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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.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.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.

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.To evaluate the effect of in-utero exposure to metformin on child health compared with no exposure.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.The number of children with BMI85th 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.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.

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.

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.To evaluate birth outcomes following the introduction of the Fetal Pillow at a tertiary maternity hospital.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.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.There was no evidence that use of the Fetal Pillow to elevate an impacted fetal head during caesarean birth when cervical dilatation is7 cm was associated with a reduced rate of adverse maternal and neonatal outcomes.

Background Wound infection is a common complication following caesarean section. Factors influencing the risk of infection may include the suture material for skin closure, and closure of the subcutaneous fascia. We assessed the effect of skin closure with absorbable versus non-absorbable suture, and closure versus non-closure of the subcutaneous fascia on risk of wound infection following Caesarean section. Methods Women undergoing caesarean birth at an Adelaide maternity hospital were eligible for recruitment to a randomised trial using a 2 × 2 factorial design. Women were randomised to either closure or non-closure of the subcutaneous fascia and to subcuticular skin closure with an absorbable or non-absorbable suture. Participants were randomised to each of the two interventions into one of 4 possible groups: Group 1 - non-absorbable skin suture and non-closure of the subcutaneous fascia; Group 2 - absorbable skin suture and non-closure of the subcutaneous fascia; Group 3 - non-absorbable skin suture and closure of the subcutaneous fascia; and Group 4 - absorbable skin suture and closure of the subcutaneous fascia. The primary outcomes were reported wound infection and wound haematoma or seroma within the first 30 days after birth. Results A total of 851 women were recruited and randomised, with 849 women included in the analyses (Group 1: 216 women; Group 2: 212 women; Group 3: 212 women; Group 4: 211 women). In women who underwent fascia closure, there was a statistically significant increase in risk of wound infection within 30 days post-operatively for those who had skin closure with an absorbable suture (Group 4), compared with women who had skin closure with a non-absorbable suture (Group 3) (adjusted RR 2.17; 95% CI 1.05, 4.45; p = 0.035). There was no significant difference in risk of wound infection for absorbable vs non-absorbable sutures in women who did not undergo fascia closure. Conclusion The combination of subcutaneous fascia closure and skin closure with an absorbable suture may be associated with an increased risk of reported wound infection after caesarean section. Trial registration Prospectively registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12608000143325, on the 20th March, 2008.

Background The infants born to women who are overweight or obese in pregnancy are at an increased risk of being born macrosomic or large for gestational age. Antenatal dietary and lifestyle interventions have been shown to be ineffective at reducing this risk. Our aim was to examine the effects of metformin in addition to a diet and lifestyle intervention on fetal growth and adiposity among women with a BMI above the healthy range. Methods Women who had a body mass index ≥25 kg/m2 in early pregnancy, and a singleton gestation, were enrolled in the GRoW trial from three public maternity hospitals in metropolitan Adelaide. Women were invited to have a research ultrasounds at 28 and 36 weeks’ gestation at which ultrasound measures of fetal biometry and adiposity were obtained. Fetal biometry z-scores and trajectories were calculated. Measurements and calculations were compared between treatment groups. This secondary analysis was pre-specified. Results Ultrasound data from 511 women were included in this analysis. The difference in femur length at 36 weeks’ gestation was (0.07 cm, 95% CI 0.01–0.14 cm, p = 0.019) and this was was statistically significant, however the magnitude of effect was small. Differences between treatment groups for all other fetal biometry measures, z-scores, estimated fetal weight, and adiposity measures at 28 and 36 weeks’ gestation were similar. Conclusions The addition of metformin to dietary and lifestyle advice in pregnancy for overweight and obese women has no clinically relevant effect on ultrasound measures of fetal biometry or adiposity. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN12612001277831).

While the effects of an antenatal dietary intervention for women with obesity or overweight on pregnancy and newborn health have been extensively studied, the longer-term effects into childhood are unknown. We followed children born to women who participated in the LIMIT randomised trial, where pregnant women were randomised to an antenatal dietary and lifestyle intervention or standard antenatal care. Our aim was to assess the effect of the intervention, on child outcomes at 3–5 years of age on children whose mothers provided consent. We assessed 1418 (Lifestyle Advice n = 727; Standard Care n = 691) (66.9%) of the 2121 eligible children. There were no statistically significant differences in the incidence of child BMI z-score >85th centile for children born to women in the Lifestyle Advice Group, compared with the Standard Care group (Lifestyle Advice 444 (41.73%) versus Standard Care 417 (39.51%); adjusted relative risk (aRR) 1.05; 95% confidence intervals 0.93–1.19; p = 0.42). There were no significant effects on measures of child growth, adiposity, neurodevelopment, or dietary intake. There is no evidence that an antenatal dietary intervention altered child growth and adiposity at age 3–5 years. This cohort of children remains at high risk of obesity, and warrants ongoing follow-up.

