Sjurdur F. Olsen

The Danish National Birth Cohort - its background, structure and aim

Background: It is well known that the time from conception to early childhood has importance for health conditions that reach into later stages of life. Recent research supports this view, and diseases such as cardiovascular morbidity, cancer, mental illnesses, asthma, and allergy may all have component causes that act early in life. Exposures in this period, which infl uence fetal growth, cell divisions, and organ functioning, may have long-lasting impact on health and disease susceptibility. Methods: To investigate these issues the Danish National Birth Cohort (Better health for mother and child) was established. A large cohort of pregnant women with long-term follow-up of the offspring was the obvious choice because many of the exposures of interest cannot be reconstructed with sufficient validity back in time. The study needs to be large, and it is aimed to recruit 100,000 women early in pregnancy, and to continue follow-up for decades. The Nordic countries are better suited for this kind of research than most other countries because of their population-based registers on diseases, demography and social conditions, linkable at the individual level by means of the unique ID-number given to all citizens. Exposure information is mainly collected by computer-assisted telephone interviews with the women twice during pregnancy and when their children are six and 18 months old. Participants are also asked to fill in a self-administered food frequency questionnaire in mid-pregnancy. Furthermore, a biological bank has been set up with blood taken from the mother twice during pregnancy and blood from the umbilical cord taken shortly after birth. Data collection started in 1996 and the project covered all regions in Denmark in 1999. By August 2000, a total of 60,000 pregnant women had been recruited to the study. It is expected that a large number of gene-environmental hypotheses need to be based on case-control analyses within a cohort like this.

Timing of postexercise protein intake is important for muscle hypertrophy with resistance training in elderly humans

1 Age‐associated loss of skeletal muscle mass and strength can partly be counteracted by resistance training, causing a net synthesis of muscular proteins. Protein synthesis is influenced synergistically by postexercise amino acid supplementation, but the importance of the timing of protein intake remains unresolved. 2 The study investigated the importance of immediate (P0) or delayed (P2) intake of an oral protein supplement upon muscle hypertrophy and strength over a period of resistance training in elderly males. 3 Thirteen men (age, 74 ± 1 years; body mass index (BMI), 25 ± 1 kg m−2 (means ± S.E.M.)) completed a 12 week resistance training programme (3 times per week) receiving oral protein in liquid form (10 g protein, 7 g carbohydrate, 3 g fat) immediately after (P0) or 2 h after (P2) each training session. Muscle hypertrophy was evaluated by magnetic resonance imaging (MRI) and from muscle biopsies and muscle strength was determined using dynamic and isokinetic strength measurements. Body composition was determined from dual‐energy X‐ray absorptiometry (DEXA) and food records were obtained over 4 days. The plasma insulin response to protein supplementation was also determined. 4 In response to training, the cross‐sectional area of m. quadriceps femoris (54.6 ± 0.5 to 58.3 ± 0.5 cm2) and mean fibre area (4047 ± 320 to 5019 ± 615 μm2) increased in the P0 group, whereas no significant increase was observed in P2. For P0 both dynamic and isokinetic strength increased, by 46 and 15 %, respectively (P < 0.05), whereas P2 only improved in dynamic strength, by 36 % (P < 0.05). No differences in glucose or insulin response were observed between protein intake at 0 and 2 h postexercise. 5 We conclude that early intake of an oral protein supplement after resistance training is important for the development of hypertrophy in skeletal muscle of elderly men in response to resistance training.

