What's New in Dementia Risk Prediction Modelling? An Updated Systematic Review.

Introduction: Identifying individuals at high risk of dementia is critical to optimized clinical care, formulating effective preventative strategies, and determining eligibility for clinical trials. Since our previous systematic reviews in 2010 and 2015, there has been a surge in dementia risk prediction modelling. The aim of this study was to update our previous reviews to explore, and critically review, new developments in dementia risk modelling. Methods: MEDLINE, Embase, Scopus, and Web of Science were searched from March 2014 to June 2022. Studies were included if they were population- or community-based cohorts (including electronic health record data), had developed a model for predicting late-life incident dementia, and included model performance indices such as discrimination, calibration, or external validation. Results: In total, 9,209 articles were identified from the electronic search, of which 74 met the inclusion criteria. We found a substantial increase in the number of new models published from 2014 (>50 new models), including an increase in the number of models developed using machine learning. Over 450 unique predictor (component) variables have been tested. Nineteen studies (26%) undertook external validation of newly developed or existing models, with mixed results. For the first time, models have also been developed in low- and middle-income countries (LMICs) and others validated in racial and ethnic minority groups. Conclusion: The literature on dementia risk prediction modelling is rapidly evolving with new analytical developments and testing in LMICs. However, it is still challenging to make recommendations about which one model is the most suitable for routine use in a clinical setting. There is an urgent need to develop a suitable, robust, validated risk prediction model in the general population that can be widely implemented in clinical practice to improve dementia prevention.

Rethinking causal assumptions about maternal BMI, gestational weight gain, and adverse pregnancy outcomes.

BACKGROUND: The aim of this study was to evaluate commonly assumed causal relationships between body mass index (BMI), gestational weight gain (GWG), and adverse pregnancy outcomes, which have formed the basis of guidelines and interventions aimed at limiting GWG in women with overweight or obesity. We explored relationships between maternal BMI, total GWG (as a continuous variable and as 'excessive' GWG), and pregnancy outcomes (including infant birthweight measures and caesarean birth). METHODS: Analysis of individual participant data (IPD) from the i-WIP (International Weight Management in Pregnancy) Collaboration, from randomised trials of diet and/or physical activity interventions during pregnancy reporting GWG and maternal and neonatal outcomes. Women randomised to the control arm of 20 eligible randomised trials (4370 of 8908 participants) from the i-WIP dataset of 36 randomised trials (total 12,240 women). The main research questions were to characterise the relationship between maternal BMI and (a) total GWG, (b) the risk of 'excessive' GWG (using the Institute of Medicine's guidelines), and (c) adverse pregnancy outcomes as mediated via GWG versus other pathways to determine the extent to which the observed effect of maternal BMI on pregnancy outcomes is mediated via GWG. We utilised generalised linear models and regression-based mediation analyses within an IPD meta-analysis framework. RESULTS: Mean GWG decreased linearly as maternal BMI increased; however, the risk of 'excessive' GWG increased markedly at BMI category thresholds (i.e. between the normal and overweight BMI category threshold and between the overweight and obese BMI category threshold). Increasing maternal BMI was associated with increased risk of all pregnancy outcomes assessed; however, there was no evidence that this effect was mediated via effects on GWG. CONCLUSIONS: There is evidence of a meaningful relationship between maternal BMI and GWG and between maternal BMI and adverse pregnancy outcomes. There is no evidence that the effect of maternal BMI on outcomes is via an effect on GWG. Our analyses also cast doubt on the existence of a relationship between 'excessive' GWG and adverse pregnancy outcomes. Our findings challenge the practice of actively managing GWG throughout pregnancy.

The Adelaide Facial Bone Rule: A simple prediction model and clinical guideline for the presence of facial fractures using CT brain scans in victims of minor trauma.

