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The importance of overall diet in modifying circulating lipoprotein particles and fatty acids during pregnancy is unclear. We examined the relationships of diet quality as assessed by the validated Healthy Food Intake Index (HFII) with serum HDL, LDL and VLDL particle concentrations and sizes and proportions of serum fatty acids in pregnant women at high risk for gestational diabetes mellitus (GDM). Overall, 161 women with a BMI of ≥30 kg/m2 and/or a history of GDM were drawn from the Finnish Gestational Diabetes Prevention Study, which is a dietary and exercise intervention trial to prevent GDM. At baseline, the HFII score was inversely related to concentrations of HDL particles (P=0·010) and MUFA (P=0·010) and positively related to concentrations of n-3 (P<0·001) and n-6 (P=0·003) PUFA. The significance for MUFA disappeared after adjustments. An increase in the HFII score from the first to second trimester of pregnancy correlated with reduced VLDL particle size (r −0·16, 95 % CI −0·31, −0·01), decreased MUFA concentrations (r −0·17, 95 % CI −0·31, −0·01) and elevated n-6 PUFA concentrations (r 0·16, 95 % CI 0·01, 0·31). In the maximum-adjusted model, the results remained significant except for VLDL particle size. These findings suggest that higher diet quality as defined by the HFII is related to a more favourable serum fatty acid profile, whereas the relationship with serum lipoprotein profile is limited in pregnant women at increased GDM risk.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Being breastfed in infancy has been shown to benefit neurodevelopment. However, whether the benefits persist to old age remains unclear.
We examined the associations between breastfeeding and its duration on cognitive ability in young adulthood and old age, and on aging-related cognitive change over five decades. In total, 931 men from the Helsinki Birth Cohort Study born in 1934–1944 in Finland took the Finnish Defence Forces Basic Intellectual Ability Test (total and verbal, arithmetic and visuospatial subtest scores) twice, at ages 20.2 and 67.9 years, and had data on breastfeeding (yes v. no) and its duration (‘never breastfed’, ‘up to 3’, ‘3 to 6’ and ‘6 or more months’). Linear and mixed model regressions tested the associations.
At 20.2 years, breastfed men had higher cognitive ability total and visuospatial subtest scores [mean differences (MDs) ranged between 3.0–3.9, p values < 0.013], and its longer duration predicted higher cognitive ability total and arithmetic and visuospatial subtest scores (MDs ranged between 3.0 and 4.8, p values < 0.039). At 67.9 years, breastfed men had higher total cognitive ability and all subtest scores (MDs ranged between 2.6 and 3.4, p values < 0.044) and its longer duration predicted all cognitive ability scores (MDs ranged between 3.1 and 4.7, p values < 0.050). Verbal subtest scores decreased over five decades in men who were never breastfed or were breastfed for 3 months or less, and increased in those breastfed for longer than 3 months.
Neurodevelopmental advantages of breastfeeding and its longer duration persist into old age, and longer duration of breastfeeding may benefit aging-related change, particularly in verbal reasoning ability.
There is strong evidence that physical activity (PA) has an influence on physical performance in later life. Also, a small body size at birth has been associated with lower physical functioning in older age and both small and high birth weight have shown to be associated with lower leisure time physical activity. However, it is unknown whether size at birth modulates the association between PA and physical performance in old age. We examined 695 individuals from the Helsinki Birth Cohort Study born in Helsinki, Finland between 1934 and 1944. At a mean age of 70.7 years PA was objectively assessed with a multisensory activity monitor and physical performance with the Senior Fitness Test (SFT). Information on birth weight and gestational age was retrieved from hospital birth records. The study participants were divided in three birth weight groups, that is <3000 g, 3000–3499 g and ⩾3500 g. The volume of PA was significantly associated with the physical performance in all birth weight groups. However, the effect size of the association was large and significant only in men with a birth weight <3000 g (β 0.59; 95% confidence interval 0.37–0.81, P<0.001). Our study shows that the association between PA and physical performance is largest in men with low birth weight. Our results suggest that men with low birth weight might benefit most from engaging in PA in order to maintain a better physical performance.
