A randomized controlled trial on the effects of blue-blocking glasses compared to partial blue-blockers on sleep outcomes in the third trimester of pregnancy.

OBJECTIVE: Sleep disturbances are common in pregnancy. Blocking blue light has been shown to improve sleep and may be a suitable intervention for sleep problems during pregnancy. The present study investigated the effects of blue light blocking in the evening and during nocturnal awakenings among pregnant women on primary sleep outcomes in terms of total sleep time, sleep efficiency and mid-point of sleep. METHODS: In a double-blind randomized controlled trial, 60 healthy nulliparous pregnant women in the beginning of the third trimester were included. They were randomized, using a random number generator, either to a blue-blocking glass intervention (n = 30) or to a control glass condition constituting partial blue-blocking effect (n = 30). Baseline data were recorded for one week and outcomes were recorded in the last of two intervention/control weeks. Sleep was measured by actigraphy, sleep diaries, the Bergen Insomnia Scale, the Karolinska Sleepiness Scale and the Pre-Sleep Arousal Scale. RESULTS: The results on the primary outcomes showed no significant mean difference between the groups at posttreatment, neither when assessed with sleep diary; total sleep time (difference = .78[min], 95%CI = -19.7, 21.3), midpoint of sleep (difference = -8.9[min], 95%CI = -23.7, 5.9), sleep efficiency (difference = -.06[%], 95%CI = -1.9, 1.8) and daytime functioning (difference = -.05[score points], 95%CI = -.33, .22), nor by actigraphy; total sleep time (difference = 13.0[min], 95%CI = -9.5, 35.5), midpoint of sleep (difference = 2.1[min], 95%CI = -11.6, 15.8) and sleep efficiency (difference = 1.7[%], 95%CI = -.4, 3.7). On the secondary outcomes, the Bergen Insomnia Scale, the Karolinska Sleepiness Scale and the Pre-Sleep Arousal Scale the blue-blocking glasses no statistically significant difference between the groups were found. Transient side-effects were reported in both groups (n = 3). CONCLUSIONS: The use of blue-blocking glasses compared to partially blue-blocking glasses in a group of healthy pregnant participants did not show statistically significant effects on sleep outcomes. Research on the effects of blue-blocking glasses for pregnant women with sleep-problems or circadian disturbances is warranted. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (NCT03114072).

Prevalence of patients "at risk of malnutrition" and nutritional routines among surgical and non-surgical patients at a large university hospital during the years 2008-2018.

BACKGROUND & AIMS: Being "at risk of malnutrition", which includes both malnutrition and the risk to be so, is associated with increased morbidity and mortality in both surgical and non-surgical patients. Several strategies and guidelines have been introduced to prevent and treat this, but the effects are scarcely investigated. This study aims to evaluate the long-term effects of these efforts by examining trends concerning: 1) the prevalence of patients «at risk of malnutrition¼ and 2) the use of nutritional support and diagnostic coding related to malnutrition over an 11-year period in a large university hospital. Moreover, we wanted to investigate if there was a difference in trends between surgical and non-surgical patients. METHODS: From 2008 to 2018, Haukeland University Hospital, Norway, conducted 34 point-prevalence surveys to investigate the prevalence of patients «at risk of malnutrition¼, as defined by Nutritional Risk Screening 2002, and the use of nutritional support at the hospital. Diagnostic coding included ICD-10 codes related to malnutrition (E43, E44 and E46) at hospital discharge, which were extracted from the electronic patient journal. Trend analysis by calendar year was investigated using logistic regression models with and without adjustment for age (continuous), gender (male/female) and Charlson Comorbidity Index (none, mild, moderate or severe). RESULTS: The number of patients included in the study was 18 933, where 52.1% were male and the median (25th, 75th percentile) age was 65 (51, 76) years. Of these, 5121 (27%) patients were identified to be «at risk of malnutrition¼. Fewer surgical patients (21.2%) were «at risk of malnutrition¼, as compared to non-surgical patients (30.9%) (p < 0.001). Adjusted trend analysis did not identify any change in the prevalence of patients «at risk of malnutrition¼ from 2008 to 2018. The percentage of patients «at risk of malnutrition¼ who received nutritional support increased from 61.6% in 2008 to 71.9% in 2018 (p < 0.001), with a range from 55.6 to 74.8%. This trend was seen for both surgical and non-surgical patients (p < 0.001 for both). Similarly, dietitians were more involved in the patients' treatment (range: 3.8-16.7%), and there was increased use of ICD-10 codes related to malnutrition during the study period (range: 13.0-41.8%) (p < 0.001). These trends were seen for both surgical patients and non-surgical patients (p < 0.001), despite use being less common for surgical patients, as compared to non-surgical patients (p < 0.001). CONCLUSIONS: This large hospital study shows no apparent change in the prevalence of patients «at risk of malnutrition¼ from 2008 to 2018. However, more patients «at risk of malnutrition¼, both surgical and non-surgical, received nutritional support, treatment from a dietitian and a related ICD-10 code over the study period, indicating improved nutritional routines as a result of the implementation of nutritional guidelines and strategies.

