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.

Maternal seafood consumption and infant birth weight, length and head circumference in the Norwegian Mother and Child Cohort Study.

Results from previous studies on associations between maternal fish and seafood intakes and fetal growth are inconclusive. The aim of the present study was to investigate how maternal intakes of seafood, subtypes of seafood and supplementary n-3 fatty acids were associated with infant birth weight, length and head circumference in a prospective study in Norway. The study population included 62 099 participants in the Norwegian Mother and Child Cohort Study. The mothers answered an FFQ in mid pregnancy. The FFQ comprised detailed questions about intake of various seafood items and n-3 supplements. Data on infant birth weight, length and head circumference were obtained from the Medical Birth Registry. We used multivariable regression to examine how total seafood, various seafood subtypes and supplementary n-3 intakes were associated with birth size measures. Total seafood intake was positively associated with birth weight and head circumference. Lean fish was positively associated with all birth size measures; shellfish was positively associated with birth weight, while fatty fish was not associated with any birth size measures. Intake of supplementary n-3 was negatively associated with head circumference. The relative risk of giving birth to a small baby ( < 2500 g) in full-term pregnancies was significantly lower in women who consumed >60 g/d of seafood than in women who consumed ≤ 5 g/d (OR = 0·56 (95 % CI 0·35, 0·88). In conclusion, maternal seafood consumption was positively associated with birth size, driven by lean fish intake, while supplementary n-3 intake was negatively associated with infant head circumference.

Prenatal mercury exposure, fish intake and child emotional behavioural regulation in the Norwegian Mother, Father and Child Cohort Study.

Objective: While maternal fish consumption in pregnancy has consistently been linked to better cognitive and emotional outcomes in children, fish is also a primary source of exposure to methyl mercury (MeHg), which has been linked to poorer child cognitive outcomes. The aim of this study was to evaluate the associations between MeHg exposure, using calculated MeHg exposure from maternal diet and total mercury (Hg) concentration in maternal blood during pregnancy, and child internalising and externalising behaviours at 3 and 5 years of age. Design and participants: The study sample comprised 51 238 mother-child pairs in the Norwegian Mother, Father and Child Cohort Study. Data on maternal blood Hg concentration in gestational week 18 were available for a sub-sample of 2936 women. Maternal MeHg exposure from diet was calculated from a validated Food Frequency Questionnaire answered in mid-pregnancy. Mothers reported children's emotional behaviour at age 3 and 5 years by questionnaires including twenty items from the Child Behaviour Checklist. Longitudinal associations were examined using generalised estimating equations, adjusted for potential confounders and stratified by maternal fish intake. Results: Maternal blood Hg concentration (median=1.02 µg/L, 90th percentile=2.22, range=0-13.8) was not associated with emotional behaviour in children. Increasing dietary MeHg intake (median 0.15 µg/kg body weight/week, 90th percentiles=0.31, range=0-1.86) was significantly associated with lower internalising ß=-0.03 (95% CI -0.05 to -0.00) and externalising child behaviours ß=-0.04 (95% CI -0.07 to -0.02) in adjusted models. The inverse associations were also apparent when stratifying by low/high maternal fish intake (<400 and ≥400 g/week). Conclusions: The results indicated that prenatal MeHg exposure, well below the weekly tolerable intake established by European Food Safety Authority (1.3 µg/kg bw), did not adversely affect child emotional regulation. Children of mothers consuming fish regularly were less likely to show signs of emotional behavioural problems.

Intakes of Fish and Long-chain n-3 Polyunsaturated Fatty Acid Supplements During Pregnancy and Subsequent Risk of Type 2 Diabetes in a Large Prospective Cohort Study of Norwegian Women.

