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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
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
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2017 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 106, no 2, p. 475-480Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2017. Vol. 106, no 2, p. 475-480
Keywords [en]
Barker hypothesis, blood pressure, cardiovascular risk, early programming, hypertension, iron supplementation, low birth weight
National Category
Pediatrics
Identifiers
URN: urn:nbn:se:umu:diva-138590DOI: 10.3945/ajcn.116.150482ISI: 000406672300009OAI: oai:DiVA.org:umu-138590DiVA, id: diva2:1143468
Available from: 2017-09-21 Created: 2017-09-21 Last updated: 2018-06-09Bibliographically approved
In thesis
1. Neurodevelopment and cardiovascular risk in 7-year old children born with marginally low birth weight
Open this publication in new window or tab >>Neurodevelopment and cardiovascular risk in 7-year old children born with marginally low birth weight
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Being born preterm (<37+0 gestational weeks) or with low birth weight (LBW, <2500 g) has been associated with a number of adverse health outcomes later in life. Most studied are cardiovascular and neurodevelopmental consequences in those born preterm and with very LBW (<1500 g). However, a majority of LBW children are born with a birth weight between 2000 and 2500 g, herein referred to as marginally LBW. The long-term risk profile for this substantially large group of children, is not known.

Aim: The aim of this study was to explore cardiovascular risk and neurocognitive development in marginally LBW children born in Sweden.

Method: This was originally a randomized controlled double-blinded trial aiming to explore the effects of iron supplementation in 285 children born with marginally LBW. The children were randomized to receive 0 mg/kg/day (placebo), 1 mg/kg/day or 2 mg/kg/day of iron supplements between 6 weeks and 6 months of age. As part of this observational follow-up study, 95 matched control children born with normal birth weight (NBW, 2501-4500 g) were recruited former to the first follow-up at 3.5-years. This thesis presents data from a follow-up at 7 years, including anthropometric data, blood pressure (BP), body composition (from a dual-energy X-ray absorptiometry) and laboratory markers of cardiovascular risk such as fasting glucose, insulin and lipid profile. Also, the children were tested using the validated neurocognitive tests WISC-IV (Wechsler Intelligence Scale for Children), Beery VMI (Beery-Buktenica developmental test of visual-motor integration) and TEA-Ch (Test of Everyday Attention for Children).

Results: The marginally LBW children were thinner (15.1 vs 15.5 kg/m2, p=0.046), shorter (122.4 vs 124.9 cm, p=0.001) and had a higher prevalence of underweight (10.7 % vs 2.9 %, p=0.050) compared to their NBW peers. In addition, the LBW children had a significantly larger prevalence of high fasting insulin levels (>90th percentile of the control group). The subgroup of children born small for gestational age (SGA) also had a higher mean fasting glucose level, compared to NBW controls. There were no differences in prevalence of overweight or having an adverse lipid profile between the groups. The marginally LBW children who had received iron supplements, as part of the original intervention trial, had approximately 2 mmHg lower systolic BP, compared to the placebo group (p=0.026). The odds of having a high BP was lowered by 68 % (OR 0.32; CI 0.11-0.96) in the supplemented groups.

The marginally LBW children had 3.1 points lower verbal comprehension IQ (p=0.004), 3.5 points lower Beery VMI (p=0.028) and poorer selective attention compared to those born with NBW.

Conclusions: The marginally LBW children were thinner and shorter and they had an imbalanced glucose and insulin homeostasis, particularly those born SGA. Early iron supplements lowered systolic BP to a level similar to controls, suggesting a novel hypothesis regarding a long term protective effect against adverse programming. Finally, the children born with marginally LBW had poorer neurocognitive outcomes, prompting particular attention at school age.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2018. p. 83
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1943
Keywords
Low birth weight, early programming, accelerated catch-up growth, neurodevelopment, cardiovascular risk
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:umu:diva-144215 (URN)978-91-7601-814-9 (ISBN)
Public defence
2018-02-23, Sal D, unodT9, by 1D, plan 9, NUS, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
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Available from: 2018-02-02 Created: 2018-01-26 Last updated: 2018-06-09Bibliographically approved

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Lindberg, JosefineDomellöf, MagnusBerglund, Staffan K.

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