Reaction mass of sodium (methylbutyl and pentyl) sulfonate and sodium 1,2-bis(pentyloxycarbonyl)ethanesulphonate

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

January 1, 1980 to June 30, 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

publication

Title:

First-Trimester Drug Use and Congenital Disorders

Author:

Aselton P. , Jick H., Milunsky A, Hunter J.R., and Stergachis A

Year:

1985

Bibliographic source:

Obstet Gynecol 65:451, 1985

Reference 2

Reference Type:

review article or handbook

Title:

Toxicity profile Dioctyl Sodium Sulphosuccinate

Author:

Bibra Information Department, Woodmansterne Road Carshalton Surrey SM5 4DS Great Britain

Year:

1989

Reference 3

Reference Type:

review article or handbook

Title:

Treating constipation during pregnancy

Author:

Trottier M, Erebara A, Bozzo P

Year:

2012

Bibliographic source:

Can Fam Physician. 2012 Aug;58(8):836-8.

Materials and methods

Study type:

human medical data

Endpoint addressed:

developmental toxicity / teratogenicity

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Docusate sodium

EC Number:

209-406-4

EC Name:

Docusate sodium

Cas Number:

577-11-7

Molecular formula:

C20H38O7S.Na

IUPAC Name:

sodium 1,4-bis[(2-ethylhexyl)oxy]-1,4-dioxobutane-2-sulfonate

Specific details on test material used for the study:

OTHER SPECIFICS:
- other information: Colace (Dioctyl sodium sulfosuccinate: Trade name of drug )

Method

Type of population:

other: live-born infants of 6509 mothers in a prepaid health plan for the 30-month period of January 1, 1980 through June 30, 1982

Details on study design:

Group Health Cooperative of Puget Sound is a consumer-owned health care cooperative in Seattle. The plan provides comprehensive prepaid medical coverage for outpatient care, drugs, and hospital services. The vast majority of drugs are provided free of charge or at a reduced cost, and with few exceptions, members are hospitalized at Seattle-area hospitals maintained by the Group Health Cooperative. Previous studies of this population indicate that approximately 98% of the membership routinely use Group Health Cooperative pharmacies to fill their prescriptions. All discharge information from hospitals maintained by the Cooperative is recorded and put on computer files by the Commission on Professional and Hospital Activities - Professional Activity Study in Ann Arbor, MI. At the Boston Collaborative Drug Surveillance Program, these files, with coded identification numbers, are merged with automated pharmacy records from Seattle, giving demographic, outpatient drug, and hospitalization information. (Patient identification numbers are scrambled in Seattle and all names blocked out in records to ensure confidentiality.)
The study included all live-born infants whose mothers had been members of the plan for at least 280 days before delivery. Eligible infants and mothers discharged from a Group Health Cooperative of Puget Sound hospital between January 1, 1980 and June 30, 1982 were identified from the Commission on Professional and Hospital Activities - Professional Activity Study computer file. 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 had minor physical abnormalities that are usually familial or positional: syndactyly of the second and third toes (two infants), postaxial polydactyly (six infants), clinodactyiy (three infants), minor ear anomalies (12 infants), and coronal or first-degree hypospadias (nine infants). These exclusions were made without knowledge of exposures.
To estimate drug use by month of gestation, each pregnancy was assumed to be of 280 days' duration, except in pregnancies where the infant was diagnosed as being premature, in which case the pregnancy was considered to be of 250 days' duration. A fetus was 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; and the third month between 190 and 219 days before delivery.
For infants with congenital disorders, drug 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.

Results and discussion

Results:

The eligible study population included 6509 women whose pregnancies terminated in a live birth. Of these, there were 105 (1.6%) who delivered an infant with one of the congenital disorders studied. In 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, there were no drugs for which the prevalence was more than twice the overall rate among nonusers for the congenital disorders studied in this population.
From 319 females who received Dioctyl sodium (Colace) during the 1st trimester of pregnancy, 3 gave birth to infants with congenital disorders which is a prevalence of 9 per 1000 women
It should be kept in mind that the authors' rates for certain disorders may be somewhat lower than those reported by others (5,6) because the authors' examined only live births, not spontaneous or induced abortions or stillbirths. The overall rates are lower than those often reported because many minor disorders were excluded, such as clubfoot and hernia, which are often included in other studies. (7,8) Also, fetuses with certain disorders such as chromosomal abnormalities and neural tube defects are being detected before birth by amniocentesis and being aborted. As only live births were included, the incidence rates for these disorders may be somewhat lower than expectations based on rates derived in previous years.
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.

5. Milis JL, Harley EE, Reed GF, et al: Are spermicides teratogenic? JAMA 248:2148, 1982
6. Heinonen OP, Slone D, Shapiro S: Birth Defects and Drugs in Pregnancy. Littleton, MA, Publishing Sciences Group, 1977
7. Cordero JF, Oakley GP, Greenberg F, et al: Is Bendectin a teratogen? JAMA 245:2307, 1981
8. Shapiro S, Heinonen O, Siskind V, et al: Antenatal exposure to doxylamine succinate and dicyclomine hydrochloride (Bendectin) in relation to congenital malformations, perinatal mortality rate, birthweight, and intelligence quotient score. Am J Obstet Gynecol 128:480, 1977

Any other information on results incl. tables

Table 1. Drugs Prescribed During the First Trimester of Pregnancy to at Least 200 of 6509 Women Having Live Births Studied*

Drug	No. of recipients	No. with infant who had congenital disorder	Prevalence per 1000 women
Dioclyl sodium sulfosuccinate (Colace)	319	3	9

* Contraceptive preparations, antacids, and topical preparations not included. The overall rate of congenital disorders in the entire group is 105 out of 6509 or 16 per 1000 women.

Applicant's summary and conclusion

Conclusions:

From 319 females who received Dioctyl sodium (Colace) during the 1st trimester of pregnancy, 3 gave birth to infants with congenital disorders which is a prevalence of 9 per 1000 women. Contraceptive preparations, antacids, and topical preparations were not included. 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.

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.

From 319 females who received Dioctyl sodium (Colace) during the 1st trimester of pregnancy, 3 gave birth to infants with congenital disorders which is a prevalence of 9 per 1000 women. Contraceptive preparations, antacids, and topical preparations were not included.

It should be kept in mind that the authors' rates for certain disorders may be somewhat lower than those reported by others^5,6 because the authors' examined only live births, not spontaneous or induced abortions or stillbirths. The overall rates are lower than those often reported because many minor disorders were excluded, such as clubfoot and hernia, which are often included in other studies.^7,8 Also, fetuses with certain disorders such as chromosomal abnormalities and neural tube defects are being detected before birth by amniocentesis and being aborted. As only live births were included, the incidence rates for these disorders may be somewhat lower than expectations based on rates derived in previous years.

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.

5. Milis JL, Harley EE, Reed GF,et al: Are spermicides teratogenic? JAMA 248:2148, 1982

6. Heinonen OP, Slone D, Shapiro S: Birth Defects and Drugs in Pregnancy. Littleton, MA, Publishing Sciences Group, 1977

7. Cordero JF, Oakley GP, Greenberg F,et al: Is Bendectin a teratogen? JAMA 245:2307, 1981

8. Shapiro S, Heinonen O, Siskind V, et al: Antenatal exposure to doxylamine succinate and dicyclomine hydrochloride (Bendectin) in relation to congenital malformations, perinatal mortality rate, birth weight, and intelligence quotient score. Am J Obstet Gynecol. 1977 Jul1; 128(5):480 -5