BACKGROUND: Facial fractures bleed, resulting in high-density fluid in the sinuses (haemosinus) on computed tomography (CT) scans. A CT brain scan includes most maxillary sinuses in the scan field, which should allow detection of haemosinus as an indirect indicator of a facial fracture without the need for an additional CT facial bone scan, yet no robust evidence for this exists in the literature. The aim of this study was to determine whether the presence of haemosinus on a CT brain scan, alone or in combination with other clinical information, can predict the presence of facial fractures. METHODS: 1231 adult patients, who had both brain and facial CT scans performed on the same day, were selected from a seven year period. Patients were eligible if scans were requested for trauma. Brain and facial scans were reviewed separately for the presence of facial fractures, haemosinus, emphysema and intra-cranial haemorrhage. Prediction modelling was used to assess whether findings from brain scans could be used to identify patients requiring further CT scanning. FINDINGS: The full prediction model included four predictors and showed excellent discrimination (AUROC 0.982; 95 % CI 0.971 - 0.993). A simplified model, more suitable for clinical implementation, used only facial fractures and haemosinus as predictors. This model showed only marginally poorer discrimination (AUROC 0.964; 95 % CI 0.945 - 0.983) and excellent performance on other measures. CONCLUSION: Based on the excellent performance of the simplified prediction model, we present the Adelaide Facial Bone Rule: The absence of blood in the sinuses or facial fractures on a CT brain scan means a CT facial bone scan does not need to be routinely performed in the setting of clinically-determined minor trauma.

Fetal Growth and Adiposity of Infants Born Large for Gestational Age in Three Harmonized Randomized Trials.

OBJECTIVE: Infants born large for gestational age (LGA) are at an increased risk of short- and longer-term adverse outcomes. Understanding fetal growth and adiposity and their trajectories may help inform interventions to prevent birth of LGA infants. We aimed to compare fetal growth and adiposity measures of infants born LGA with those born not LGA, to determine whether the discrepancy at birth was primarily due to larger size throughout gestation, or instead to different trajectories of fetal growth. STUDY DESIGN: This was a secondary analysis of secondary outcomes of fetal growth and adiposity from three harmonized randomized trials-the LIMIT, GRoW, and Optimise randomized trials. These trials recruited women in early pregnancy, and a singleton gestation, from three major public metropolitan Adelaide maternity hospitals. Maternal body mass index (BMI) ranged from 18.5 to ≥40.0 kg/m2. Data were obtained from enrolled women who underwent research ultrasounds at 28 and 36 weeks' gestation. Outcome measures were ultrasound measures of fetal biometry and adiposity. RESULTS: Infants born LGA had larger fetal biometry measures, and higher growth trajectories, from 20 weeks' gestation. Fetal adiposity measures were consistently larger among infants born LGA and these differences increased over time. We did not find evidence that the differences in biometry and adiposity measurements varied according to maternal BMI. CONCLUSION: Infants born LGA had larger fetal biometry measures at all time points from 20 weeks' gestation, compared with infants born not LGA suggesting any interventions to prevent LGA likely need to commence earlier in pregnancy or prior to conception. KEY POINTS: · Infants born LGA had larger fetal biometry measures from 20 weeks' gestation.. · Infants born LGA had larger fetal adiposity measures.. · Interventions to prevent LGA need to start earlier in pregnancy or prior to conception..

Effects of an antenatal dietary intervention in women with obesity or overweight on child outcomes at 8-10 years of age: LIMIT randomised trial follow-up.

BACKGROUND: The LIMIT randomised controlled trial looked at the effect of a dietary and lifestyle intervention compared with routine antenatal care for pregnant women with overweight and obesity on pregnancy outcomes. While women in the intervention group improved diet and physical activity with a reduction of high birth weight, other outcomes were similar. We have followed the children born to women in this study at birth, 6 and 18 months and 3-5 years of age and now report follow-up of children at 8-10 years of age. METHODS: Children at 8-10 years of age who were born to women who participated in the LIMIT randomised trial, and whose mother provided consent to ongoing follow-up were eligible for inclusion. The primary study endpoint was the incidence of child BMI z-score > 85th centile for child sex and age. Secondary study outcomes included a range of anthropometric measures, neurodevelopment, child dietary intake, and physical activity. Analyses used intention to treat principles according to the treatment group allocated in pregnancy. Outcome assessors were blinded to the allocated treatment group. RESULTS: We assessed 1,015 (Lifestyle Advice n = 510; Standard Care n = 505) (48%) of the 2,121 eligible children. BMI z-score > 85th percentile was similar for children of women in the dietary Lifestyle Advice Group compared with children of women in the Standard Care Group (Lifestyle Advice 479 (45%) versus Standard Care 507 (48%); adjusted RR (aRR) 0.93; 95% CI 0.82 to 1.06; p = 0.302) as were secondary outcomes. We observed that more than 45% of all the children had a BMI z-score > 85th percentile, consistent with findings from follow-up at earlier time-points, indicating an ongoing risk of overweight and obesity. CONCLUSIONS: Dietary and lifestyle advice for women with overweight and obesity in pregnancy has not reduced the risk of childhood obesity, with children remaining at risk of adolescent and adult obesity. Other strategies are needed to address the risk of overweight and obesity in children including investigation of preconception interventions to assess whether this can modify the effects of maternal pre-pregnancy BMI. The LIMIT randomised controlled trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).