Nutritional treatment is associated with longer survival in patients with pancreatic disease and concomitant risk of malnutrition.

BACKGROUND: Pancreatic diseases involve complex nutritional challenges. Despite this, conflicting evidence exists regarding the clinical relevance of detecting the risk of malnutrition and implementing systematic nutrition support for these patients. Thus, our aims were to investigate whether screening for malnutrition risk and initiating nutrition support are predictive of mortality for hospitalized patients with pancreatic diseases. DESIGN: From 2008 to 2018, 34 prevalence surveys of nutrition were conducted at Haukeland University Hospital (HUH), Norway. Risk of malnutrition was defined by a score of ≥3 in Nutritional Risk Screening 2002 (NRS 2002). Primary outcomes included overall, one-year, and one-month mortality, and were compared according to malnutrition risk and nutrition support for adult patients with ICD-10 codes of K85: acute pancreatitis, K86: other diseases of pancreas, and C25: malignant neoplasm of pancreas. Length of hospital stay (LOS) was included as a secondary outcome. RESULTS: Of the 283 patients investigated, risk of malnutrition was present in 61.5%. Risk of malnutrition was associated with higher overall mortality (Hazard Ratio (HR) = 1.67, 95% confidence interval (CI): 1.2-2.4, P = 0.003) and one-year mortality (HR = 1.89, 95% CI: 1.2-2.9, P = 0.004) compared to patients not at risk. Not receiving nutrition support for at-risk patients was associated with higher overall mortality (HR = 1.60, 95% CI: 1.1-2.4, P = 0.019) and one-year mortality (HR = 1.64, 95% CI: 1.04-2.6, P = 0.034) compared to patients at risk who received nutrition support. Patients at risk of malnutrition had increased LOS (20.5 nights vs 15.2 nights, P = 0.044) compared to patients not at risk of malnutrition. CONCLUSION: This study of hospitalized patients with pancreatic disease suggests that risk of malnutrition may be associated with higher mortality rates, whereas nutrition support may decrease mortality rates. CLINICAL TRIAL REGISTRY: Not registered.

No association between subnormal serum vitamin B12 and anemia in older nursing home patients.

PURPOSE: Since evidence of an association between vitamin B12 (B12) deficiency and anemia in older people is limited and inconclusive, we wanted to investigate this association in old, frail nursing home patients. METHODS: The study includes patients admitted to short-term, post-acute care (n = 765) and residents in long-term care (LTC) (n = 1665), in the municipality of Bergen. Anemia was defined according to the WHO criteria: Hb < 13 g/dL in men and < 12 g/dL in women, and as Hb < 11 g/dL, in both sex (moderate/severe anemia). The presence of anemia was analyzed in patients with subnormal (< 250 pmol/L), normal (250-650 pmol/L) and high (> 650 pmol/L) B12, and the association between anemia and clinical parameters, and including B12, was analyzed using logistic regression models. The use of B12 supplementation was investigated in the LTC patients. RESULTS: Mean age of the 2430 patients was 86 ± 7 years. WHO-defined anemia was seen in 1023 (42%), and moderate/severe anemia in 384 (16%) of the patients. In multiple logistic regression analyses, we found no statistically significant associations of subnormal B12 with WHO-defined anemia or moderate/severe anemia. Renal insufficiency, iron deficiency and CRP > 10 mg/L were significantly associated with both types of anemia, (p < 0.001). Among the LTC residents, 405 (24%) received B12 supplements, 112 (7%) of them had elevated B12 > 650 pmol/L. CONCLUSION: In older nursing home patients, no association was observed between subnormal B12 and anemia. Older patients in Western societies with mild/moderate anemia should not be treated with B12 supplements without further investigation.

