TABLE 3.
Relation of prenatal alcohol exposure to maternal, neonatal, and postnatal infant iron and hematologic outcomes
| Drinking frequency (days/wk) univariate model | Drinking frequency (days/wk) multivariable model1 | Drinking frequency (days/wk) multivariable model1 adjusted for placental weight2 | Drinking frequency (days/wk) multivariable model1 adjusted for maternal vascular underperfusion2 | |
|---|---|---|---|---|
| β (95% CI) | β (95% CI) | β (95% CI) | β (95% CI) | |
| Mothers, n = 126 drinkers, 80 controls | ||||
| Ferritin,3,4,5 % change | 0.286 (0.16–0.42) | 0.216 (0.09–0.34) | — | — |
| sTfR,4,7,8 mg/L | −0.349 (−0.62 to −0.07) | −0.20 (−0.47 to 0.07) | — | — |
| sTfR:log(ferritin)4,7,8 | −0.189 (−0.33 to −0.03) | −0.08 (−0.22 to 0.06) | — | — |
| Hemoglobin,4,5,7,8,10–14 g/dL | 0.05 (−0.08 to 0.18) | 0.02 (−0.02 to 0.05) | — | — |
| Anemia,4,5,13,14 yes = 1, no = 0 | 0.03 (−0.04 to 0.09) | 0.03 (−0.03 to 0.10) | — | — |
| Mean corpuscular volume,4 fL | 2.526 (1.58–3.46) | 2.186 (1.24–3.12) | — | — |
| Mean corpuscular hemoglobin, pg | 0.936 (0.55–1.30) | 0.936 (0.55–1.30) | — | — |
| Red cell distribution width,4,5,7,8,10–14 % | −0.06 (−0.25 to 0.13) | 0.00 (−0.21 to 0.22) | — | — |
| Reticulocyte count,4,5,7,10–14 % | 0.02 (−0.07 to 0.11) | 0.02 (−0.08 to 0.12) | — | — |
| Hemoglobin:log(ferritin)4,5 | −0.296 (−0.41 to −0.16) | −0.2115 (−0.35 to −0.07) | — | — |
| Hepcidin,5,8,10 urine; ng/mg creatinine | 75.9215 (23.77–128.1) | 64.179 (2.37–125.97) | — | — |
| Iron deficiency,4,5,8 yes = 1, no = 0 | −0.116 (−0.16 to −0.05) | −0.079 (−0.13 to −0.01) | — | — |
| Iron deficiency anemia,4,5,7,8,10,11,14,16,17 yes = 1, no = 0 | −0.03 (−0.10 to 0.03) | 0.00 (−0.07 to 0.07) | — | — |
| Anemia of inflammation,5,17 yes = 1, no = 0 | 0.076 (0.04–0.10) | 0.066 (0.02–0.09) | — | — |
| Erythrocyte folate,4,5,10,11 nmol/L | 25.00 (−53.75 to 103.72) | 40.72 (−38.99 to 120.43) | — | — |
| Vitamin B12,4,5,7,11 pmol/L | −3.37 (−11.43 to 4.68) | −5.13 (−13.77 to 3.50) | — | — |
| Placental iron transport, n = 33 exposed, 30 controls | ||||
| Iron concentration,4,5,7,10,11,14,16 ug/g wet tissue | 12.55 (−14.55 to 39.65) | −2.23 (−35.80 to 31.34) | 0.00 (−34.66 to 34.66) | −6.41 (−41.92 to 29.10) |
| Iron regulatory protein-2,3,5,10,11,14,18 % change | −0.09 (−0.36 to 0.14) | −0.14 (−0.43 to 0.12) | −0.07 (−0.35 to 0.16) | −0.14 (−0.45 to 0.12) |
| TfR-1,3,5,7,10,11,14,18 % change | 0.09 (−0.07 to 0.28) | −0.01 (−0.22 to 0.21) | 0.02 (−0.20 to 0.25) | −0.02 (−0.25 to 0.21) |
| Divalent metal transporter-1,3,4,7 % change | −0.05 (−0.22 to 0.11) | −0.08 (−0.27 to 0.08) | −0.06 (−0.22 to 0.09) | −0.09 (−0.28 to 0.08) |
| FPN-1,3,4,5,7,10,11,14,16,18 % change | −0.02 (−0.51 to 0.43) | −0.03 (−0.72 to 0.63) | −0.04 (−0.80 to 0.68) | −0.02 (−0.80 to 0.72) |
| FPN-1:TfR-1,3,4,5,7 % change | −0.4519 (−0.27 to 0.08) | −0.779 (−1.80 to −0.11) | −0.809 (−1.97 to −0.11) | −0.779 (−1.94 to −0.07) |
| Neonates, n = 99 exposed, 59 controls | ||||
| Ferritin,3,20,21 % change | 0.1119 (−0.01 to 0.22) | 0.139 (0.01–0.25) | 0.149 (0.02–0.27) | 0.1219 (0.00–0.25) |
| Hemoglobin,21 g/dL | −0.27 (−0.67 to 0.13) | −0.2919 (−0.60 to 0.03) | −0.3719 (−0.76 to 0.02) | −0.3419 (−0.73 to 0.04) |