Review of outpatient procedural sedation clinics in a tertiary paediatric hospital in South Australia.

AIM: Procedures, such as immunisation and venepuncture, can be distressing for paediatric patients, especially those with needle phobia and neurodevelopmental disorders. Procedural sedation helps provide access to equitable health care in this population. The aim of this study was to evaluate the pilot outpatient procedural sedation clinics at the Women's and Children's Hospital and the impact on patient care and outcomes. METHODS: A prospective review was undertaken between July 2021 and May 2022 on all patients who attended the procedural sedation clinics at the Women's and Children's Hospital. These clinics were the COVID Specialist Immunisation Sedation Clinic (SISC) and Paediatric Sedation Clinic (PSC). RESULTS: There were 182 visits in a total of 110 children with a 92% primary procedure success rate. Sixty-three per cent of patients had neurodevelopmental disorders with autism spectrum disorder being most common. There was a significant reduction in anxiety scores pre- and post-sedation and a reduction in anxiety scores if patients were to return without the use of sedation. CONCLUSIONS: Outpatient procedural sedation is beneficial for a specific cohort of the paediatric population. This can also have a significant positive impact on patient care and potentially, long-term outcomes.

Handling misclassified stratification variables in the analysis of randomised trials with continuous outcomes.

Many trials use stratified randomisation, where participants are randomised within strata defined by one or more baseline covariates. While it is important to adjust for stratification variables in the analysis, the appropriate method of adjustment is unclear when stratification variables are affected by misclassification and hence some participants are randomised in the incorrect stratum. We conducted a simulation study to compare methods of adjusting for stratification variables affected by misclassification in the analysis of continuous outcomes when all or only some stratification errors are discovered, and when the treatment effect or treatment-by-covariate interaction effect is of interest. The data were analysed using linear regression with no adjustment, adjustment for the strata used to perform the randomisation (randomisation strata), adjustment for the strata if all errors are corrected (true strata), and adjustment for the strata after some errors are discovered and corrected (updated strata). The unadjusted model performed poorly in all settings. Adjusting for the true strata was optimal, while the relative performance of adjusting for the randomisation strata or the updated strata varied depending on the setting. As the true strata are unlikely to be known with certainty in practice, we recommend using the updated strata for adjustment and performing subgroup analyses, provided the discovery of errors is unlikely to depend on treatment group, as expected in blinded trials. Greater transparency is needed in the reporting of stratification errors and how they were addressed in the analysis.

Validation of RAH VQ SPECT/CT lobar quantification program using a modified version of GE Q lung.

OBJECTIVE: The value of ventilation-perfusion (VQ) single photon emission tomography/computed tomography (SPECT/CT) lobar quantification for pre-operative assessment of lobectomy and lung volume reduction is known. Our in-house developed software, RAH ventilation perfusion SPECT/CT quantification (RAHVQSQ) has been shown to be able to identify the target lobe for collapse in bronchoscopic lung volume reduction (BLVR) for advanced emphysema. We have proven inter and intra observer reproducibility but are yet to validate the accuracy of our program. This study aims to validate the accuracy of our quantitative program through comparison with a modified version of GE Q lung which is a commercial program certified for clinical use. SUBJECTS AND METHODS: Ventilation-perfusion SPECT/CT data of 19 subjects from our previous study using RAHVQSQ for BLVR assessment were re-analysed using Q lung by 2 technologists independently and in a blinded fashion to determine lobar differential ventilation, perfusion and volume percentages. The data were from GE Hawkeye 4 and external CT, thus a modified version of Q lung was used. To determine interobserver variation in the 3 parameters between the 3 assessors, intraclass correlation coefficient (ICC) and Bland-Altman limits of agreement (LoA) were generated. RESULTS: Paired comparisons between the 3 assessors had high ICC (range for ventilation: 0.69-0.97; perfusion: 0.69-0.97; volume: 0.63-0.97) and means of LoA differences close to zero (range for ventilation: -0.04 - 0.10; perfusion: 0.00-0.02; volume: -0.12 - 0.09) were noted indicative of good concordance for all parameters. CONCLUSION: Using VQ SPECT/CT data of participants with advanced airway disease, our study has found a close concordance of estimated differential lobar ventilation, perfusion and volume percentages using RAHVQSQ when compared with a duplicated blinded assessment using Q lung. The good concordance supports the validity of our quantitative methodology.