Visual processing problems may be one underlying factor for cognitive impairments related to autism spectrum disorders (ASDs). We examined associations between ASD-traits (Autism-Spectrum Quotient) and visual processing performance (Rey–Osterrieth Complex Figure Test; Block Design task of the Wechsler Adult Intelligence Scale-III) in young adults (mean age=25.0, s.d.=2.1 years) born preterm at very low birth weight (VLBW; <1500 g) (n=101) or at term (n=104). A higher level of ASD-traits was associated with slower global visual processing speed among the preterm VLBW, but not among the term-born group (P<0.04 for interaction). Our findings suggest that the associations between ASD-traits and visual processing may be restricted to individuals born preterm, and related specifically to global, not local visual processing. Our findings point to cumulative social and neurocognitive problems in those born preterm at VLBW.
Results of adulthood mental health of those born late-preterm (34 + 0–36 + 6 weeks + days of gestation) are mixed and based on national registers. We examined if late-preterm birth was associated with a higher risk for common mental disorders in young adulthood when using a diagnostic interview, and if this risk decreased as gestational age increased.
A total of 800 young adults (mean = 25.3, s.d. = 0.62 years), born 1985–1986, participated in a follow-up of the Arvo Ylppö Longitudinal Study. Common mental disorders (mood, anxiety and substance use disorders) during the past 12 months were defined using the Composite International Diagnostic Interview (Munich version). Gestational age was extracted from hospital birth records and categorized into early-preterm (<34 + 0, n = 37), late-preterm (34 + 0–36 + 6, n = 106), term (37 + 0–41 + 6, n = 617) and post-term (⩾42 + 0, n = 40).
Those born late-preterm and at term were at a similar risk for any common mental disorder [odds ratio (OR) 1.11, 95% confidence interval (CI) 0.67–1.84], for mood (OR 1.11, 95% CI 0.54–2.25), anxiety (OR 1.00, 95% CI 0.40–2.50) and substance use (OR 1.31, 95% CI 0.74–2.32) disorders, and co-morbidity of these disorders (p = 0.38). While the mental disorder risk decreased significantly as gestational age increased, the trend was driven by a higher risk in those born early-preterm.
Using a cohort born during the advanced neonatal and early childhood care, we found that not all individuals born preterm are at risk for common mental disorders in young adulthood – those born late-preterm are not, while those born early-preterm are at a higher risk. Available resources for prevention and intervention should be targeted towards the preterm group born the earliest.
Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
Previous studies suggest that the inverse association between birth weight and adult blood pressure amplifies with age. Rapid childhood growth has also been linked to hypertension. The objective of this study was to determine whether the association between childhood growth and adult blood pressure amplifies with age. The study comprised 574 women and 462 men from the Helsinki Birth Cohort Study who attended a clinical study in 2001–2004 and a follow-up in 2006–2008. Mean age at the clinic visits was 61.5 and 66.4 years, respectively. Blood pressure was measured at both occasions. Conditional growth models were used to assess relative weight gain and linear growth. We studied the associations between conditional growth and blood pressure as well as the presence of hypertension. Relative weight gain and linear growth between ages 2 and 11 years were inversely associated with systolic blood pressure at mean age 66.4 years, after adjustment for sex, blood pressure at mean age 61.5 years, as well as other covariates. A one s.d. increase in linear growth between 2 and 11 years was associated with an OR of 0.61 for hypertension at mean age 66.4 years. Contrary to previous studies, we have shown an inverse association between childhood growth and adult blood pressure. There were, however, no associations between childhood growth and systolic blood pressure at mean age 61.5 years indicating that the beneficial effects of a more rapid than expected childhood growth might become more apparent with increasing age.
Changes in anthropometrics often reflect changes in living conditions, and one’s characteristics at birth may be associated with future health. The aim of this study was to investigate the secular trends in maternal and neonatal anthropometrics in the Helsinki Birth Cohort Study. The study participants, thus, comprised all 13,345 live births recorded in Helsinki, Finland, between 1934 and 1944. Adult characteristics of the clinical subsample comprised of 2003 individuals, alive during 2003, were also analyzed. Linear Regression analysis with seasonal terms was applied to see whether clinically and statistically significant trends can be found in maternal age, height and body mass index (BMI) at pregnancy; gestational age, birth weight, ponderal index and sex ratio; and adult height, BMI and fat percentage. Statistically significant trends were found in maternal age and maternal BMI with abrupt changes between 1941 and 1944. Gestational age increased by an average of 0.11% per year (P<0.0001), and the proportion of premature births dropped from 7.9% in 1934 to 4.5% in 1944 (P<0.0001). In the clinical sample, a statistically significant, although small, average annual increase of 0.1% in adult heights was detected (P=0.0012 for men and P=0.0035 for women). In conclusion, although no significant changes were found in either neonatal or adult anthropometrics of babies born in Helsinki between 1934 and 1944, there were abrupt changes in the characteristics of their mothers.
