Associations of Weight Gain From Early to Middle Adulthood With Major Health Outcomes Later in Life

Question  What is the association of weight gain from early to middle adulthood with health outcomes later in life?

Findings  During a follow-up of 18 years in 92 837 US women and 15 years in 25 303 US men, compared with participants who maintained a stable weight (weight loss ≤2.5 kg or gain <2.5 kg), those who gained a moderate amount of weight (≥2.5-<10.0 kg) had increased incidence of type 2 diabetes (absolute rate difference/100 000 person-years of 98 in women and 111 in men), cardiovascular disease (61 in women), obesity-related cancer (37 in women and 42 in men), and mortality (51 among women who never smoked).

Meaning  Among women and men, moderate weight gain from early to middle adulthood was associated with significantly increased risk of major chronic diseases and mortality.

Reference: JAMA. 2017;318(3):255-269.

Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children

Question  Does high-dose vitamin D supplementation (2000 IU/d) help to prevent wintertime viral upper respiratory tract infections compared with standard-dose vitamin D supplementation (400 IU/d) among preschool children?

Findings  In this multisite randomized clinical trial that included 703 children, the number of wintertime laboratory-confirmed viral upper respiratory tract infections was higher in the high-dose group than the standard-dose group, not a statistically significant difference.

Meaning  Vitamin D dosing higher than 400 IU/d may not be indicated for preventing wintertime viral upper respiratory tract infections in children.

Reference: JAMA. 2017;318(3):245-254.

The Effect of Nursing Quality Improvement and Mobile Health Interventions on Infant Sleep Practices

Question  Will 2 separate, complementary interventions (nursing quality improvement intervention and mobile health intervention) promote safe infant sleep practices?

Findings  In a 4-group cluster randomized clinical trial with 1263 families, mothers who received a mobile health intervention with regular text or email messages and videos reported statistically significantly higher rates of placing their infants supine to sleep compared with mothers who received control interventions (adjusted prevalence, 89.1% vs 80.2%, respectively), room sharing without bed sharing (82.8% vs 70.4%), no soft bedding use (79.4% vs 67.6%), and any pacifier use (68.5% vs 59.8%). A nursing quality improvement intervention did not influence infant safe sleep practices.

Meaning  A mobile health intervention improved adherence with infant safe sleep practices. Whether widespread use of this type of intervention is feasible and reduces sudden and unexpected infant death rates remains to be studied.

Reference: JAMA. 2017;318(4):351-359.

Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study


Lifelong antiplatelet treatment is recommended after ischaemic vascular events, on the basis of trials done mainly in patients younger than 75 years. Upper gastrointestinal bleeding is a serious complication, but had low case fatality in trials of aspirin and is not generally thought to cause long-term disability. Consequently, although co-prescription of proton-pump inhibitors (PPIs) reduces upper gastrointestinal bleeds by 70–90%, uptake is low and guidelines are conflicting. We aimed to assess the risk, time course, and outcomes of bleeding on antiplatelet treatment for secondary prevention in patients of all ages.


We did a prospective population-based cohort study in patients with a first transient ischaemic attack, ischaemic stroke, or myocardial infarction treated with antiplatelet drugs (mainly aspirin based, without routine PPI use) after the event in the Oxford Vascular Study from 2002 to 2012, with follow-up until 2013. We determined type, severity, outcome (disability or death), and time course of bleeding requiring medical attention by face-to-face follow-up for 10 years. We estimated age-specific numbers needed to treat (NNT) to prevent upper gastrointestinal bleeding with routine PPI co-prescription on the basis of Kaplan–Meier risk estimates and relative risk reduction estimates from previous trials.


3166 patients (1582 [50%] aged ≥75 years) had 405 first bleeding events (n=218 gastrointestinal, n=45 intracranial, and n=142 other) during 13 509 patient-years of follow-up. Of the 314 patients (78%) with bleeds admitted to hospital, 117 (37%) were missed by administrative coding. Risk of non-major bleeding was unrelated to age, but major bleeding increased steeply with age (≥75 years hazard ratio [HR] 3·10, 95% CI 2·27–4·24; p<0·0001), particularly for fatal bleeds (5·53, 2·65–11·54; p<0·0001), and was sustained during long-term follow-up. The same was true of major upper gastrointestinal bleeds (≥75 years HR 4·13, 2·60–6·57; p<0·0001), particularly if disabling or fatal (10·26, 4·37–24·13; p<0·0001). At age 75 years or older, major upper gastrointestinal bleeds were mostly disabling or fatal (45 [62%] of 73 patients vs 101 [47%] of 213 patients with recurrent ischaemic stroke), and outnumbered disabling or fatal intracerebral haemorrhage (n=45 vs n=18), with an absolute risk of 9·15 (95% CI 6·67–12·24) per 1000 patient-years. The estimated NNT for routine PPI use to prevent one disabling or fatal upper gastrointestinal bleed over 5 years fell from 338 for individuals younger than 65 years, to 25 for individuals aged 85 years or older.


