Maternal pre-pregnancy body mass index and risk of preterm birth: a collaboration using large routine health datasets.

BACKGROUND: Preterm birth (PTB) is a leading cause of child morbidity and mortality. Evidence suggests an increased risk with both maternal underweight and obesity, with some studies suggesting underweight might be a greater factor in spontaneous PTB (SPTB) and that the relationship might vary by parity. Previous studies have largely explored established body mass index (BMI) categories. Our aim was to compare associations of maternal pre-pregnancy BMI with any PTB, SPTB and medically indicated PTB (MPTB) among nulliparous and parous women across populations with differing characteristics, and to identify the optimal BMI with lowest risk for these outcomes. METHODS: We used three UK datasets, two USA datasets and one each from South Australia, Norway and Denmark, together including just under 29 million pregnancies resulting in a live birth or stillbirth after 24 completed weeks gestation. Fractional polynomial multivariable logistic regression was used to examine the relationship of maternal BMI with any PTB, SPTB and MPTB, among nulliparous and parous women separately. The results were combined using a random effects meta-analysis. The estimated BMI at which risk was lowest was calculated via differentiation and a 95% confidence interval (CI) obtained using bootstrapping. RESULTS: We found non-linear associations between BMI and all three outcomes, across all datasets. The adjusted risk of any PTB and MPTB was elevated at both low and high BMIs, whereas the risk of SPTB was increased at lower levels of BMI but remained low or increased only slightly with higher BMI. In the meta-analysed data, the lowest risk of any PTB was at a BMI of 22.5 kg/m2 (95% CI 21.5, 23.5) among nulliparous women and 25.9 kg/m2 (95% CI 24.1, 31.7) among multiparous women, with values of 20.4 kg/m2 (20.0, 21.1) and 22.2 kg/m2 (21.1, 24.3), respectively, for MPTB; for SPTB, the risk remained roughly largely constant above a BMI of around 25-30 kg/m2 regardless of parity. CONCLUSIONS: Consistency of findings across different populations, despite differences between them in terms of the time period covered, the BMI distribution, missing data and control for key confounders, suggests that severe under- and overweight may play a role in PTB risk.

Maternal plasma cortisol's effect on offspring birth weight: a Mendelian Randomisation study.

BACKGROUND: Observational studies and randomized controlled trials have found evidence that higher maternal circulating cortisol levels in pregnancy are associated with lower offspring birth weight. However, it is possible that the observational associations are due to residual confounding. METHODS: We performed two-sample Mendelian Randomisation (MR) using a single genetic variant (rs9989237) associated with morning plasma cortisol (GWAS; sample 1; N = 25,314). The association between this maternal genetic variant and offspring birth weight, adjusted for fetal genotype, was obtained from the published EGG Consortium and UK Biobank meta-analysis (GWAS; sample 2; N = up to 406,063) and a Wald ratio was used to estimate the causal effect. We also performed an alternative analysis using all GWAS reported cortisol variants that takes account of linkage disequilibrium. We also tested the genetic variant's effect on pregnancy cortisol and performed PheWas to search for potential pleiotropic effects. RESULTS: The estimated effect of maternal circulating cortisol on birth weight was a 50 gram (95% CI, -109 to 10) lower birth weight per 1 SD higher log-transformed maternal circulating cortisol levels, using a single variant. The alternative analysis gave similar results (-33 grams (95% CI, -77 to 11)). The effect of the cortisol variant on pregnancy cortisol was 2-fold weaker than in the original GWAS, and evidence was found of pleiotropy. CONCLUSIONS: Our findings provide some evidence that higher maternal morning plasma cortisol causes lower birth weight. Identification of more independent genetic instruments for morning plasma cortisol are necessary to explore the potential bias identified.

Socio-economic disadvantage and utilisation of labour epidural analgesia in Scotland: a population-based study†.

Socio-economic deprivation is associated with adverse maternal and childhood outcomes. Epidural analgesia, the gold standard for labour analgesia, may improve maternal well-being. We assessed the association of socio-economic status with utilisation of epidural analgesia and whether this differed when epidural analgesia was advisable for maternal safety. This was a population-based study of NHS data for all women in labour in Scotland between 1 January 2007 and 23 October 2020, excluding elective caesarean sections. Socio-economic status deciles were defined using the Scottish Index of Multiple Deprivation. Medical conditions for which epidural analgesia is advisable for maternal safety (medical indications) and contraindications were defined according to national guidelines. Of 593,230 patients in labour, 131,521 (22.2%) received epidural analgesia. Those from the most deprived areas were 16% less likely to receive epidural analgesia than the most affluent (relative risk 0.84 [95%CI 0.82-0.85]), with the inter-decile mean change in receiving epidural analgesia estimated at -2% ([95%CI -2.2% to -1.7%]). Among the 21,219 deliveries with a documented medical indication for epidural analgesia, the socio-economic gradient persisted (relative risk 0.79 [95%CI 0.75-0.84], inter-decile mean change in receiving epidural analgesia -2.5% [95%CI -3.1% to -2.0%]). Women in the most deprived areas with a medical indication for epidural analgesia were still less likely (absolute risk 0.23 [95%CI 0.22-0.24]) to receive epidural analgesia than women from the most advantaged decile without a medical indication (absolute risk 0.25 [95%CI 0.24-0.25]). Socio-economic deprivation is associated with lower utilisation of epidural analgesia, even when epidural analgesia is advisable for maternal safety. Ensuring equitable access to an intervention that alleviates pain and potentially reduces adverse outcomes is crucial.