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

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

Awareness of Listeriosis and Methylmercury toxicity recommendations are associated with decreased intake of high-risk foods. Whether awareness of the recommendations affect dietary quality of pregnant women in Australian is unknown.To evaluate awareness of Listeriosis and Methylmercury toxicity recommendations during pregnancy and its impact on dietary quality.Pregnant women (n=81) were recruited from antenatal clinics. Awareness of Listeriosis and Methylmercury toxicity recommendations and high-risk foods consumption were assessed via questionnaire at 10-23 weeks gestation. Diet quality was measured using the 2005 Healthy Eating Index using a validated food frequency questionnaire at 10-23 and 34-36 weeks gestation.A higher proportion of women were aware of Methylmercury toxicity compared with Listeriosis recommendations (75.3 vs. 59.2%, p0.001). The proportion of women who decreased or avoided consumption of certain high-risk Listeriosis foods were higher in those who were aware compared with those who were unaware of Listeriosis recommendations [raw fish (96.0 vs 69.2%, p=0.046), soft-serve ice cream (93.9 vs 58.3%, p=0.004) and alfalfa/bean sprouts (68.7 vs 28.5%, p=0.006)]. A large proportion of women (96.8%) met recommendations for limiting consumption of high Methylmercury fish. There was no difference in the change in dietary quality over pregnancy regardless of women's awareness of the recommendations.Awareness of Listeriosis and Methylmercury toxicity recommendations has little impact on dietary quality of pregnant women in this small study. Further research in a large representative population of pregnant women is needed to confirm our findings and to optimise dietary quality during pregnancy.

Introduction: The aim of this secondary analysis was to investigate the relationship between maternal body mass index (BMI) and fetal biometry, body composition, and velocity measurements at 28 and...

Background Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach. Methods We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool. Discussion Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing “standard” UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial. Trial identifiers Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018–004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.

A passive sulfate reduction system with iron scrubbers was identified as the most viable option for treatment of elevated sulfate within leachate from an old landfill and bench scale trials were established in 2019 at the site to test the theory. This included the use of Biochemical Reactor (BCR) with different proportions of wood chips, straw, manure, limestone, and biochar to culture sulfate reducing bacteria. In addition, the concept of using alcohol to fee the bacteria was trialled, using Fix Bed Anaerobic Bioreactor (FBAR), where alcohol was added to enhance the sulfate reducer activity. In total three BCRs and two FBARs were set up for this stage of the assessment. The resulting treated leachate was then passed through different iron media types (haematite, magnetite and iron filings) to remove sulfide generated by the bacteria, with an aerobic wetland used to polish the effluent. The success of the bench scale project led to a pilot scale system being constructed and monitored in Spring 2020, the results of which confirm the success of the bench scale testing and provides useful insights into management of the system particular in winter months. The COVID crises has had its impact, but the system has operated continuously and will run through 2021.

Worldwide, half of women begin a pregnancy with overweight or obesity, which increases the risk of pregnancy and birth complications and adversely affects the lifelong health of the offspring. In order for metabolic changes to influence the gestational environment, research suggests that weight loss should take place before conception. This study aimed to understand women&rsquo, s emotional and social contexts, knowledge, motivations, skills and self-efficacy in making healthy change. Semi-structured interviews conducted with twenty-three women with overweight or obesity, informed by the Information&ndash, Motivation&ndash, Behavioural Skills (IMB) model, were analysed using reflexive thematic analysis. Information-related themes identified included poor health risk knowledge, healthy food decisions and health versus convenience. The Motivation themes comprised taking responsibility, flexible options, social expectations, interpersonal challenges and accountability. Behavioural Skills entailed themes such as the mental battle, time management, self-care and inspiration. An environmental factor was identified in affordability&mdash, limiting access to healthier alternatives. Women wanted simple, flexible options that considered family commitments, time and budgetary constraints. Unprompted, several mentioned the importance of psychological support in managing setbacks, stress and maintaining motivation. Strategies for enhancing self-efficacy and motivational support are required to enable longstanding health behaviour change. Findings will inform intervention mapping development of an eHealth solution for women preconception.

Our aim was to investigate the underlying assumptions of the current gestational weight gain (GWG) paradigm, specifically that&mdash, (1) GWG is modifiable through diet and physical activity, (2) optimal GWG and risk of excess GWG, vary by pre-pregnancy body mass index (BMI) category and (3) the association between GWG and adverse pregnancy outcomes is causal. Using data from three large, harmonized randomized controlled trials (RCTs) of interventions to limit GWG and improve pregnancy outcomes and with appropriate regression models, we investigated the link between diet and physical activity and GWG, the relationships between pre-pregnancy BMI, GWG and birth weight z-score, and the evidence for a causal relationship between GWG and pregnancy outcomes. We found little evidence that diet and physical activity in pregnancy affected GWG and that the observed relationships between GWG and adverse pregnancy outcomes are causal in nature. Further, while there is evidence that optimal GWG may be lower for women with higher BMI, target ranges defined by BMI categories do not accurately reflect risk of adverse outcomes. Our findings cast doubt upon current advice regarding GWG, particularly for overweight and obese women and suggest that a change in focus is warranted.

