Butanedioic acid, sulfo-, monoesters with lanolin alcs., disodium salts

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

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

Adequacy of study:

key study

Study period:

From January 1, 1980 to January 30, 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data have been obtained from a publication of a study on a substance with structural similarity.

Data source

Reference

Reference Type:

publication

Title:

First-Trimester Drug Use and Congenital Disorder

Author:

Aselton P., Jick H., Milunsky A., Hunter JR., Stergachis A.,

Year:

1985

Bibliographic source:

Obstet Gynecol. 1985 Apr;65(4):451-5

Materials and methods

Study type:

clinical case study

Endpoint addressed:

developmental toxicity / teratogenicity

Principles of method if other than guideline:

Prepaid health plan with mother and enfant that used a wide variety of drugs during the first trimester of pregnancy.

Test material

Test material information

Constituent 1

Reference substance name:

Dioctyl Sodium Sulfosuccinate (Colace)

IUPAC Name:

Dioctyl Sodium Sulfosuccinate (Colace)

Method

Type of population:

other: The eligible study population included 6509 women whose pregnancies terminated in a live birth.

Subjects:

- Live-born infants whose mothers had been members of the plan for at least 280 days before delivery.
- Source: Group Health Cooperative of Puget Sound hospital
- Period of study: between January 1, 1980 and June 30, 1982
- Selection: subjects were identified from the Commission on Professional and Hospital Activities-Professional Activity Study computer file.

Route of exposure:

oral

Reason of exposure:

intentional

Details on exposure:

Fetus were considered exposed if the mother filled one or more prescriptions for the drug concerned. Exposure was considered to have occurred during the first month of pregnancy if a prescription had been filled between 365 and 250 days before delivery; the second month between 220 and 249 days before delivery; the third month between 190 and 219 days before delivery.
For infants with congenital disorders, drugs exposure was tabulated individually from the automated files.
For the population at large, the proportion exposed was determined from the computer files using the identical criteria. Multiple births were considered only
once in the denominator. Contraceptive preparations, antacids, vitamins, minerals, and topical preparations were not considered.

Examinations:

All infants with certain disorders that could, in principle, be drug induced diagnosed at or around the time of birth were identified from automated hospital discharge files. For each infant, the clinical record was abstracted and reviewed for validation of diagnosis.
Some disorders diagnosed at birth were not considered, such as benign skin conditions (ie, hemangioma), functional disorders (ie, physiologic jaundice), infectious disorders, positional disorders (ie, clubfoot), and hernia. For all disorders about which there was any question on final diagnosis, the record was reviewed by a clinical geneticist (AM), using the same exclusion criteria.
After clinical review, infants with presumptive abnormalities noted at birth, such as transient cardiac murmur, that were not confirmed at clinical follow-up examination were classified as not having a disorder. Also removed from consideration were infants who bad minor physical abnormalities that are usually familial or positional: syndactyly of the second and third toes (two infants), postaxial polydactyly (six infants), clinodactyly (three infants), minor ear anomalies (12 infants), and corona} or first-degree hypospadias (nine infants). These exclusions were made without knowledge of exposures.

Medical treatment:

Various drugs (see table 1)

Results and discussion

Results of examinations:

For Dioctyl Sodium Sulfosuccinate (Colace) n.3 infant had congenital disorder, with a prevalence of 9 per 1000 women.
There were no drugs for which the prevalence was more than twice the overall rate among nonusers for the congenital disorders studied in the population. No strong positive association with any of the drugs studied was present.

Effectivity of medical treatment:

Table 1 presents a list of drugs used by at least 200 of the pregnant women along with the number who had an infant with a congenital disorder.

Applicant's summary and conclusion

Conclusions:

No strong associations between any of the commonly used drugs and the congenital disorders studied were present.

Executive summary:

The authors determined the prevalence of certain major congenital disorders among live-born infants of 6509 mothers in a prepaid health plan for the 30-month period of January 1, 1980 through June 30, 1982 who used a wide variety of drugs during the first trimester of pregnancy. The results were similar to those obtained in this population in a prior 30-month study. No strong associations between any of the commonly used drugs and the congenital disorders studied were present.

Although the data presented on most of the drugs in this study are insufficient to rule out a modest association, they do rule out a strong association with many commonly used drugs and the generally serious congenital defects included in this evaluation.