Motor development related to duration of exclusive breastfeeding, B vitamin status and B12 supplementation in infants with a birth weight between 2000-3000 g, results from a randomized intervention trial

Background: Exclusive breastfeeding for 6 months is assumed to ensure adequate micronutrients for term infants. Our objective was to investigate the effects of prolonged breastfeeding on B vitamin status and neurodevelopment in 80 infants with subnormal birth weights (2000-3000 g) and examine if cobalamin supplementation may benefit motor function in infants who developed biochemical signs of impaired cobalamin function (total homocysteine (tHcy) > 6.5 μmol/L) at 6 months. Methods: Levels of cobalamin, folate, riboflavin and pyridoxal 5´-phosphate, and the metabolic markers tHcy and methylmalonic acid (MMA), were determined at 6 weeks, 4 and 6 months (n = 80/68/66). Neurodevelopment was assessed with the Alberta Infants Motor Scale (AIMS) and the parental questionnaire Ages and Stages (ASQ) at 6 months. At 6 months, 32 of 36 infants with tHcy > 6.5 μmol/L were enrolled in a double blind randomized controlled trial to receive 400 μg hydroxycobalamin intramuscularly (n = 16) or sham injection (n = 16). Biochemical status and neurodevelopment were evaluated after one month. Results: Except for folate, infants who were exclusively breastfed for >1 month had lower B vitamin levels at all assessments and higher tHcy and MMA levels at 4 and 6 months. At 6 months, these infants had lower AIMS scores (p = 0.03) and ASQ gross motor scores (p = 0.01). Compared to the placebo group, cobalamin treatment resulted in a decrease in plasma tHcy (p < 0.001) and MMA (p = 0.001) levels and a larger increase in AIMS (p = 0.02) and ASQ gross motor scores (p = 0.03). Conclusions: The findings suggest that prolonged exclusive breastfeeding may not provide sufficient B vitamins for small infants, and that this may have a negative effect on early gross motor development. In infants with mild cobalamin deficiency at 6 months, cobalamin treatment significantly improvement cobalamin status and motor function, suggesting that the observed impairment in motor function associated with long-term exclusive breastfeeding, may be due to cobalamin deficiency.publishedVersio

Device-measured physical activity and cardiovascular disease risk in adolescent childhood cancer survivors. A physical activity in childhood cancer survivors (PACCS) study

Objectives: We aimed to compare cardiovascular disease (CVD) risk factors in childhood cancer survivors (CCS) with age- and sex-stratified reference material and examine the association between physical activity (PA) intensities and CVD risk factors in CCS. Materials and methods: Within the cross-sectional, multicenter Physical Activity in Childhood Cancer Survivors (PACCS) study, we collected data on CVD risk factors [VO2-peak (mL⋅kg-1⋅min-1), body mass index (BMI, kg/m2), systolic blood pressure (SBP, mmHg), and total-cholesterol/HDL-cholesterol (Total/HDL)] among CCS aged 9-18 years. CVD risk factors were compared to references with immediate t-tests. We transformed CVD risk factors into z-scores based on international references and generated an individual CVD risk score: [inverse ZVO2-peak + Z BMI + Z SBP + Z Total/HDL )/4]. Multivariable mixed linear regression models were used to analyze the associations between device-measured PA intensities and CVD risk factors. Results: We included 157 CCS aged on average 13.4 years at inclusion and 8.2 years from diagnosis. Male CCS had lower VO2-peak compared to references (45.4 vs. 49.4 mL⋅kg-1⋅min-1, P = 0.001), higher diastolic BP (67 vs. 63 mmHg, P < 0.001), lower HDL (1.35 vs. 1.44 mmol/L, P = 0.012), as well as a tendency to higher CVD risk score (z-score=0.14 vs. 0.00, P = .075). Female CCS' CVD risk factors were comparable to references. Vigorous-intensity PA (VPA) was associated with CVD risk factors. A 10-min increase in VPA was associated with higher VO2-peak (β = 4.9, 95% CI, 2.1-7.7), lower Total/HDL (β = -0.3, 95% CI, -0.6 to -0.1) and a lower CVD risk score (β = -0.4, 95% CI, -0.6 to -0.2). Conclusion: Male adolescent CCS had less favorable values of CVD risk factors compared to references. VPA in adolescent CCS is associated with clinically meaningful favorable values of CVD risk factors. Keywords: accelerometry; cardiometabolic risk; cardiovascular disease risk; childhood cancer survivors; physical activity

The Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) Study: Protocol for an International Mixed Methods Study

BACKGROUND Survivors of childhood cancer represent a growing population with a long life expectancy but high risks of treatment-induced morbidity and premature mortality. Regular physical activity (PA) may improve their long-term health; however, high-quality empirical knowledge is sparse. OBJECTIVE The Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) study comprises 4 work packages (WPs) aiming for the objective determination of PA and self-reported health behavior, fatigue, and quality of life (WP 1); physical fitness determination (WP 2); the evaluation of barriers to and facilitators of PA (WP 1 and 3); and the feasibility testing of an intervention to increase PA and physical fitness (WP 4). METHODS The PACCS study will use a mixed methods design, combining patient-reported outcome measures and objective clinical and physiological assessments with qualitative data gathering methods. A total of 500 survivors of childhood cancer aged 9 to 18 years with ≥1 year after treatment completion will be recruited in follow-up care clinics in Norway, Denmark, Finland, Germany, and Switzerland. All participants will participate in WP 1, of which approximately 150, 40, and 30 will be recruited to WP 2, WP3, and WP 4, respectively. The reference material for WP 1 is available from existing studies, whereas WP 2 will recruit healthy controls. PA levels will be measured using ActiGraph accelerometers and self-reports. Validated questionnaires will be used to assess health behaviors, fatigue, and quality of life. Physical fitness will be measured by a cardiopulmonary exercise test, isometric muscle strength tests, and muscle power and endurance tests. Limiting factors will be identified via neurological, pulmonary, and cardiac evaluations and the assessment of body composition and muscle size. Semistructured, qualitative interviews, analyzed using systematic text condensation, will identify the perceived barriers to and facilitators of PA for survivors of childhood cancer. In WP 4, we will evaluate the feasibility of a 6-month personalized PA intervention with the involvement of local structures. RESULTS Ethical approvals have been secured at all participating sites (Norwegian Regional Committee for Medical Research Ethics [2016/953 and 2018/739]; the Oslo University Hospital Data Protection Officer; equivalent institutions in Finland, Denmark [file H-19032270], Germany, and Switzerland [Ethics Committee of Northwestern and Central Switzerland, project ID: 2019-00410]). Data collection for WP 1 to 3 is complete. This will be completed by July 2022 for WP 4. Several publications are already in preparation, and 2 have been published. CONCLUSIONS The PACCS study will generate high-quality knowledge that will contribute to the development of an evidence-based PA intervention for young survivors of childhood cancer to improve their long-term care and health. We will identify physiological, psychological, and social barriers to PA that can be targeted in interventions with immediate benefits for young survivors of childhood cancer in need of rehabilitation. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/35838

Systolic myocardial function measured by echocardiographic speckle-tracking and peak oxygen consumption in pediatric childhood cancer survivors—a PACCS study