OBJECTIVE: To investigate associations between intakes of total fish, lean fish, fatty fish, and long-chain n-3 polyunsaturated fatty acid (LCn-3PUFA) supplements and risk of type 2 diabetes in women after pregnancy. Furthermore, we sought to compare the estimated intakes of methylmercury (MeHg) and sum of dioxins and dioxin-like polychlorinated biphenyls (dl-PCBs) with tolerable weekly intakes (TWI). RESEARCH DESIGN AND METHODS: Women free of diabetes at baseline (n = 60,831) who participated in the population-based Norwegian Mother, Father and Child Cohort Study (MoBa) were prospectively evaluated for incident type 2 diabetes, identified on the basis of medication usage >90 days after delivery, ascertained through the Norwegian Prescription Database. Dietary intake data were obtained with a validated 255-item food-frequency questionnaire (FFQ), which assessed habitual diet during the first 4-5 months of pregnancy. Intakes of MeHg and sum of dioxins and dl-PCBs were derived with use of a contaminant database and the FFQ. RESULTS: Median age was 31 years (interquartile range 27, 34) at time of delivery, and follow-up time was 7.5 years (6.5, 8.5). Type 2 diabetes occurred in 683 (1.1%) participants. Multivariable Cox regression analyses identified lower risk of type 2 diabetes with increasing energy-adjusted lean fish intake, 25 g/1,000 kcal (25 g/1,000 kcal: hazard ratio 0.71, 95% CI 0.53-0.95, P = 0.022). However, in stratified analyses, a lower risk was found only in women with prepregnancy BMI ≥25 kg/m2. There were no associations between intake of total fish, fatty fish, or LCn-3PUFA supplements and type 2 diabetes. MeHg intake was low, but the intake of the sum of dioxins and dl-PCBs (picograms of toxic equivalents/kilograms of body weight/week) exceeded the TWI set by the European Food Safety Authority (EFSA) for the majority of participants. CONCLUSIONS: Intake of lean fish, but not fatty fish or LCn-3PUFA supplements, was associated with lower risk of pharmacologically treated type 2 diabetes in Norwegian women who were overweight or obese. Fatty fish, which contain dioxins and dl-PCBs, did not increase the risk of type 2 diabetes, but the exceedance of the EFSA TWI for dioxins and dl-PCBs is a health concern.

Associations between maternal dietary patterns and infant birth weight, small and large for gestational age in the Norwegian Mother and Child Cohort Study.

BACKGROUND/OBJECTIVES: To assess whether quality of maternal diet affects birth weight and the risk of small for gestational age (SGA) and/or large for gestational age (LGA) babies. SUBJECTS/METHODS: This study is based on the Norwegian Mother and Child Cohort Study (MoBa) and includes 65,904 pregnant women who answered a validated food frequency questionnaire at mid-pregnancy. Three maternal dietary patterns were extracted based on characteristics of food items in each pattern. From these we created four non-overlapping groups: "high prudent," "high Western," "high traditional," and "mixed". We obtained information about birth weight from the Norwegian Medical Birth Registry and calculated birth weight z-scores, SGA, and LGA according to an ultrasound-based, population-based, and a customized growth standards. Associations were studied by linear and multiple logistic regression. RESULTS: Compared to the high Western group, the high prudent group was associated with lower birth weight (ßultrasound z-scores -0.041 (95% confidence interval (CI): -0.068, -0.013)) and the high traditional group with higher birth weight (ßultrasound 0.067 (95% CI: 0.040, 0.094)) for all three growth standards. The high prudent pattern was associated with increased SGA risk (SGAultrasound odds ratio (OR) 1.25 (95% CI: 1.02, 1.54)) and decreased LGA risk (LGApopulation OR 0.84 (95% CI: 0.75, 0.94)), while the high traditional group on the contrary was associated with decreased SGA (SGAcustomized OR 0.92 (95% CI: 0.84, 0.99)) and increased LGA risk (LGApopulation OR 1.12 (95% CI: 1.02, 1.24)). CONCLUSIONS: Food quality was associated with birth weight in this well-nourished Norwegian population. Food quality may affect a woman's risk of giving birth to a SGA or LGA baby.

Vitamin A and D intake in pregnancy, infant supplementation, and asthma development: the Norwegian Mother and Child Cohort.

