Gry Poulsen

Effects of gestational age at birth on health outcomes at 3 and 5 years of age: population based cohort study

Objective To investigate the burden of later disease associated with moderate/late preterm (32-36 weeks) and early term (37-38 weeks) birth. Design Secondary analysis of data from the Millennium Cohort Study (MCS). Setting Longitudinal study of infants born in the United Kingdom between 2000 and 2002. Participants 18u2009818 infants participated in the MCS. Effects of gestational age at birth on health outcomes at 3 (n=14u2009273) and 5 years (n=14u2009056) of age were analysed. Main outcome measures Growth, hospital admissions, longstanding illness/disability, wheezing/asthma, use of prescribed drugs, and parental rating of their children’s health. Results Measures of general health, hospital admissions, and longstanding illness showed a gradient of increasing risk of poorer outcome with decreasing gestation, suggesting a “dose-response” effect of prematurity. The greatest contribution to disease burden at 3 and 5 years was in children born late/moderate preterm or early term. Population attributable fractions for having at least three hospital admissions between 9 months and 5 years were 5.7% (95% confidence interval 2.0% to 10.0%) for birth at 32-36 weeks and 7.2% (1.4% to 13.6%) for birth at 37-38 weeks, compared with 3.8% (1.3% to 6.5%) for children born very preterm (<32 weeks). Similarly, 2.7% (1.1% to 4.3%), 5.4% (2.4% to 8.6%), and 5.4% (0.7% to 10.5%) of limiting longstanding illness at 5 years were attributed to very preterm birth, moderate/late preterm birth, and early term birth. Conclusions These results suggest that health outcomes of moderate/late preterm and early term babies are worse than those of full term babies. Additional research should quantify how much of the effect is due to maternal/fetal complications rather than prematurity itself. Irrespective of the reason for preterm birth, large numbers of these babies present a greater burden on public health services than very preterm babies.

Early term and late preterm birth are associated with poorer school performance at age 5 years: a cohort study

Objective To compare school performance at age 5 years in children born at full term (39–41 weeks gestation) with those born at early term (37–38 weeks gestation), late preterm (34–36 weeks gestation), moderately preterm (32–33 weeks gestation) and very preterm (<32 weeks gestation). Design Population-based cohort (UK Millennium Cohort Study). Participants Seven thousand six hundred and fifty children born in 2000–2001 and attending school in England in 2006. Methods School performance was measured using the foundation stage profile (FSP), a statutory assessment by teachers at the end of the childs first school year. The FSP comprises 13 assessment scales (scored from 1 to 9). Children who achieve an average of 6 points per scale and at least 6 in certain scales are classified as ‘reaching a good level of overall achievement’. Results Fifty-one per cent of full term children had not reached a good level of overall achievement; this proportion increased with prematurity (55% in early term, 59% in late preterm, 63% in moderately preterm and 66% in very preterm children). Compared with full term children, an elevated risk remained after adjustment, even in early term (adjusted RR 1.05, 95% 1.00 to 1.11) and late preterm children (adjusted RR 1.12, 95% CI 1.04 to 1.22). Similar effects were noted for ‘not working securely’ in mathematical development, physical development and creative development. The effects of late preterm and early term birth were small in comparison with other risk factors. Conclusions Late preterm and early term birth are associated with an increased risk of poorer educational achievement at age 5 years.

Pregnancy and Birth Cohort Resources in Europe: a Large Opportunity for Aetiological Child Health Research

BACKGROUNDnDuring the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net.nnnMETHODSnEuropean pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection.nnnRESULTSnIn total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500,000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions.nnnCONCLUSIONnThis work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.

Gestational Age and Cognitive Ability in Early Childhood: a Population-based Cohort Study

BACKGROUNDnRecent studies suggest that children born at late preterm (34-36 weeks gestation) and early term (37-38 weeks) may have poorer developmental outcomes than children born at full term (39-41 weeks). We examined how gestational age is related to cognitive ability in early childhood using the U.K. Millennium Cohort Study.nnnMETHODSnCognitive development was assessed using Bracken School Readiness Assessment at age 3 years, British Ability Scales II at ages 3, 5 and 7 years and Progress in Mathematics at age 7 years. Sample size varied according to outcome between 12,163 and 14,027. Each gestational age group was compared with the full-term group using differences in z-scores and risk ratios for scoring more than -1 SD below the mean.nnnRESULTSnChildren born at <32 weeks gestation scored lower (Pu2009<u20090.05) than the full-term group on all scales with unadjusted z-score differences ranging between -0.8 to -0.2 SD. In all groups, there was an increased risk (Pu2009<u20090.05) of scoring less than -1 SD below the mean compared with the full-term group for some of the tests: those born at <u200932 weeks had a 40-140% increased risk in seven tests, those born at 32-33 weeks had a 60-80% increased risk in three tests, those born at 34-36 weeks had a 30-40% increased risk in three tests, and those born at 37-38 weeks had a 20% increased risk in two tests.nnnCONCLUSIONSnCognitive ability is related to the entire range of gestational age, including children born at 34-36 and 37-38 weeks gestation.

