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Higher maternal and biomarker levels of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) have been associated with improved perinatal outcomes and may also influence offspring metabolic health. Past studies were not powered to examine metabolic outcomes and few have specifically targeted metabolically vulnerable populations. We examined the associations of prenatal n-3 LCPUFA status with markers of metabolic health in early and mid-childhood in the full population as well as stratified by maternal glucose tolerance. Our data consisted of 1418 mother–child dyads from Project Viva, a longitudinal, prospective pre-birth cohort enrolled in eastern Massachusetts. We assessed maternal dietary intake of fish and n-3 LCPUFA in mid-pregnancy using a validated food frequency questionnaire. N-3 LCPUFA levels were quantified in maternal second trimester and umbilical cord plasma using liquid-gas chromatography. We assessed offspring anthropometry, adiposity, and blood pressure at early (median age: 3.2 years) and mid-childhood (median age: 7.7 years); and assayed blood samples collected at these visits for metabolic biomarkers. We report here multivariable effect estimates and 95% CI. Early childhood BMI z-score was on average 0.46 (1.03) units and waist circumference 51.3 (3.7) cm. At mid-childhood these measures were 0.39 (1.00) units and 60.0 (8.3) cm, respectively. Higher cord plasma DHA levels were associated with lower BMI z-score ((Q)uartile 4 vs. Q1: −0.21, 95% CI: −0.38, −0.03), waist circumference (Q4 vs. Q1: −0.63, 95% CI: −1.27, 0.00 cm), and leptin levels (Q4 vs. Q1: −0.36, 95% CI: −0.77, 0.05 ng/mL) in early childhood. These associations were strongest and reached significance in offspring of women with isolated hyperglycemia vs. better or worse glycemic status. Higher maternal DHA + EPA (Q4 vs. Q1: −1.59, 95% CI: −2.80, −0.38 μg/mL) and fish (≥3 vs. 0 portions/week: −2.18, 95% CI: −3.90, −0.47 μg/mL) intake was related to lower adiponectin in early childhood. None of these associations persisted with mid-childhood outcomes. We did not find associations with any of the other outcomes. This study supports early and possibly transient effects of prenatal n-3 LCPUFA status on anthropometric measures and adipokine levels. It also raises the possibility that offspring of women with isolated hyperglycemia derive the most benefits from higher n-3 LCPUFA status.

Background: Results from 2 cohort studies in Scotland established in the 1940s and 1950s (Aberdeen and Motherwell) suggested that a high protein diet during pregnancy might adversely influence offspring blood pressure at adult age. Our objective was to examine this association in the Danish Fetal Origins Cohort (DaFO88). Methods and Results: This was a prospective birth cohort of 965 women who gave birth in 1988–1989 in Aarhus, Denmark, and whose offspring (n=434) participated in a clinical examination ≈20 years later. Macronutrient intake was assessed in gestational week 30. Multivariable adjusted linear regression was used to examine the relation between higher maternal protein intake, at the expense of carbohydrates, and offspring blood pressure (isocaloric substitution). Main analyses were adjusted for mother's age during pregnancy, prepregnancy body mass index, parity, smoking during pregnancy, educational level, and offspring's sex. The mean total energy intake was 8.7 MJ/day (SD 2.3 MJ/day). The mean energy from carbohydrate, fat, and protein intake was 51, 31, and 16 of total energy, respectively. The results showed that after adjustment, higher maternal protein intake was associated with slightly higher offspring diastolic blood pressure (highest compared with the lowest quintile of protein intake: ∆=2.4 mm Hg; 95% CI 0.4–4.4; P=0.03 for trend). Similar differences, although not significant, were found for systolic blood pressure (∆=2.6 mm Hg; 95% CI −0.0 to 5.3; P=0.08 for trend). Conclusions: Higher maternal dietary protein intake at the expense of carbohydrates was associated with a modest increase in offspring blood pressure in young adulthood.