Background: Western diets may provide excess vitamin A, which is potentially toxic and could adversely affect respiratory health and counteract benefits from vitamin D. Objective: The aim of this study was to examine child asthma at age 7 y in relation to maternal intake of vitamins A and D during pregnancy, infant supplementation with these vitamins, and their potential interaction. Design: We studied 61,676 school-age children (born during 2002-2007) from the Norwegian Mother and Child Cohort with data on maternal total (food and supplement) nutrient intake in pregnancy (food-frequency questionnaire validated against biomarkers) and infant supplement use at age 6 mo (n = 54,142 children). Linkage with the Norwegian Prescription Database enabled near-complete follow-up (end of second quarter in 2015) for dispensed medications to classify asthma. We used log-binomial regression to calculate adjusted RRs (aRRs) for asthma with 95% CIs. Results: Asthma increased according to maternal intake of total vitamin A [retinol activity equivalents (RAEs)] in the highest (≥2031 RAEs/d) compared with the lowest (≤779 RAEs/d) quintile (aRR: 1.21; 95% CI: 1.05, 1.40) and decreased for total vitamin D in the highest (≥13.6 µg/d) compared with the lowest (≤3.5 µg/d) quintile (aRR: 0.81; 95% CI: 0.67, 0.97) during pregnancy. No association was observed for maternal intake in the highest quintiles of both nutrients (aRR: 0.99; 95% CI: 0.83, 1.18) and infant supplementation with vitamin D or cod liver oil. Conclusions: Excess vitamin A (≥2.5 times the recommended intake) during pregnancy was associated with increased risk, whereas vitamin D intake close to recommendations was associated with a reduced risk of asthma in school-age children. No association for high intakes of both nutrients suggests antagonistic effects of vitamins A and D. This trial was registered at http://www.clinicaltrials.gov as NCT03197233.

Fetal and Maternal Genetic Variants Influencing Neonatal Vitamin D Status.

Objective: Several genetic polymorphisms determine vitamin D status. We aimed to estimate the strength of association of established 25-hydroyxvitamin D (25OHD)-associated variants in the mother and in the fetus, with 25OHD concentration in newborn umbilical cord plasma. Methods: We randomly selected 578 mother and child dyads from the prospective Norwegian Mother and Child Cohort study. 25OHD was assayed in maternal samples taken shortly after delivery and in cord samples. We genotyped the mother and child for single nucleotide polymorphisms in or near GC, DHCR7, CYP2R1, and CYP24A1, previously confirmed to be associated with 25OHD, and computed genetic risk score (GRS). The genetic associations were replicated in an independent sample of 594 subjects. Results: Although both fetal and maternal GRS were associated with cord 25OHD, only fetal GRS remained significantly associated with cord 25OHD in a regression model with maternal and fetal GRS simultaneously (1.6 nmol/L per fetal 25OHD-increasing allele; 95% confidence interval, 0.6 to 2.5, P = 0.0001). Two fetal single nucleotide polymorphisms in the GC gene (rs2282679 and rs222040) were the strongest genetic predictors of cord 25OHD [4.0 (2.1 to 5.9) and 3.0 (1.3 to 4.8) nmol/L per fetal allele, P < 0.001], followed by rs12785878 in DHCR7 [2.0 (0.1 to 3.8) nmol/L, P = 0.037]. The independent replication sample gave similar results. With fetal genotype included in a regression model with environmental factors, R2 for cord 25OHD was 0.28. Conclusions: We show that fetal 25OHD-modifying genotype was a stronger predictor of cord 25OHD than corresponding maternal genotype. This raises interesting questions about fetal acquisition and placental transfer of 25OHD.

Meal frequency patterns and glycemic properties of maternal diet in relation to preterm delivery: Results from a large prospective cohort study.