IntroductionGestational diabetes mellitus (GDM) is a common disorder of pregnancy and contributes to adverse pregnancy outcomes. Metformin is often used for the prevention and management of GDM; however, its use in pregnancy continues to be debated. The Metformin in Pregnancy Study aims to use individual patient data (IPD) meta-analysis to clarify the efficacy and safety of metformin use in pregnancy and to identify relevant knowledge gaps.Methods and analysisMEDLINE, EMBASE and all Evidence-Based Medicine will be systematically searched for randomised controlled trials (RCT) testing the efficacy of metformin compared with placebo, usual care or other interventions in pregnant women. Two independent reviewers will assess eligibility using prespecified criteria and will conduct data extraction and quality appraisal of eligible studies. Authors of included trials will be contacted and asked to contribute IPD. Primary outcomes include maternal glycaemic parameters and GDM, as well as neonatal hypoglycaemia, anthropometry and gestational age at delivery. Other adverse maternal, birth and neonatal outcomes will be assessed as secondary outcomes. IPD from these RCTs will be harmonised and a two-step meta-analytic approach will be used to determine the efficacy and safety of metformin in pregnancy, with a priori adjustment for covariates and subgroups to examine effect moderators of treatment outcomes. Sensitivity analyses will assess heterogeneity, risk of bias and the impact of trials which have not provided IPD.Ethics and disseminationAll IPD will be deidentified and studies contributing IPD will have ethical approval from their respective local ethics committees. This study will provide robust evidence regarding the efficacy and safety of metformin use in pregnancy, and may identify subgroups of patients who may benefit most from this treatment modality. Findings will be published in peer-reviewed journals and disseminated at scientific meetings, providing much needed evidence to inform clinical and public health actions in this area.

There are well-recognised associations between excessive gestational weight gain (GWG) and adverse pregnancy outcomes, including an increased risk of pre-eclampsia, gestational diabetes and caesarean birth. The aim of the OPTIMISE randomised trial was to evaluate the effect of dietary and exercise advice among pregnant women of normal body mass index (BMI), on pregnancy and birth outcomes. The trial was conducted in Adelaide, South Australia. Pregnant women with a body mass index in the healthy weight range (18.5&ndash, 24.9 kg/m2) were enrolled in a randomised controlled trial of a dietary and lifestyle intervention versus standard antenatal care. The dietitian-led dietary and lifestyle intervention over the course of pregnancy was based on the Australian Guide to Healthy Eating. Baseline characteristics of women in the two treatment groups were similar. There was no statistically significant difference in the proportion of infants with birth weight above 4.0 kg between the Lifestyle Advice and Standard Care groups (24/316 (7.59%) Lifestyle Advice versus 26/313 (8.31%) Standard Care, adjusted risk ratio (aRR) 0.91, 95% confidence interval (CI) 0.54 to 1.55, p = 0.732). Despite improvements in maternal diet quality, no significant differences between the treatment groups were observed for total GWG, or other pregnancy and birth outcomes.

Context Many international clinical guidelines recommend that overweight and obese women lose weight prior to pregnancy to reduce the risk of adverse pregnancy outcomes. Women who have recently given birth and plan future pregnancies are an important target population for preconception weight-loss interventions. Objective A systematic review to evaluate postpartum dietary and/or physical activity interventions to promote weight loss and improve health in a subsequent pregnancy was conducted. Data sources Five databases-the Cochrane Central Register of Controlled Trials, MEDLINE (through PubMed), Embase, the Australian New Zealand Clinical Trials Registry, and the International Clinical Trials Registry-were searched using the following terms: preconception, pregnancy, postpartum, pregnancy outcomes, body mass index, weight gain, weight loss, weight change, postpartum weight retention, dietary or lifestyle intervention, and randomiz(s)ed controlled trial. The date of last search was November 2017. Data extraction Data were extracted from each identified study using a standard form. The primary outcomes were weight loss at the completion of the intervention and at follow-up assessments. Secondary endpoints included maternal and infant outcomes in a subsequent pregnancy. Data analysis Mean differences (MDs) were calculated for continuous data and risk ratios for dichotomous data, both with 95%CIs. Results A total of 235 abstracts (193 after duplicates were excluded) were identified, from which 37 manuscripts were selected for full-text review. In total, 27 trials were identified for inclusion. Outcome data were available for approximately 75% of participants (n = 3485). A combined dietary and physical activity intervention provided post partum produced greater postpartum weight loss (MD, -2.49 kg; 95%CI, -3.34 to -1.63 kg [random-effects model]; 12 studies, 1156 women), which was maintained at 12 months post partum (MD, -2.41 kg; 95%CI, -3.89 to -0.93 kg [random-effects model]; 4 studies, 405 women), compared with no intervention. No studies reported maternal or infant health outcomes in a subsequent pregnancy. Conclusions Providing a postpartum intervention is associated with weight loss after birth, but effects on maternal and infant health in a subsequent pregnancy are uncertain.

