| 1. |
- Berglund, Staffan, 1975-
(författare)
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Effects of iron supplementation on iron status, health and neurological development in marginally low birth weight infants.
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Due to small iron stores and rapid growth during the first months of life, infants with low birth weight (LBW) are at risk of iron deficiency (ID). ID in infancy is associated with irreversible impaired neurodevelopment. Preventive iron supplementation may reduce the risk of ID and benefit neurodevelopment, but there is also a possible risk of adverse effects. More than 50% of all LBW infants are born with marginally LBW (MLBW, 2000-2500g), and it is not known if they benefit from iron supplementation. Methods We randomized 285 healthy, Swedish, MLBW infants to receive 3 different doses of oral iron supplements; 0 (Placebo), 1, and 2 mg/kg/day from six weeks to six months of age. Iron status, during and after the intervention was assessed and so was the prevalence of ID and ID anemia (IDA), growth, morbidity and the interplay with iron and the erythropoetic hormones hepcidin and erythropoietin (EPO). As a proxy for conduction speed in the developing brain, auditory brainstem response (ABR) was analyzed at six months. In a follow up at 3.5 years of age, the children were assessed with a cognitive test (WPPSI-III) and a validated parental checklist of behavioral problems (CBCL), and compared to a matched reference group of 95 children born with normal birth weight. Results At six months of age, the prevalence of ID and IDA was significantly higher in the placebo group compared to the iron supplemented infants. 36% had ID in the placebo group, compared to 8% and 4 % in the 1 and 2mg/kg/day-groups, respectively. The prevalence of IDA was 10%, 3% and 0%, respectively. ABR-latencies did not correlate with the iron intake and was not increased in infants with ID or IDA. ABR wave V latencies were similar in all three groups. Hepcidin correlated to ferritin and increased in supplemented infants while EPO, which was negatively correlated to iron status indicators, decreased. At follow up there were no differences in cognitive scores between the groups but the prevalence of behavioral problems was significantly higher in the placebo group compared to those supplemented and to controls. The relative risk increase of CBCL-scores above a validated cutoff was 4.5 (1.4 – 14.2) in the placebo-group compared to supplemented children. There was no detected difference in growth or morbidity at any age. Conclusion MLBW infants are at risk of ID in infancy and behavioral problems at 3 years of age. Iron supplementation at a dose of 1-2 mg/kg/day from six weeks to six months of age reduces the risks with no adverse effects, suggesting both short and long term benefit. MLBW infants should be included in general iron supplementation programs during their first six months of life.
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| 2. |
- Berglund, Staffan K., et al.
(författare)
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Effects of iron supplementation of low-birth-weight infants on cognition and behavior at 7 years : a randomized controlled trial
- 2018
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Ingår i: Pediatric Research. - New York : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 83, s. 111-118
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Tidskriftsartikel (refereegranskat)abstract
- Background Low-birth-weight infants (LBW) are at an increased risk of iron deficiency that has been associated with impaired neurodevelopment. We hypothesized that iron supplementation of LBW infants improves cognitive scores and reduces behavioral problems until school age.Methods We randomized 285 marginally LBW (2,000-2,500 g) infants to receive 0, 1, or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age. At 7 years of age, 205 participants were assessed regarding cognition using Wechsler Intelligence Scale for Children (WISC-IV) and behavior using the parental questionnaires Child Behavior Checklist (CBCL) and Five to Fifteen (FTF).Results There were no significant differences between the intervention groups in WISC-IV or FTF. However, the CBCL scores for externalizing problems were significantly different, in favor of supplemented children (P=0.045). When combining the supplemented groups, they had significantly lower scores for externalizing behavior compared with placebo (median (interquartile range): 44 [34;51] vs. 48.5 [41;56] P=0.013), and their risk ratio (95% confidence interval) for a total behavioral score above the cutoff for clinical problems was 0.31 (0.09-1.0), P=0.054.Conclusion Lower scores of externalizing behavior in supplemented children support our previous findings at 3 years, and suggest that iron supplementation may have long-lasting effects on behavioral functions.
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| 3. |
- Berglund, Staffan K, et al.
(författare)
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Effects of iron supplements and perinatal factors on fetal hemoglobin disappearance in LBW infants
- 2014
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Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 76:5, s. 477-482
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Tidskriftsartikel (refereegranskat)abstract
- 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 (2,000-2,500g) 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.