The effect of low dose marine protein hydrolysates on short-term recovery after high intensity performance cycling: a double-blinded crossover study.

BACKGROUND: Knowledge of the effect of marine protein hydrolysate (MPH) supplementation to promote recovery after high intensity performance training is scarce. The aim of this study was to examine the effect of MPH supplementation to whey protein (WP) and carbohydrate (CHO): (CHO-WP-MPH), on short-term recovery following high intensity performance, compared to an isoenergetic and isonitrogenous supplement of WP and CHO: (CHO-WP), in male cyclists. METHODS: This was a double-blinded crossover study divided into three phases. Fourteen healthy men participated. In phase I, an incremental bicycle exercise test was performed for establishment of intensities used in phase II and III. In phase II (9-16 days after phase 1), the participants performed first one high intensity performance cycling session, followed by nutrition supplementation (CHO-WP-MPH or CHO-WP) and 4 hours of recovery, before a subsequent high intensity performance cycling session. Phase III (1 week after phase II), was similar to phase II except for the nutrition supplementation, where the participants received the opposite supplementation compared to phase II. Primary outcome was difference in time to exhaustion between the cycling sessions, after nutrition supplementations containing MPH or without MPH. Secondary outcomes were differences in heart rate (HR), respiratory exchange ratio (RER), blood lactate concentration and glucose. RESULTS: The mean age of the participants was 45.6 years (range 40-58). The maximal oxygen uptake (mean ± SD) measured at baseline was 54.7 ± 4.1 ml∙min- 1∙kg- 1. There were no significant differences between the two nutrition supplementations measured by time to exhaustion at the cycling sessions (meandiff = 0.85 min, p = 0.156, 95% confidence interval (CI), - 0.37, 2.06), HR (meandiff = 0.8 beats pr.min, p = 0.331, 95% CI, - 0.9, 2.5), RER (meandiff = - 0.05, p = 0.361, 95% CI -0.07 - 0.17), blood lactate concentration (meandiff = - 0.24, p = 0.511, 95% CI, - 1.00, 0.53) and glucose (meandiff = 0.23, p = 0.094, 95% CI, - 0.05, 0.51). CONCLUSIONS: A protein supplement with MPH showed no effects on short-term recovery in middle-aged healthy male cyclists compared to a protein supplement without MPH. TRIAL REGISTRATION: The study was registered 02.05.2017 at ClinicalTrials.gov (Protein Supplements to Cyclists, NCT03136133 , https://clinicaltrials.gov/ct2/show/NCT03136133?cond=marine+peptides&rank=1 .

Preconception Folic Acid Supplement Use in Immigrant Women (1999-2016).

This study examines how preconception folic acid supplement use varied in immigrant women compared with non-immigrant women. We analyzed national population-based data from Norway from 1999-2016, including 1,055,886 pregnancies, of which 202,234 and 7,965 were to 1st and 2nd generation immigrant women, respectively. Folic acid supplement use was examined in relation to generational immigrant category, maternal country of birth, and length of residence. Folic acid supplement use was lower overall in 1st and 2nd generation immigrant women (21% and 26%, respectively) compared with Norwegian-born women (29%). The lowest use among 1st generation immigrant women was seen in those from Eritrea, Ethiopia, Morocco, and Somalia (around 10%). The highest use was seen in immigrant women from the United States, the Netherlands, Denmark, and Iceland (>30%). Folic acid supplement use increased with increasing length of residence in immigrant women from most countries, but the overall prevalence was lower compared with Norwegian-born women even after 20 years of residence (adjusted odds ratio: 0.63; 95% confidence interval: 0.60-0.67). This study suggests that immigrant women from a number of countries are less likely to use preconception folic acid supplements than non-immigrant women, even many years after settlement.