BackgroundCancer therapy-related cardiotoxicity is a major cause of cardiovascular morbidity in childhood cancer survivors. The aims of this study were to investigate systolic myocardial function and its association to cardiorespiratory fitness in pediatric childhood cancer survivors.MethodsIn this sub-study of the international study “Physical Activity and fitness in Childhood Cancer Survivors” (PACCS), echocardiographic measures of left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) were measured in 128 childhood cancer survivors aged 9–18 years and in 23 age- and sex-matched controls. Cardiorespiratory fitness was measured as peak oxygen consumption achieved on treadmill and correlated to myocardial function.ResultsMean LV-GLS was reduced in the childhood cancer survivors compared to the controls, −19.7% [95% confidence interval (CI) −20.1% to −19.3%] vs. −21.3% (95% CI: −22.2% to −20.3%) (p = 0.004), however, mainly within normal range. Only 13% of the childhood cancer survivors had reduced LV longitudinal strain z-score. Mean RV-LS was similar in the childhood cancer survivors and the controls, −23.2% (95% CI: −23.7% to −22.6%) vs. −23.3% (95% CI: −24.6% to −22.0%) (p = 0.8). In the childhood cancer survivors, lower myocardial function was associated with lower peak oxygen consumption [correlation coefficient (r) = −0.3 for LV-GLS]. Higher doses of anthracyclines (r = 0.5 for LV-GLS and 0.2 for RV-LS) and increasing time after treatment (r = 0.3 for LV-GLS and 0.2 for RV-LS) were associated with lower myocardial function.ConclusionsLeft ventricular function, but not right ventricular function, was reduced in pediatric childhood cancer survivors compared to controls, and a lower left ventricular myocardial function was associated with lower peak oxygen consumption. Furthermore, higher anthracycline doses and increasing time after treatment were associated with lower myocardial function, implying that long-term follow-up is important in this population at risk

B vitamin and iron status during infancy

Adequate nutrition during infancy is essential to ensure normal growth and development. Since 2001, World Health Organization (WHO) has recommended exclusive breast-feeding for the first 6 months of life, which puts great nutritional demands on the mothers. Breast milk is important for the growing infant, but deficiency of both vitamins D and K have been well described in breastfed infants. There has also been concern about low levels of other micronutrients like iron, cobalamin (vitamin B12) and pyridoxal 5´-phosphate (PLP, the active form of vitamin B6), micronutrients that are important for brain development. Both cobalamin and iron deficiency may cause impaired psychomotor development with potential permanent intellectual defects. Gross motor function is an important marker of neurodevelopment in early infancy and known to be related to micronutrient status. The objectives of this thesis were to 1) investigate whether cobalamin supplementation can normalize the metabolic profile related to cobalamin status commonly observed in breastfed infants, 2) evaluate the effect of cobalamin supplementation in infants with developmental delay and /or feeding difficulties and biochemical signs of a moderate cobalamin deficiency and 3) investigate vitamin B and iron status in infants with a subnormal birth weight (BW) (2000-3000 grams (g)) during the first 6 months of life according to nutrition, and relate this to nutrition and gross motor development. The study included three populations with a total of 309 infants aged 6 weeks to 8 months, and their 298 mothers. These populations and main results are: 1. Healthy term infants with an appropriate BW for gestational age (AGA), n=107. Two-thirds of these mainly breastfed infants aged 1½ – 4 months had moderate cobalamin deficiency judged from total plasma homocysteine (tHcy) level > 6.5 μmol. In a randomized intervention study, cobalamin supplementation changed all markers of impaired cobalamin status toward a profile observed in cobalamin-replete older children and adults. 2. Infants less than 8 months, admitted to a pediatric outpatient clinic at Haukeland University Hospital due to feeding difficulties, subtle neurological symptoms and/or delayed psychomotor development, n=105. The majority of these infants, 80%, had indices of moderate cobalamin deficiency and a randomized intervention study showed that cobalamin supplementation resulted in significant improvements in regurgitations and motor skills compared to infants who were not supplemented. 3. Healthy infants with BW 2000-3000 g, n=97. In these infants with a suboptimal BW, formula feeding was associated with a better B vitamin status and better motor development at 6 months compared to infants who were mainly breastfeed. In infants with a BW ≤ 2500 g, iron supplementation resulted in an improved iron status at 6 months compared to non-supplemented infants with BW 2501 – 3000 g. A high weight gain, exclusively breastfeeding and male gender were associated with a poorer iron status in the non-supplemented infants. As B vitamins and iron play an important role in the development of the brain, an optimal nutrition during the first 6 months is important. Breast milk is important for the infant, but prolonged exclusive breastfeeding during a period characterized by rapid growth and development, may not provide sufficient B vitamins and iron for the infant, particularly for those with a suboptimal BW. We suggest that the recommendation of exclusive breastfeeding for 6 months needs to be reconsidered, and more data on micronutrient status in exclusively breastfed infants are warranted

