Assessment of vitamin B6 status in never-pregnant, pregnant and postpartum women and their infants.

PURPOSE: Pyridoxal 5´-phosphate (PLP) is the main form of vitamin B6 in humans and functions a coenzyme for more than 160 different enzymatic reactions. The purpose of the study was to find plasma PLP concentrations, which ensure an optimal vitamin B6 status determined by a metabolic marker, in never-pregnant, pregnant and lactating women and their infants. METHODS: In an observational, prospective study, plasma PLP and the metabolic marker, HKr (hydroxykynurenine/(kynurenic acid + anthranilic acid + xanthurenic acid + hydroxyanthranilic acid) were assessed in women (n = 114) from pregnancy week 18 to 6 months postpartum and related to infant status. Never-pregnant women 18-40 years (n = 127) were included as controls. RESULTS: Compared to controls, plasma PLP decreased during pregnancy and increased postpartum, while HKr increased from week 18 to 6 weeks postpartum, indicating maternal vitamin B6 insufficiency during this period. In never-pregnant women, HKr increased gradually with plasma PLP < 100 nmol/L, and in pregnancy week 28 a sharp increase in HKr was seen at plasma PLP < 30 nmol/L. Despite correcting for maternal vitamin B6 status, infant median plasma PLP decreased with months of exclusive breastfeeding. CONCLUSIONS: Plasma PLP and kynurenine concentrations differ substantially between never-pregnant, pregnant and postpartum women and infants. A plasma PLP concentration in the range of 50-100 nmol/L seems to ensure an optimal vitamin B6 status for never-pregnant women, whereas a plasma PLP > 30 nmol/L in pregnancy week 28 ensures an adequate vitamin B6 status during pregnancy and lactation. Infant vitamin B6 status at age 6 months is inversely correlated to number of months of exclusive breastfeeding.

Dietary behaviors and attitudes among Norwegian medical students.

BACKGROUND: Dietary patterns and beliefs are influenced by socioeconomic status, cultural influences, as well as medical advice, social media and marketing. Medical doctors are expected to provide correct, updated and non-biased nutritional advice to their patients, but their own dietary behaviors and attitudes may influence nutritional counselling. METHODS: We have investigated dietary habits and food attitudes among medical students by using an anonymous survey distributed to all students at the Medical Faculty, University of Bergen, Norway. The survey included a 36-item questionnaire covering information about demographics, former and current diet, use of nutritional supplements, tobacco and alcohol, in addition to food attitudes and nutritional knowledge. Descriptive statistics were calculated for each survey item. RESULTS: Of the 880 students, 394 responded to the survey. Although 90% of the students were omnivores, the majority had a negative attitude towards meat, and considered fish to be healthier than meat. Significantly more women than men reported use of a special diet and excluded meat from their diet, even if they were omnivores. The most frequently used supplement was cod liver oil or omega 3 fatty acids. CONCLUSION: The medical students' diet and food attitudes not only reflect current health recommendations, but also popular beliefs and marketing in Norway. Curriculum planners should make the students capable of recognizing the influence of social media, marketing and medicine-food industry interactions, to ensure relevant nutrition knowledge for future doctors.

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.

Nitrous oxide in labour predicted newborn screening total homocysteine and is a potential risk factor for infant vitamin B12 deficiency.

AIM: Risk factors for vitamin B12 deficiency in infants are not fully understood. The aim of the study was to assess predictors of total homocysteine and methylmalonic acid analysed in newborn screening dried blood spots. METHODS: In a Norwegian case control study, we analysed total homocysteine and methylmalonic acid in newborn screening dried blood spots of 86 infants clinically diagnosed with vitamin B12 deficiency during 2012-2018. Results were compared to 252 healthy infants and 400 dried blood spot controls. Medical records were reviewed, and mothers completed questionnaires. RESULTS: Both total homocysteine and methylmalonic acid were significantly higher on newborn screening dried blood spots in infants later clinically diagnosed with vitamin B12 deficiency than controls. Multiple regression analysis showed that the dose of nitrous oxide during labour was the strongest predictor for total homocysteine level in newborn screening dried blood spots for all infants, with larger effect in infants later clinically diagnosed with vitamin B12 deficiency than controls. CONCLUSION: Nitrous oxide dose during labour was a predictor for total homocysteine and may impact the interpretation of total homocysteine analysis in newborn screening. Nitrous oxide is suggested as a contributing risk factor for infants prone to develop vitamin B12 deficiency.