The Åland Islands were recently ranked as Finland’s healthiest region with lower prevalence of several non-communicable diseases compared with the national mean. We have compared birth characteristics of 1697 individuals born on the Åland Islands between 1937 and 1944 with contemporaneous data from the Helsinki Birth Cohort Study (HBCS; n=11,808). This is a first step towards a potential future analysis of Ålandic health from a life-course perspective. Mean birth weight and length were calculated for both cohorts. Birth weight was entered into a multiple linear regression model with sex, maternal age, marital status and birth year as predictors. Mean birth weight in the Åland cohort was 3499 g, 87 g (95% CI 62; 111) higher compared with the HBCS. Sex and maternal marital status were the strongest predictors of birth weight. More detailed studies are needed to explore the potential effects of this difference in average birth weight between cohorts.
Late preterm births constitute the majority of preterm births. However, most evidence suggesting that preterm birth predicts the risk of mental disorders comes from studies on earlier preterm births. We examined if late preterm birth predicts the risks of severe mental disorders from early to late adulthood. We also studied whether adulthood mental disorders are associated with post-term birth or with being born small (SGA) or large (LGA) for gestational age, which have been previously associated with psychopathology risk in younger ages.
Of 12 597 Helsinki Birth Cohort Study participants, born 1934–1944, 664 were born late preterm, 1221 post-term, 287 SGA, and 301 LGA. The diagnoses of mental disorders were identified from national hospital discharge and cause of death registers from 1969 to 2010. In total, 1660 (13.2%) participants had severe mental disorders.
Individuals born late preterm did not differ from term-born individuals in their risk of any severe mental disorder. However, men born late preterm had a significantly increased risk of suicide. Post-term birth predicted significantly increased risks of any mental disorder in general and particularly of substance use and anxiety disorders. Individuals born SGA had significantly increased risks of any mental and substance use disorders. Women born LGA had an increased risk of psychotic disorders.
Although men born late preterm had an increased suicide risk, late preterm birth did not exert widespread effects on adult psychopathology. In contrast, the risks of severe mental disorders across adulthood were increased among individuals born SGA and individuals born post-term.
Strong epidemiological evidence suggests that slow prenatal or postnatal growth is associated with an increased risk of CVD and other metabolic diseases. However, little is known whether early growth affects postprandial metabolism and, especially, the appetite regulatory hormone system. Therefore, we investigated the impact of early growth on postprandial appetite regulatory hormone responses to two high-protein and two high-fat content meals. Healthy, 65–75-year-old volunteers from the Helsinki Birth Cohort Study were recruited; twelve with a slow increase in BMI during the first year of life (SGI group) and twelve controls. Subjects ate a test meal (whey meal, casein meal, SFA meal and PUFA meal) once in a random order. Plasma glucose, insulin, TAG, NEFA, ghrelin, peptide tyrosine-tyrosine (PYY), glucose-dependent insulinotropic peptide, glucagon-like peptide-1 and a satiety profile were measured in the fasting state and for 4 h after each test meal. Compared with the controls, the SGI group had about 1·5-fold higher insulin responses after the whey meal (P= 0·037), casein meal (P= 0·023) and PUFA meal (P= 0·002). TAG responses were 34–69 % higher for the SGI group, but only the PUFA-meal responses differed significantly between the groups. The PYY response of the SGI group was 44 % higher after the whey meal (P= 0·046) and 115 % higher after the casein meal (P= 0·025) compared with the controls. No other statistically significant differences were seen between the groups. In conclusion, early growth may have a role in programming appetite regulatory hormone secretion in later life. Slow early growth is also associated with higher postprandial insulin and TAG responses but not with incretin levels.
