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Neurodevelopment and cardiovascular risk in 7-year old children born with marginally low birth weight
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.ORCID iD: 0000-0001-7341-8254
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 [en]
Low birth weight, early programming, accelerated catch-up growth, neurodevelopment, cardiovascular risk
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
URN: urn:nbn:se:umu:diva-144215ISBN: 978-91-7601-814-9 (print)OAI: oai:DiVA.org:umu-144215DiVA, id: diva2:1177858
Public defence
2018-02-23, Sal D, unodT9, by 1D, plan 9, NUS, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2018-02-02 Created: 2018-01-26 Last updated: 2018-06-09Bibliographically approved
List of papers
1. Overweight, Obesity, and Body Composition in 3.5-and 7-Year-Old Swedish Children Born with Marginally Low Birth Weight
Open this publication in new window or tab >>Overweight, Obesity, and Body Composition in 3.5-and 7-Year-Old Swedish Children Born with Marginally Low Birth Weight
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2015 (English)In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 167, no 6, p. 1246-1252.e3Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-113853 (URN)10.1016/j.jpeds.2015.08.045 (DOI)000366143900018 ()26394823 (PubMedID)
Available from: 2016-03-13 Created: 2016-01-04 Last updated: 2018-06-07Bibliographically approved
2. Early signs of cardiovascular risk at 7 years of age in children born with marginally low birth weight
Open this publication in new window or tab >>Early signs of cardiovascular risk at 7 years of age in children born with marginally low birth weight
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Low birth weight (LBW, <2500 g) may predict an increased risk of an adverse cardiovascular profile later in life, but the magnitude in different settings and age at appearance are still unclear. We explored laboratory markers of cardiovascular risk inchildren born with marginally LBW (2000-2500 g).

Methods: This was a prospective observational study including 285 Swedish marginally LBW children and 95 normal birth weight (NBW, 2501-4500 g) controls. At 3.5 and 7 years of age, blood samples for glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), high-sensitive C-reactive protein (hs-CRP), cholesterol, triglycerides, high- and low-density lipoprotein (HDL and LDL), apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) were assessed and compared between the groups.

Results: No significant differences in levels of insulin, HOMA-IR, hs-CRP or blood lipids were observed between marginally LBW and NBW children. However, at 7 years there was a higher proportion of marginally LBW children with elevated levels of insulin, defined as above the 90th percentile of the control group (21 % vs 8.6 %, p=0.038). Furthermore, in marginally LBW children born small for gestational age, fasting glucose was significantly higher compared to controls (4.7 vs 4.5 mmol/L, p=0.020).

Conclusions: While there were no significant differences in lipid profile or hs-CRP between marginally LBW children and controls, marginally LBW children showed, already at age 7, increased prevalence of elevated insulin levels, partly confounded by maternal birth country. The results indicate that a long-term risk of imbalanced glucose homeostasis is present, also in this common group of LBW children.

National Category
Pediatrics
Research subject
Pediatrics; Internal Medicine
Identifiers
urn:nbn:se:umu:diva-144213 (URN)
Available from: 2018-01-26 Created: 2018-01-26 Last updated: 2018-06-09Bibliographically approved
3. 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
Open this publication in new window or tab >>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
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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.

Keywords
Barker hypothesis, blood pressure, cardiovascular risk, early programming, hypertension, iron supplementation, low birth weight
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-138590 (URN)10.3945/ajcn.116.150482 (DOI)000406672300009 ()
Available from: 2017-09-21 Created: 2017-09-21 Last updated: 2018-06-09Bibliographically approved
4. Lower cognitive test scores at age 7 in children born with marginally low birth weight
Open this publication in new window or tab >>Lower cognitive test scores at age 7 in children born with marginally low birth weight
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2018 (English)In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447Article in journal (Refereed) Accepted
Abstract [en]

Background: Being born with very low birth weight (<1500 g) is associated with poorer neurocognition later in life. The aim of this study was to explore neurodevelopmental functions in those born with marginally low birth weight (marginally LBW; 2000-2500 g).

Methods: This was originally a randomized controlled trial investigating the effects of early iron supplementation in 285 marginally LBW children. Herein, we explored the combined marginally LBW group and compared their results to 95 normal birth weight (NBW; 2501-4500 g) controls in an observational design. At 7 years, a paediatric psychologist tested the children using 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 had lower verbal comprehension IQ (104 vs 107, p=0.004), lower VMI-scores (96.5 vs 100, p=0.028) and lower total mean TEA-Ch scores (8.5 vs 9.7, p=0.006), compared to controls. Also, the marginally LBW children had a higher proportion of children below -1 SD for VMI and TEA-Ch.

Conclusions: Marginally LBW children had lower verbal comprehension IQ, lower visual-motor integration, and lower attention performance than NBW children, suggesting an increased risk of cognitive difficulties in early school age.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Pediatrics
Research subject
Pediatrics; Neurology; Psychiatry
Identifiers
urn:nbn:se:umu:diva-144211 (URN)
Available from: 2018-01-26 Created: 2018-01-26 Last updated: 2018-06-09

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