Background Misreporting of energy intake is common and can contribute to biased estimates of the relationship between diet and disease. Energy intake misreporting is poorly understood in pregnancy and there is limited research assessing characteristics of women who misreport energy intake or changes in misreporting of energy intake across pregnancy. Methods An observational study in n = 945 overweight or obese pregnant women receiving standard antenatal care who participated in the LIMIT randomised trial. Diet, physical activity, psychological factors, body image satisfaction and dieting behaviour were assessed at trial entry (10–20 weeks gestation) and 36 weeks gestation. Energy misreporting status was assessed through the ratio of daily energy intake over basal metabolic rate. Logistic regression analyses were conducted with the dependent variable of under reporting of energy intake at study entry or 36 weeks in separate analysis. Results At study entry and 36 weeks, women were classified as under reporters (38 vs 49.4%), adequate reporters (59.7 vs 49.8%) or over reporters of energy intake (2.3 vs 0.8%) respectively. The prevalence of under reporting energy intake at 36 weeks was higher than at study entry (early pregnancy). Body mass index (BMI) at study entry and 36 weeks and socioeconomic status, dieting behaviour and risk of depression at 36 weeks were independent predictors of under reporting of energy intake. Conclusions Under reporting of energy intake was present in over a third of overweight and obese pregnant women and was higher in late compared to early pregnancy. Characteristics such as BMI, socioeconomic status, past dieting behaviour and risk of depression may aid in identifying women who either require support in accurate recording of food intake or attention for improving diet quality. Results were unable to distinguish whether under reporting reflects misreporting or a true restriction of dietary intake. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12607000161426, registered 9/3/2007. Electronic supplementary material The online version of this article (10.1186/s12884-018-1826-x) contains supplementary material, which is available to authorized users.

Background The immediate impact of providing an antenatal dietary intervention during pregnancy has been extensively studied, but little is known of the effects beyond the neonatal period. Our objective was to evaluate the effect of an antenatal dietary intervention in overweight or obese women on infant outcomes 6 months after birth. Methods We conducted a follow up study of infants born to women who participated in the LIMIT trial during pregnancy. Live-born infants at 6-months of age, and whose mother provided consent to ongoing follow-up were eligible. The primary follow-up study endpoint was the incidence of infant BMI z-score ≥90th centile for infant sex and age. Secondary study outcomes included a range of infant anthropometric measures, neurodevelopment, general health, and infant feeding. Analyses used intention to treat principles according to the treatment group allocated in pregnancy. Missing data were imputed and analyses adjusted for maternal early pregnancy BMI, parity, study centre, socioeconomic status, age, and smoking status. Outcome assessors were blinded to the allocated treatment group. Results A total of 1754 infants were assessed at age 6 months (Lifestyle Advice n = 869; Standard Care n = 885), representing 82.1% of the eligible sample (n = 2136). There were no statistically significant differences in the incidence of infant BMI z-score ≥90th centile for infants born to women in the Lifestyle Advice group, compared with the Standard Care group (Lifestyle Advice 233 (21.71%) vs. Standard Care 233 (21.90%); adjusted relative risk (aRR) 0.99; 95% confidence interval 0.82 to 1.18; p = 0.88). There were no other effects on infant growth, adiposity, or neurodevelopment. Conclusion Providing pregnant women who were overweight or obese with an antenatal dietary and lifestyle intervention did not alter 6-month infant growth and adiposity. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).

Aim Trials on diet and physical activity in pregnancy report on various outcomes. We aimed to assess the variations in outcomes reported and their quality in trials on lifestyle interventions in pregnancy. Methods We searched major databases without language restrictions for randomized controlled trials on diet and physical activity-based interventions in pregnancy up to March 2015. Two independent reviewers undertook study selection and data extraction. We estimated the percentage of papers reporting ‘critically important’ and ‘important’ outcomes. We defined the quality of reporting as a proportion using a six-item questionnaire. Regression analysis was used to identify factors affecting this quality. Results Sixty-six randomized controlled trials were published in 78 papers (66 main, 12 secondary). Gestational diabetes (57.6%, 38/66), preterm birth (48.5%, 32/66) and cesarian section (60.6%, 40/66), were the commonly reported ‘critically important’ outcomes. Gestational weight gain (84.5%, 56/66) and birth weight (87.9%, 58/66) were reported in most papers, although not considered critically important. The median quality of reporting was 0.60 (interquartile range 0.25, 0.83) for a maximum score of one. Study and journal characteristics did not affect quality. Conclusion Many studies on lifestyle interventions in pregnancy do not report critically important outcomes, highlighting the need for core outcome set development.

Objective Optimizing maternal diet during pregnancy improves maternal and infant health. This study assessed the effect of an antenatal lifestyle intervention for women with overweight or obesity on dietary patterns during pregnancy and post partum. Methods This study is a secondary analysis of a randomized controlled trial in which pregnant women (BMI ≥ 25 kg/m2) received lifestyle advice (n = 943) or standard care (n = 924). Dietary pattern analysis was undertaken using factor analysis with comparisons between trial entry and 28 weeks, 36 weeks, and 4 months post partum. Results The dietary pattern analysis revealed two distinct patterns: “prudent” and “Western.” There was a significant difference between groups in the change over time for both patterns (P

Prevention of obesity in women of reproductive age is widely recognised to be important both for their health and for that of their offspring. Weight-control interventions, including drug treatment, in pregnant women who are obese or overweight have not had sufficient impact on pregnancy and birth outcomes, which suggests that the focus for intervention should include preconception or post-partum periods. Further research is needed into the long-term effects of nutritional and lifestyle interventions before conception. To improve preconception health, an integrated approach, including pregnancy prevention, planning, and preparation is needed, involving more than the primary health-care sector and adopting an ecological approach to risk reduction that addresses personal, societal, and cultural influences. Raising awareness of the importance of good health in the period before pregnancy will require a new social movement: combining bottom-up mobilisation of individuals and communities with a top-down approach from policy initiatives. Interventions to reduce or prevent obesity before conception and during pregnancy could contribute substantially to achievement of the global Sustainable Development Goals, in terms of health, wellbeing, productivity, and equity in current and future generations.