Vitamin B status and association with antiseizure medication in pregnant women with epilepsy.

OBJECTIVE: Antiseizure medication (ASM) use interacts with vitamin B status in nonpregnant epilepsy populations. We aimed to examine the association between ASM and vitamin B status in pregnant women with epilepsy. METHODS: We performed a cross-sectional study of pregnancies in women with epilepsy enrolled in the Norwegian Mother, Father and Child Cohort Study from 1999 to 2008. Data on ASM and vitamin supplement use were collected from questionnaires. We analyzed maternal plasma concentrations of ASM and metabolites of folate, including unmetabolized folic acid (UMFA), riboflavin (vitamin B2), pyridoxine (vitamin B6), and niacin (vitamin B3) during gestational weeks 17-19. RESULTS: We included 227 singleton pregnancies exposed to ASM with available plasma samples (median maternal age 29 years, range 18 to 41 years). From the preconception period to gestational week 20, any supplement of folic acid was reported in 208 of pregnancies (94%), riboflavin in 72 (33%), pyridoxine in 77 (35%), and niacin in 45 (20%). High ASM concentrations correlated with high concentrations of UMFA and inactive folate metabolites, and with low concentrations of riboflavin and metabolically active pyridoxine. There was no association between ASM and niacin status. SIGNIFICANCE: ASM concentrations during pregnancy were associated with vitamin B status in pregnant women with epilepsy. Additional studies are needed to determine the clinical impact of these findings, and to define the optimal vitamin doses that should be recommended to improve pregnancy outcomes.

Serum concentrations of C-reactive protein in healthy term-born Norwegian infants 48-72 hours after birth.

AIM: To determine serum C-reactive protein (CRP) concentrations in healthy term-born infants shortly after birth. METHODS: We sampled blood from 182 infants along with the routine neonatal screening programme at 48-72 hours of age from consecutively recruited healthy infants without signs of infection and a gestational age (GA) of at least 37 weeks. The blood was stored at minus 20°C until analysis in one assay after the end of the study. RESULTS: The CRP levels were positively skewed. The median concentration was 5.0 mg/L, 48.9% of the neonates had values <5.0 mg/L, 19.8% ≥10.0 mg/L, 7.1% ≥20.0 mg/L and 1.1% (2 neonates) >30 mg/L. The CRP level was positively related to GA and duration of labour, slightly higher in boys than girls and after vaginal compared to Caesarean delivery. CONCLUSION: In healthy neonates born at term, the CRP concentrations did not vary substantially with various common perinatal clinical conditions, and levels above 30 mg/L were uncommon at two to three days of age.

Maternal Serum Cobalamin at 18 Weeks of Pregnancy Predicts Infant Cobalamin Status at 6 Months-A Prospective, Observational Study.

Background: An adequate maternal cobalamin status is crucial for fetal and infant neurodevelopment. Pregnancy-induced physiologic changes make evaluation of maternal cobalamin status in pregnancy difficult. Objective: We have investigated maternal cobalamin status during pregnancy in order to establish a maternal cobalamin concentration which secures an optimal infant cobalamin status during the first 6 mo of life. Methods: In an observational, prospective study, markers of cobalamin status including serum cobalamin, plasma total homocysteine (tHcy), and plasma methylmalonic acid (MMA) were assessed in healthy pregnant women (n = 114) from week 18 of pregnancy through 6 mo postpartum and related to infant cobalamin status at 6 mo. Healthy, never-pregnant women aged 18-40 y (n = 123) were included as controls. Results: Compared to controls, all markers of cobalamin status were lower in pregnant women. Median serum cobalamin concentration progressively decreased from week 18 to week 36 of pregnancy (356 to 302 pmol/L, P < 0.001) and increased by >40% by 6 wk postpartum (518 pmol/L). The metabolic markers increased from week 18 of pregnancy to 6 wk postpartum: median plasma tHcy 3.9 to 7.7 µmol/L (P < 0.001), and MMA 0.13 to 0.17 µmol/L (P < 0.001). The serum cobalamin concentration of infants at age 6 mo correlated with maternal serum cobalamin concentration during pregnancy and postpartum (rho = 0.36-0.55, P < 0.001). A maternal serum cobalamin concentration <394 pmol/L during week 18 of pregnancy was associated with an increased risk (OR: 4.2; 95% CI: 1.5, 11.5) of infant biochemical cobalamin deficiency at 6 mo (defined as tHcy ≥6.5 µmol/L). Conclusions: The maternal serum cobalamin concentration in early pregnancy is a strong predictor for later maternal and infant cobalamin status. To secure an optimal infant cobalamin status during the first 6 mo of life, we recommend a maternal serum cobalamin concentration >394 pmol/L at week 18 of pregnancy. This should be confirmed in an intervention study. This trial was registered at clinicaltrials.gov as NCT03272022.