Paternal characteristics associated with maternal periconceptional use of folic acid supplementation.

BACKGROUND: Maternal predictors of folic acid (FA) supplementation use to reduce offspring risk of neural tube defects are well known, while paternal determinants for maternal FA use are less known. Such knowledge is important to increase women's compliance to recommended periconceptional FA use. METHODS: In a nation-wide study of 683,785 births registered in the Medical Birth Registry of Norway during 1999-2010, the associations between paternal characteristics (age, education, occupation, country of origin) and maternal FA use were estimated by relative risks (RR) with 95% confidence intervals (CI), using log-binomial regression. RESULTS: Maternal FA use before and during pregnancy (adequate FA use) was found in 16% of the births. The association between paternal age and adequate FA use was inversely U-shaped; adjusted RRs for adequate FA use were 0.35 (95% CI 0.28-0.43) and 0.72 (95% CI 0.71-0.74) for paternal age < 20 and ≥ 40 years, respectively, comparing age 30-34 years. Compulsory education (1-9 years) among fathers was compared to tertiary education; the RR was 0.69 (95% CI 0.68-0.71) for adequate FA use. The lower risk of adequate FA use for paternal compulsory education was present in all categories of maternal education. Occupation classes other than "Higher professionals" were associated with decreased risk of adequate FA use, compared with the reference "Lower professionals". RR for adequate FA use was 0.58 (95% CI 0.56-0.60) comparing fathers from "Low/middle-income countries" with fathers born in Norway. CONCLUSION: Adequate FA use in the periconceptional period was lower when fathers were younger or older than 30-34 years, had shorter education, had manual or self-employed occupations, or originated from low/middle-income countries. Partners may contribute to increase women's use of periconceptional FA supplementation.

Maternal intake of seafood and supplementary long chain n-3 poly-unsaturated fatty acids and preterm delivery.

BACKGROUND: Preterm delivery increases the risk of neonatal morbidity and mortality. Studies suggest that maternal diet may affect the prevalence of preterm delivery. The aim of this study was to assess whether maternal intakes of seafood and marine long chain n-3 polyunsaturated fatty acids (LCn-3PUFA) from supplements were associated with preterm delivery. METHODS: The study population included 67,007 women from the Norwegian Mother and Child Cohort Study. Maternal food and supplement intakes were assessed by a validated self-reported food frequency questionnaire in mid-pregnancy. Information about gestational duration was obtained from the Medical Birth Registry of Norway. We used Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (CI) for associations between total seafood, lean fish, fatty fish, and LCn-3PUFA intakes and preterm delivery. Preterm was defined as any onset of delivery before gestational week 37, and as spontaneous or iatrogenic deliveries and as preterm delivery at early, moderate, and late preterm gestations. RESULTS: Lean fish constituted 56%, fatty fish 34% and shellfish 10% of seafood intake. Any intake of seafood above no/rare intake (>5 g/d) was associated with lower prevalence of preterm delivery. Adjusted HRs were 0.76 (CI: 0.66, 0.88) for 1-2 servings/week (20-40 g/d), 0.72 (CI: 0.62, 0.83) for 2-3 servings/week (40-60 g/d), and 0.72 (CI: 0.61, 0.85) for ≥3 servings/week (>60 g/d), p-trend <0.001. The association was seen for lean fish (p-trend: 0.005) but not for fatty fish (p-trend: 0.411). The intake of supplementary LCn-3PUFA was associated only with lower prevalence of early preterm delivery (before 32 gestational weeks), while increasing intake of LCn-3PUFA from food was associated with lower prevalence of overall preterm delivery (p-trend: 0.002). Any seafood intake above no/rare was associated with lower prevalence of both spontaneous and iatrogenic preterm delivery, and with lower prevalence of late preterm delivery. CONCLUSIONS: Any intake of seafood above no/rare consumption was associated with lower prevalence of preterm delivery. The association was stronger for lean than for fatty fish. Intake of supplementary LCn-3PUFA was associated only with early preterm delivery. The findings corroborate the current advice to include fish and seafood as part of a balanced diet during pregnancy.