Characteristics associated with antenatally unidentified small-for-gestational-age fetuses: prospective cohort study nested within DESiGN randomized controlled trial.

OBJECTIVE: To identify the clinical characteristics and patterns of ultrasound use amongst pregnancies with an antenatally unidentified small-for-gestational-age (SGA) fetus, compared with those in which SGA is identified, to understand how to design interventions that improve antenatal SGA identification. METHODS: This was a prospective cohort study of singleton, non-anomalous SGA (birth weight < 10th centile) neonates born after 24 + 0 gestational weeks at 13 UK sites, recruited for the baseline period and control arm of the DESiGN trial. Pregnancy with antenatally unidentified SGA was defined if there was no scan or if the final scan showed estimated fetal weight (EFW) at the 10th centile or above. Identified SGA was defined if EFW was below the 10th centile at the last scan. Maternal and fetal sociodemographic and clinical characteristics were studied for associations with unidentified SGA using unadjusted and adjusted logistic regression models. Ultrasound parameters (gestational age at first growth scan, number and frequency of ultrasound scans) were described, stratified by presence of indication for serial ultrasound. Associations of unidentified SGA with absolute centile and percentage weight difference between the last scan and birth were also studied on unadjusted and adjusted logistic regression, according to time between the last scan and birth. RESULTS: Of the 15 784 SGA babies included, SGA was not identified antenatally in 78.7% of cases. Of pregnancies with unidentified SGA, 47.1% had no recorded growth scan. Amongst 9410 pregnancies with complete data on key maternal comorbidities and antenatal complications, the risk of unidentified SGA was lower for women with any indication for serial scans (adjusted odds ratio (aOR), 0.56 (95% CI, 0.49-0.64)), for Asian compared with white women (aOR, 0.80 (95% CI, 0.69-0.93)) and for those with non-cephalic presentation at birth (aOR, 0.58 (95% CI, 0.46-0.73)). The risk of unidentified SGA was highest among women with a body mass index (BMI) of 25.0-29.9 kg/m2 (aOR, 1.15 (95% CI, 1.01-1.32)) and lowest in those with underweight BMI (aOR, 0.61 (95% CI, 0.48-0.76)) compared to women with BMI of 18.5-24.9 kg/m2 . Compared to women with identified SGA, those with unidentified SGA had fetuses of higher SGA birth-weight centile (adjusted odds for unidentified SGA increased by 1.21 (95% CI, 1.18-1.23) per one-centile increase between the 0th and 10th centiles). Duration between the last scan and birth increased with advancing gestation in pregnancies with unidentified SGA. SGA babies born within a week of the last growth scan had a mean difference between EFW and birth-weight centiles of 19.5 (SD, 13.8) centiles for the unidentified-SGA group and 0.2 (SD, 3.3) centiles for the identified-SGA group (adjusted mean difference between groups, 19.0 (95% CI, 17.8-20.1) centiles). CONCLUSIONS: Unidentified SGA was more common amongst women without an indication for serial ultrasound, and in those with cephalic presentation at birth, BMI of 25.0-29.9 kg/m2 and less severe SGA. Ultrasound EFW was overestimated in women with unidentified SGA. This demonstrates the importance of improving the accuracy of SGA screening strategies in low-risk populations and continuing performance of ultrasound scans for term pregnancies. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Improving antenatal detection of small-for-gestational-age fetus: economic evaluation of Growth Assessment Protocol.