Should we eat more fish - or less? / Bør vi spise mer fisk ­ eller mindre?

All food contains environmental toxins. The EU has set a new threshold for the level of environmental toxins that can be considered safe in the body. In Norway, the average intake exceeds this threshold, and fatty fish is the main source. Nevertheless, the Norwegian authorities recommend that all age groups eat more fish.

Increased Bronchial Hyperresponsiveness and Higher Asymmetric Dimethylarginine Levels after Fetal Growth Restriction.

Bronchial hyperresponsiveness (BHR), a feature of asthma, is observed in preterm-born children and has been linked to intrauterine growth restriction. BHR is mediated via airway smooth muscle tone and is modulated by the autonomic nervous system, nitric oxide, and airway inflammation. Interactions among these factors are insufficiently understood. Methacholine-induced BHR (Met-BHR), fractional exhaled NO, and systemic soluble markers of nitric oxide metabolism and inflammation were determined in a population-based sample of 57 eleven-year-old children born extremely preterm (gestational age [GA] < 28 wk) or with extremely low birth weight (<1,000 g), and in a matched normal-birth weight term-born control group (n = 54). Bronchopulmonary dysplasia (BPD) was defined as the need for oxygen treatment at a GA of 36 weeks. In preterm-born children, birth weight below the 10th percentile for GA was associated with increased Met-BHR and higher plasma levels of asymmetric dimethylarginine (ADMA), with an increased odds ratio for being in the upper tertile of Met-BHR (11.8; 95% confidence interval, 3.3-42.4) and of ADMA (5.2; 95% confidence interval, 1.3-20.3). Met-BHR was correlated to ADMA level (r = 0.27, P = 0.007). There were no significant differences in Met-BHR, fractional exhaled NO, or z-FEV1 according to BPD status. No associations with systemic soluble markers of inflammation were observed for Met-BHR, birth, or BPD status. Intrauterine growth restriction in preterm-born children was associated with substantially increased Met-BHR and higher ADMA levels, suggesting altered nitric oxide regulation. These findings contribute to the understanding of the consequences from an adverse fetal environment; they should also be tested in term-born children.

High level of heavy metals in crab meat. / Høyt nivå av tungmetaller i krabbe.

Crab meat is a popular seafood, but it sometimes contains large amounts of environmental toxins. The content is so high in many places in Norway that consumption of brown crab meat should generally be discouraged.

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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01201005.

Folic acid supplementation and interpregnancy interval.

BACKGROUND: Maternal folic acid supplementation between subsequent pregnancies may be important to reduce the risk of low folate status associated with short interpregnancy intervals. We examined how the prevalence of preconception folic acid use for a given pregnancy in Norwegian women varied according to the time interval from the previous pregnancy. METHODS: Analysis was based on 48 855 pairs of pregnancies with the second pregnancy included in the Norwegian Mother and Child Cohort Study (birth years 1999-2009). Interpregnancy interval was defined as the time from birth of a child to the conception of the subsequent sibling. Preconception folic acid use was defined as any use of folic acid-containing supplements within the last 4 weeks before the second pregnancy. RESULTS: The prevalence of preconception folic acid use was 31%. Among women with a term birth (≥37 weeks) in the previous pregnancy (92%), those with interpregnancy intervals ≤12 and ≥49 months were associated with up to 35% lower prevalence of preconception folic acid use for the second pregnancy, relative to the reference group (13-24 months). The low use in short intervals was mainly attributable to lower proportion of planned pregnancies and fewer women with higher education. Among women with a preterm birth (<37 weeks) in the previous pregnancy (8%), preconception folic acid use significantly decreased with increasing pregnancy spacing. CONCLUSIONS: Our finding of a lower preconception folic acid use in women with both short and long interpregnancy intervals might help identifying those with higher risk of folate deficiency and preventing unwanted pregnancy outcomes.