The associations between school performance and cognitive abilities with birth characteristics have mostly been studied without taking into consideration the effects of gestational age (GA). Our aim was to study the association between prenatal growth and cognitive function in term-born Chilean school children. A cohort of over 200,000 term-born fourth graders who took the regular national test for school performance was studied. Outcome parameters were language and mathematics test scores in relation to prenatal growth. A total of 256,040 subjects took the test and 220,940 were included in the final study sample. Prenatal growth was modestly, but significantly, associated with school performance. Adjusted β coefficients for 1 cm increase in birth length were 1.28 and 0.77 for mathematics and language, respectively; the corresponding values for 100 g increase in birth weight were 0.59 and 0.34, respectively. Increased GA was associated with lower test scores. Adjusted β coefficients for the birth measurements generally had a lower strength of association than those of socio-economic factors. However, the confounders most strongly associated with educational achievements were socio-economic factors, known to be associated with birth size. Lower socio-economic status is known to negatively influence both prenatal growth and cognitive function, supporting the overall importance of prenatal growth in relation to cognitive outcomes.
The association of prenatal growth with metabolic syndrome (MS) components and insulin resistance (IR) in children has not been studied in Chile and most developing countries. Some associations found in developed countries are controversial. A retrospective cohort study was designed linking present information on MS components and IR in children with register-based information on birth weight (BW), birth length (BL) and gestational age (GA). Examinations included anthropometry and blood pressure (BP), as well as self-report of pubertal status. A fasting blood sample was taken to determine lipids, glucose, insulin and homeostasis model assessment (HOMA)-IR was calculated. The study cohort of 2152 children was on average 11.4 ± 1.0 years old. The prevalence of MS, IR and overweight were 7.6%, 24.5% and 34%, respectively. Elevated BP was negatively associated with dichotomized risk categories of the perinatal factors studied (BW, BL and GA). Contingency tables showed that high waist circumference (WC) and elevated BP had a U-shaped association with various categories of BW and BL, respectively. Stepwise linear regressions selected: (a) WC as inversely associated to GA and directly associated to BW, (b) BP as inversely associated to GA and (c) HOMA-IR as inversely associated to BL. Non-optimal prenatal growth seems to predispose to high WC, elevated BP and IR in school-age children, supporting the early life origin of several non-communicable diseases. Those associations were rather weak as estimated by the slopes of the regressions and probably reduced by their U-shaped nature; they would reasonably become stronger with a longer follow-up.
Early attachment relationships from infancy onward contribute to attachment patterns later in life, to the ability to build up close relationships and to well-being in general. Severely preterm birth may challenge the development of these attachment relationships. We studied whether there are differences in attachment patterns related to romantic relationships between young adults (mean age 22.4 years, s.d. 2.2 years) with very low birth weight (VLBW, <1500 g; n = 162) and their peers born at term (n = 172), who completed the Experiences in Close Relationships Questionnaire – Revised. Young adults born at VLBW showed lower attachment-related anxiety than their peers born at term (mean difference −9.5%, 95% CI −16.0 to −2.6) when adjusted for sex, age, parental education and being in a romantic relationship currently. The groups did not differ in attachment-related avoidance. In subgroup analyses, the VLBW women born small for gestational age (SGA, birth weight <−2 s.d.) scored on average 14.8% (95% CI 3.1–26.6) higher than the control women on attachment avoidance. The effects remained after the exclusion of 18 participants with neurosensory deficits. We found no evidence for a compromised attachment pattern in young adults born at VLBW, with a possible exception of women born SGA at VLBW. VLBW adults were rather characterized by a lower level of attachment-related anxiety.
New findings on the maternal and placental programming of chronic disease lead to four conclusions: (1) Growth of the placental surface is polarized from the time of implantation, so that growth along the major axis, the length, is qualitatively different from growth along the minor axis, the breadth. (2) The human fetus may attempt to compensate for undernutrition by expansion of the placental surface along its minor axis. This only occurs if the mother was well nourished before conception, and may have long-term costs that include hypertension. (3) The effects of placental size on long-term health are conditioned by the mother’s nutritional state, as indicated by her socio-economic status, height and body mass index. (4) The maternal–placental programming of chronic disease differs in boys and girls. Boys invest less than girls in placental growth but more readily expand the placental surface if they become undernourished in mid-late gestation. Boys are more responsive to their mothers’ current diets while girls respond more to their mothers’ lifetime nutrition and metabolism.