosis of BPD and prior exposure to phthalate mixtures with DEHP predominance at 26- to 30-weeks PMA or 34–36-weeks PMA. This information is critically important as it identifies a previously unrecognized and modifiable contributing factor to BPD.
AB - Objective: Bronchopulmonary dysplasia (BPD) is a serious yet common morbidity of preterm birth. Although prior work suggests a possible role for phthalate exposure in the development of BPD, no study has rigorously evaluated this. Our objective was to determine whether hospital-based phthalate exposure is associated with the development of BPD and to identify developmental windows sensitive to exposure. Study Design: This is a prospective multicenter cohort study of 360 preterm infants born at 23–33 weeks gestation participating in the Developmental Impact of NICU Exposures (DINE) cohort. 939 urine specimens collected during the NICU stay were analyzed for biomarkers of phthalate exposure by liquid chromatography with tandem mass spectrometry. The modified Shennan definition was used to diagnose bronchopulmonary dysplasia. Reverse distributed-lag modeling identified developmental windows sensitive to specific phthalate exposure, controlling for relevant covariates including sex and respiratory support. Results: Thirty-five percent of participants were diagnosed with BPD. Exposure to specific phthalate mixtures at susceptible points in preterm infant development are associated with later diagnosis of BPD in models adjusted for use of respiratory support. The weighted influence of specific phthalate metabolites in the mixtures varied by sex. Metabolites of di(2-ethylhexyl) phthalate, a phthalate previously linked to neonatal respiratory support equipment, drove this association, particularly among female infants, at 26- to 30-weeks post-menstrual age. Conclusions: This is the largest and only multi-site study of NICU-based phthalate exposure and clinical impact yet reported. In well-constructed models accounting for infant sex and respiratory support, we found a significant positive association between ultimate diagnosis of BPD and prior exposure to phthalate mixtures with DEHP predominance at 26- to 30-weeks PMA or 34–36-weeks PMA. This information is critically important as it identifies a previously unrecognized and modifiable contributing factor to BPD.
KW - Bronchopulmonary dysplasia
KW - Chronic lung disease of prematurity
KW - DEHP
KW - Neonatal intensive care
KW - Phthalate
KW - Preterm birth
UR - http://www.scopus.com/inward/record.url?scp=85166245074&partnerID=8YFLogxK
U2 - 10.1016/j.envint.2023.108117
DO - 10.1016/j.envint.2023.108117
M3 - Article
C2 - 37517179
AN - SCOPUS:85166245074
SN - 0160-4120
VL - 178
JO - Environment international
JF - Environment international
M1 - 108117
ER -