Peru 2004.

Methods	A double‐blind, RCT.
Participants	242 (low‐income) Peruvian pregnant women at 10 to 16 weeks’ gestation receiving prenatal care at the Hospital Materno Infantil San Jose in Lima, Peru were recruited. The maternal dietary zinc intake is approximately 8 mg/d,12 an intake much lower than recommended intakes at that time of 15 mg/d (US Recommended Dietary Allowance) in this region. Women who were with singleton pregnancy, and had lived in coastal Peru for at least 6 months before becoming pregnant were included in the study. Exclusions was made according to a protocol for fetal neurobehavioural assessment.
Interventions	Women were randomly assigned to receive a daily supplement containing 60 mg iron (ferrous sulphate) and 250 mg folic acid, with 25 mg zinc (zinc sulphate) or the same supplement but without 25 mg zinc (zinc sulphate). The supplements were manufactured in Lima, had the same appearance and taste, and both study personnel and study subjects were masked to treatment assignment. The supplements were distributed in blister packs at monthly intervals, beginning at entry into the study at 10 to 16 weeks’ gestation and continuing until 1 month postpartum. Adherence with supplementation was checked biweekly by health workers who visited the women in their homes and observed the number of tablets remaining in each blister pack. The level of adherence was calculated as the percentage of tablets taken over the number of days in the study. They used a standard questionnaire with specific questions regarding potential benefits or side effects of supplement consumption. Zinc: zinc + iron + folate (n = 109 [94]). No zinc: iron + folate (n = 113 [101]).
Outcomes	Maternal outcomes Preterm birth with complications; gestational age at birth. Neonatal and infant outcomes Fetal heart rate measures; birthweight; length; biparietal diameter; abdominal circumference; femur diaphysis length; infant feeding; infant growth; child development at 54 months; dietary and nutritional status at 54 months; mean arterial pressure at 54 months; BMI at 54 months; haemoglobin concentration at 54 months; plasma zinc concentration at 54 months; C‐reactive protein concentration at 54 months; Home Observation for the Measurement of the Environment (HOME) Scale assessment at 54 months; heart rate measures at 54 months.
Notes	Adherence: mean adherence rate was 87% (86% in the zinc group and 88% in the no zinc group).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Women were randomly assigned in blocks of 2 using computer‐generated lists from Johns Hopkins and sent to Peru.
Allocation concealment (selection bias)	Low risk	The randomisation code was made by the pharmaceutical company and maintained in a sealed and secured envelope in Lima; supplements had the same appearance and taste.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Both study personnel and participants were blinded.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Not specifically stated, but we have assumed that outcome assessors were blinded and remained blinded for the longer‐term analyses.
Incomplete outcome data (attrition bias) All outcomes	Low risk	222/242 (90.1%) women completed the protocol and 195 (80.6%) were included in the analysis of birth outcomes ‐ 94 (78%) zinc and 101 (84%) no zinc. The 47 lost were made up of 20 change of address, declining to continue in the study, or travel and 27 exclusions for significant obstetric or medical complications. At 54‐month follow‐up, there were 205 eligible children (includes children of 10 mothers excluded from the initial analysis), and evaluations were completed for 184 (90%) of these children (86 (87%) from the zinc group and 98 (92%) from the non‐zinc group.
Selective reporting (reporting bias)	High risk	A number of birth outcomes such as postpartum haemorrhage, stillbirth or neonatal death, low birthweight or Apgar scores were not reported; and preterm birth was only reported as preterm birth with complications which were treated as study exclusions.
Other bias	Low risk	No apparent source of other bias although the study was designed to primarily assess neonatal and infant outcomes (see selective reporting above).