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Early signs of cardiovascular risk at 7 years of age in children born with marginally low birth weight
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.ORCID iD: 0000-0001-7341-8254
Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.ORCID iD: 0000-0003-4191-3781
Division of Neonatology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.ORCID iD: 0000-0002-3187-067X
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.ORCID iD: 0000-0002-0726-7029
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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: urn:nbn:se:umu:diva-144213OAI: oai:DiVA.org:umu-144213DiVA, id: diva2:1177830
Available from: 2018-01-26 Created: 2018-01-26 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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Supervisors
Available from: 2018-02-02 Created: 2018-01-26 Last updated: 2018-06-09Bibliographically approved

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Starnberg, JosefineNorman, MikaelWestrup, BjörnDomellöf, MagnusBerglund, Staffan

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