Persistent pulmonary hypertension of the newborn and smoking and aspirin and nonsteroidal antiinflammatory drug consumption during pregnancy.
OBJECTIVE
Prenatal causation of persistent pulmonary hypertension of the newborn (PPHB) is suggested by a specific pattern of pulmonary vascular remodeling observed immediately after birth in some infants with fatal PPHN. The goal of this study was to determine whether PPHN is associated with fetal exposure to: (1) tobacco and marijuana smoking (ie, contributors to fetal hypoxemia), (2) consumption of aspirin and other nonsteroidal antiinflammatory drugs (ie, inhibitors of prostaglandin synthesis), and (3) cocaine use (ie, a contributor to vasospasm).


METHODS
Case-control interview study.


METHODS
Two Harvard-affiliated newborn intensive care units.


METHODS
Mothers of case infants who had PPHN or who met criteria for the referent group.


METHODS
During July 1985 through April 1989, we interviewed mothers of 103 infants with PPHN and 298 control infants. Because of potential selection bias that might result from recruiting only inborn control infants even though two-thirds of cases were outborn, separate analyses compared the 103 total and 35 inborn infants with PPHN with the 298 inborn control infants. Multivariate analyses were used to adjust for potential confounding factors, including maternal education and Medicaid health insurance (ie, two markers of socioeconomic status), other antenatal factors found to be associated with PPHN (ie, maternal urinary tract infection and diabetes mellitus), and the infant's sex.


METHODS
Self-reported use or consumption of tobacco, marijuana, cocaine, aspirin, and other nonsteroidal antiinflammatory drugs during pregnancy.


RESULTS
The adjusted odds ratios (and 95% confidence intervals) for maternal pregnancy exposures to the factors of principal interest among the total study population were: aspirin, 4.9 (1.6-15.3); and nonsteroidal antiinflammatory drugs, 6.2 (1.8-21.8); for the inborn group they were aspirin, 9.6 (2.4-39.0); and nonsteroidal antiinflammatory drugs, 17.5 (4.3-71.6). Although the association between tobacco smoking during pregnancy and PPHN was elevated in univariate analyses, with odds ratios (and 95% confidence intervals) of 2.0 (1.2-3.4) and 1.3 (0.6-3.3) for total and inborn populations, respectively, the relationship was not significant after adjustment for all other factors in the final logistic regression model. Acknowledged illicit drug use was too infrequent (3.2%) to evaluate.


CONCLUSIONS
Maternal consumption of nonsteroidal antiinflammatory drugs and aspirin during pregnancy or the reasons these drugs were ingested seem to contribute to an increased risk of PPHN.
Van Marter
L J
LJ
Department of Pediatrics, Children's Hospital, Boston, MA 02115, USA.
Leviton
A
A
Allred
E N
EN
Pagano
M
M
Sullivan
K F
KF
Cohen
A
A
Epstein
M F
MF
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D016022:Case-Control Studies; D003042:Cocaine / Q000009:adverse effects; D015986:Confounding Factors, Epidemiologic; D004522:Educational Status; D005260:Female; D005315:Fetal Diseases / Q000453:epidemiology; D006801:Humans; D000860:Hypoxia / Q000453:epidemiology; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D008385:Marijuana Smoking / Q000453:epidemiology; D008484:Medicaid; D015999:Multivariate Analysis; D010547:Persistent Fetal Circulation Syndrome / Q000453:epidemiology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology; D011297:Prenatal Exposure Delayed Effects; D011448:Prostaglandin Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D012907:Smoking / Q000453:epidemiology*; D019966:Substance-Related Disorders / Q000453:epidemiology; D014481:United States; D014666:Vasomotor System / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011448:Prostaglandin Antagonists; D003042:Cocaine; D001241:Aspirin