Background: Road traffic is a major source of air pollution and noise. Both exposures have been associated with hypertension in adults, but pregnant women have been less studied. Methods: We examined single and joint effects of ambient air pollution and road traffic noise on pre-eclampsia and pregnancy-induced hypertensive disorders among 72,745 singleton pregnancies (1997–2002) from the Danish National Birth Cohort with complete covariate data and residential address history from conception until live born birth. Nitrogen dioxide (NO2) and noise from road traffic (Lden) were modeled at all addresses. Outcome and covariate data were derived from registries, hospital records, and questionnaires. Results: A 10-µg/m3 increase in NO2 exposure during first trimester was associated with increased risk of pre-eclampsia (n = 1,880, adjusted odds ratio = 1.07 [95% confidence interval = 1.01, 1.14]) and pregnancy-induced hypertensive disorders (n = 2,430, adjusted odds ratio = 1.07 [1.01, 1.13]). A 10 dB higher road traffic noise was also associated with increased risk of pre-eclampsia (1.10 [1.02, 1.18]) and pregnancy-induced hypertensive disorders (1.08 [1.02, 1.15]). For both exposures, the associations were strongest for mild pre-eclampsia (n = 1,393) and early-onset pre-eclampsia (n = 671), whereas higher risk for severe pre-eclampsia (n = 487) was not evident. In mutually adjusted models, estimates for both exposures decreased and only the association between NO2 and mild pre-eclampsia remained. Conclusions: Road traffic may increase the risk of pre-eclampsia and hypertensive disorders in pregnancy through exposure to both ambient air pollution and noise, although associations with the two exposures were generally not found to be independent of one another. See video abstract, http://links.lww.com/EDE/B112.

Background: Studies suggest that fish consumption can restrict weight gain. However, little is known about how fish consumption affects gestational weight gain (GWG), and whether this relationship depends on genetic makeup. Objective: To examine the association between fish consumption and GWG, and whether this relationship is dependent on molecular genetic predisposition to obesity. Design: A nested case-cohort study based on the Danish National Birth Cohort (DNBC) sampling the most obese women (n = 990) and a random sample of the remaining participants (n = 1,128). Replication of statistically significant findings was attempted in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 4,841). We included 32 body mass index (BMI) associated single nucleotide polymorphisms (SNPs) and 5 SNPs found associated with GWG. BMI associated SNPs were combined in a genetic risk score (GRS). Associations between consumption of fish, GRS or individual variants and GWG were analysed, and interactions between fish and the GRS or individual variants were examined. Results: In the DNBC, each portion/week (150 g) of fatty fish was associated with a higher GWG of 0.58 kg (95% CI: 0.16, 0.99, P<0.01). For total fish and lean fish, similar patterns were observed, but these associations were not statistically significant. We found no association between GRS and GWG, and no interactions between GRS and dietary fish on GWG. However, we found an interaction between the PPARG Pro12Ala variant and dietary fish. Each additional Pro12Ala G-allele was associated with a GWG of -0.83 kg (95% CI: -1.29, -0.37, P<0.01) per portion/week of dietary fish, with the same pattern for both lean and fatty fish. In ALSPAC, we were unable to replicate these findings. Conclusion: We found no consistent evidence of association between fish consumption and GWG, and our results indicate that the association between dietary fish and GWG has little or no dependency on GRS or individual SNPs.

Objective: As a means to prevent neural tube defects (NTDs), women planning pregnancy in Denmark are recommended to take a dietary supplement of 400 microg folic acid daily during the periconceptional period. We examined compliance with this recommendation in a national survey.Design: Cohort study on pregnant women in Denmark.Setting: The Danish National Birth Cohort (DNBC).Subjects: From November 2000 to February 2002, 22,000 pregnant women were recruited for DNBC. Use of dietary supplements was recorded at enrollment. Compliance with the recommendation was related to an information campaign that took place during the second half of 2001, and to lifestyle factors provided in a telephone interview by the end of the first trimester of pregnancy.Results: An increase was seen in the proportion of women complying with the recommendation in the study period and this coincided with the information campaign events. However, even at the end of the period, only 22.3% of the women who had planned their pregnancy fully complied with the recommendation. No increase at all was seen in periconceptional folic acid use among women with unplanned pregnancies. Young age, low education and smoking were identified as factors that determined non-compliance.Conclusions: Alternative and more effective strategies are needed if the Danish population is to benefit fully from the knowledge that folic acid prevents NTDs. Future strategies should not only target vulnerable groups, such as the less educated and the young, but also women who get pregnant without planning this. The only possible way to reach the last group may be through fortification of foods with folic acid. [ABSTRACT FROM AUTHOR]