BACKGROUND: Dietary habits are linked to high maternal glucose levels, associated with preterm delivery. The aim of this study was to examine the associations between meal frequency and glycemic properties of maternal diet in relation to preterm delivery. METHODS: This prospective cohort study included 66,000 women from the Norwegian Mother and Child Cohort Study (MoBa). Meal frequency and food intake data were obtained from a validated food frequency questionnaire during mid-pregnancy. Principal component factor analysis was used with a data-driven approach, and three meal frequency patterns were identified: "snack meal", "main meal", and "evening meal". Pattern scores were ranked in quartiles. Glycemic index and glycemic load were estimated from table values. Intakes of carbohydrates, added sugar, and fiber were reported in grams per day and divided into quartiles. Gestational age was obtained from the Medical Birth Registry of Norway. Preterm delivery was defined as birth at <37 gestational weeks. A Cox regression model was used to assess associations with preterm delivery. RESULTS: After adjustments, the "main meal" pattern was associated with a reduced risk of preterm delivery, with hazard ratios (HRs) of 0.89 (95% confidence interval (CI): 0.80, 0.98) and 0.90 (95% CI: 0.81, 0.99) for the third and fourth quartiles, respectively, and p for trend of 0.028. This was mainly attributed to the group of women with BMI ≥25 kg/m2, with HRs of 0.87 (95% CI: 0.79, 0.96) and 0.89 (95% CI: 0.80, 0.98) for the third and fourth quartiles, respectively, and p for trend of 0.010. There was no association between glycemic index, glycemic load, carbohydrates, added sugar, fiber, or the remaining meal frequency patterns and preterm delivery. CONCLUSION: Regular consumption of main meals (breakfast, lunch, dinner) was associated with a lower risk of preterm delivery. Diet should be further studied as potential contributing factors for preterm delivery.

Maternal and neonatal vitamin D status, genotype and childhood celiac disease.

BACKGROUND: Low concentration of 25-hydroxyvitamin D during pregnancy may be associated with offspring autoimmune disorders. Little is known about environmental triggers except gluten for celiac disease, a common immune-mediated disorder where seasonality of birth has been reported as a risk factor. We therefore aimed to test whether low maternal and neonatal 25-hydroxyvitamin D predicted higher risk of childhood celiac disease. METHODS AND FINDINGS: In this Norwegian nationwide pregnancy cohort (n = 113,053) and nested case-control study, we analyzed 25-hydroxyvitamin D in maternal blood from mid-pregnancy, postpartum and cord plasma of 416 children who developed celiac disease and 570 randomly selected controls. Mothers and children were genotyped for established celiac disease and vitamin D metabolism variants. We used mixed linear regression models and logistic regression to study associations. There was no significant difference in average 25-hydroxyvitamin D between cases and controls (63.1 and 62.1 nmol/l, respectively, p = 0.28), and no significant linear trend (adjusted odds ratio per 10 nM increase 1.05, 95% CI: 0.93-1.17). Results were similar when analyzing the mid-pregnancy, postpartum or cord plasma separately. Genetic variants for vitamin D deficiency were not associated with celiac disease (odds ratio per risk allele of the child, 1.00; 95% CI, 0.90 to 1.10, odds ratio per risk allele of the mother 0.94; 95% CI 0.85 to 1.04). Vitamin D intake in pregnancy or by the child in early life did not predict later celiac disease. Adjustment for established genetic risk markers for celiac disease gave similar results. CONCLUSIONS: We found no support for the hypothesis that maternal or neonatal vitamin D status is related to the risk of childhood celiac disease.

Maternal dietary patterns and preterm delivery: results from large prospective cohort study.