Prevalence and determinants of preconception folic acid use: an Italian multicenter survey.

BACKGROUND: Women in many countries are advised to use folic acid supplements before and early during pregnancy to reduce the risk of neural tube defects in their infants. This study aimed to update the prevalence and to identify possible determinants of preconception folic acid supplement use in Italian women. METHODS: The study was based on cross-sectional data from seven maternity clinics located in six Italian regions from January to June, 2012. Data on maternal characteristics and supplement use were collected for 2,189 women using a self-administered questionnaire. RESULTS: Preconception folic acid use was reported by 23.5 % (n = 515) of the participants. Of these, 479 (93 %) women had taken folic acid supplements on a daily basis as recommended by the health authorities. Women who both had intended their pregnancy and had requested a preconception health visit to a doctor/gynecologist were substantially more likely than the reference group to initiate folic acid supplementation before their pregnancy (48.6 versus 4.8 %). Preconception folic acid use was also associated with higher maternal age, higher education, marriage/cohabitation, lower parity, infertility treatments, and chronic disease. CONCLUSIONS: Data from seven maternity clinics located in six Italian regions indicate that preconception folic acid supplement use in many Italian women is low. Women who do not plan their pregnancy or do not request a preconception health visit to their doctor have among the lowest prevalence of preconception folic acid use. Improving folate status in these and other supplemental non-users may have important disease preventive effects.

Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns.

Folate is vital for fetal development. Periconceptional folic acid supplementation and food fortification are recommended to prevent neural tube defects. Mechanisms whereby periconceptional folate influences normal development and disease are poorly understood: epigenetics may be involved. We examine the association between maternal plasma folate during pregnancy and epigenome-wide DNA methylation using Illumina's HumanMethyl450 Beadchip in 1,988 newborns from two European cohorts. Here we report the combined covariate-adjusted results using meta-analysis and employ pathway and gene expression analyses. Four-hundred forty-three CpGs (320 genes) are significantly associated with maternal plasma folate levels during pregnancy (false discovery rate 5%); 48 are significant after Bonferroni correction. Most genes are not known for folate biology, including APC2, GRM8, SLC16A12, OPCML, PRPH, LHX1, KLK4 and PRSS21. Some relate to birth defects other than neural tube defects, neurological functions or varied aspects of embryonic development. These findings may inform how maternal folate impacts the developing epigenome and health outcomes in offspring.

Prevalence of maternal preconception risk factors: an Italian multicenter survey.

OBJECTIVES: Adequate preconception maternal health care is essential to reduce the risk of unwanted pregnancy outcomes and complications. Still, many women are exposed to a number of unhealthy risk factors both before and early in pregnancy. This study aimed to estimate the prevalence of a number of important preconception risk factors using data from a recent multicenter study in Italy. METHODS: The study was based on cross-sectional data from seven maternity clinics located in six different regions in Italy during the period January - June, 2012. Data on maternal preconception risk factors and characteristics were collected from 1,892 women who delivered healthy children and 320 women who were pregnant in the first trimester. RESULTS: About 97% of the women (n =2,212) were exposed to one or more preconception risk factors. The overall prevalence of the most essential maternal risk factors was as follows: 41% had a age ≥35 years, 36% mistimed or did not intend their pregnancy, 58% did not request a preconception health visit to their doctor, 76% did not use folic acid supplements before pregnancy, 26% smoked at the last menstrual period, 19% had a body mass index ≥25 kg/m2 before pregnancy, and 10% suffered from pregestational chronic diseases. The prevalence of certain variables varied between the maternity clinics. CONCLUSIONS: Many Italian women are exposed to a number of preconception risk factors that have been associated with adverse pregnancy complications and outcomes. More effective intervention programs to improve preconception health in Italian women are strongly needed.

