Risk Factors for Pulmonary Hypertension of the Newborn

NCT ID: NCT00005497

Last Updated: 2016-05-13

Basic Information

• Recruitment Status: COMPLETED
• Study Classification: OBSERVATIONAL
• Study Start Date: 1998-04-30
• Study Completion Date: 2004-03-31

Brief Summary

To conduct a multicenter case-control study of persistent pulmonary hypertension of the newborn (PPHN) in relation to maternal exposure to smoking and non-steroidal anti-inflammatory drugs (NSAIDs). Also, to assess other potential antenatal risk factors and collect and store buccal cell specimens for future analyses.

Detailed Description

BACKGROUND:

Persistent pulmonary hypertension of the newborn (PPHN), previously called persistent fetal circulation, is a birth defect affecting approximately 1 in 1250 liveborn term infants; even with complex and high-risk interventions, PPHN results in substantial mortality and morbidity. This defect results from the inappropriate muscularization of fetal pulmonary vessels, and experimental and human evidence consistently suggests that maternal cigarette smoking and antenatal exposure to NSAIDs, particularly aspirin or ibuprofen, may play a role in the etiology of this condition. Because these exposures are quite prevalent (e.g., ibuprofen is currently taken in the first trimester or later in pregnancy by 15 percent and 3.2 percent of women, respectively), testing these hypotheses is of considerable public health importance.

DESIGN NARRATIVE:

The multicenter study had a case-control design. There were 560 case infants with PPHN and four controls per case (2240). All controls were drawn from the birth hospitals of cases; half the controls had malformations other than PPHN, and half had normal formations. Cases and controls were identified within five months of birth at 88 birth and tertiary hospitals in the areas surrounding Boston, Philadelphia, and Toronto. Mothers of subjects were interviewed by telephone within six months of delivery; a standardized questionnaire inquired in detail about demographic factors; reproductive, medical, and pregnancy illness histories; medication use (including a detailed focus on use of over-the-counter analgesic/antipyretic medications), smoking, and nutrition. Because of emerging genetic research suggesting an effect of NSAIDs on pathways possibly related to the etiology of PPHN, buccal swabs were also collected and stored for future analyses. Exposure prevalences were compared between mothers of cases and controls and relative risks were estimated, controlling for potential confounding factors.

The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record.

Conditions

Persistent Fetal Circulation Syndrome; Lung Diseases

Eligibility Criteria

Inclusion Criteria

No eligibility criteria

• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: lead

Principal Investigators

Allen Mitchell

Role:

Boston University

References

Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med. 2000 Nov 30;343(22):1608-14. doi: 10.1056/NEJM200011303432204.

Reference Type: BACKGROUND

PMID: 11096168 (View on PubMed)

Hernandez-Diaz S, Werler MM, Louik C, Mitchell AA. Risk of gestational hypertension in relation to folic acid supplementation during pregnancy. Am J Epidemiol. 2002 Nov 1;156(9):806-12. doi: 10.1093/aje/kwf129.

Reference Type: BACKGROUND

PMID: 12396998 (View on PubMed)

Louik C, Werler MM, Mitchell AA. Erythromycin use during pregnancy in relation to pyloric stenosis. Am J Obstet Gynecol. 2002 Feb;186(2):288-90. doi: 10.1067/mob.2002.119718.

Reference Type: BACKGROUND

PMID: 11854652 (View on PubMed)

Hernan MA, Hernandez-Diaz S, Werler MM, Mitchell AA. Causal knowledge as a prerequisite for confounding evaluation: an application to birth defects epidemiology. Am J Epidemiol. 2002 Jan 15;155(2):176-84. doi: 10.1093/aje/155.2.176.

Reference Type: BACKGROUND

PMID: 11790682 (View on PubMed)

Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA. Neural tube defects in relation to use of folic acid antagonists during pregnancy. Am J Epidemiol. 2001 May 15;153(10):961-8. doi: 10.1093/aje/153.10.961.

Reference Type: BACKGROUND

PMID: 11384952 (View on PubMed)

Waller DK, Tita AT, Werler MM, Mitchell AA. Association between prepregnancy maternal body mass index and the risk of having an infant with a congenital diaphragmatic hernia. Birth Defects Res A Clin Mol Teratol. 2003 Jan;67(1):73-6. doi: 10.1002/bdra.10003.

Reference Type: BACKGROUND

PMID: 12749387 (View on PubMed)

Werler MM, Louik C, Mitchell AA. Epidemiologic analysis of maternal factors and amniotic band defects. Birth Defects Res A Clin Mol Teratol. 2003 Jan;67(1):68-72. doi: 10.1002/bdra.10001.

Reference Type: BACKGROUND

PMID: 12749386 (View on PubMed)

Hernandez-Diaz S, Hernan MA, Meyer K, Werler MM, Mitchell AA. Case-crossover and case-time-control designs in birth defects epidemiology. Am J Epidemiol. 2003 Aug 15;158(4):385-91. doi: 10.1093/aje/kwg144.

Reference Type: BACKGROUND

PMID: 12915504 (View on PubMed)

de Jong-Van den Berg LT, Hernandez-Diaz S, Werler MM, Louik C, Mitchell AA. Trends and predictors of folic acid awareness and periconceptional use in pregnant women. Am J Obstet Gynecol. 2005 Jan;192(1):121-8. doi: 10.1016/j.ajog.2004.05.085.

Reference Type: BACKGROUND

PMID: 15672013 (View on PubMed)

Hernandez-Diaz S, Wu XF, Hayes C, Werler MM, Ashok TD, Badovinac R, Kelsey KT, Mitchell AA. Methylenetetrahydrofolate reductase polymorphisms and the risk of gestational hypertension. Epidemiology. 2005 Sep;16(5):628-34. doi: 10.1097/01.ede.0000172132.13513.e0.

Reference Type: BACKGROUND

PMID: 16135938 (View on PubMed)

Other Identifiers

R01HL058763

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5015

Identifier Type: -

Identifier Source: org_study_id