OBJECTIVE: To examine whether an association exists between maternal dietary patterns and risk of preterm delivery. DESIGN: Prospective cohort study. SETTING: Norway, between 2002 and 2008. PARTICIPANTS: 66 000 pregnant women (singletons, answered food frequency questionnaire, no missing information about parity or previously preterm delivery, pregnancy duration between 22+0 and 41+6 gestational weeks, no diabetes, first enrolment pregnancy). MAIN OUTCOME MEASURE: Hazard ratio for preterm delivery according to level of adherence to three distinct dietary patterns interpreted as "prudent" (for example, vegetables, fruits, oils, water as beverage, whole grain cereals, fibre rich bread), "Western" (salty and sweet snacks, white bread, desserts, processed meat products), and "traditional" (potatoes, fish). RESULTS: After adjustment for covariates, high scores on the "prudent" pattern were associated with significantly reduced risk of preterm delivery hazard ratio for the highest versus the lowest third (0.88, 95% confidence interval 0.80 to 0.97). The prudent pattern was also associated with a significantly lower risk of late and spontaneous preterm delivery. No independent association with preterm delivery was found for the "Western" pattern. The "traditional" pattern was associated with reduced risk of preterm delivery for the highest versus the lowest third (hazard ratio 0.91, 0.83 to 0.99). CONCLUSION: This study showed that women adhering to a "prudent" or a "traditional" dietary pattern during pregnancy were at lower risk of preterm delivery compared with other women. Although these findings cannot establish causality, they support dietary advice to pregnant women to eat a balanced diet including vegetables, fruit, whole grains, and fish and to drink water. Our results indicate that increasing the intake of foods associated with a prudent dietary pattern is more important than totally excluding processed food, fast food, junk food, and snacks.

Association between intake of artificially sweetened and sugar-sweetened beverages and preterm delivery: a large prospective cohort study.

BACKGROUND: Artificially sweetened (AS) and sugar-sweetened (SS) beverages are commonly consumed during pregnancy. A recent Danish study reported that the daily intake of an AS beverage was associated with an increased risk of preterm delivery. OBJECTIVE: We examined the intake of AS and SS beverages in pregnant women to replicate the Danish study and observe whether AS intake is indeed associated with preterm delivery. DESIGN: This was a prospective study of 60,761 pregnant women in the Norwegian Mother and Child Cohort Study. Intakes of carbonated and noncarbonated AS and SS beverages and use of artificial sweeteners in hot drinks were assessed by a self-reported food-frequency questionnaire in midpregnancy. Preterm delivery was the primary outcome, and data were obtained from the Norwegian Medical Birth Registry. RESULTS: Intakes of both AS and SS beverages increased with increasing BMI and energy intake and were higher in women with less education, in daily smokers, and in single women. A high intake of AS beverages was associated with preterm delivery; the adjusted OR for those drinking >1 serving/d was 1.11 (95% CI: 1.00, 1.24). Drinking >1 serving of SS beverages per day was also associated with an increased risk of preterm delivery (adjusted OR: 1.25; 95% CI: 1.08, 1.45). The trend tests were positive for both beverage types. CONCLUSION: This study suggests that a high intake of both AS and SS beverages is associated with an increased risk of preterm delivery.

Effect of dietary factors in pregnancy on risk of pregnancy complications: results from the Norwegian Mother and Child Cohort Study.

There has been a thrilling development , as well as profound changes, in our understanding of the effect of fetal nutrition on the development and health of the child. The Norwegian Mother and Child Cohort Study (MoBa) is an ongoing nationwide population-based pregnancy cohort study that between 1999 and 2008 recruited 90,723 women with 106,981 pregnancies and 108,487 children. The objective of MoBa is to test specific etiologic hypotheses by estimating the association between exposures and diseases with a special focus on disorders that may originate in early life. An important aspect in this regard is maternal diet and nutritional status during pregnancy. Nutritional factors have long been considered to be important determinants of maternal and fetal health, and dietary information is currently being collected in a number of pregnancy cohorts in Europe and the United States. Thus far, pregnancy complications studied in MoBa are preterm birth, preeclampsia, and fetal growth; and the aim of this article is to report results of recently published studies of dietary factors in relation to these outcomes. Numerous studies are planned using MoBa data, and the aim is to add to the knowledge of the interplay between dietary factors, nonnutrients, and toxic dietary substances and epigenetic modulation on fetal development and health later in life.