| Methods |
Study design: quasi‐randomized trial Unit of allocation: appears to be individual Time period of recruitment and data collection: unclear about recruitment period but injections were given in the first week of October 1966, and repeated in the original and additional cohort at 3 years after first injection. Data were collected for up to 7 years (as reported in the 1994 study) |
| Participants |
Description: women of childbearing age Location/setting: 3 central sierra villages, Tapo, Huasahuasi and Ataquero in the Province of Tarma, Peru, a mountainous region with an altitude of ˜3000 m. Tarma, a nearby town equipped with laboratory and hospital facilities, served as headquarters for the field work and more detailed laboratory work was carried out in Lima, about 5 hours away by automobile. How participants were recruited and selected: women of childbearing age 16‐45 years of age from 3 central sierra villages Inclusion criteria: not specified Exclusion criteria: not specified Sample size: 792 (this number is given in the 1972 paper, though it is not clear if it is the number that were randomised) Age: between 16‐45 years Socioeconomic status: not specified Nutritional status: not specified Baseline iodine status of participants/area: mean UIE in the 3 villages = 17 μg/100 mL – including pregnant/and non‐pregnant cohort; (in the 1969 paper, it was reported as mean UIE (μg/24 hour): 17.2 ± 1.1 (for 159 subjects which would include non‐pregnant cohort) Baseline coverage of iodized salt: report specifies that salt iodization had not been implemented in these areas Breastfeeding practices: not specified Other important information about participants or setting: none |
| Interventions |
Experimental intervention: injected iodized oil
Total number randomised: n = 390 Timing: at baseline and after 3 years Form: intramuscular injection Frequency and duration: 2 times (baseline and after 3 years) single dose Iodine compound: iodine Iodine dose: 2 mL iodized oil containing 950 mg iodine. Adult women with nodular disease were given 0.2 mL (95 mg iodine) Other nutrients: no other nutrients Adherence: not specified
Control/comparison intervention: placebo
Co‐intervention(s): none reported |
| Outcomes |
Pregnancy: maternal thyroid hormone concentrations in the last 5 months of pregnancy, blood and urine samples during pregnancy Postpartum: iodine content in breast milk, iodine content in breast milk at 19th month post‐injection (initial injection), blood and urine sample at the time of delivery and postpartum (not stated when postpartum) Infant/child: clinical evaluation, goitre, body weight, stature or supine length, sitting height or crown‐rump length, head and chest circumference, upper arm circumference, triceps, subscapular and waist skinfold thickness and bi‐acromial and bi‐ilio cristal diameters, bone maturation by radiologic tests, bone age, motor and neuropsychological by Gesell test, neuropsychological development was measured by the Stanford‐Binet and the Brunet‐Lezine tests, audiometry, voice, buccofacial praxis, articulation praxis and verbal expression and comprehension tests, EEG, UIE, other blood and urine tests |
| Notes |
The 1972 report is mainly concerned with the evaluation of children who were born into the iodine programme and have been followed up to 5 years after the injection of their mothers. The 1994 report provides additional details about maternal blood and urine sample as well as infant neurodevelopmental outcomes. From the 1969 study, description of follow‐up for the entire cohort (i.e. all children, women, men). It is not entirely clear whether childbearing women received follow‐up at these specified time points regardless of conception date. Follow‐ups were performed on: Goitre: at 6, 12, and 18 months after injection (examiners were ignorant of both the prior estimated gland size and the type of injection. The size of goitre and presence of nodularity were recorded) Clinical assessment: made by members of the same team throughout the program, looking out for any side effects, especially thyrotoxicosis I131 scans – unclear about timing Thyroid function – unclear about timing UIE – at 6, 9, 13, 15, and 19 months after injection (in a subgroup) |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
High risk |
"In other groups (excluding schoolchildren), random injection of placebo and iodine was accomplished by consecutive alternation of iodine and placebo injection." |
| Allocation concealment (selection bias) |
High risk |
Alternate allocation evident |
| Blinding of participants and personnel (performance bias)
All outcomes |
Unclear risk |
Not described in sufficient detail to make judgement |
| Blinding of outcome assessment (detection bias)
All outcomes |
Unclear risk |
Goitre: “Examiners were ignorant of both the prior estimated gland size and the type of injection”, but unclear about other outcomes such as child development |
| Incomplete outcome data (attrition bias)
All outcomes |
Unclear risk |
Unclear whether all pregnancies and births were captured: “As many pregnancies as possible occurring in both the treatment and placebo groups were followed throughout gestation”
Only a subgroup of individuals received thyroid function tests, I131 and UIE. No clear description of how these subjects were selected. Also, unclear how many childbearing women continued in the study at subsequent follow‐up time points as Table 3 (p 423) refers to entire cohort |
| Selective reporting (reporting bias) |
Unclear risk |
As above for incomplete outcome data
In addition, in the 1994 paper it was mentioned, “Accordingly, in a recalculation of results, only the children of mothers who had UIE or T4 levels that were verified and found to be consistent with a definition of iodine deficient or normal were included" (Table 2) |
| Other bias |
High risk |
This trial recruited women and provided the intervention before they became pregnant. The intervention may have affected their probability of becoming pregnant, potentially leading to differences between groups and introducing bias |