| Mean corpuscular volume,21 fL | 0.86 (−0.17 to 1.89) | 0.8219 (−0.13 to 1.76) | 0.33 (−0.70 to 1.37) | 0.83 (−0.23 to 1.90) |
| Mean corpuscular hemoglobin,21 pg | 0.489 (0.10–0.86) | 0.469 (0.10–0.83) | 0.22 (−0.18 to 0.61) | 0.34 (−0.07 to 0.75) |
| Red cell distribution width,5,7,10,18,20,21 % | 0.03 (−0.14 to 0.20) | −0.04 (−0.23 to 0.15) | 0.12 (−0.06 to 0.31) | 0.1619 (−0.01 to 0.34) |
| Reticulocyte count,4,5,7,10,11,16,18,20,21 % | −0.02 (−0.14 to 0.11) | −0.01 (−0.12 to 0.11) | 0.01 (−0.12 to 0.14) | 0.03 (−0.10 to 0.16) |
| Hemoglobin:log(ferritin)5,20,21 | −0.119 (−0.20 to −0.02) | −0.156 (−0.24 to −0.06) | −0.176 (−0.26 to −0.07) | −0.166 (−0.26 to −0.06) |
| 6.5-month-old infants, n = 113 exposed, 69 controls | ||||
| Ferritin,3,5,10,18,20,22 % change | −0.04 (−0.15 to 0.07) | −0.06 (−0.20 to 0.07) | −0.04 (−0.20 to 0.11) | −0.04 (−0.21 to 0.11) |
| sTfR,5,16,18,20–22 mg/L | 0.26 (−0.06 to 0.57) | 0.15 (−0.19 to 0.49) | 0.07 (−0.33 to 0.47) | 0.08 (−0.31 to 0.47) |
| sTfR:log(ferritin)18,20–22 | 0.16 (−0.07 to 0.39) | 0.13 (−0.11 to 0.36) | 0.10 (−0.15 to 0.36) | 0.12 (−0.14 to 0.37) |
| Hemoglobin,20,23 g/dL | −0.199 (−0.34 to −0.03) | −0.189 (−0.33 to −0.02) | −0.249 (−0.44 to −0.05) | −0.229 (−0.40 to −0.03) |
| Anemia5,6,10,11,16,18,20,23 | 0.04 (−0.04 to 0.11) | 0.02 (−0.06 to 0.10) | 0.04 (−0.06 to 0.14) | 0.03 (−0.07 to 0.12) |
| Mean corpuscular volume,4,5,7,10,11,16,18,20,22–25 fL | −0.15 (−0.91 to 0.62) | −0.15 (−1.10 to 0.80) | 0.05 (−1.07 to 0.97) | 0.03 (−0.93 to 0.98) |
| Mean corpuscular hemoglobin,4,5,7,10,11,16,18,20–25 pg | −0.09 (−0.41 to 0.24) | −0.03 (−0.43 to 0.36) | −0.03 (−0.45 to 0.39) | −0.02 (−0.43 to 0.39) |
| Red cell distribution width,5,10,11,16,18,20,22,25,26 % | 0.14 (−0.04 to 0.33) | 0.06 (−0.18 to 0.30) | 0.19 (−0.08 to 0.47) | 0.19 (−0.09 to 0.46) |
| Reticulocyte count,5,7,16,20,22,23 % | −0.07 (−0.17 to 0.03) | −0.06 (−0.18 to 0.07) | −0.10 (−0.24 to 0.05) | −0.09 (−0.24 to 0.06) |
| Hemoglobin:log(ferritin)4,5,7,10,16,18,20–22,25–27 | −0.02 (−0.18 to 0.14) | −0.01 (−0.21 to 0.19) | −0.03 (−0.26 to 0.19) | −0.02 (−0.25 to 0.21) |
| Iron deficiency,5,10,20,22 yes = 1, no = 0 | 0.05 (−0.02 to 0.12) | 0.099 (0.02–0.17) | 0.109 (0.01–0.19) | 0.109 (0.01–0.19) |
| Iron deficiency anemia,5,7,10,16,17,22 yes = 1, no = 0 | 0.0719 (0.00–0.15) | 0.1315 (0.04–0.23) | 0.129 (0.01–0.23) | 0.139 (0.02–0.24) |
| Anemia of inflammation,5,11,17,18,20,21 yes = 1, no = 0 | −0.02 (−0.08 to 0.05) | −0.01 (−0.08 to 0.06) | −0.02 (−0.11 to 0.07) | −0.02 (−0.11 to 0.07) |
| Erythrocyte folate,20,22 nmol/L | −2.26 (−97.27 to 92.75) | −65.98 (−168.15 to 36.19) | −85.20 (−213.38 to 42.98) | −74.11 (−201.52 to 53.30) |
| Vitamin B12,10,20,22 pmol/L | 2.89 (−21.79 to 27.57) | −22.3019 (−48.46 to 3.86) | −21.03 (−48.32 to 6.27) | −20.79 (−48.20 to 6.62) |
β = raw regression coefficients from mixed models with repeated measures for all maternal outcomes, except for hepcidin (measured once) and linear regression models for hepcidin and all placenta and infant outcomes. Abbreviations: FPN-1, ferroportin-1; PAE, prenatal alcohol exposure; sTfR, soluble transferrin receptor; TfR-1, transferrin receptor 1.