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| 4. |
- Berglund, Staffan K., et al.
(författare)
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Hepcidin is a relevant iron status indicator in infancy : results from a randomized trial of early vs. delayed cord clamping
- 2021
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Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 89:5, s. 1216-1221
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate whether serum hepcidin is a useful indicator of iron status in infants.Methods: Term infants (n = 400) were randomized to delayed (≥180 s) or early (≤10 s) cord clamping (CC). Iron status was assessed at 4 and 12 months. In all cases with iron depletion or iron deficiency (ID) (as defined in “Methods”) (n = 30) and 97 randomly selected iron-replete infants, we analyzed hepcidin and explored its correlation to the intervention, iron status, and perinatal factors.Results: Serum hepcidin concentrations were significantly lower in the early CC group at both time points and in ID infants at 4 months. Median (2.5th–97.5th percentile) hepcidin in non-ID infants in the delayed CC group (suggested reference) was 64.5 (10.9–142.1), 39.5 (3.5–157.7), and 32.9 (11.2–124.2) ng/mL in the cord blood and at 4 and 12 months, respectively. The value of 16 ng/mL was a threshold detecting all cases of iron depletion/ID at 4 months. No similar threshold for ID was observed at 12 months. The strongest predictor of hepcidin at both ages was ferritin.Conclusions: Hepcidin is relevant as iron status indicator in early infancy and may be useful to detect ID. Levels <16 ng/mL at 4 months of age indicates ID.ImpactSerum hepcidin is a relevant indicator of iron status in early infancy.Normal reference in healthy infants is suggested in this study.Serum hepcidin may be useful in clinical practice to detect iron deficiency.
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| 5. |
- Berglund, Staffan K., et al.
(författare)
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Iron deficiency in infancy : current insights
- 2021
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Ingår i: Current opinion in clinical nutrition and metabolic care. - : Wolters Kluwer. - 1363-1950 .- 1473-6519. ; 24:3, s. 240-245
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE OF REVIEW: Iron deficiency is the most common micronutrient deficiency and infants are at particular risk. The purpose of this review is to summarize recent studies that explored the metabolism of iron in infants as well as the risks and benefits of iron supplementation in different populations.RECENT FINDINGS: The ability of infants to regulate iron homeostasis is not fully known but most likely different from adults. Reducing iron deficiency has beneficial effects on neurodevelopment but iron overload may have adverse functional effects including diarrhea and even poor neurodevelopment. Recent studies have confirmed benefits of delayed cord clamping and supplementation of infants in risk groups while iron supplementation to pregnant women has shown limited effect in the offspring with regard to iron status and neurodevelopment. Further support is given to the recommendation that exclusive breast feeding, without supplementation, is safe for normal birth weight infants until 6 months whereafter an iron-rich diet should be given.SUMMARY: Iron deficiency negatively impacts global health but efforts to identify optimal interventions are progressing. Yet, questions remain, particularly regarding long-term risks, benefits and optimal interventions for low birth weight infants as well as the level of iron fortification in infant formula.
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| 6. |
- Berglund, Staffan K, et al.
(författare)
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Iron Supplementation Until 6 Months Protects Marginally Low-Birth-Weight Infants From Iron Deficiency During Their First Year of Life
- 2015
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Lippincott Williams & Wilkins. - 0277-2116 .- 1536-4801. ; 60:3, s. 390-395
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Low-birth-weight (LBW) infants (<2500 g) have an increased risk of iron deficiency (ID) during their first 6 months of life. The optimal dose and duration of iron supplementation to LBW infants are, however, unknown. The objective of the present study was to investigate the long-term effect on iron status and growth in marginally LBW (2000-2500 g) infants, of iron supplements given until 6 months of life. Methods: In a randomized controlled trial, 285 healthy marginally LBW infants received 0, 1, or 2 mg . kg(-1).day(-1) of iron supplements from 6 weeks to 6 months of age: At 12 months and 3.5 years of life we measured length, weight, head circumference, and indicators of iron status (hemoglobin, ferritin, mean corpuscular volume, and transferrin saturation) and assessed the prevalence of iron depletion, functional ID, and ID anemia. Results: At 12 months of age, there was a significant difference in ferritin between the groups (P = 0.00 6). Furthermore, there was a significant difference in the prevalence of iron depletion (23.7%, 10.6%, and 6.8%, respectively, in the placebo, 1-mg, and 2-mg groups, P = 0.009) and similar nonsignificant trends for functional ID and ID anemia. At 3.5 years of life there were no significant differences in iron status and the mean prevalence of iron depletion was 3.2%. Anthropometric data were not affected by the intervention. Conclusions: Iron supplements with 2 mg . kg(-1) . day(-1) until 6 months of life effectively reduces the risk of ID during the first 12 months of life and is an effective intervention for preventing early ID in marginally LBW infants.