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP), as implemented in the DESiGN trial, is cost-effective in terms of antenatal detection of small-for-gestational-age (SGA) neonate, when compared with standard care. METHODS: This was an incremental cost-effectiveness analysis undertaken from the perspective of a UK National Health Service hospital provider. Thirteen maternity units from England, UK, were recruited to the DESiGN (DEtection of Small for GestatioNal age fetus) trial, a cluster randomized controlled trial. Singleton, non-anomalous pregnancies which delivered after 24 + 0 gestational weeks between November 2015 and February 2019 were analyzed. Probabilistic decision modeling using clinical trial data was undertaken. The main outcomes of the study were the expected incremental cost, the additional number of SGA neonates identified antenatally and the incremental cost-effectiveness ratio (ICER) (cost per additional SGA neonate identified) of implementing GAP. Secondary analysis focused on the ICER per infant quality-adjusted life year (QALY) gained. RESULTS: The expected incremental cost (including hospital care and implementation costs) of GAP over standard care was £34 559 per 1000 births, with a 68% probability that implementation of GAP would be associated with increased costs to sustain program delivery. GAP identified an additional 1.77 SGA neonates per 1000 births (55% probability of it being more clinically effective). The ICER for GAP was £19 525 per additional SGA neonate identified, with a 44% probability that GAP would both increase cost and identify more SGA neonates compared with standard care. The probability of GAP being the dominant clinical strategy was low (11%). The expected incremental cost per infant QALY gained ranged from £68 242 to £545 940, depending on assumptions regarding the QALY value of detection of SGA. CONCLUSION: The economic case for replacing standard care with GAP is weak based on the analysis reported in our study. However, this conclusion should be viewed taking into account that cost-effectiveness analyses are always limited by the assumptions made. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

UK stillbirth trends in over 11 million births provide no evidence to support effectiveness of Growth Assessment Protocol program.

OBJECTIVE: Use of the Growth Assessment Protocol (GAP) has increased internationally under the assumption that it reduces the stillbirth rate. The evidence for this is limited and based largely on an ecological time-trend study. Discordance in the uptake of the GAP program between Scotland and England/Wales enabled us to assess the assertion that implementation of GAP leads to a reduced stillbirth rate. METHODS: We analyzed data from the National Records for Scotland and the Office for National Statistics on the number of singleton maternities and stillbirths in Scotland and in England and Wales, respectively, from 1 January 2000 to 31 December 2015. National uptake of the GAP program over time in each of the regions was recorded. Stillbirth rate per 1000 maternities was calculated, according to year of delivery, and compared between Scotland and England/Wales. RESULTS: During the study period, there were 870 632 singleton maternities in Scotland, of which 4243 were stillbirths, and there were 10 469 120 singleton maternities in England and Wales, of which 51 562 were stillbirths. There was a marked difference in uptake of the GAP program between the two regions, with substantially fewer maternity units in Scotland implementing the program. Stillbirth rates were static up to 2010, with a decline thereafter in both regions, to 3.75 (95% CI, 3.25-4.30) per 1000 maternities in Scotland and 4.30 (95% CI, 4.15-4.46) per 1000 maternities in England and Wales in 2015. From 2010 onwards, the decline in Scotland was faster, equating to 48 (95% CI, 47.9-48.1) fewer stillbirths per 100 000 maternities in Scotland than in England and Wales from 2010 to 2015 compared with 2000 to 2009. CONCLUSIONS: We observed a decline in stillbirth rate in England and Wales, which coincided with implementation of the GAP program. However, a concurrent decline in stillbirth rate was observed in Scotland in the absence of increased implementation of GAP. The secular rates of change in stillbirth rate in England and Wales cannot be used to infer efficacy of the GAP program. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Breech presentation is associated with lower adolescent tibial bone strength.

We compared bone outcomes in adolescents with breech and cephalic presentation. Tibia bone mineral content, density, periosteal circumference, and cross-sectional moment of inertia were lower in breech presentation, and females with breech presentation had lower hip CSA. These findings suggest that prenatal loading may exert long-lasting influences on skeletal development. INTRODUCTION: Breech position during pregnancy is associated with reduced range of fetal movement, and with lower limb joint stresses. Breech presentation at birth is associated with lower neonatal bone mineral content (BMC) and area, but it is unknown whether these associations persist into later life. METHODS: We examined associations between presentation at onset of labor, and tibia and hip bone outcomes at age 17 years in 1971 participants (1062 females) from a UK prospective birth cohort that recruited > 15,000 pregnant women in 1991-1992. Cortical BMC, cross-sectional area (CSA) and bone mineral density (BMD), periosteal circumference, and cross-sectional moment of inertia (CSMI) were measured by peripheral quantitative computed tomography (pQCT) at 50% tibia length. Total hip BMC, bone area, BMD, and CSMI were measured by dual-energy X-ray absorptiometry (DXA). RESULTS: In models adjusted for sex, age, maternal education, smoking, parity, and age, singleton/multiple births, breech presentation (n = 102) was associated with lower tibial cortical BMC (- 0.14SD, 95% CI - 0.29 to 0.00), CSA (- 0.12SD, - 0.26 to 0.02), BMD (- 0.16SD, - 0.31 to - 0.01), periosteal circumference (- 0.14SD, - 0.27 to - 0.01), and CSMI (- 0.11SD, - 0.24 to 0.01). In females only, breech presentation was associated with lower hip CSA (- 0.24SD, - 0.43 to 0.00) but not with other hip outcomes. Additional adjustment for potential mediators (delivery method, birthweight, gestational age, childhood motor competence and adolescent height and body composition) did not substantially affect associations with either tibia or hip outcomes. CONCLUSIONS: These findings suggest that prenatal skeletal loading may exert long-lasting influences on skeletal size and strength but require replication.