Over fifty percent of women entering pregnancy are overweight or obese. This has a significant impact on short and long term maternal and infant health outcomes, and the intergenerational effects of obesity are now a major public health problem globally. Areas covered: There are two major pathways contributing to fetal growth. Glucose and insulin directly affect growth, while other substrates such as leptin, adiponectin and insulin-like growth factors indirectly influence growth through structural and morphological effects on the placenta, uteroplacental blood flow, and regulation of placental transporters. Advances in ultrasonography over the past decade have led to interest in the prediction of the fetus at risk of overgrowth and adiposity utilizing both standard ultrasound biometry and fetal body composition measurements. However, to date there is no consensus regarding the definition of fetal overgrowth, its reporting, and clinical management. Expert commentary: Maternal dietary intervention targeting the antenatal period appear to be too late to sufficiently affect fetal growth. The peri-conceptual period and early pregnancy are being evaluated to determine if the intergenerational effects of maternal obesity can be altered to improve newborn, infant and child health.

Previous studies have suggested that maternal supplementation with n-3 long-chain polyunsaturated fatty acids may reduce the incidence of preterm delivery but may also prolong gestation beyond term; however, more data are needed regarding the role of n-3 long-chain polyunsaturated fatty acids in pregnancy.We performed a multicenter, double-blind, randomized trial in which women who were pregnant with single or multiple fetuses were assigned to receive either fish-oil capsules that contained 900 mg of n-3 long-chain polyunsaturated fatty acids (n-3 group) or vegetable-oil capsules that contained trace n-3 long-chain polyunsaturated fatty acids (control group) daily, beginning before 20 weeks of gestation and continuing to 34 weeks of gestation or delivery, whichever occurred first. The primary outcome was early preterm delivery, defined as delivery before 34 completed weeks of gestation. Other pregnancy and neonatal outcomes were also assessed.A total of 5544 pregnancies in 5517 women were randomly assigned at six centers in Australia; 5486 pregnancies were included in the primary analysis. Early preterm delivery occurred in the case of 61 of 2734 pregnancies (2.2%) in the n-3 group and 55 of 2752 pregnancies (2.0%) in the control group; the between-group difference was not significant (adjusted relative risk, 1.13; 95% confidence interval [CI], 0.79 to 1.63; P = 0.50). There were no significant differences between the groups in the incidence of interventions in post-term (41 weeks of gestation) deliveries, in adverse events, or in other pregnancy or neonatal outcomes, except that a higher percentage of infants born to women in the n-3 group than in the control group were very large for gestational age at birth (adjusted relative risk, 1.30; 95% CI, 1.02 to 1.65). Percentages of serious adverse events did not differ between the groups. Minor gastrointestinal disturbances were more commonly reported in the n-3 group than in the control group.Supplementation with n-3 long-chain polyunsaturated fatty acids from early pregnancy (20 weeks of gestation) until 34 weeks of gestation did not result in a lower incidence of early preterm delivery or a higher incidence of interventions in post-term deliveries than control. (Funded by the Australian National Health and Medical Research Council and the Thyne Reid Foundation; ORIP Australian New Zealand Clinical Trials Registry number, ACTRN12613001142729.).

ObjectivesTo identify if maternal educational attainment is a prognostic factor for gestational weight gain (GWG), and to determine the differential effects of lifestyle interventions (diet based, physical activity based or mixed approach) on GWG, stratified by educational attainment.DesignIndividual participant data meta-analysis using the previously established International Weight Management in Pregnancy (i-WIP) Collaborative Group database (https://iwipgroup.wixsite.com/collaboration). Preferred Reporting Items for Systematic reviews and Meta-Analysis of Individual Participant Data Statement guidelines were followed.Data sourcesMajor electronic databases, from inception to February 2017.Eligibility criteriaRandomised controlled trials on diet and physical activity-based interventions in pregnancy. Maternal educational attainment was required for inclusion and was categorised as higher education (≥tertiary) or lower education (≤secondary).Risk of biasCochrane risk of bias tool was used.Data synthesisPrinciple measures of effect were OR and regression coefficient.ResultsOf the 36 randomised controlled trials in the i-WIP database, 21 trials and 5183 pregnant women were included. Women with lower educational attainment had an increased risk of excessive (OR 1.182; 95% CI 1.008 to 1.385, p =0.039) and inadequate weight gain (OR 1.284; 95% CI 1.045 to 1.577, p =0.017). Among women with lower education, diet basedinterventions reduced risk of excessive weight gain (OR 0.515; 95% CI 0.339 to 0.785, p = 0.002) and inadequate weight gain (OR 0.504; 95% CI 0.288 to 0.884, p=0.017), and reduced kg/week gain (B −0.055; 95% CI −0.098 to −0.012, p=0.012). Mixed interventions reduced risk of excessive weight gain for women with lower education (OR 0.735; 95% CI 0.561 to 0.963, p=0.026). Among women with high education, diet based interventions reduced risk of excessive weight gain (OR 0.609; 95% CI 0.437 to 0.849, p=0.003), and mixed interventions reduced kg/week gain (B −0.053; 95% CI −0.069 to −0.037,pConclusionsPregnant women with lower education are at an increased risk of excessive and inadequate GWG. Diet based interventions seem the most appropriate choice for these women, and additional support through mixed interventions may also be beneficial.