Impaired gross motor development in infants with higher PFAS concentrations

Industrial produced perfluoroalkyl substances (PFAS) are environmentally persistent and found in humans around the globe. PFAS is transferred from mother to child during pregnancy and lactation and PFAS concentrations are high in infants. PFAS exposure in early life has been linked to a range of negative health effects. In the present study we have investigated PFAS concentrations in mothers (pregnancy week 18, 28 and 36 and six weeks, four and six months postpartum, n = 114) and in infants at six months age (n = 94), and studied the effects of PFAS status on infant gross motor development by Alberta Infant Motor Scale (AIMS) at age six months. PFAS concentrations declined in the mothers during pregnancy and postpartum period, and the highest concentrations were seen in infants aged six months. Parity was a strong negative predictor and fish intake a strong positive predictor of maternal PFAS status, while maternal concentrations of PFAS in pregnancy week 18 and months of exclusive breastfeeding determined the PFAS concentrations in infants at six months. Infants who scored below the median on gross motor development had higher PFAS concentrations than infants with a better gross motor development. Ninety percent of the women reported having fish for dinner at least once a week, with fatty fish as the most popular choice (72%). A higher maternal fish intake in pregnancy week 18 was associated with a poorer gross motor development in the infants at six months. Infant gross motor development is a marker of later cognitive outcome and our findings indicate that higher PFAS concentrations in young infants and maternal fatty fish intake may impair neurodevelopment

Impaired gross motor development in infants with higher PFAS concentrations

Industrial produced perfluoroalkyl substances (PFAS) are environmentally persistent and found in humans around the globe. PFAS is transferred from mother to child during pregnancy and lactation and PFAS concentrations are high in infants. PFAS exposure in early life has been linked to a range of negative health effects. In the present study we have investigated PFAS concentrations in mothers (pregnancy week 18, 28 and 36 and six weeks, four and six months postpartum, n = 114) and in infants at six months age (n = 94), and studied the effects of PFAS status on infant gross motor development by Alberta Infant Motor Scale (AIMS) at age six months. PFAS concentrations declined in the mothers during pregnancy and postpartum period, and the highest concentrations were seen in infants aged six months. Parity was a strong negative predictor and fish intake a strong positive predictor of maternal PFAS status, while maternal concentrations of PFAS in pregnancy week 18 and months of exclusive breastfeeding determined the PFAS concentrations in infants at six months. Infants who scored below the median on gross motor development had higher PFAS concentrations than infants with a better gross motor development. Ninety percent of the women reported having fish for dinner at least once a week, with fatty fish as the most popular choice (72%). A higher maternal fish intake in pregnancy week 18 was associated with a poorer gross motor development in the infants at six months. Infant gross motor development is a marker of later cognitive outcome and our findings indicate that higher PFAS concentrations in young infants and maternal fatty fish intake may impair neurodevelopment

Impact of Maternal Selenium Status on Infant Outcome during the First 6 Months of Life

Pregnant women and infants are at risk for selenium deficiency, which is known to have negative effects on immune and brain function. We have investigated selenium levels in 158 healthy never-pregnant women and in 114 pregnant and lactating women and their infants at age 6 months and related this to clinical outcomes during the first 6 months of life. Neurodevelopment was assessed with the parental questionnaire Ages and Stages (ASQ) at 6 months. A maternal selenium level ≤0.90 µmol/L in pregnancy week 18 was negatively related to infant neurodevelopment at 6 months (B = −20, p = 0.01), whereas a selenium level ≤0.78 µmol/L in pregnancy week 36 was associated with an increased risk (odds ratio 4.8) of having an infant infection during the first 6 weeks of life. A low maternal selenium status in pregnancy was found to be associated with an increased risk of infant infection during the first 6 weeks of life and a lower psychomotor score at 6 months. We suggest a cutoff for maternal serum selenium deficiency of 0.90 µmol/L in pregnancy week 18 and 0.78 µmol/L in pregnancy week 36. This should be reevaluated in an intervention study