Birth weight and cardiac function assessed by echocardiography in adolescence: Avon Longitudinal Study of Parents and Children.

OBJECTIVE: Maternal hemodynamics in pregnancy is associated with fetal growth and birth weight, which in turn are associated with offspring cardiovascular disease later in life. The aim of this study was to quantify the extent to which birth weight is associated with cardiac structure and function in adolescence. METHODS: A subset of offspring (n = 1964; 55% female) of the Avon Longitudinal Study of Parents and Children were examined with echocardiography at a mean age of 17.7 (SD, 0.3) years. The associations of birth-weight Z-score for sex and gestational age with cardiac structure (assessed by relative wall thickness, left ventricular mass index (LVMI) and left atrial diameter index), systolic function (assessed by ejection fraction and left ventricular wall velocity) and diastolic function (assessed by early/late mitral inflow velocity (E/A) and early mitral inflow velocity/mitral annular early diastolic velocity (E/e')) were evaluated. Linear regression models were adjusted for several potential confounders, including maternal prepregnancy body mass index, age, level of education and smoking during pregnancy. RESULTS: Higher birth-weight Z-score was associated with lower E/A (mean difference, -0.024; 95% CI, -0.043 to -0.005) and E/e' (mean difference, -0.05; 95% CI, -0.10 to -0.001) and higher LVMI (mean difference, 0.38 g/m2.7 ; 95% CI, 0.09 to 0.67). There was no or inconsistent evidence of associations of birth-weight Z-score with relative wall thickness, left atrial diameter and measurements of systolic function. Further analyses suggested that the association between birth-weight Z-score and LVMI was driven mainly by an association observed in participants born small-for-gestational age and it did not persist when risk factors in adolescence were accounted for. CONCLUSIONS: Higher birth weight adjusted for sex and gestational age was associated with differences in measures of diastolic function in adolescence, but the observed associations were small. It remains to be determined the extent to which these associations translate into increased susceptibility to cardiovascular disease later in life. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Infant adiposity following a randomised controlled trial of a behavioural intervention in obese pregnancy.

OBJECTIVES: Randomised controlled trials are required to address causality in the reported associations between maternal influences and offspring adiposity. The aim of this study was to determine whether an antenatal lifestyle intervention, associated with improvements in maternal diet and reduced gestational weight gain (GWG) in obese pregnant women leads to a reduction in infant adiposity and sustained improvements in maternal lifestyle behaviours at 6 months postpartum. SUBJECTS AND METHODS: We conducted a planned postnatal follow-up of a randomised controlled trial (UK Pregnancies Better Eating and Activity Trial (UPBEAT)) of a complex behavioural intervention targeting maternal diet (glycaemic load (GL) and saturated fat intake) and physical activity in 1555 obese pregnant women. The main outcome measure was infant adiposity, assessed by subscapular and triceps skinfold thicknesses. Maternal diet and physical activity, indices of the familial lifestyle environment, were assessed by questionnaire. RESULTS: A total of 698 (45.9%) infants (342 intervention and 356 standard antenatal care) were followed up at a mean age of 5.92 months. There was no difference in triceps skinfold thickness z-scores between the intervention vs standard care arms (difference -0.14 s.d., 95% confidence interval -0.38 to 0.10, P=0.246), but subscapular skinfold thickness z-score was 0.26 s.d. (-0.49 to -0.02; P=0.03) lower in the intervention arm. Maternal dietary GL (-35.34; -48.0 to -22.67; P<0.001) and saturated fat intake (-1.93% energy; -2.64 to -1.22; P<0.001) were reduced in the intervention arm at 6 months postpartum. Causal mediation analysis suggested that lower infant subscapular skinfold thickness was partially mediated by changes in antenatal maternal diet and GWG rather than postnatal diet. CONCLUSIONS: This study provides evidence from follow-up of a randomised controlled trial that a maternal behavioural intervention in obese pregnant women has the potential to reduce infant adiposity and to produce a sustained improvement in maternal diet at 6 months postpartum.

Haemoglobin concentrations in pregnancy and respiratory and allergic outcomes in childhood: Birth cohort study.