Data processing choices can affect findings in differential methylation analyses: an investigation using data from the LIMIT RCT.

Objective: A wide array of methods exist for processing and analysing DNA methylation data. We aimed to perform a systematic comparison of the behaviour of these methods, using cord blood DNAm from the LIMIT RCT, in relation to detecting hypothesised effects of interest (intervention and pre-pregnancy maternal BMI) as well as effects known to be spurious, and known to be present. Methods: DNAm data, from 645 cord blood samples analysed using Illumina 450K BeadChip arrays, were normalised using three different methods (with probe filtering undertaken pre- or post- normalisation). Batch effects were handled with a supervised algorithm, an unsupervised algorithm, or adjustment in the analysis model. Analysis was undertaken with and without adjustment for estimated cell type proportions. The effects estimated included intervention and BMI (effects of interest in the original study), infant sex and randomly assigned groups. Data processing and analysis methods were compared in relation to number and identity of differentially methylated probes, rankings of probes by p value and log-fold-change, and distributions of p values and log-fold-change estimates. Results: There were differences corresponding to each of the processing and analysis choices. Importantly, some combinations of data processing choices resulted in a substantial number of spurious 'significant' findings. We recommend greater emphasis on replication and greater use of sensitivity analyses.

Maternal and neonatal outcomes following the introduction of the Fetal Pillow at a tertiary maternity hospital: A retrospective cohort study.

BACKGROUND: Caesarean birth at full cervical dilatation can be technically challenging and may be associated with increased risks of maternal and neonatal morbidity, often secondary to difficulties in delivering a deeply impacted fetal head. The Fetal Pillow is a device designed to elevate an impacted fetal head out of the pelvis and reduce birth trauma. AIMS: To evaluate birth outcomes following the introduction of the Fetal Pillow at a tertiary maternity hospital. MATERIALS AND METHODS: This retrospective cohort study included all caesarean births at full cervical dilatation where the Fetal Pillow was utilised and compared with caesarean births where the Fetal Pillow was not used from October 2018 to December 2019. Maternal outcomes included uterine incision extension, blood loss, high dependency unit admission and postoperative length of stay. Neonatal outcomes included Apgar scores, resuscitation, cord arterial blood pH and lactate, nursery admission, birth trauma, jaundice and seizures. RESULTS: There were 53 caesarean births where the Fetal Pillow was utilised and 48 where it was not. Baseline characteristics were similar between groups with mean maternal age across both groups of 30.4 (±5.3) years, mean gestational age at birth of 39.5 (±1.2) weeks and mean infant birth weight of 3543 (±441) g. There were no statistically significant differences between the two study groups for the maternal and neonatal outcomes considered. CONCLUSIONS: There was no evidence that use of the Fetal Pillow to elevate an impacted fetal head during caesarean birth when cervical dilatation is >7 cm was associated with a reduced rate of adverse maternal and neonatal outcomes.

Childhood follow-up of the GRoW randomized trial: Metformin in addition to dietary and lifestyle advice for pregnant women with overweight or obesity.

BACKGROUND: Metformin for women with overweight or obesity during pregnancy has been evaluated in randomized trials to reduce adverse pregnancy and birth outcomes. The effect on longer-term child health remains of interest. OBJECTIVES: To evaluate the effect of in-utero exposure to metformin on child health compared with no exposure. METHODS: We assessed children born to 513 women who participated in the Metformin in addition to dietary and lifestyle advice for pregnant women with overweight or obesity: the GRoW randomized trial, where women were randomized to receive either metformin or placebo during pregnancy. Child weight, height, anthropometry, diet, physical activity and neurodevelopment were assessed at six and 18 months and three to five years of age. The main outcome was BMI z-score > 85th centile for age and sex. RESULTS: The number of children with BMI >85th centile was similar between treatment groups at all time points. At 18 months and three to five years of age, more than half of the children had a BMI z-score > 85th centile, indicating a high risk of childhood obesity. CONCLUSIONS: We did not show evidence of the benefit of metformin for children of women with overweight or obesity during pregnancy adding to the growing literature on the lack of effect of pregnancy interventions in reducing longer-term risks of childhood obesity.

Cardiovascular disease, associated risk factors, and risk of dementia: An umbrella review of meta-analyses.

