Registration Dossier

Toxicological information

Direct observations: clinical cases, poisoning incidents and other

Currently viewing:

Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1989

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
developmental toxicity / teratogenicity
Principles of method if other than guideline:
A double blind trial was conducted on pregnant women to determine the effects zinc supplementation during pregnancy on maternal and fetal
outcome.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): zinc sulphate

Method

Type of population:
general
Subjects:
- Number of subjects exposed: 494 (246 in test and 248 in control group); sample size was calculated on the basis of an earlier study
- Eligibility: Women booking for delivery at Southmead Hospital, Bristol, were eligible for entry if they were less than 20 wk pregnant (confirmed by ultrasound) at the first visit.
- Sex: Female
- Age: 26 (approximate mean)
- Demographic information: Mostly European

Ethical approval:
confirmed and informed consent free of coercion received
Route of exposure:
oral
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
66 mg zinc sulphate (equivalent to 20 mg elemental zinc) capsules or placebo, prescribed for once daily use (after breakfast) starting from the day of booking till delivery in a double blind randomised manner.

At each visit information was obtained about the use of any other drugs or iron or vitamin supplementation. Compliance was assessed by the
regularity with which the study capsules were taken. Those who took the supplement daily or on most days were grouped as compliers, and the rest were regarded as non-compliers.

Note: If iron and folate tablets were also prescribed due to medical reasons, then subjects were advised to take them in the evening to avoid any interaction with zinc supplement.
Examinations:
-Maternal characteristics, such as body weight, haemoglobin, blood pressure, proteinuria, zinc concentration in leucocytes, were measured at booking and at visit between 28 to 32 wk of gestation.
- Maternal complications of pregnancy were examined.
-Labour and delivery parameters, such as gestation period, blood pressure during labour, type of membrane rupture, type of delivery, duration of labour, postpartum haemorrhage/infection, were determined.
-Fetuses/neonates parameters, such as sex, birth weight, body dimensions, stillbirths, ponderal index, Apgar scores, zinc concentrations in cord blood, congenital defects, other abnormalities, were determined.
Medical treatment:
None

Results and discussion

Clinical signs:
No data
Results of examinations:
Maternal characteristics: No differences in maternal weights, blood pressure measurements, haemoglobin, ferritin, leucocyte zinc concentrations between the two groups at booking. At the subsequent visit (between 28 and 32 wk gestation), there were no significant differences between the two groups. There was a suggestion, however, that the mothers receiving the zinc supplement had lower zinc concentrations (p = 0.06) than the controls (see Table I and II in full study report for details).

Complications of pregnancy: There were no significant differences in complications of pregnancy between the two groups. The mothers given zinc supplementation had similar weights, weight gains, and blood pressures, but there was a suggestion of more proteinuric hypertension in this group (11/241 mothers) than in the controls (3/238) (p = 0.06) (mainly because the incidence rate was less than expected in the control group).

Labour and deliver: There was no difference between the groups in any aspect of labour or delivery. In particular, mothers receiving zinc supplements were not less likely to deliver before term or to have premature rupture of the membranes, abnormal labour, postpartum haemorrhage, or postpartum infection (see Table IV in full study report for details)

Fetuses and neonates: There were no differences in outcome between the groups. In particular there was no evidence of a lower incidence of growth retardation or neonatal abnormalities in the zinc treated group. The condition of the infant at birth was identical in the two groups. There were three perinatal deaths in each group. In all, however, six pregnancies had either been terminated or ended in spontaneous abortion during the study, but the difference in distribution between the groups (one case in the zinc treated group, five cases in the control group) did not approach significance (see Table V in full study report for details).
Effectivity of medical treatment:
Not applicable
Outcome of incidence:
Not applicable

Any other information on results incl. tables

Social and biological background information of participants: There were no significant differences between the two groups in their social and biological backgrounds. They were of similar ages and had similar obstetric histories. The proportion of mothers who were smoking

was similar, as was the prevalence of a history of nausea or vomiting and of urinary infection (see Table I in the attached full study report for details).

Dietary intake estimation: Of the 494 mothers, 375 (76%) completed a seven day dietary diary, 347 giving details for the whole seven days. There was no difference in nutrient intake between the groups. In particular, there was no difference in mean zinc intake. Dietary items known to reduce the absorption of zinc, such as alcohol, iron, total fibre (and cereal fibre), were consumed in equal amounts in the two groups. Similar number of iron supplements (and at similar timings) were taken between the groups (see Table III in the attached full study report for details).

Compliance: Compliance did not vary significantly between the two groups. No difference in measures of outcome when compared among compliers only. Similarly there was no significant difference between compliers and noncompliers apart from a significantly lower risk of postpartum infection among the compliers.

Applicant's summary and conclusion

Conclusions:
Under the test conditions, zinc supplementation during pregnancy did not affect maternal or fetal outcome.
Executive summary:

A double blind trial was conducted on pregnant women to determine the effects zinc supplementation during pregnancy on maternal and fetal

outcome.

 

494 women booking before 20 wk of gestation in a hospital were prescribed either 66 mg zinc sulphate (equivalent to 20 mg elemental zinc) capsules or placebo for once daily use, starting from day of booking till delivery. Various adverse outcomes were tested, including maternal bleeding,

hypertension, complications of labour and delivery, gestational age, Apgar scores, and neonatal abnormalities. The main outcome measure was birth weight.

There were no differences between the mothers and neonates of the zinc supplemented and placebo group.

Under the test conditions, zinc supplementation during pregnancy did not affect maternal or fetal outcome.