Lower systolic blood pressure at age 7 y in low-birth-weight children who received iron supplements in infancy: results from a randomized controlled trial.

Background: Low birth weight (LBW) (≤2500 g) is associated with iron deficiency in infancy and high blood pressure (BP) later in life.Objective: We investigated the effect of iron supplementation that was given to LBW infants on midchildhood BP.Design: The study was a randomized, double-blind, controlled trial that included 285 marginally LBW (2000-2500-g) infants at 2 Swedish centers between May 2004 and November 2007. The infants were randomly assigned to receive a placebo or 1 or 2 mg Fe · kg-1 · d-1 from 6 wk to 6 mo of age. In secondary analyses at the age of 7 y, systolic blood pressure (SBP), diastolic blood pressure (DBP), and the prevalence of children with BP within the hypertensive range (>90th percentile) were compared between the groups.Results: BP was analyzed via intention to treat in 189 children (66%). The mean ± SD SBP was 103 ± 8.1, 101 ± 7.5, and 101 ± 7.8 mm Hg in children who had received the placebo (n = 70), 1 mg Fe · kg-1 · d-1 (n = 54), or 2 mg Fe · kg-1 · d-1 (n = 65), respectively. When the iron-supplemented groups were combined in covariate-adjusted analyses, the mean SBP in LBW children who had received iron supplementation in infancy was 2.2 mm Hg (95% CI: 0.3, 4.2 mm Hg) lower than in those who were unsupplemented (P = 0.026). Multivariate logistic regression showed that iron supplementation in infancy reduced the odds of having an SBP within the hypertensive range at 7 y of age (OR: 0.32; 95% CI: 0.11, 0.96). For DBP, there were no significant differences between the intervention groups.Conclusions: LBW children who receive iron supplementation (1 or 2 mg Fe · kg-1 · d-1) in infancy have lower SBP at 7 y. This (to our knowledge) novel observation suggests that the increased risk of hypertension that is observed in children and adults who are born small might be reduced with early micronutrient interventions. This trial was registered at clinicaltrials.gov as NCT00558454.

Marginally low birthweight increases the risk of underweight and short stature at three and a half years of age.

AIM: Little is known about the long-term health of marginally low birthweight (LBW) children. This study characterised growth among infants weighing 2000 g-2500 g and explored the prevalence and predictors of sustained growth restriction. METHOD: This prospective observational trial followed the weight and height of 281 Swedish marginally LBW children from birth to 3.5 years of age. Children with a standard deviation score (SDS) for body mass index or height below -2 were considered underweight and short, respectively. RESULTS: The mean SDS for weight and height showed a rapid increase before 12-19 weeks of age. The most rapid weight gain was in infants born small for gestational age. However, at 3.5 years of age, 9.5% of the children remained underweight and 6.5% had short stature. Regression models showed that slow weight gain before 19 weeks of age was the strongest predictor for lasting underweight, while slow height gain before 19 weeks of age and male sex were associated with short stature. CONCLUSION: Marginally LBW infants were more likely to be underweight and have a short stature at 3.5 years of age and the absence of catch-up growth during the first five months after birth identified those at highest risk.

Overweight, Obesity, and Body Composition in 3.5- and 7-Year-Old Swedish Children Born with Marginally Low Birth Weight.

OBJECTIVES: To assess the prevalence of overweight/obese children and to explore body composition in a Swedish cohort of preschool children born with marginally low birth weight (MLBW, ie, 2000-2500 g). STUDY DESIGN: We included 285 Swedish children with MLBW (44% small for gestational age), and 95 control children with normal birth weights. At 3.5 years and 7 years of age, we assessed anthropometrics, including the prevalence of overweight/obese children. At 7 years, dual-energy X-ray was used for body composition. RESULTS: There were no significant differences between groups in the prevalence of overweight/obesity or in skinfold thickness; however, at 3.5 years, mean height, weight, and BMI in children with MLBW were 2.1 cm (95% CI 1.2-3.1), 1.2 kg (95% CI 0.7-1.6), and 0.47 kg/m(2) (95% CI 0.17-0.76) lower compared with controls. The corresponding mean differences also were lower in children with MLBW compared with control children at 7 years; 2.5 cm (95% CI 0.9-4.1), 1.6 kg (95% CI 0.6-2.8), and 0.48 kg/m(2) (95% CI 0.01-0.94). The differences were greater in those born small for gestational age. Dual-energy X-ray analyses showed lower fat-free mass index in MLBW infants and a similar trend in fat mass index. Within children with MLBW, BMI at 7 years correlated positively to growth velocity in infancy. CONCLUSION: Children with MLBW had lower BMI and did not show increased risk of overweight or obesity up to 7 years. Nevertheless, the BMI in MLBW children was positively correlated to growth-velocity in infancy. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00558454.

Effects of iron supplements and perinatal factors on fetal hemoglobin disappearance in LBW infants.

BACKGROUND: The homeostatic mechanisms of iron metabolism and erythropoiesis in infants are unclear. Infants synthesize both fetal hemoglobin (HbF) and adult hemoglobin (HbA), and it is not known how the hemoglobin switch is regulated. We hypothesized that iron supplements to infants affect the disappearance of HbF. METHODS: We randomized 285 low-birth-weight infants (2,000-2,500 g) into three intervention groups receiving 0, 1, or 2 mg/kg/d of iron supplements from 6 wk to 6 mo of age. In the present secondary analysis, we analyzed iron status, total hemoglobin (Hb), and HbF fraction at 6 wk, 12 wk, and at 6 mo and calculated absolute levels of HbF. RESULTS: We observed dose-dependent increased levels of Hb in iron-supplemented groups at 6 mo of age. However, for absolute HbF concentration, there was no similar effect of intervention. Mean (SD) HbF was 81.2 (16.8), 37.0 (13.8), and 8.1 (5.6) g/l at 6 wk, 12 wk, and 6 mo, respectively, similar in all groups. In linear regression analyses, postconceptional age turned out as the major predictor of HbF, independent of gestational age at birth. CONCLUSION: Our hypothesis was rejected. Instead, we confirmed a close correlation to postconceptional age, supporting a genetically programmed switch, insensitive to most environmental factors including birth.