Analysis of self-selection bias in a population-based cohort study of autism spectrum disorders.

BACKGROUND: This study examined potential self-selection bias in a large pregnancy cohort by comparing exposure-outcome associations from the cohort to similar associations obtained from nationwide registry data. The outcome under study was specialist-confirmed diagnosis of autism spectrum disorders (ASDs). METHODS: The cohort sample (n = 89 836) was derived from the population-based prospective Norwegian Mother and Child Cohort Study and its substudy of ASDs, the Autism Birth Cohort (ABC) study. The nationwide registry data were derived from the Medical Birth Registry of Norway (n = 507 856). The children were born in 1999­2007, and seven prenatal and perinatal exposures were selected for analyses. RESULTS: ASDs were reported for 234 (0.26%) children in the cohort and 2072 (0.41%) in the nationwide population. Compared with the nationwide population, the cohort had an under-representation of the youngest women (<25 years), those who had single status, mothers who smoked during pregnancy, and non-users of prenatal folic acid supplements. The ratios of the adjusted odds ratios (ORs) in the cohort over the adjusted ORs in the nationwide population were as follows; primipara pregnancy: 1.39/1.22, prenatal folic acid use: 0.85/0.86, prenatal smoking: 1.20/1.17, preterm birth (<37 weeks): 1.48/1.42, low birthweight (<2500 g): 1.60/1.58, male sex: 4.39/4.59 (unadjusted only); and caesarean section history: 1.03/1.04. CONCLUSIONS: Associations estimated between ASDs and perinatal and prenatal exposures in the cohort are close to those estimated in the nationwide population. Self-selection does not appear to compromise validity of exposure-outcome associations in the ABC study.

Folic acid supplementation, dietary folate intake during pregnancy and risk for spontaneous preterm delivery: a prospective observational cohort study.

BACKGROUND: Health authorities in numerous countries recommend periconceptional folic acid to pregnant women to prevent neural tube defects. The objective of this study was to examine the association of folic acid supplementation during different periods of pregnancy and of dietary folate intake with the risk of spontaneous preterm delivery (PTD). METHODS: The Norwegian Mother and Child Cohort Study is a population-based prospective cohort study. A total of 65,668 women with singleton pregnancies resulting in live births in 1999-2009 were included. Folic acid supplementation was self-reported from 26 weeks before pregnancy until week 24 during pregnancy. At gestational week 22, the women completed a food frequency questionnaire, which allowed the calculation of their average total folate intake from foods and supplements for the first 4-5 months of pregnancy. Spontaneous PTD was defined as the spontaneous onset of delivery between weeks 22+0 and 36+6 (n = 1,628). RESULTS: The median total folate intake was 266 µg/d (interquartile range IQR 154-543) in the overall population and 540 µg/d (IQR 369-651) in the supplement users. Eighty-three percent reported any folic acid supplementation from <8 weeks before to 24 weeks after conception while 42% initiated folic acid supplementation before their pregnancy. Cox regression analysis showed that the amount of folate intake from the diet (hazard ratio HR 1.16; confidence interval CI 0.65-2.08) and from the folic acid supplements (HR 1.04; CI 0.95-1.13) was not significantly associated with the risk of PTD. The initiation of folic acid supplementation more than 8 weeks before conception was associated with an increased risk for PTD (HR 1.19; CI 1.05-1.34) compared to no folic acid supplementation pre-conception. There was no significant association with PTD when supplementation was initiated within 8 weeks pre-conception (HR 1.01; CI 0.88-1.16). All analyses were adjusted for maternal characteristics and socioeconomic, health and dietary variables. CONCLUSIONS: Our findings do not support a protective effect of dietary folate intake or folic acid supplementation on spontaneous PTD. Pre-conceptional folic acid supplementation starting more than 8 weeks before conception was associated with an increased risk of PTD. These results require further investigation before discussing an expansion of folic acid supplementation guidelines.

Evaluating iron status and the risk of anemia in young infants using erythrocyte parameters.