INTAKE OF MARINE FAT, RICH IN (n-3)-POLYUNSATURATED FATTY ACIDS, MAY INCREASE BIRTHWEIGHT BY PROLONGING GESTATION

Birthweights in the Faroe Islands are among the highest in the world. Compared with Denmark, the average birthweight of liveborn singleton infants of primiparous mothers is 194 g higher, and a substantial part of this difference seems to be attributable to longer gestation. Prostaglandins play an important part in the timing of parturition in human beings. Dietary (n-3)-polyunsaturated fatty acids (PUFA) in high amounts influence endogenous prostaglandin metabolism. Owing to the large consumption of marine fat, the average intake of (n-3)-PUFA in the Faroes by far exceeds that in Denmark. The hypothesis proposed is that dietary (n-3)-PUFA in high amounts prolong gestation in human beings by interfering with uterine production of prostaglandins, possibly by inhibiting the production of dienoic prostaglandins, primarily PGF2 alpha and PGE2, which are mediators of uterine contractions and cervical ripening.

Prenatal Exposure to Perfluorooctanoate and Risk of Overweight at 20 Years of Age: A Prospective Cohort Study

Background: Perfluoroalkyl acids are persistent compounds used in various industrial -applications. Of these compounds, perfluorooctanoate (PFOA) is currently detected in humans worldwide. A recent study on low-dose developmental exposure to PFOA in mice reported increased weight and elevated biomarkers of adiposity in postpubertal female offspring. Objective: We examined whether the findings of increased weight in postpubertal female mice could be replicated in humans. Methods: A prospective cohort of 665 Danish pregnant women was recruited in 1988–1989 with offspring follow-up at 20 years. PFOA was measured in serum from gestational week 30. Offspring body mass index (BMI) and waist circumference were recorded at follow-up (n = 665), and biomarkers of adiposity were quantified in a subset (n = 422) of participants. Results: After adjusting for covariates, including maternal pre-pregnancy BMI, smoking, education, and birth weight, in utero exposure to PFOA was positively associated with anthropometry at 20 years in female but not male offspring. Adjusted relative risks comparing the highest with lowest quartile (median: 5.8 vs. 2.3 ng/mL) of maternal PFOA concentration were 3.1 [95% confidence interval (CI): 1.4, 6.9] for overweight or obese (BMI ≥ 25 kg/m2) and 3.0 (95% CI: 1.3, 6.8) for waist circumference > 88 cm among female offspring. This corresponded to estimated increases of 1.6 kg/m2 (95% CI: 0.6, 2.6) and 4.3 cm (95% CI: 1.4, 7.3) in average BMI and waist circumference, respectively. In addition, maternal PFOA concentrations were positively associated with serum insulin and leptin levels and inversely associated with adiponectin levels in female offspring. Similar associations were observed for males, although point estimates were less precise because of fewer observations. Maternal perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), and perfluorononanoate (PFNA) concentrations were not independently associated with offspring anthropometry at 20 years. Conclusions: Our findings on the effects of low-dose developmental exposures to PFOA are in line with experimental results suggesting obesogenic effects in female offspring at 20 years of age.

Essential fatty acid status in neonates after fish-oil supplementation during late pregnancy

Healthy pregnant women (n 23) were supplemented with fish-oil capsules (2.7 g n-3 polyunsaturated fatty acids/d) from the 30th week of gestation until delivery. Subjects in a control group were either supplemented with olive-oil capsules (4 g/d, n 6) or received no supplementation (n 10). Fatty acid compositions of the phospholipids isolated from umbilical plasma and umbilical arterial and venous vessel walls were determined. Fatty acid compositions of maternal venous plasma phospholipids were determined as well. Maternal plasma phospholipids of the fish-oil-supplemented group contained more n-3 fatty acids and less n-6 fatty acids. Moreover, the amounts of the essential fatty acid deficiency markers Mead acid (20:3n-9) and Osbond acid (22:5n-6) were significantly lower. The extra amount of n-3 fatty acids consumed by the mothers resulted in higher contents of n-3 fatty acids, and of docosahexaenoic acid (22:6n-3) in particular, in the phospholipids of umbilical plasma and vessel walls. It is, indeed, possible to interfere with the docosahexaenoic acid status at birth: children born to mothers supplemented with fish oil in the last trimester of pregnancy start with a better docosahexaenoic acid status at birth, which may be beneficial to neonatal neurodevelopment.