Objective: To examine the relation between the protein:carbohydrate (P/C) ratio and added sugar intake in pregnancy and gestational weight gain (GWG). Design: A prebirth cohort including 103 119 pregnancies enrolled between 1996 and 2003. Setting: All women in Denmark were eligible to participate if they spoke Danish and were planning to carry to term.The pregnant women were recruited and enrolled during their first antenatal visit (6–10 weeks of gestation). Participants: Participants included women with live-born singletons and complete data on dietary intake and GWG, leaving 46 262 women for the analysis. Exposure Macronutrient intake was quantified using a validated food frequency questionnaire administered in the 25th week of gestation. The P/C ratio and added sugar intake were examined in quintiles. Primary outcome measures GWG was based on self-reported weight in gestational weeks 12 and 30 and defined as gain in g/week. We used multivariable linear regression, including adjusting for pre-pregnancy body mass index, to calculate relative change in GWG and 95% CI. Results: Average GWG was 471(224) g/week. The adjusted weight gain was 16 g/week lower (95% CI 9 to 22, p for trend <0.001) in the highest (Q5) versus lowest (Q1) quintile of the P/C ratio (∼3% average reduction across the entire pregnancy). Weight gain for those with >20%E vs <12%E from protein was 36 g/week lower (95% CI 20 to 53, p for trend <0.0001; ∼8% average reduction). A high P/C ratio was inversely related to intake of added sugars. Added sugar consumption was strongly associated with GWG (Q5 vs Q1: 34, 95% CI 28 to 40 g/week, p for trend <0.0001). Conclusions: A high P/C ratio was associated with reduced GWG. This association appeared to be partly driven by a decrease in intake of added sugar. These results are consistent with randomised trials in non-pregnant participants. A dietary intervention targeting an increased P/C ratio with emphasis on reducing added sugar can contribute to reducing excessive GWG.

Background: Lifestyle interventions targeting obese pregnant women often result in modest reduction in gestational weight gain, pregnancy complications and related risk factors. Examining adherence to the intervention can, however, provide valuable information on the importance of the different factors targeted. Objective: To evaluate improvements and relevance of different dietary factors targeted with respect to gestational weight gain in a 3-arm Randomised Controlled Trial (n=342) among obese pregnant women with BMI≥30 kg/m2. Methods: Randomisation 1:1:1 to either hypocaloric Mediterranean type of diet and physical activity intervention (D+PA); physical activity intervention alone (PA); or control (C). Diet was assessed at baseline (weeks 11–14) and endpoint (weeks 36–37) using a validated food frequency questionnaire. Results: During the intervention women in the D+PA group significantly lowered their intakes of added sugars and saturated fat and increased their protein intake by ~1% of total energy compared to controls. Of these dietary variables only intakes of added sugar appeared to be related to GWG, while no association was observed for saturated fat or protein. Further analyses revealed that foods that contributed to intake of added sugars, including sweets, snacks, cakes, and soft drinks were strongly associated with weight gain, with women consuming sweets ≥2/day having 5.4 kg (95% CI 2.1-8.7) greater weight gain than those with a low (<1wk) intake. The results for soft drinks were more conflicting, as women with high weight gain tended to favour artificially sweetened soft drinks. Conclusion: In our sample of obese pregnant women, craving for sweets, snacks, and soft drinks strongly predicts GWG. Emphasis on reducing intakes of these foods may be more relevant for limiting gestational weight gain than encouraging strict compliance to more specific diets. Trial Registration ClinicalTrials.gov NCT01345149

Limited evidence exists for an association between maternal diet during pregnancy and offspring bone health. In a prospective study, we examined the association between dietary patterns in mid-pregnancy and offspring forearm fractures. In total, 101,042 pregnancies were recruited to the Danish National Birth Cohort (DNBC) during 1996–2002. Maternal diet was collected by a food frequency questionnaire. Associations were analyzed between seven dietary patterns extracted by principal component analysis and offspring first occurrence of any forearm fracture diagnosis, extracted from the Danish National Patient Register, between time of birth and end of follow-up (<16 year) (n = 53,922). In multivariable Cox regression models, offspring of mothers in the fourth vs. first quintile of the Western pattern had a significant increased risk (Hazard ratio, 95% confidence interval: 1.11, 1.01–1.23) of fractures, and there was a borderline significant positive trend (p = 0.06). The other dietary patterns showed no associations and neither did supplementary analyses of macro- and micronutrients or single food groups, except for the intake of artificially sweetened soft drinks, which was positively associated with offspring forearm fractures (p = 0.02). In the large prospective DNBC high mid-pregnancy consumption of Western diet and artificially sweetened soft drinks, respectively, indicated positive associations with offspring forearm fractures, which provides interesting hypotheses for future research.