Accurate reporting of expected delivery date by mothers 9 months after birth

OBJECTIVEnTo measure agreement between gestational age based on maternal report of expected date of delivery (EDD) 9 months after birth and gestational age at birth in routine hospital data. Furthermore, to examine whether sociodemographic and perinatal factors influenced agreement and whether disagreement affected classification of infants in preterm groups.nnnSTUDY DESIGN AND SETTINGnThe study used data on 8,058 singleton infants from the UK Millennium Cohort Study. Women were interviewed 9 months after birth and interviews were linked to routine hospital data. The infants date of birth and EDD were used to calculate gestational age in completed weeks.nnnRESULTSnAgreement between maternal report and hospital data was 72% for exact number of weeks gestation and 94% for agreement within 1 week. Disagreement was associated with the infant not being firstborn, unplanned pregnancy, late or no antenatal care, and low socioeconomic status. Maternal report of gestational age resulted in slightly more children being classified as preterm (6.4%) than gestational age based on hospital data (6.1%). Agreement was found to be poor for postterm births.nnnCONCLUSIONnGestational age based on retrospective maternal reporting of EDD is reliable within 1 week or when used to assign infants to broad gestational groups.

Exploring Educational Disparities in Risk of Preterm Delivery: A Comparative Study of 12 European Birth Cohorts

BACKGROUNDnAn association between education and preterm delivery has been observed in populations across Europe, but differences in methodology limit comparability. We performed a direct cross-cohort comparison of educational disparities in preterm delivery based on individual-level birth cohort data.nnnMETHODSnThe study included data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal, and Spain. The cohorts included between 2434 and 99u2009655 pregnancies. The association between maternal education and preterm delivery (22-36 completed weeks of gestation) was reported as risk ratios, risk differences, and slope indexes of inequality with 95% confidence intervals (CIs).nnnRESULTSnSingleton preterm live delivery proportion varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and maternal characteristics. Nevertheless, there were similar educational differences in risk of preterm delivery in 8 of the 12 cohorts with slope index of inequality varying between 2.2 [95% CI 1.1, 3.3] and 4.0 [95% CI 1.4, 6.6] excess preterm deliveries per 100 singleton deliveries among the educationally most disadvantaged, and risk ratio between the lowest and highest education category varying from 1.4 [95% CI 1.1, 1.8] to 1.9 [95% CI 1.2, 3.1]. No associations were found in the last four cohorts.nnnCONCLUSIONSnEducational disparities in preterm delivery were found all over Europe. Despite differences in the distributions of education and preterm delivery, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics did not explain the differences.

Accumulation of Major Life Events in Childhood and Adult Life and Risk of Type 2 Diabetes Mellitus

Background The aim of the study was to estimate the effect of the accumulation of major life events (MLE) in childhood and adulthood, in both the private and working domains, on risk of type 2 diabetes mellitus (T2DM). Furthermore, we aimed to test the possible interaction between childhood and adult MLE and to investigate modification of these associations by educational attainment. Methods The study was based on 4,761 participants from the Copenhagen City Heart Study free of diabetes at baseline and followed for 10 years. MLE were categorized as 0, 1, 2, 3 or more events. Multivariate logistic regression models adjusted for age, sex, education and family history of diabetes were used to estimate the association between MLE and T2DM. Results In childhood, experiencing 3 or more MLE was associated with a 69% higher risk of developing T2DM (Odds Ratio (OR) 1.69; 95% Confidence Interval (CI) 1.60, 3.27). The accumulation of MLE in adult private (p-trend = 0.016) and work life (p-trend = 0.049) was associated with risk of T2DM in a dose response manner. There was no evidence that experiencing MLE in both childhood and adult life was more strongly associated with T2DM than experiencing events at only one time point. There was some evidence that being simultaneously exposed to childhood MLE and short education (OR 2.28; 95% C.I. 1.45, 3.59) and work MLE and short education (OR 2.86; 95% C.I. 1.62, 5.03) was associated with higher risk of T2DM, as the joint effects were greater than the sum of their individual effects. Conclusions Findings from this study suggest that the accumulation of MLE in childhood, private adult life and work life, respectively, are risk factors for developing T2DM.

Association of light-to-moderate alcohol drinking in pregnancy with preterm birth and birth weight: elucidating bias by pooling data from nine European cohorts

Women who drink light-to-moderately during pregnancy have been observed to have lower risk of unfavourable pregnancy outcomes than abstainers. This has been suggested to be a result of bias. In a pooled sample, including 193 747 live-born singletons from nine European cohorts, we examined the associations between light-to-moderate drinking and preterm birth, birth weight, and small-for-gestational age in term born children (term SGA). To address potential sources of bias, we compared the associations from the total sample with a sub-sample restricted to first-time pregnant women who conceived within six months of trying, and examined whether the associations varied across calendar time. In the total sample, drinking up to around six drinks per week as compared to abstaining was associated with lower risk of preterm birth, whereas no significant associations were found for birth weight or term SGA. Drinking six or more drinks per week was associated with lower birth weight and higher risk of term SGA, but no increased risk of preterm birth. The analyses restricted to women without reproductive experience revealed similar results. Before 2000 approximately half of pregnant women drank alcohol. This decreased to 39% in 2000–2004, and 14% in 2005–2011. Before 2000, every additional drink was associated with reduced mean birth weight, whereas in 2005–2011, the mean birth weight increased with increasing intake. The period-specific associations between low-to-moderate drinking and birth weight, which also were observed for term SGA, are indicative of bias. It is impossible to distinguish if the bias is attributable to unmeasured confounding, which change over time or cohort heterogeneity.