In patients receiving aspirin-based antiplatelet treatment without routine PPI use, the long-term risk of major bleeding is higher and more sustained in older patients in practice than in the younger patients in previous trials, with a substantial risk of disabling or fatal upper gastrointestinal bleeding. Given that half of the major bleeds in patients aged 75 years or older were upper gastrointestinal, the estimated NNT for routine PPI use to prevent such bleeds is low, and co-prescription should be encouraged.


Wellcome Trust, Wolfson Foundation, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), and the NIHR Oxford Biomedical Research Centre.

Antidepressants during pregnancy and autism in offspring: population based cohort study

Objectives To study the association between maternal use of antidepressants during pregnancy and autism spectrum disorder (ASD) in offspring.

Design Observational prospective cohort study with regression methods, propensity score matching, sibling controls, and negative control comparison.

Setting Stockholm County, Sweden.

Participants 254 610 individuals aged 4-17, including 5378 with autism, living in Stockholm County in 2001-11 who were born to mothers who did not take antidepressants and did not have any psychiatric disorder, mothers who took antidepressants during pregnancy, or mothers with psychiatric disorders who did not take antidepressants during pregnancy. Maternal antidepressant use was recorded during first antenatal interview or determined from prescription records.

Main outcome measure Offspring diagnosis of autism spectrum disorder, with and without intellectual disability.

Results Of the 3342 children exposed to antidepressants during pregnancy, 4.1% (n=136) had a diagnosis of autism compared with a 2.9% prevalence (n=353) in 12 325 children not exposed to antidepressants whose mothers had a history of a psychiatric disorder (adjusted odds ratio 1.45, 95% confidence interval 1.13 to 1.85). Propensity score analysis led to similar results. The results of a sibling control analysis were in the same direction, although with wider confidence intervals. In a negative control comparison, there was no evidence of any increased risk of autism in children whose fathers were prescribed antidepressants during the mothers’ pregnancy (1.13, 0.68 to 1.88). In all analyses, the risk increase concerned only autism without intellectual disability.

Conclusions The association between antidepressant use during pregnancy and autism, particularly autism without intellectual disability, might not solely be a byproduct of confounding. Study of the potential underlying biological mechanisms could help the understanding of modifiable mechanisms in the aetiology of autism. Importantly, the absolute risk of autism was small, and, hypothetically, if no pregnant women took antidepressants, the number of cases that could potentially be prevented would be small.

Reference: BMJ 2017;358:j2811

Effect of diet and physical activity based interventions in pregnancy on gestational weight gain and pregnancy outcomes: meta-analysis of individual participant data from randomised trials

Objective To synthesise the evidence on the overall and differential effects of interventions based on diet and physical activity during pregnancy, primarily on gestational weight gain and maternal and offspring composite outcomes, according to women’s body mass index, age, parity, ethnicity, and pre-existing medical condition; and secondarily on individual complications.

Design Systematic review and meta-analysis of individual participant data (IPD).

Data sources Major electronic databases from inception to February 2017 without language restrictions.

Eligibility criteria for selecting studies Randomised trials on diet and physical activity based interventions in pregnancy.

Data synthesis Statistical models accounted for clustering of participants within trials and heterogeneity across trials leading to summary mean differences or odds ratios with 95% confidence intervals for the effects overall, and in subgroups (interactions).

Results IPD were obtained from 36 randomised trials (12 526 women). Less weight gain occurred in the intervention group than control group (mean difference −0.70 kg, 95% confidence interval −0.92 to −0.48 kg, I2=14.1%; 33 studies, 9320 women). Although summary effect estimates favoured the intervention, the reductions in maternal (odds ratio 0.90, 95% confidence interval 0.79 to 1.03, I2=26.7%; 24 studies, 8852 women) and offspring (0.94, 0.83 to 1.08, I2=0%; 18 studies, 7981 women) composite outcomes were not statistically significant. No evidence was found of differential intervention effects across subgroups, for either gestational weight gain or composite outcomes. There was strong evidence that interventions reduced the odds of caesarean section (0.91, 0.83 to 0.99, I2=0%; 32 studies, 11 410 women), but not for other individual complications in IPD meta-analysis. When IPD were supplemented with study level data from studies that did not provide IPD, the overall effect was similar, with stronger evidence of benefit for gestational diabetes (0.76, 0.65 to 0.89, I2=36.8%; 59 studies, 16 885 women).

Conclusion Diet and physical activity based interventions during pregnancy reduce gestational weight gain and lower the odds of caesarean section. There is no evidence that effects differ across subgroups of women.

Reference: BMJ 2017;358:j3119

The financial challenges facing general practice

Future-Focused Finance and the HFMA have worked together to produce this briefing on the current financial challenges facing general practice.

We asked general practitioners (GPs) and practice managers about the current financial challenges they are facing Their responses highlight a number of serious concerns about the issues facing general practice and in this briefing we make a number of recommendations to address some of the most pressing issues.

General practice is facing unprecedented pressures and, with GPs managing heavier and more complex workloads, uncertainty about a sustainable future in a rapidly changing landscape is understandable. In such a stretched environment general practice needs guidance and support to manage the status quo, let alone deliver the increasing expectations set out in Next steps on the NHS five year forward view.

Further information is available here.