BACKGROUND: Correct evaluation of iron status is important in young infants because both iron deficiency and excess may have negative effects on development, growth, and morbidity. METHODS: We evaluated iron status using erythrocyte parameters, including reticulocyte hemoglobin content (CHr) in infants with birth weight <3,000 g (n = 80). Blood samples and infant characteristics were recorded at 6 wk and at 4 and 6 months. Infants with a birth weight ≤2,500 g (n = 36) were recommended for iron supplementation. RESULTS: Despite a significantly poorer status at 6 wk, iron-supplemented infants had significantly higher hemoglobin level (Hb): 12.2 (SD = 0.8) g/dl and CHr: 28.3 (SD = 1.4) pg at 6 mo, as compared with nonsupplemented infants, Hb: 11.7 (SD = 1.0) g/dl, P = 0.02 and CHr: 26.5 (SD = 2.5) pg, P < 0.001. Prolonged exclusive breastfeeding, high weight gain, and male gender were the predisposing factors for a low iron status at 6 mo. A CHr cutoff level of 26.9 pg at 4 mo proved to be a sensitive predictor for anemia at 6 mo. CONCLUSION: Signs of an iron-restricted erythropoiesis were observed in nonsupplemented infants (birth weight 2,501-3,000 g), and CHr was a useful tool for evaluating iron status. The need for iron supplementation in certain infant risk populations should be further evaluated.

Maternal B vitamin status in pregnancy week 18 according to reported use of folic acid supplements.

SCOPE: Epidemiological studies on the association between pregnancy outcomes and use of periconceptional folic acid are often based on maternal reported intake. Use of folic acid during pregnancy is associated with a higher socioeconomic status known to have an impact on diet quality. We have studied plasma B vitamin status according to reported use of folic acid supplements during the periconceptional period in Norwegian women. METHODS AND RESULTS: Plasma levels of folate, cobalamin, pyridoxal 5'-phosphate (vitamin B6), riboflavin, and the metabolic markers total homocysteine, methylmalonic acid and 3-hydro-xykynurenine were measured in pregnancy week 18 and related to reported intake of folic acid from 4 weeks prior to conception throughout week 18 in 2911 women from the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Being a folic acid user during the periconceptional period was associated with a better socioeconomic status, and a higher intake of several micronutrients, including vitamins, trace-metals, and omega 3 fatty acids. Folic acid users had a significantly better plasma B vitamin status. CONCLUSION: Epidemiological data based on maternal reported intake of folic acid supplements during pregnancy, should take into account the numerous nutritional implications, in addition to higher blood folate levels, of being a folic acid user.

Use of folic acid supplements in early pregnancy in relation to maternal plasma levels in week 18 of pregnancy.

SCOPE: Birth cohorts typically measure plasma folate in midgestation, but effects of folic acid supplementation are sometimes specific to the periconceptional period. The relationship between midgestation plasma folate and periconceptional supplementation is not known. We compared plasma folate at week 18 of gestation with self-report use of supplements comtaining folic acid from before pregnancy to week 17 of gestation. METHODS AND RESULTS: The sample comprised 2911 women from The Norwegian Mother and Child Cohort Study. For women reporting continuous supplementation from gestational week -4 to 17 (N = 238), median plasma folate was 15.72 at week 18 (in nmol/L). This was about threefold higher than the median plasma folate of 5.67 for women reporting no supplementation from week -4 to 17 (N = 844), but only slightly higher than the median plasma folate of 13.34 for all women reporting supplementation in weeks 13-17 (N = 1158). Reported supplementation before week 8 was not associated with plasma folate at week 18, in an analysis that adjusted for continued supplementation after week 8. CONCLUSION: Overall we found a strong and coherent relationship between self-reported folic acid use and plasma folate at week 18. We also found that plasma folate at week 18 did not reflect self-reported supplementation before week 8. For periconceptional supplementation per se, self-report data may offer a better measure.

Infant birth size is not associated with maternal intake and status of folate during the second trimester in Norwegian pregnant women.

