TABLE 2.
Fetal iron status indicators and infant iron status at the 9-mo assessment by group in the combined pregnancy and infancy RCT1
| Placebo/placebo (PP) | Placebo/iron (PI) | Iron/placebo (IP) | Iron/iron (II) | P value2 | Significant contrasts3 | RR (95% CI) | |
| n | 305 | 311 | 305 | 318 | |||
| Fetal iron status indicators | |||||||
| Maternal ID,4 n/total n (%) | 183/300 (61.0) | 205/309 (66.3) | 121/297 (40.7) | 129/310 (41.6) | <0.01 | II < PI | 0.63 (0.53, 0.73) |
| II < PP | 0.68 (0.58, 0.80) | ||||||
| IP < PI | 0.61 (0.52, 0.72) | ||||||
| IP < PP | 0.67 (0.57, 0.79) | ||||||
| ID at birth,5 n/total n (%) | 123/300 (41.0) | 131/310 (42.3) | 131/301 (43.5) | 132/313 (42.2) | 0.94 | ||
| Iron measures: birth and 9 mo | |||||||
| Hb, g/L | |||||||
| Birth | 149 (147, 151) | 153 (151, 155) | 151 (149, 153) | 154 (152, 155) | <0.01 | IP, PP < II | |
| PP < PI | |||||||
| 9 mo | 111 (110, 112) | 113 (112, 114) | 111 (110, 113) | 113 (111, 114) | 0.15 | ||
| MCV, fL | |||||||
| Birth | 103 (102, 103) | 102 (102, 103) | 102 (102, 103) | 102 (102, 103) | 0.54 | ||
| 9 mo | 68.9 (68.5, 69.4) | 69.1 (68.7, 69.6) | 69.1 (68.6, 69.5) | 68.8 (68.3, 69.2) | 0.62 | ||
| SF, μg/L | |||||||
| Birth | 113 (107, 121) | 114 (107, 121) | 116 (109, 123) | 113 (106, 120) | 0.96 | ||
| 9 mo | 11.2 (10.1, 12.4) | 12.2 (11.1, 13.5) | 11.5 (10.4, 12.8) | 11.7 (10.6, 13.0) | 0.65 | ||
| ZPP/H, μmol/mol heme | |||||||
| Birth | 97.8 (94.2, 101.5) | 95.8 (92.4, 99.4) | 95.0 (91.5, 98.6) | 94.3 (90.9, 97.8) | 0.55 | ||
| 9 mo | 80.6 (76.1, 85.3) | 70.8 (67.0, 74.9) | 75.7 (71.6, 80.2) | 72.6 (68.6, 76.7) | <0.01 | PI, II < PP | |
| sTfR, nmol/L | |||||||
| Birth | 31.0 (29.9, 32.1) | 29.5 (28.5, 30.5) | 29.9 (28.9, 30.9) | 29.9 (28.9, 30.9) | 0.21 | PI < PP | |
| 9 mo | 24.0 (23.1, 24.9) | 23.8 (23.0, 24.7) | 23.1 (22.3, 24.0) | 24.6 (23.7, 25.5) | 0.13 | IP < II | |
| BI, mg/kg | |||||||
| Birth | 7.31 (7.05, 7.58) | 7.42 (7.16, 7.67) | 7.40 (7.14, 7.66) | 7.41 (7.15, 7.66) | 0.95 | ||
| 9 mo | −0.09 (−0.53, 0.35) | 0.27 (−0.17, 0.71) | 0.16 (−0.28, 0.61) | 0.00 (−0.43, 0.44) | 0.68 | ||
| 9-mo iron status outcomes | |||||||
| Anemia, Hb <110 g/L, n/total n (%) | 138/305 (45.3) | 108/311 (34.7) | 121/305 (39.7) | 125/318 (39.3) | 0.07 | PI < PP | 0.77 (0.63, 0.93) |
| ID,6 n/total n (%) | |||||||
| Cutoff (≥2 abnormal iron measures) | 208/305 (68.2) | 188/311 (60.5) | 210/305 (68.9) | 189/318 (59.4) | 0.02 | PI < PP | 0.89 (0.79, 1.00) |
| PI < IP | 0.79 (0.63, 0.98) | ||||||
| II < PP | 0.87 (0.77, 0.98) | ||||||
| II < IP | 0.86 (0.77, 0.97) | ||||||
| BI <0 mg/kg | 137/305 (44.9) | 135/311 (43.4) | 141/305 (46.2) | 147/318 (46.2) | 0.88 | ||
| IDA,6 n/total n (%) | |||||||
| Hb <110 g/L + ID by cutoff | 117/305 (38.4) | 87/311 (28.0) | 101/305 (33.1) | 106/318 (33.3) | 0.06 | PI < PP | 0.73 (0.58, 0.92) |
| Hb <110 g/L + ID by BI | 90/305 (29.5) | 70/311 (22.5) | 83/305 (27.2) | 92/318 (28.9) | 0.18 | PI < PP | 0.76 (0.58, 1.00) |
| Serum CRP, mg/L | 0.11 (0.099, 0.14) | 0.15 (0.12, 0.18) | 0.09 (0.08, 0.12) | 0.14 (0.11, 0.17) | 0.02 | IP < PI, II |
Values are means (95% CIs) for continuous variables and n/total n (%) for categorical ones. Numbers (n) vary slightly due to missing data. BI, body iron; CRP, C-reactive protein; fL, femtoliters; Hb, hemoglobin; ID, iron deficiency; IDA, iron deficiency anemia; II, iron in pregnancy/iron in infancy; IP, iron in pregnancy/placebo in infancy; MCV, mean corpuscular volume; PI, placebo in pregnancy/iron in infancy; PP, placebo in pregnancy/placebo in infancy; RCT, randomized clinical trial; SF, serum ferritin; sTfR, serum transferrin receptor; ZPP/H, zinc protoporphyrin/heme.
Based on general linear models or logistic regression. ZPP/H, SF, sTfR, and CRP (cord blood and 9 mo) were log-transformed to normalize the distribution. Geometric means are shown. Higher values of ZPP/H and sTfR indicate poorer iron status.
Statistically significant pairwise comparison(s) between groups, P < 0.05.
Maternal ID defined as BI <0 mg/kg. BI for mothers and infants was calculated by using SF and sTfR according to the formula in Cook et al. (24): body iron (mg/kg) = −[log10(sTfR · 1000/ferritin) – 2.8229]/0.1207. This formula uses an sTfR assay described in Flowers et al. (25). To convert Beckman Coulter sTfR concentrations for use in the formula, we built on published data for Flowers, Ramco, and Beckman Coulter sTfRs. As reported in Pfeiffer et al. (26), the Ramco assay was similar to Flowers et al. (25). Ramco and Beckman Coulter assays were part of a WHO study that used a standard reference reagent for sTfR (27). The Ramco assay yielded sTfR concentrations 4.3 times higher than Beckman Coulter, so the Flowers sTfR equivalent was calculated by the following formula: Flowers sTfR = 4.3 × Beckman Coulter sTfR.
ID at birth defined as cord SF <75 μg/L or ZPP/H >118 μmol heme/mol. SF <75 μg/L has been used in studies of prenatal ID neurodevelopmental effects (28–30), and ZPP/H >118 μmol/mol heme is the US 90th percentile (31).
ID and IDA results are presented by 2 different criteria for ID: cutoff, ≥2 abnormal iron measures and BI <0 mg/kg.