Amoxicillin

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From 1 January 1991–31 December 2000.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Although no specific guideline was reported, a scientifically defensible approach was used to conduct the study.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2003

Materials and methods

Endpoint addressed:

developmental toxicity / teratogenicity

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study examined the association between amoxicillin exposure during pregnancy and birth weight, preterm delivery, congenital malformations, perinatal death, and spontaneous abortion of 401 primiparous women who filled prescriptions for amoxicillin, compared to 10237 controls who did not redeem any prescription drug from 3 months before pregnancy until the end of pregnancy.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Amoxicillin

EC Number:

248-003-8

EC Name:

Amoxicillin

Cas Number:

26787-78-0

Molecular formula:

C16H19N3O5S

IUPAC Name:

6-{[amino(4-hydroxyphenyl)acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Test material form:

not specified

Method

Ethical approval:

confirmed, but no further information available

Remarks:

Study carried out in accordance with the guidelines of the regional science ethics committee for use of clinical and registry data.

Details on study design:

The association between amoxicillin exposure and birth weight, preterm delivery, congenital malformations, and perinatal death was examined in a
cohort of primiparous women with either a live birth or a stillbirth after the 28th gestational week between 1 January 1991 and 31 December 2000. A case-control design was used to study the association between amoxicillin exposure and spontaneous abortion.

Exposure assessment:

estimated

Details on exposure:

The exposed group consisted of those who redeemed a prescription for amoxicillin during pregnancy, and these women were further divided by trimester of exposure, based on prescription date recorded in the Pharmaco-Epidemiological Prescription Database and on gestational age as reported to the Danish Medical Birth Registry. Use of amoxicillin in pregnancy was determined as having redeemed a prescription for amoxicillin.

Results and discussion

Results:

The adjusted mean birth weight of children born to amoxicillin-exposed mothers was 57 g [95% confidence interval (CI) 9, 105] higher than that of children born to controls. No cases of perinatal death were observed in the amoxicillin-exposed women. No adverse effects were observed associated with amoxicillin exposure during pregnancy.

Any other information on results incl. tables

Table 1. Characteristics of the study cohort.

	Exposed in the first trimester	Exposed during pregnancy	Controls
No. women	147	401	10237
No. prescriptions	150	445	-
Mean age	27.4	27.0	26.8
Proportion of smokers (%)	35.4	33.4	25.9
Gestational age (weeks)
·        ≥ 37	139	381	9588
·        34-36	8	18	450
·        28-33	0	2	199
Mean birth weight	3518	3498	3429
No. low birth weight (%)	2	5	183
No. preterm deliveries (%)	9	20	649
No. malformations (%)	7	16	416
No. prenatal deaths (%)	0	0	60

Applicant's summary and conclusion

Conclusions:

Amoxicillin use during pregancy may cause an increased weight on babies, but does not appear to increase the risk of adverse pregnancy outcomes.

Executive summary:

A cohort study was performed to examine the association between amoxicillin exposure during pregnancy and birth weight, preterm delivery, congenital malformations, perinatal death, and spontaneous abortion of 401 primiparous women who filled prescriptions for amoxicillin, compared to 10237 controls who did not redeem any prescription drug from 3 months before pregnancy until the end of pregnancy. Based on the observations throughout the study, amoxicillin use during pregancy may cause an increased weight on babies, but does not appear to increase the risk of adverse pregnancy outcomes.