Introduction: Cardiovascular diseases (CVDs) have been associated with an increased risk of dementia; yet the evidence is mixed. This review critically appraises and synthesises current evidence exploring associations between dementia risk and CVD and their risk factors, including coronary heart disease, heart failure, atrial fibrillation, hypertension, hyperlipidaemia, and arterial stiffness. Methods: MEDLINE, Embase, PsycINFO, and the Cochrane Database of Systematic Reviews were searched to identify systematic reviews with meta-analyses investigating the association between at least one of the CVDs of interest and dementia risk. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Systematic Reviews was used to assess methodological quality. Results: Twenty-five meta-analyses published between 2007 and 2021 were included. Studies largely consisted of cohorts from North America and Europe. Findings were variable, with coronary heart disease, heart failure, and atrial fibrillation consistently associated with increased risk for all-cause dementia, but results were inconsistent for Alzheimer's disease. Hypertension was more frequently associated with dementia during mid-life compared to late life. Findings concerning cholesterol were complex, and while results were inconsistent for low-density lipoprotein cholesterol and total cholesterol, there appeared to be no associations between triglycerides and high-density lipoprotein cholesterol. All meta-analyses investigating hypercholesterolaemia showed significant increases in dementia risk. There was a paucity of research on the association between arterial stiffness and dementia risk. Conclusion: Targeted CVD dementia prevention strategies could reduce dementia prevalence. Future research should determine the underpinning mechanisms linking heart and brain health to determine the most effective strategies for dementia risk reduction in CVD populations.

"Identified", "probable", "possible" or "exclude": The influence of task-irrelevant information on forensic odontology identification opinion.

In a mass disaster situation, identification of the deceased utilising comparison of dental features is frequently heavily relied upon to facilitate rapid and accurate outcomes. The method consists of the comparison of clinical and radiographic records depicting oral structures and dentition to allow an opinion to be produced on a presumed identity. Current forensic odontology identification opinions are expressed as categories of levels of identification. Categories such as "Identified", "Probable", "Possible" and "Exclude" are used in various forensic odontology identification scales. The boundaries between the levels of the scales are not fixed; hence, category selection is highly subjective. It is uncertain how extrinsic factors such as exposure to contextual task-irrelevant information or operator experience influence category selection. In this study, forensic odontologist and dentist participants read task-irrelevant context case information containing either strong or weak identification or non-identification suggestions before evaluating and comparing pairs of true matching and non-matching dental radiographs. They were then asked to form an opinion regarding identification using one of four categories from the INTERPOL scale. Context information was found to influence categorical decisions. The magnitude and direction of influence depended on the type of participant, the true match status of the radiographs, and the strength and direction of bias of the context. The results of this study demonstrate the contextual effect and fluidity of the boundaries between the categories on the identification scale and highlight the need for stringent protocols to be developed regarding the use of these categorical scales to enable decision making to be more objective.

Maternal overweight and obesity during pregnancy: strategies to improve outcomes for women, babies, and children.

INTRODUCTION: Women with overweight and obesity, and their children, are at increased risk of adverse pregnancy, birth, and longer term health outcomes, believed to be compounded by excessive gestational weight gain (GWG). Research to date has focused on interventions to reduce excessive GWG through changes to maternal diet and/or lifestyle. AREAS COVERED: Current clinical recommendations for GWG vary according to a woman's early pregnancy body mass index, based on assumptions that associations between GWG and adverse pregnancy outcomes are causal in nature, and modifiable. While there are small differences in GWG following pregnancy interventions, there is little evidence for clinically relevant effects on pregnancy, birth, and longer term childhood outcomes. This review considers interventional studies targeting women with overweight or obesity to reduce GWG in an effort to improve maternal and infant health, and the current evidence for interventions prior to conception. EXPERT OPINION: GWG is not modifiable via diet and lifestyle change, and continued efforts to find the 'right' intervention for women with overweight and obesity during pregnancy are unjustified. Researchers should focus on gathering evidence for interventions prior to pregnancy to optimize maternal health and weight to improve pregnancy, birth, and longer term health outcomes associated with obesity.

Effect of an antenatal diet and lifestyle intervention and maternal BMI on cord blood DNA methylation in infants of overweight and obese women: The LIMIT Randomised Controlled Trial.