Fifty percent of women who enter pregnancy are overweight or obese, increasing complications for both the mother and the infant, along with significant burden on individuals and the health care system. Pregnancy represents a "teachable moment" in a woman's life, however, antenatal interventions focusing on improving dietary and physical activity patterns have been associated with modest behavior change. There are many barriers that need to be overcome, including lack of knowledge, access and time pressures. Advancing mobile and electronic health technologies may represent an adjunct tool to support traditional face-to-face consultations and facilitate behavior change, but further rigorous evaluation of the technologies and their impact on health outcomes is required. Well-designed antenatal intervention trials with particular attention to the structure and method of information provision are required to further assess the feasibility of such technology.

Obesity represents a significant global health problem, contributing to the overall burden of disease worldwide and a 30% increase in cost of health care provision. Over 50% of women who enter pregnancy are classified as overweight or obese resulting in short and long term effects on maternal and child health outcomes. There is a substantial amount of literature focusing on interventions in the antenatal period have been associated with modest changes in weight gain during pregnancy. There has been little effect on clinical pregnancy and birth outcomes. The article discusses the evidence supporting the shift from harm minimization via antenatal intervention, to one of prevention by targeting the time prior to conception to optimize maternal weight.

Introduction. Women who commence pregnancy with a normal body mass index (BMI) are at the greatest risk of excessive gestational weight gain, impacting on infant birthweight, pregnancy-related complications and postpartum weight retention. Our aim was to review systematically the effect of antenatal dietary and lifestyle interventions in pregnant women with a normal BMI on maternal and infant outcomes. Material and methods. We searched the Cochrane Controlled Trials Register, PubMed, Medline, and the Australian and International Clinical Trials Registry with the date of the last search in July 2015. We included all published, unpublished and ongoing randomized trials recruiting women of a normal BMI, comparing dietary and/or lifestyle interventions with standard antenatal care. Results. Twelve randomized controlled trials were identified, involving a total of 2713 pregnant women, with five studies reporting clinical data for 714 women with a normal BMI. Women who received a dietary and lifestyle intervention were less likely to experience gestational weight gain [four studies, 446 women; mean difference −1.25 kg; 95% confidence interval (CI) −2.39 to −0.11], weight gain above the Institute of Medicine guidelines (four studies, 446 women; risk ratio 0.66; 95% CI 0.53–0.83) and hypertension (two studies; 243 women; risk ratio 0.34; 95% CI 0.13–0.91). There were no statistically significant differences in the occurrence of gestational diabetes, cesarean section or birthweight greater than 4 kg. Conclusions. While providing an antenatal dietary and lifestyle intervention for pregnant women of normal BMI appears to reduce gestational weight gain, the review was limited by the relatively small available sample size. Further well-designed randomized controlled trials are required.

Objective To report the influence of maternal overweight and obesity on fetal growth and adiposity and effects of an antenatal dietary and lifestyle intervention among these women on measures of fetal growth and adiposity as secondary outcomes of the LIMIT Trial. Design Randomised controlled trial. Setting Public maternity hospitals in metropolitan Adelaide, South Australia. Population Pregnant women with a body mass index ≥ 25 kg/m2, and singleton gestation between 10+0 and 20+0 weeks. Methods Women were randomised to Lifestyle Advice or continued Standard Care and offered two research ultrasound scans at 28 and 36 weeks of gestation. Main outcome measures Ultrasound measures of fetal growth and adiposity. Results For each fetal body composition parameter, mean Z-scores were substantially higher when compared with population standards. Fetuses of women receiving Lifestyle Advice demonstrated significantly greater mean mid-thigh fat mass, when compared with fetuses of women receiving Standard Care (adjusted difference in means 0.17; 95% CI 0.02–0.32; P = 0.0245). While subscapular fat mass increased between 28 and 36 weeks of gestation in fetuses in both treatment groups, the rate of adipose tissue deposition slowed among fetuses of women receiving Lifestyle Advice, when compared with fetuses of women receiving Standard Care (P = 0.0160). No other significant differences were observed. Conclusions These findings provide the first evidence of changes to fetal growth following an antenatal dietary and lifestyle intervention among women who are overweight or obese. Tweetable abstract Lifestyle advice for overweight and obese pregnant women modifies fetal body composition.

Objective To develop maternal, fetal, and neonatal composite outcomes relevant to the evaluation of diet and lifestyle interventions in pregnancy by individual patient data (IPD) meta-analysis. Design Delphi survey. Setting The International Weight Management in Pregnancy (i-WIP) collaborative network. Sample Twenty-six researchers from the i-WIP collaborative network from 11 countries. Methods A two-generational Delphi survey involving members of the i-WIP collaborative network (26 members in 11 countries) was undertaken to prioritise the individual outcomes for their importance in clinical care. The final components of the composite outcomes were identified using pre-specified criteria. Main outcome measures Composite outcomes considered to be important for the evaluation of the effect of diet and lifestyle in pregnancy. Results Of the 36 maternal outcomes, nine were prioritised and the following were included in the final composite: pre-eclampsia or pregnancy-induced hypertension, gestational diabetes mellitus (GDM), elective or emergency caesarean section, and preterm delivery. Of the 27 fetal and neonatal outcomes, nine were further evaluated, with the final composite consisting of intrauterine death, small for gestational age, large for gestational age, and admission to a neonatal intensive care unit (NICU). Conclusions Our work has identified the components of maternal, fetal, and neonatal composite outcomes required for the assessment of diet and lifestyle interventions in pregnancy by IPD meta-analysis. Tweetable abstract Composite outcomes in IPD meta-analysis on diet and lifestyle in pregnancy. Tweetable abstract Composite outcomes in IPD meta-analysis on diet and lifestyle in pregnancy. This article includes Author Insights, a video abstract available at https://vimeo.com/148890226