BACKGROUND: Limited epidemiological evidence suggests that low maternal iron status and anaemia in pregnancy may increase the risk of childhood respiratory and allergic outcomes. OBJECTIVES: To investigate the relation between maternal haemoglobin concentrations in pregnancy and childhood respiratory and allergic outcomes. METHODS: In the Avon Longitudinal Study of Parents and Children (ALSPAC), we examined associations of maternal haemoglobin concentrations (g/dL) in pregnancy with hayfever, eczema, wheezing, doctor-diagnosed asthma, allergic sensitisation and total IgE at 7 years, and with lung function at 8-9 years in the offspring, after controlling for potential confounders (N = 3234-5335). RESULTS: Maternal haemoglobin was not associated with offspring hayfever, eczema, wheezing or asthma. However, the first haemoglobin measurement in pregnancy (<18 weeks' gestation) and the last measurement (>28 weeks' gestation) were negatively associated with allergic sensitisation (adjusted odds ratio [95% CI] per g/dL 0.91 [0.83 to 0.99] and 0.90 [0.83 to 0.98], respectively). The last haemoglobin measurement was also negatively associated with total IgE (adjusted geometric mean ratio 0.94 [0.88 to 0.99]). Anaemia (haemoglobin <11 g/dL) in late pregnancy was negatively associated with forced vital capacity (difference in standard deviation score -0.07 [-0.13 to -0.01]). CONCLUSIONS AND CLINICAL RELEVANCE: Lower maternal haemoglobin in pregnancy may be a risk factor for allergic sensitisation, elevated IgE and lower FVC in childhood, which may reflect effects of lower prenatal iron status. However, maternal haemoglobin was not associated with risk of childhood asthma or other allergic disorders.

Ethnic differences in the clustering and outcomes of health behaviours during pregnancy: results from the Born in Bradford cohort.

Background: Pregnancy is a time of optimal motivation for many women to make positive behavioural changes. We aim to describe pregnant women with similar patterns of self-reported health behaviours and examine associations with birth outcomes. Methods: We examined the clustering of multiple health behaviours during pregnancy in the Born in Bradford cohort, including smoking physical inactivity, vitamin d supplementation and exposure to second-hand smoke. Latent class analysis was used to identify groups of individuals with similar patterns of health behaviours separately for White British (WB) and Pakistani mothers. Multinomial regression was then used to examine the association between group membership and birth outcomes, which included preterm birth and mean birthweight. Results: For WB mothers, offspring of those in the 'Unhealthiest' group had lower mean birthweight than those in the 'Mostly healthy but inactive' class, although no association was observed for preterm birth. For Pakistani mothers, group membership was not associated with birthweight differences, although the odds of preterm birth was higher in 'Inactive smokers' compared to the 'Mostly healthy but inactive' group. Conclusions: The use of latent class methods provides important information about the clustering of health behaviours which can be used to target population segments requiring behaviour change interventions considering multiple risk factors. Given the dominant negative association of smoking with the birth outcomes investigated, latent class groupings of other health behaviours may not confer additional risk information for these outcomes.

Lessons learned from the AFLY5 RCT process evaluation: implications for the design of physical activity and nutrition interventions in schools.

BACKGROUND: Systematic reviews have highlighted that school-based diet and physical activity (PA) interventions have had limited effects. This study used qualitative methods to examine how the effectiveness of future primary (elementary) school diet and PA interventions could be improved. METHODS: Data are from the Active For Life Year 5 (AFLY5) study, which was a cluster randomised trial conducted in 60 UK primary schools. Year 5 (8-9 years of age) pupils in the 30 intervention schools received a 12-month intervention. At the end of the intervention period, interviews were conducted with: 28 Year 5 teachers (including 8 teachers from control schools); 10 Headteachers (6 control); 31 parents (15 control). Focus groups were conducted with 70 year 5 pupils (34 control). Topics included how the AFLY5 intervention could have been improved and how school-based diet and PA interventions should optimally be delivered. All interviews and focus groups were transcribed and thematically analysed across participant groups. RESULTS: Analysis yielded four themes. Child engagement: Data suggested that programme success is likely to be enhanced if children feel that they have a sense of autonomy over their own behaviour and if the activities are practical. School: Finding a project champion within the school would enhance intervention effectiveness. Embedding diet and physical activity content across the curriculum and encouraging teachers to role model good diet and physical activity behaviours were seen as important. Parents and community: Encouraging parents and community members into the school was deemed likely to enhance the connection between schools, families and communities, and "create a buzz" that was likely to enhance behaviour change. Government/Policy: Data suggested that there was a need to adequately resource health promotion activity in schools and to increase the infrastructure to facilitate diet and physical activity knowledge and practice. DISCUSSION AND CONCLUSIONS: Future primary school diet and PA programmes should find ways to increase child engagement in the programme content, identify programme champions, encourage teachers to work as role models, engage parents and embed diet and PA behaviour change across the curriculum. However, this will require adequate funding and cost-effectiveness will need to be established. TRIAL REGISTRATION: ISRCTN50133740.

