Bismuth oxide salicylate

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

Not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Large case-control study (respective).

Data source

Reference

Reference Type:

publication

Title:

Aspirin use during early pregnancy and the risk of congenital abnormalities: a population-based case-control study

Author:

Norgard B, Puho E, Czeizel AE et al

Year:

2005

Bibliographic source:

Am J Obstet Gynecol 182:992-993

Materials and methods

Study type:

case control study (retrospective)

Endpoint addressed:

developmental toxicity / teratogenicity

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Population based case control study (retrospective)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

O-acetyl salicylic acid

IUPAC Name:

O-acetyl salicylic acid

Constituent 2

Reference substance name:

O-acetylsalicylic acid

EC Number:

200-064-1

EC Name:

O-acetylsalicylic acid

Cas Number:

50-78-2

IUPAC Name:

2-acetoxybenzoic acid

Details on test material:

- Name of test material (as cited in study report): aspirin

Method

Type of population:

other: pregnant women

Ethical approval:

not specified

Details on study design:

HYPOTHESIS TESTED: Association of risk of certain congenital abnormalities (in particular, neural tube defects, gastroschisis, and cleft lip G palate). with maternal aspirin use during weeks 5 to 12 of gestation.

METHOD OF DATA COLLECTION
- Type: Analysis of a population-based dataset of the Hungarian Case Control Surveillance of Congenital Abnormalities (HCCSCA).

STUDY PERIOD: 1980-1996

STUDY POPULATION
- Total population: 3415 children
- Selection criteria: children with 4 selected and isolated CAs diagnosed: neural-tube defects (N = 1202), exomphalos/gastroschisis (N = 238), cleft
lip G palate (N = 1374), and posterior cleft palate (N = 601).

COMPARISON POPULATION
- Type: the control group comprised all children with CAs other than the 4 above-mentioned CA groups.
- 19428 children

HEALTH EFFECTS STUDIED
- Disease(s): Certain congenital abnormalities: neural tube defects, exomphalos/gastroschisis, cleft lip/palate

Exposure assessment:

estimated

Details on exposure:

Exposure of pregnant women to aspirin during 5 to 12 weeks of gestation.
No further information provided.

Statistical methods:

Logistic regression models to estimate the relative risk (odds ratio), with 95% CI.

Results and discussion

Results:

There were no statistically significant increases in the incidence of specific congenital abnormalities associated with maternal aspirin use in weeks 5 to 12 of pregnancy.
Cases with selected types of congenital anomaly: maternal aspirin use/total (%):
Neural tube defects: 25/1202 (2.1%)
Exomphalos/Gastroschisis: 3/238 (1.3%)
Cleft lip/palate: 28/1374 (2.0%)
Posterior cleft palate: 12/601 (2.0%)
Reference group (all other CAs): 272/19428 (4.0%)

Unadjusted odds ratio:
Neural tube defects: OR: 1.5; 95% C.I. 0.9-2.3)
Exomphalos/Gastroschisis: OR: 0.9; 95% C.I. 0.3-2.8
Cleft lip/palate: OR: 1.5; 95% C.I. 0.9-2.2
Posterior cleft palate: OR: 1.4; 95% C.I. 0.8-2.6

Odds ratio adjusted for maternal age (<25, 25-29, and >/= 30 y), parity (1 or>1), use of folic acid during the first trimester of pregnancy, nausea/vomiting or common cold/influenza (during the first trimester of pregnancy), and mothers’ underlying diseases of diabetes mellitus or epilepsy:
Neural tube defects: OR: 1.1; 95% C.I. 0.7-1.6)
Exomphalos/Gastroschisis: OR: 0.7; 95% C.I. 0.2-2.2
Cleft lip/palate: OR: 0.9; 95% C.I. 0.6-1.3
Posterior cleft palate: OR: 1.0; 95% C.I. 0.6-1.8

Confounding factors:

Mothers of children with CAs tend to recall antenatal drug exposure differently from mothers of infants without CAs. To offset this potential bias, the control group comprised all children with CAs other than the 4 above-mentioned CA groups.
No information on dose of aspirin or maternal smoking in all pregnancies.

Strengths and weaknesses:

The use of a control group of mothers of children with CAs reduces the risk of recall bias, which is a major concern in case-control studies based on self reported data. Analyses of neural-tube defects, cleft lip G palate, and posterior cleft palate were controlled for maternal age, birth order, use of folic acid, maternal diseases of nausea/vomiting, common cold/influenza, and diabetes mellitus and epilepsy. The analysis of exomphalos/gastroschisis was adjusted for the same, except for diabetes mellitus and epilepsy.
No information was available on dose of aspirin or maternal smoking in all pregnancies.

Applicant's summary and conclusion

Conclusions:

The results of this study suggest that maternal use of aspirin in early pregnancy is not associated with a statistically significant increased risk of neural-tube defects, exomphalos/gastroschisis, cleft lip G palate, or posterior cleft palate in the offspring compared with non-users of aspirin.

Executive summary:

This retrospective, case control study (Norgard et al, 2005) examined the association between maternal aspirin use during 5 to 12 weeks of gestation and specific congenital anomalies (neural-tube defects, exomphalos/gastroschisis, cleft lip G palate, or posterior cleft palate) in population-based dataset of the Hungarian Case Control Surveillance of Congenital Abnormalities (HCCSCA) from 1980 to 1996. A total of 3415 children with these specific congenital anomalies were identified from the dataset. To offset potential recall bias, the control group comprised all children with congenital anomalies other than the 4 above-mentioned congenital anomaly groups (N = 19,428). Analyses of neural-tube defects, cleft lip G palate, and posterior cleft palate were controlled for maternal age, birth order, use of folic acid, maternal diseases of nausea/vomiting, common cold/influenza, and diabetes mellitus and epilepsy. The analysis of exomphalos/gastroschisis was adjusted for the same, except for diabetes mellitus and epilepsy.

The results of this study suggest that maternal use of aspirin in early pregnancy is not associated with a statistically significant increased risk of neural-tube defects, exomphalos/gastroschisis, cleft lip G palate, or posterior cleft palate in the offspring compared with non-users of aspirin.