A new population-based observational cohort study involving more than 1.2 million live births highlights the increased risk of congenital anomalies with increasing degrees of maternal overweight and obesity. However, by only considering data on live-born infants, the full impact of maternal overweight and obesity on this aspect of reproductive and child health is underestimated.

OBJECTIVE: Our objective was to evaluate the effect of an antenatal dietary and lifestyle intervention in pregnant women who are overweight or obese on child outcomes at age 18 months. METHODS: We conducted a follow-up study of children at 18 months of age who were born to women who participated in the Limiting Weight Gain in Overweight and Obese Women during Pregnancy to Improve Health Outcomes randomized trial. The primary follow-up study outcome was prevalence of child BMI z scores >85th percentile. Secondary study outcomes included a range of anthropometric measures, neurodevelopment, general health, and child feeding. Intention to treat principles were used in analyses, according to the treatment group allocated at randomization. RESULTS: A total of 1602 children were assessed at age 18 months (lifestyle advice, n = 816; standard care, n = 786), representing 75.0% of the eligible sample (n = 2136). There were no statistically significant differences in the prevalence of child BMI z scores >85th percentile for children born to women in the lifestyle advice group, compared with the standard care group (lifestyle advice, 505 [47.11%] versus standard care, 483 [45.36%]; adjusted relative risk: 1.04; 95% confidence interval: 0.94 to 1.16; P = .45). There was no evidence of effects on child growth, adiposity, neurodevelopment, or dietary and physical activity patterns. CONCLUSIONS: There is no evidence that providing pregnant women who were overweight or obese with an antenatal dietary and lifestyle intervention altered 18-month child growth and adiposity.

BACKGROUND: There has been considerable interest in providing antenatal dietary and lifestyle advice for women with obesity or who are overweight during pregnancy, as a strategy to limit gestational weight gain and improve maternal and infant health. However, such antenatal interventions appear to have a modest effect on gestational weight gain and other clinical pregnancy and birth outcomes and additional strategies are required. Metformin is an oral insulin‐sensitising medication that acts to decrease blood glucose concentrations. Metformin is commonly used in the treatment of type 2 diabetes mellitus and polycystic ovarian syndrome, and is being used increasingly in the treatment of gestational diabetes, having been shown to result in decreased rates of caesarean birth and neonatal hypoglycaemia. Metformin may be an adjuvant therapy to current antenatal strategies in pregnant women with obesity or who are overweight, acting to reduce glucose production in the liver and improve glucose uptake in smooth muscle cells, and therefore improve the overall metabolic health of women in pregnancy and reduce the risk of known adverse pregnancy outcomes. OBJECTIVES: To evaluate the role of metformin in pregnant women with obesity or who are overweight, on maternal and infant outcomes, including adverse effects of treatment and costs. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (11 October 2017), and reference lists of retrieved studies. SELECTION CRITERIA: All published and unpublished randomised controlled trials evaluating metformin use (compared with placebo or no metformin) in women with obesity or who are overweight in pregnancy for improving outcomes, alone or in combination with other interventions were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS: We included three studies which randomised women (1099) with a body mass index (BMI) of 30 kg/m(2) (1 study) and 35 kg/m(2) (2 studies), with outcomes available for 1034 participants. None of the studies assessed women with a BMI between 25 kg/m(2)and 29.9 kg/m(2), therefore we could not assess the use of metformin in women considered overweight. We did not identify studies of metformin in combination with another treatment. Two other studies are ongoing. All three included studies were randomised controlled trials and compared metformin with placebo, commencing early in the second trimester. Doses ranged from 500 mg twice daily to 3.0 g per day. All three studies (two in the UK, one in Egypt) included women attending hospitals for antenatal care. Two studies were generally at a low risk of bias across the majority of domains. We assessed the third study as being at an unclear risk of selection bias, performance and detection bias due to insufficient information in the report. We assessed the trial as being at a low risk of attrition bias and other bias; we felt it was at a high risk of reporting bias. The primary outcome for this review was infant birthweight large‐for‐gestational‐age (> 90th centile for gestational age and infant sex). Women who received metformin or placebo had a similar risk of their baby being born large for his or her gestational age (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.70 to 1.30; 2 studies, 831 infants; high‐quality evidence). Women who received metformin may have a slightly lower gestational weight gain (mean difference (MD) ‐2.60 kg, 95% CI ‐5.29 to 0.10; 3 studies, 899 women; low‐quality evidence). Metformin may make little or no difference in the risk of women developing gestational hypertension (average RR 1.02, 95% CI 0.54 to 1.94; 3 studies, 1040 women; low‐quality evidence) or pre‐eclampsia (RR 0.74, 95% CI 0.09 to 6.28; 2 studies, 840 women; low‐quality evidence). Metformin probably makes little or no difference in the risk of women developing gestational diabetes (RR 0.85, 95% CI 0.61 to 1.19; 3 studies, 892 women; moderate‐quality evidence). One study of 400 women reported women receiving metformin were more likely to experience any adverse effect compared with women receiving placebo (RR 1.63, 95% CI 1.27 to 2.08; 1 study, 400 women). Adverse effects included abdominal pain, diarrhoea, or headache. When considering individual side effects, women receiving metformin were more likely to experience diarrhoea than women receiving placebo (RR 2.34, 95% CI 1.74 to 3.14; 797 women; 2 studies, 797 women; high‐quality evidence). No other important differences were identified between Metformin and placebo for other maternal secondary outcomes, including: caesarean birth, birth before 37 weeks of pregnancy, shoulder dystocia, perineal tear, or postpartum haemorrhage. In terms of other infant outcomes, there was little or no difference in the infant birthweight (MD 6.39 g, 95% CI ‐81.15 to 93.92; 2 studies, 834 infants; high‐quality evidence). There were no other important differences identified for other infant secondary outcomes in this review: hypoglycaemia (low blood sugar); hyperbilirubinaemia (jaundice); Apgar score less than 7 at five minutes; or stillbirth and neonatal death. Only one study reported admission to the neonatal intensive care unit (NICU), indicating similar rates of admission between women receiving metformin or placebo; no other admission data were reported to assess differences in costs. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of metformin for women with obesity in pregnancy for improving maternal and infant outcomes. Metformin was, however, associated with increased risk of adverse effects, particularly diarrhoea. The quality of the evidence in this review varied from high to low, with downgrading decisions based on study limitations and inconsistency. There were only a small number of studies included in this review. Furthermore, none of the included studies included women categorised as 'overweight' and no trials looked at metformin in combination with another treatment. Future research is required in order to further evaluate the role of metformin therapy in pregnant women with obesity or who are overweight, as a strategy to improve maternal and infant health, alone or as an adjuvant to dietary and lifestyle advice.