The potential covariates for multivariable models examining maternal and placental outcomes included factors known to affect maternal iron status (age, gravidity, cigarette smoking, average daily dietary iron intake, iron supplementation, household food security), energy intake, weeks gestation at visit, and, for red cell indices, erythrocyte folate and serum vitamin B12 concentrations. Potential covariates for infant outcome models included the above maternal factors that affect iron status as well as prenatal methamphetamine use, gestational hypertension, and age at time of blood draw; the 6.5-month outcome models included weeks breastfeeding, weeks feeding formula, weeks giving complementary foods, and, for red cell indices, erythrocyte folate and serum vitamin B12 concentrations were also considered. Covariates were included in multivariable models if their removal from a model regressing a given outcome on PAE and all potential covariates resulted in a change in the PAE regression coefficient by >10%. Given the rapid changes in erythrocytes and ferritin that occur in the first few weeks of life (55), age at time of assessment was included in all neonatal outcome models.
Available for 65 exposed and 41 control infants with neonatal iron measures and 72 exposed and 45 control infants with 6.5-month iron measures.
Values are antilog − 1 of β (95% CI) from models using logged values due to skewness >3.0, signifying % change per each additional day/week of prenatal drinking.
Maternal age was included as a covariate in multivariable models.
Food insecurity was included as a covariate in multivariable models (53).
P ≤ 0.001.
Prenatal cigarettes/d was included as a covariate in multivariable models.
Weeks gestation at visit was included as a covariate in multivariable models.
P ≤ 0.05.
Prenatal iron supplementation was included as a covariate in multivariable models (yes = 1, no = 0).
Dietary iron intake (mg/day) was included as a covariate in multivariable models.
Maternal erythrocyte folate (nmol/L) was included as a covariate in multivariable models.
Maternal serum vitamin B12 (pmol/L) was included as a covariate in multivariable models.
Energy intake (kcal/day) was included as a covariate in multivariable models.
P ≤ 0.01.
Gravidity was included as a covariate in multivariable models.
Those with anemia of indeterminate cause were excluded.
Weeks gestation at delivery was included as a covariate in multivariable models.
P ≤ 0.10.
Days/month prenatal methamphetamine use was included as a covariate in multivariable models.
Infant age at time of blood draw was included as a covariate in multivariable models.
Weeks infant fed formula was included as a covariate in multivariable models.
6.5-month infant serum vitamin B12 (pmol/L) was included as a covariate in multivariable models.
6.5-month infant erythrocyte folate (nmol/L) was included as a covariate in multivariable models.
Weeks infant fed complementary foods was included as a covariate in multivariable models.
Weeks infant breastfed was included as a covariate in multivariable models.
Maternal gestational hypertension was included as a covariate in multivariable models.