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| 7. |
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| 8. |
- Berglund, Staffan K., et al.
(författare)
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Marginally low birth weight increases the risk of underweight and short stature at three and a half years of age
- 2016
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 105:6, s. 610-617
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Little is known about the long-term health of marginally low birth weight (LBW) children. This study characterised growth among infants weighing 2,000g-2,500g 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.
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| 9. |
- Berglund, Staffan K., et al.
(författare)
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Maternal, fetal and perinatal alterations associated with obesity, overweight and gestational diabetes : an observational cohort study (PREOBE)
- 2016
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Maternal overweight, obesity, and gestational diabetes (GD) have been negatively associated with offspring development. Further knowledge regarding metabolic and nutritional alterations in these mother and their offspring are warranted.Methods: In an observational cohort study we included 331 pregnant women from Granada, Spain. The mothers were categorized into four groups according to BMI and their GD status; overweight (n:56), obese (n:64), GD (n:79), and healthy normal weight controls (n:132). We assessed maternal growth and nutritional biomarkers at 24 weeks (n = 269), 34 weeks (n = 310) and at delivery (n = 310) and the perinatal characteristics including cord blood biomarkers.Results: Obese and GD mothers had significantly lower weight gain during pregnancy and infant birth weight, waist circumference, and placental weight were higher in the obese group, including a significantly increased prevalence of macrosomia. Except for differences in markers of glucose metabolism (glucose, HbA1c, insulin and uric acid) we found at some measures that overweight and/or obese mothers had lower levels of transferrin saturation, hemoglobin, Vitamin B12 and folate and higher levels of C-reactive protein, erythrocyte sedimentation rate, ferritin, and cortisol. GD mothers had similar differences in hemoglobin and C-reactive protein but higher levels of folate. The latter was seen also in cord blood.Conclusions: We identified several metabolic alterations in overweight, obese and GD mothers compared to controls. Together with the observed differences in infant anthropometrics, these may be important biomarkers in future research regarding the programming of health and disease in children.
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| 10. |
- Berglund, Staffan K., et al.
(författare)
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The impacts of maternal iron deficiency and being overweight during pregnancy on neurodevelopment of the offspring
- 2017
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Ingår i: British Journal of Nutrition. - : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 118:7, s. 533-540
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Tidskriftsartikel (refereegranskat)abstract
- Both maternal Fe deficiency (ID) and being overweight or obese (Ow/Ob, BMI >= 25 kg/m(2)) may negatively affect offspring brain development. However, the two risk factors correlate and their independent effects on infant neurodevelopment are unclear. PREOBE is a prospective observational study that included 331 pregnant Spanish women, of whom 166 had pre-gestational Ow/Ob. Fe status was analysed at 34 weeks and at delivery, and babies were assessed using Bayley III scales of neurodevelopment at 18 months. In confounder-adjusted analyses, maternal ID at 34 weeks was associated with lower composite motor scores at 18 months (mean 113.3 (SD 9.9) v. 117.1 (SD 9.2), P=0.039). Further, the offspring of mothers with ID at delivery had lower cognitive scores (114.0 (SD 9.7) v. 121.5 (SD 10.9), P = 0.039) and lower receptive, expressive and composite (99.5 (SD 8.6) v. 107.6 (SD 8.3), P= 0.004) language scores. The negative associations between maternal ID at delivery and Bayley scores remained even when adjusting for maternal Ow/Ob and gestational diabetes. Similarly, maternal Ow/Ob correlated with lower gross motor scores in the offspring (12.3 (SD 2.0) v. 13.0 (SD 2.1), P = 0.037), a correlation that remained when adjusting for maternal ID. In conclusion, maternal ID and pre-gestational Ow/Ob are both negatively associated with Bayley scores at 18 months, but independently and on different subscales. These results should be taken into account when considering Fe supplementation for pregnant women.
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