BACKGROUND: To investigate the effect of an antenatal diet and lifestyle intervention, and maternal pre-pregnancy overweight or obesity, on infant cord blood DNA methylation. METHODS: We measured DNA methylation in 645 cord blood samples from participants in the LIMIT study (an antenatal diet and lifestyle intervention for women with early pregnancy BMI ≥25.0 kg/m2) using the Illumina 450K BeadChip array, and tested for any differential methylation related to the intervention, and to maternal early pregnancy BMI. We also analysed differential methylation in relation to selected candidate genes. RESULTS: No CpG sites were significantly differentially methylated in relation to either the diet and lifestyle intervention, or with maternal early pregnancy BMI. There was no significant differential methylation in any of the selected genes related to the intervention, or to maternal BMI. CONCLUSION: We found no evidence of an effect of either antenatal diet and lifestyle, or of maternal early pregnancy BMI, on cord blood DNA methylation. CLINICAL TRIALS REGISTRATION: ACTRN12607000161426.

No evidence for clinical efficacy of adjunctive celecoxib with vortioxetine in the treatment of depression: A 6-week double-blind placebo controlled randomized trial.

Given the role of low-grade inflammation in the pathophysiology of major depressive disorder (MDD), anti-inflammatory strategies may improve treatment outcomes in some patients. However, it is controversial whether they can be used as adjunctive treatments and whether pre-treatment levels of inflammation can predict treatment outcomes. This study was conducted to measure the efficacy of anti-inflammatory augmentation of antidepressant treatment in MDD patients; and to investigate whether treatment response was dependent on baseline inflammation levels. This parallel-group randomised, double-blind, placebo-controlled trial was conducted at the University of Adelaide (Australia). Participants with MDD were randomised to receive vortioxetine with celecoxib or vortioxetine with placebo for six weeks, and baseline blood high sensitivity C reactive protein levels were measured. Primary outcome was change in depressive symptoms (Montgomery-Åsberg Depression Rating Scale) and secondary outcomes included change in cognition (THINC-integrated tool - Codebreaker task) and functioning (Functioning Assessment Short Test) over 6 weeks. There was no evidence of superior efficacy of celecoxib augmentation over placebo on depressive symptom severity, response and remission rates, cognition and psychosocial functioning. There was also no evidence that pre-treatment inflammation levels modified the effect of celecoxib augmentation versus placebo. This observed lack of efficacy of celecoxib add-on does not support the use of celecoxib augmentation of antidepressants in the treatment of MDD in a cohort that mostly comprises treatment-resistant individuals. Additionally, C-reactive protein may not be suitable to predict treatment selection and response in MDD. The study was registered on the Australian New Zealand Clinical Trials Registry: ACTRN12617000527369 (www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p).

The effects of dietary and lifestyle interventions among pregnant women with overweight or obesity on early childhood outcomes: an individual participant data meta-analysis from randomised trials.

BACKGROUND: The impact of maternal obesity extends beyond birth, being independently associated with an increased risk of child obesity. Current evidence demonstrates that women provided with a dietary intervention during pregnancy improve their dietary quality and have a modest reduction in gestational weight gain. However, the effect of this on longer-term childhood obesity-related outcomes is unknown. METHODS: We conducted an individual participant data meta-analysis from RCTs in which women with a singleton, live gestation between 10+0 and 20+0 weeks and body mass index (BMI) ≥ 25 kg/m2 in early pregnancy were randomised to a diet and/or lifestyle intervention or continued standard antenatal care and in which longer-term maternal and child follow-up at 3-5 years of age had been undertaken. The primary childhood outcome was BMI z-score above the 90th percentile. Secondary childhood outcomes included skinfold thickness measurements and body circumferences, fat-free mass, dietary and physical activity patterns, blood pressure, and neurodevelopment. RESULTS: Seven primary trials where follow-up of participants occurred were identified by a systematic literature search within the International Weight Management in Pregnancy (i-WIP) Collaborative Group collaboration, with six providing individual participant data. No additional studies were identified after a systematic literature search. A total of 2529 children and 2383 women contributed data. Approximately 30% of all child participants had a BMI z-score above the 90th percentile, with no significant difference between the intervention and control groups (aRR 0.97; 95% CI 0.87, 1.08; p=0.610). There were no statistically significant differences identified for any of the secondary outcome measures. CONCLUSIONS: In overweight and obese pregnant women, we found no evidence that maternal dietary and/or lifestyle intervention during pregnancy modifies the risk of early childhood obesity. Future research may need to target the pre-conception period in women and early childhood interventions. TRIAL REGISTRATION: PROSPERO, CRD42016047165.