Major dietary patterns in pregnancy and fetal growth

Objectives:To investigate possible associations between maternal diet during pregnancy and fetal growth.Method:Factor analysis was used to explore dietary patterns among pregnant women. The association between maternal dietary patterns and fetal growth (in terms of small for gestational age, SGA) was investigated by logistic regression. Prospective cohort study, including information on 44 612 women in Denmark.Results:Two major dietary patterns were defined: the first pattern was characterized by red and processed meat, high-fat dairy, and the second pattern was characterized by intake of vegetables, fruits, poultry and fish. Women were classified into three classes according to their diet: the first class had high intake of foods of the first dietary pattern, and was classified as ‘the Western diet’, the second class preferred foods of the second pattern and was classified as the ‘Health Conscious’; and the third one had eaten foods of both patterns, and was classified as the ‘Intermediate’. The odds ratio of having a small for gestational-age infant (with a birth weight below the 2.5th percentile for gestational age and gender) was 0.74 (95% CI 0.64–0.86) for women in the Health Conscious class compared with women in the Western Diet class. The analyses were adjusted for parity, maternal smoking, age, height, pre-pregnancy weight and fathers height.Conclusions:Our results indicated that a diet in pregnancy, based on red and processed meat and high-fat diary, was associated with increased risk for SGA. Further studies are warranted to identify specific macro-, or micronutrients that may be underlying these associations.

Maternal fish oil supplementation in lactation: Effect on visual acuity and n−3 fatty acid content of infant erythrocytes

Studies on formula-fed infants indicate a beneficial effect of dietary DHA on visual acuity. Cross-sectional studies have shown an association between breast-milk DHA levels and visual acuity in breast-fed infants. The objective in this study was to evaluate the biochemical and functional effects of fish oil (FO) supplements in lactating mothers. In this double-blinded randomized trial, Danish mothers with habitual fish intake below the 50th percentile of the Danish National Birth Cohort were randomized to microencapsulated FO [1.3 g/d long-chain n−3 FA (n−3 LCPUFA)] or olive oil (OO). The intervention started within a week after delivery and lasted 4 mon. Mothers with habitual high fish intake and their infants were included as a reference group. Ninety-seven infants completed the trial (44 OO-group, 53 FO-group) and 47 reference infants were followed up. The primary outcome measures were: DHA content of milk samples (0, 2, and 4 mon postnatal) and of infant red blood cell (RBC) membranes (4 mon postnatal), and infant visual acuity (measured by swept visual evoked potential at 2 and 4 mon of age). FO supplementation gave rise to a threefold increase in the DHA content of the 4-mon milk samples (P<0.001). DHA in infant RBC reflected milk contents (r=0.564, P<0.001) and was increased by almost 50% (P<0.001). Infant visual acuity was not significantly different in the randomized groups but was positively associated at 4 mon with infant RBC-DHA (P=0.004, multiple regression). We concluded that maternal FO supplementation during lactation did not enhance visual acuity of the infants who completed the intervention. However, the results showed that infants with higher RBC levels of n−3 LCPUFA had a better visual acuity at 4 mon of age, suggesting that n−3 LCPUFA may influence visual maturation.

Frequency of seafood intake in pregnancy as a determinant of birth weight: evidence for a dose dependent relationship.