A comparison of South Asian specific and established BMI thresholds for determining obesity prevalence in pregnancy and predicting pregnancy complications: findings from the Born in Bradford cohort.

OBJECTIVE: To describe how maternal obesity prevalence varies by established international and South Asian specific body mass index (BMI) cut-offs in women of Pakistani origin and investigate whether different BMI thresholds can help to identify women at risk of adverse pregnancy and birth outcomes. DESIGN: Prospective bi-ethnic birth cohort study (the Born in Bradford (BiB) cohort). SETTING: Bradford, a deprived city in the North of the UK. PARTICIPANTS: A total of 8478 South Asian and White British pregnant women participated in the BiB cohort study. MAIN OUTCOME MEASURES: Maternal obesity prevalence; prevalence of known obesity-related adverse pregnancy outcomes: mode of birth, hypertensive disorders of pregnancy (HDP), gestational diabetes, macrosomia and pre-term births. RESULTS: Application of South Asian BMI cut-offs increased prevalence of obesity in Pakistani women from 18.8 (95% confidence interval (CI) 17.6-19.9) to 30.9% (95% CI 29.5-32.2). With the exception of pre-term births, there was a positive linear relationship between BMI and prevalence of adverse pregnancy and birth outcomes, across almost the whole BMI distribution. Risk of gestational diabetes and HDP increased more sharply in Pakistani women after a BMI threshold of at least 30 kg m(-2), but there was no evidence of a sharp increase in any risk factors at the new, lower thresholds suggested for use in South Asian women. BMI was a good single predictor of outcomes (area under the receiver operating curve: 0.596-0.685 for different outcomes); prediction was more discriminatory and accurate with BMI as a continuous variable than as a binary variable for any possible cut-off point. CONCLUSION: Applying the new South Asian threshold to pregnant women would markedly increase those who were referred for monitoring and lifestyle advice. However, our results suggest that lowering the BMI threshold in South Asian women would not improve the predictive ability for identifying those who were at risk of adverse pregnancy outcomes.

The association of birth order with later body mass index and blood pressure: a comparison between prospective cohort studies from the United Kingdom and Brazil.

BACKGROUND: Previous studies have found greater adiposity and cardiovascular risk in first born children. The causality of this association is not clear. Examining the association in diverse populations may lead to improved insight. METHODS: We examine the association between birth order and body mass index (BMI), systolic and diastolic blood pressure (SBP/DBP) in the 2004 Pelotas cohort from southern Brazil and the Avon Longitudinal Study of Parents and Children (ALSPAC) from Bristol, south-west England, restricting analysis to families with two children in order to remove confounding by family size. RESULTS: No consistent differences in BMI, SBP or DBP were observed comparing first and second born children. Within the Pelotas 2004 cohort, first born females were thinner, with lower SBP and DBP; for example, mean difference in SBP comparing first with second born was -0.979 (95% confidence interval -2.901 to 0.943). In ALSPAC, first born females had higher BMI, SBP and DBP. In both cohorts, associations tended to be in the opposite direction in males, although no statistical evidence for gender interactions was found. CONCLUSIONS: The findings do not support an association between birth order and BMI or blood pressure. Differences to previous studies may be explained by differences in populations and/or confounding by family size in previous studies.

Maternal 25-hydroxyvitamin D and its association with childhood atopic outcomes and lung function.

BACKGROUND: It has been suggested that maternal vitamin D status in pregnancy influences the risk of asthma and atopy in the offspring. The epidemiological evidence to support these claims is conflicting and may reflect chance findings and differences in how vitamin D was assessed. OBJECTIVE: To examine the association between blood total maternal 25-hydroxy vitamin D (25(OH)D) concentrations in pregnancy and offspring asthma, atopy and lung function in the largest birth cohort study to date. METHODS: Participants were largely of white European origin and resident in the South West of England. We examined the associations of maternal 25(OH)D concentrations in pregnancy with the following outcomes in the offspring: wheeze, asthma, atopy, eczema, hayfever, at mean age 7.5 years (n = 3652-4696 depending on outcome), IgE at 7 years (n = 2915) and lung function and bronchial responsiveness at mean age 8.7 years (n = 3728-3784). RESULTS: Sixty-eight per cent of mothers had sufficient (> 50 nmol/L) concentrations of 25(OH)D, 27% were insufficient (27.5-49.99 nmol/L) and 5% were deficient (< 27.5 nmol/L). There was no evidence to suggest that maternal 25(OH)D concentration in pregnancy was associated with any respiratory or atopic outcome in the offspring. These findings remained after adjustment for season of measurement and for potential confounders. There was also no evidence that these relationships followed a non-linear form and no evidence that either deficient or high concentrations of maternal 25(OH)D were associated with atopic or respiratory outcomes. CONCLUSIONS: We found no evidence that maternal blood 25(OH)D concentration in pregnancy is associated with childhood atopic or respiratory outcomes.