Maternal folate status and smoking are potentially strong risk factors for infant birth size. We assessed the association of several folate indicators and smoking with birth outcomes in a subsample of participants in the Norwegian Mother and Child Cohort Study, consisting of 2934 singleton pregnancies in 2002-2003. Blood plasma folate and cotinine concentrations and self-reported intake of food folate and supplemental folic acid were measured during the second trimester (median 18 wk). Birth outcomes included gestational age, infant birth weight, head circumference, crown-heel length, and small for gestational age (SGA). Mean total dietary folate intake from foods (mean 268.0 microg/d) and supplements (mean 187.7 microg/d) was 455.7 microg/d. Smokers (plasma cotinine > or = 85 nmol/L) had substantially lower supplemental folic acid intake than nonsmokers, but they did not differ regarding folate intake from food only. Nevertheless, smoking was correlated with plasma folate both before and after adjusting for total dietary folate intake (both P < 0.001). We found no significant associations of food folate intake, supplemental folic acid use, total dietary folate intake, or plasma folate with the various birth outcomes after adjustment for potential confounders. Consistent with previous studies, infant birth size was strongly predicted by maternal smoking (adjusted odds ratio for SGA: 2.3; 95% CI: 1.6, 3.3). This study of well-nourished Norwegian pregnant women suggests that dietary folate and plasma folate during the second trimester are not risk factors for infant birth size.

Self-selection and bias in a large prospective pregnancy cohort in Norway.

Self-selection in epidemiological studies may introduce selection bias and influence the validity of study results. To evaluate potential bias due to self-selection in a large prospective pregnancy cohort in Norway, the authors studied differences in prevalence estimates and association measures between study participants and all women giving birth in Norway. Women who agreed to participate in the Norwegian Mother and Child Cohort Study (43.5% of invited; n = 73 579) were compared with all women giving birth in Norway (n = 398 849) using data from the population-based Medical Birth Registry of Norway in 2000-2006. Bias in the prevalence of 23 exposure and outcome variables was measured as the ratio of relative frequencies, whereas bias in exposure-outcome associations of eight relationships was measured as the ratio of odds ratios. Statistically significant relative differences in prevalence estimates between the cohort participants and the total population were found for all variables, except for maternal epilepsy, chronic hypertension and pre-eclampsia. There was a strong under-representation of the youngest women (<25 years), those living alone, mothers with more than two previous births and with previous stillbirths (relative deviation 30-45%). In addition, smokers, women with stillbirths and neonatal death were markedly under-represented in the cohort (relative deviation 22-43%), while multivitamin and folic acid supplement users were over-represented (relative deviation 31-43%). Despite this, no statistically relative differences in association measures were found between participants and the total population regarding the eight exposure-outcome associations. Using data from the Medical Birth Registry of Norway, this study suggests that prevalence estimates of exposures and outcomes, but not estimates of exposure-outcome associations are biased due to self-selection in the Norwegian Mother and Child Cohort Study.

Folic acid and multivitamin supplement use and risk of placental abruption: a population-based registry study.

The authors investigated a possible association of supplemental folic acid and multivitamin use with placental abruption by using data on 280,127 singleton deliveries recorded in 1999-2004 in the population-based Medical Birth Registry of Norway. Odds ratios, adjusted for maternal age, marital status, parity, smoking, pregestational diabetes, and chronic hypertension, were estimated with generalized estimating equations for logistic regression models. Use of folic acid and/or multivitamin supplements before or any time during pregnancy was reported for 36.4% of the abruptions (0.38% of deliveries) and 44.4% of the nonabruptions. Compared with no use, any supplement use was associated with a 26% risk reduction of placental abruption (adjusted odds ratio = 0.74, 95% confidence interval: 0.65, 0.84). Women who had taken folic acid alone had an adjusted odds ratio of 0.81 (95% confidence interval: 0.68, 0.98) for abruption, whereas multivitamin users had an adjusted odds ratio of 0.72 (95% confidence interval: 0.57, 0.91), relative to supplement nonusers. The strongest risk reduction was found for those who had taken both folic acid and multivitamin supplements (adjusted odds ratio = 0.68, 95% confidence interval: 0.56, 0.83). These data suggest that folic acid and other vitamin supplementation during pregnancy may be associated with reduced risk of placental abruption.