Polygenic Risk, Early Adverse Life Events And Depression In The Ipsych Cohort

Background Major depressive disorder (MDD) is moderately genetic, with population-based heritability estimates of 30-40% and SNP-based heritability estimates of 20-25%. However, a large proportion of risk for MDD is attributable to the environment. Early adverse life events (EALEs), such as the death of a parent, are well-established risk factors for MDD. Candidate gene studies indicate that EALEs interact with single genes to influence MDD risk. However, mounting evidence suggests that the underlying genetic architecture of MDD is polygenic. To date, only two studies have examined whether polygenic risk (PR) interacts with early adversity to predict MDD. Peyrot et al. (2014) found in the NESDA study that the effect of PR on MDD was stronger among individuals with a history of childhood trauma. Mullins et al. (2016) found the opposite: among people with moderate/severe trauma, the log odds of MDD decreased as PR increased. The goal of this study is to evaluate the extent to which EALEs interact with PR to predict MDD in the Danish iPSYCH cohort. The iPSYCH cohort contains 88,764 individuals, including 24,693 MDD cases, making this by far the largest study on the topic to date. Methods The iPSYCH cohort has a case-cohort design, containing individuals randomly sampled from the population of people born in Denmark between May 1, 1981-Dec 31, 2005, along with additional psychiatric cases identified from the Danish Central Psychiatric Research Register. DNA was extracted from dried blood spots and amplified in triplicate. Individuals were genotyped using the PSYCH chip. In this study, we will use data from controls and cases with an MDD diagnosis (ICD-10 codes F32, F33). EALEs, including death of a parent, death of a sibling, parental hospitalization, parental imprisonment, parental unemployment, parental divorce/separation, foster care and abuse, will be assessed using information from other Danish nationwide registers. EALEs will be operationalized as a weighted count variable of the number of events experienced by each individual before the age of 15. PR scores will be calculated using the PGC2 MDD results (not including the iPSYCH sample) as the training dataset (Purcell, 2009). Statistical analyses will be conducted using Cox Proportional Hazards Models, with weights to account for the case-cohort design (Self & Prentice, 1988). Results The PR scores which will be used in this study are currently being finalized. We anticipate that this process will be finished in August, 2016, which will give us over two months to conduct the analyses and prepare the results for presentation at the WCPG conference. Discussion Pending finalization of results.

CHILDREN WHO ARE BORN JUST A FEW WEEKS PREMATURE ARE MORE LIKELY TO HAVE POORER SCHOOL PERFORMANCE THAN THOSE BORN AT FULL TERM

Objective While it is well known that extreme prematurity is associated with poorer health and cognitive development, less is known about the effect of being born just a few weeks premature. We compared school performance at age 5 years in children born at full term (39–41 weeks gestation) with those born at varying levels of prematurity, from ‘early term’ (gestational age 37–38 weeks), ‘late preterm’ (gestational age 34–36 weeks) to ‘moderately/very preterm’ (gestational age <34 weeks). Design Population-based cohort (UK Millennium Cohort Study). Setting UK. Participants 7,655 children born in 2000–2001 and attending school in England in 2006. Main outcome measure The main outcome was the Foundation Stage Profile (FSP), a statutory assessment by teachers at the end of the childs first school year (age 5). The FSP captures the Early Learning Goals as a set of 13 assessment scales (scored from 0 to 9) in 6 domains (Personal, social and emotional development; Communication, language and literacy; Mathematical development; Physical development; Creative development; and Knowledge and understanding of the world). Children who achieve an average of 6 points per scale and a score of at least 6 in the ‘Personal, social and emotional development’ and ‘Communication, language and literacy development’ scales are classified as ‘reaching a good level of overall achievement’; this was the primary outcome. Results 51% of full term children had not reached a good level of overall achievement at the end of their first school year and this increased with prematurity (55% in early term children, 59% in late preterm children, 64% in moderately/very preterm children). After adjustment for confounders using logistic regression, there were significantly elevated odds even in late preterm (adjusted OR 1.3, 95% CI: 1.1 to 1.7) and early term (adjusted OR 1.2, 95% 1.0, 1.3) children. Although the elevated odds for early term birth were relatively small, early term birth accounted for a similar population attributable fraction (2.7%) as for all the preterm groups combined (gestation 23–36 weeks) (2.6%). The elevated odds associated with late preterm and early term birth were consistent across all areas of learning. Conclusions Late preterm and early term birth are associated with an elevated risk of poorer educational achievement at age 5. Early term children account for a relatively large proportion of all births (21% of all births in our study) and therefore even a small increase in risk will have implications for education planning.