Parental depressive and anxiety symptoms during pregnancy and attention problems in children: a cross-cohort consistency study.

BACKGROUND: Maternal depression and anxiety during pregnancy have been associated with offspring-attention deficit problems. AIM: We explored possible intrauterine effects by comparing maternal and paternal symptoms during pregnancy, by investigating cross-cohort consistency, and by investigating whether parental symptoms in early childhood may explain any observed intrauterine effect. METHODS: This study was conducted in two cohorts (Generation R, n = 2,280 and ALSPAC, n = 3,442). Pregnant women and their partners completed questionnaires to assess symptoms of depression and anxiety. Child attention problems were measured in Generation R at age 3 with the Child Behavior Checklist, and in ALSPAC at age 4 with the Strengths and Difficulties Questionnaire. RESULTS: In both cohorts, antenatal maternal symptoms of depression (Generation R: OR 1.23, 95% CI 1.05-1.43; ALSPAC: OR 1.33, 95% CI 1.19-1.48) and anxiety (Generation R: OR 1.24, 95% CI 1.06-1.46; ALSPAC: OR 1.32, 95% CI 1.19-1.47) were associated with a higher risk of child attention problems. In ALSPAC, paternal depression was also associated with a higher risk of child attention problems (OR 1.11, 95% CI 1.00-1.24). After adjusting for maternal symptoms after giving birth, antenatal maternal depression and anxiety were no longer associated with child attention problems in Generation R. Moreover, there was little statistical evidence that antenatal maternal and paternal depression and anxiety had a substantially different effect on attention problems of the child. CONCLUSIONS: The apparent intrauterine effect of maternal depression and anxiety on offspring-behavioural problems may be partly explained by residual confounding. There was little evidence of a difference between the strength of associations of maternal and paternal symptoms during pregnancy with offspring-attention problems. That maternal symptoms after childbirth were also associated with offspring-behavioural problems may indicate a contribution of genetic influences to the association.

Do women exhibit greater differences in established and novel risk factors between diabetes and non-diabetes than men? The British Regional Heart Study and British Women's Heart Health Study.

AIMS/HYPOTHESIS: Type 2 diabetes is associated with greater relative risk of CHD in women than in men, which is not fully explained by conventional cardiovascular risk factors. We assessed whether cardiovascular risk factors including more novel factors such as markers of insulin resistance, inflammation, activated coagulation and endothelial dysfunction differ more between diabetic and non-diabetic women than between diabetic and non-diabetic men, and the role of insulin resistance. METHODS: A cross-sectional study of non-diabetic and diabetic men and women (n = 7,529) aged 60-79 years with no previous myocardial infarction who underwent an examination was conducted. Measurements of anthropometry, blood pressure and fasting measurements of lipids, insulin, glucose and haemostatic and inflammatory markers were taken. RESULTS: Non-diabetic women tended to have more favourable risk factors and were less insulin resistant than non-diabetic men, but this was diminished in the diabetic state. Levels of waist circumference, BMI, von Willebrand factor (VWF), WBC count, insulin resistance (HOMA-IR), diastolic blood pressure, HDL-cholesterol, tissue plasminogen activator (t-PA) and factor VIII differed more between diabetic and non-diabetic women than between diabetic and non-diabetic men (test for diabetes × sex interaction p < 0.05). The more adverse effect of diabetes on these risk markers in women was associated with, and thereby largely attenuated by, insulin resistance. CONCLUSIONS/INTERPRETATION: The greater adverse influence of diabetes per se on adiposity and HOMA-IR and downstream blood pressure, lipids, endothelial dysfunction and systemic inflammation in women compared with men may contribute to their greater relative risk of coronary heart disease.

Economic evaluation of lifestyle interventions to treat overweight or obesity in children.