STUDY OBJECTIVE--The aim was to explore whether maternal consumption of seafood is a determinant of birth weight in a dose dependent manner. DESIGN--A population based survey of lifestyle factors in pregnancy was linked with information from antenatal and obstetric records. SETTING AND PARTICIPANTS--Seventy five per cent of all 1362 women who delivered in the Faroe Islands during the study period 1986-87 who gave a structured post partum interview on lifestyle factors. MAIN RESULTS--Altogether, 2, 6, 16, 33, 26, 14, and 3% of women had consumed approximately 0, 1, 2, 3, 4, 5, and 6+ respectively seafood (fish or whale) dinner meals per week during pregnancy. The average birth weight (p = 0.02) and birth length (p = 0.002) varied significantly between the seven groups, and increased by about 0.2 kg and 1 cm, respectively between women who ate 0 and those who consumed 3 seafood meals per week. Mean birth weight and length tended to level off with further fish consumption: when fitting a second degree polynomial, the quadratic terms were negative and significant for both birth weight (p = 0.005) and length (p = 0.001). Analogous analyses for pregnancy duration were not significant, but exhibited similar trends. All analyses were adjusted for maternal height, weight, parity, age, marital status, and smoking. CONCLUSIONS--The weight and length of the newborn increased with the frequency of seafood dinner meals consumed in pregnancy but only up to a consumption level of about 3 meals per week.

A prospective study of smoking during pregnancy and SIDS

AIMS To study the association between smoking during pregnancy and sudden infant death syndrome (SIDS) using prospectively collected data, making it possible to account for a number of potential confounders. DESIGN Prospective follow up study (n = 24 986). RESULTS The overall rate of SIDS was 0.80 per 1000 live births (n = 20). Children of smokers had more than three times the risk of SIDS compared with children of non-smokers (OR = 3.5; 95% CI 1.4–8.7), and the risk of SIDS increased with the number of cigarettes smoked per day (p < 0.05). Adjustment for parity, alcohol, and caffeine intake during pregnancy, maternal height and weight before pregnancy, years of school, occupational status, marital status, and number of antenatal care visits did not change the results. Adjustment for mothers age marginally reduced the risk of SIDS associated with smoking (OR = 3.0; 95% CI 1.2–7.3). CONCLUSIONS Given the prospective nature of the study, the number of deaths is small; however, if our results reflect a true association between smoking during pregnancy and SIDS, approximately 30–40% of all cases of SIDS could be avoided if all pregnant women stopped smoking in a population with 30% pregnant smokers. Our study adds to earlier evidence for an association between smoking during pregnancy and SIDS. The strengths of the study are the possibility to adjust for a number of potential confounders and the fact that information about smoking habits during pregnancy was prospectively collected.

Validity of protein, retinol, folic acid and n-3 fatty acid intakes estimated from the food-frequency questionnaire used in the Danish National Birth Cohort

OBJECTIVE To validate intakes of protein, folic acid, retinol and n-3 fatty acids estimated from a food-frequency questionnaire in week 25 of pregnancy (FFQ-25). DESIGN Validation was done against a 7-day weighed food diary (FD) and biomarkers of the nutrients in gestation week 32-38. SUBJECTS AND SETTING The FFQ-25 to be validated was used in the Danish National Birth Cohort comprising 101 042 pregnant Danish women, of whom 88 participated in the present validation study. RESULTS Estimated intakes of protein, retinol and folic acid did not differ significantly between the two dietary methods, but intake of n-3 fatty acids was one third larger when estimated from the FFQ-25. The intakes estimated from the two dietary methods were all significantly correlated, ranging from 0.20 for retinol intake to 0.57 for folic acid intake. Sensitivities of being correctly classified into low and high quintiles were between 0.22 and 0.77, and specificities were between 0.62 and 0.89. Urinary protein content did not correlate significantly with protein estimated from the FFQ (r = 0.17, P > 0.05), but did with intake estimated from the FD (r = 0.56, P < 0.0001). Erythrocyte folate correlated significantly with the estimated total intake from the FFQ (r = 0.55, P < 0.0001) and the FD (r = 0.52, P < 0.0001). No correlations with plasma retinol were found. Erythrocyte eicosapentaenoic acid (C20:5n-3) correlated significantly with n-3 fatty acids intake estimated from both the FFQ-25 (r = 0.37, P < 0.001) and the FD (r = 0.62, P < 0.0001). CONCLUSION The FFQ-25 gives reasonable valid estimates of protein, retinol and folic acid intakes, but seems to overestimate intake of n-3 fatty acids.