OBJECTIVE: To estimate lifetime cost effectiveness of lifestyle interventions to treat overweight and obese children, from the UK National Health Service perspective. DESIGN: An adaptation of the National Heart Forum economic model to predict lifetime health service costs and outcomes of lifestyle interventions on obesity-related diseases. SETTING: Hospital or community-based weight-management programmes. POPULATION: Hypothetical cohorts of overweight or obese children based on body mass data from the National Child Measurement Programme. INTERVENTIONS: Lifestyle interventions that have been compared with no or minimal intervention in randomized controlled trials (RCTs). MAIN OUTCOME MEASURES: Reduction in body mass index (BMI) standard deviation score (SDS), intervention resources/costs, lifetime treatment costs, obesity-related diseases and cost per life year gained. RESULTS: Ten RCTs were identified by our search strategy. The median effect of interventions versus control from these 10 RCTs was a difference in BMI SDS of -0.13 at 12 months, but the range in effects among interventions was broad (0.04 to -0.60). Indicative costs per child of these interventions ranged from £108 to £662. For obese children aged 10-11 years, an intervention that resulted in a median reduction in BMI SDS at 12 months at a moderate cost of £400 increased life expectancy by 0.19 years and intervention costs were offset by subsequent undiscounted savings in treatment costs (net saving of £110 per child), though this saving did not emerge until the sixth or seventh decade of life. The discounted cost per life year gained was £13 589. Results were broadly similar for interventions aimed at children aged 4-5 years and which targeted both obese and overweight children. For more costly interventions, savings were less likely. CONCLUSION: Interventions to treat childhood obesity are potentially cost effective although cost savings and health benefits may not appear until the sixth or seventh decade of life.

25-Hydroxyvitamin-D3 levels are positively related to subsequent cortical bone development in childhood: findings from a large prospective cohort study.

UNLABELLED: In exploring relationships between vitamin D status in childhood and cortical bone, little relationship was observed with plasma concentrations of 25-hydroxyvitamin-D(2) [25(OH)D(2)], whereas 25-hydroxyvitamin-D(3) [25(OH)D(3)] was positively related to cortical bone mineral content (BMC(C)) and cortical thickness, suggesting D(3) exerts a beneficial effect on cortical bone development in contrast to D(2). INTRODUCTION: The study is aimed to determine whether vitamin D status in childhood is related to cortical bone development by examining prospective relationships between plasma concentrations of 25(OH)D(2) and 25(OH)D(3) at 7.6, 9.9 or 11.8 years and peripheral quantitative computed tomography (pQCT) measurements of the mid-tibia at age 15.5 years, in children from the Avon Longitudinal Study of Parents and Children. METHODS: Relationships between vitamin D status and pQCT outcomes were analysed by bootstrap linear regression, adjusted for age, sex, body composition, socioeconomic position and physical activity, in 2,247 subjects in whom all covariates were available. 25(OH)D(3) was also adjusted for season and 25(OH)D(2), and 25(OH)D(2) for 25(OH)D(3). RESULTS: 25(OH)D(3) was positively related to BMC(C) [0.066(0.009,0.122), P = 0.02], whereas no association was seen with 25(OH)D(2) [-0.008(-0.044,0.027), P = 0.7] [beta (with 95% CI) represents SD changes per doubling of vitamin D], P = 0.03 for difference in associations of 25(OH)D(2) and 25(OH)D(3) with BMC(C). There were also differences in associations with cortical geometry, since 25(OH)D(3) was positively related to cortical thickness [0.11(0.04, 0.19), P = 0.002], whereas no association was seen with 25(OH)D(2) [-0.04(-0.08,0.009), P = 0.1], P = 0.0005 for difference. These relationships translated into differences in biomechanical strength as reflected by buckling ratio, which was positively related to 25(OH)D(2) [0.06(0.01,0.11), P = 0.02] indicating less resistance to buckling, but inversely related to 25(OH)D(3) [-0.1(-0.19,-0.02), P = 0.03], P = 0.001 for difference. CONCLUSIONS: In contrast to 25(OH)D(2), 25(OH)D(3) was positively related to subsequent cortical bone mass and predicted strength. In vitamin D-deficient children in whom supplementation is being considered, our results suggest that D(3) should be used in preference to D(2).

Developing parent involvement in a school-based child obesity prevention intervention: a qualitative study and process evaluation.

BACKGROUND: Little is known about the effectiveness of parent involvement in school-based obesity prevention interventions. METHODS: A qualitative study with parents of children aged 9-10 years was conducted to identify possible methods to involve them in a school-based obesity prevention intervention, followed by a process evaluation of homework and school newsletters to involve parents. RESULTS: Qualitative study: parents supported the use of homework and school newsletters to involve them and overcome the main barriers of their work and time. Process evaluation: Ten homeworks and inserts for the school newsletter about the obesity prevention intervention were developed and delivered. The majority of homeworks were given out (73%), completed by children (84%) and recalled by parents (60-68%). The majority of homeworks were enjoyed by parents and children. All the schools put information about the project in the newsletter and this was recalled by parents. Most parents felt the homeworks were a practical way of involving them. CONCLUSIONS: Homeworks are routinely given to children and provide a means of engaging potentially all parents if parental support is required. Homeworks which are novel, fun and involve activities and social contact are enjoyed by parents and children and may increase awareness of healthy diet and physical activity.