Background: Maternal obesity and gestational diabetes are characterised by insulin resistance, hyperglycemia, and low-grade chronic inflammation, contributing to excess availability of nutrients and fetal growth. Metformin is used increasingly in treatment of gestational diabetes. Aim: To evaluate the effects of prenatal metformin among overweight and obese pregnant women on maternal and infant outcomes. Methods: We conducted a randomized, placebo controlled trial. Women were recruited from public maternity hospitals in Adelaide, with a singleton, pregnancy between 10+0 and 20+0 weeks, and BMI ≥25.0 kg/m2 at their first prenatal visit. We used a computer randomization service, with stratification for parity, BMI (overweight vs. obese) and center of birth. Women were randomized to either Metformin or Placebo. Women used Metformin tablets (up to 2g daily) or identical appearing placebo. All women received a dietary and lifestyle intervention, consisting of three face-to-face sessions and three telephone calls over their pregnancy. Outcomes included infant birth weight >4kg, gestational weight gain, gestational diabetes and other pregnancy and birth outcomes. Results: We randomized 524 pregnant women. Baseline characteristics at randomization were comparable. Women who received prenatal metformin in addition to the dietary intervention gained significantly less weight during pregnancy compared with women who received the dietary intervention and placebo (7.7 + 5.9kg vs. 8.9 +5.7kg; mean difference -1.16 (95% CI -2.3 to -0.05; p=0.04). There were no statistically significant differences with regards other clinical outcomes, including diagnosis of gestational diabetes. Conclusions: The combination of prenatal metformin and a dietary intervention reduced gestational weight gain during pregnancy, but did not impact clinical pregnancy and birth outcomes. Disclosure J.M. Dodd: None. J. Louise: None. A.R. Deussen: None.

Objective To describe the mediating effect of maternal gestational diabetes on fetal biometry and adiposity measures among overweight or obese pregnant women. Design Secondary analysis of the LIMIT randomised trial. Setting Public hospitals, metropolitan Adelaide, South Australia. Population Pregnant women with body mass index (BMI) ≥25 kg/m2 and singleton gestation. Methods Fetal ultrasound measures at 36 weeks of gestation and baseline BMI from women randomised to the LIMIT trial Standard Care group (n = 912 women) were used to conduct causal mediation analyses using regression-based methods. Main outcomes measures Ultrasound measures of fetal biometry and adiposity at 36 weeks of gestation. Results Increased maternal BMI was associated with increased measures of fetal head circumference [direct (unmediated) effect 0.18 (95% CI: 0.05-0.31), P = 0.005; total effect 0.17 (95% CI: 0.02-0.31), P = 0.018], abdominal circumference [direct effect 0.26 (95% CI: 0.11-0.41), P = 0.001; total effect 0.26 (95% CI: 0.11-0.42), P = 0.001] and estimated fetal weight [direct effect 0.22 (95% CI: 0.08-0.35), P = 0.002; total effect 0.22 (95% CI: 0.08-0.35), P = 0.002], with no evidence of mediation by treated gestational diabetes. There was no apparent association between maternal BMI and fetal adiposity measures, or mediation by treated gestational diabetes. Conclusions We show an important association between increased maternal BMI and fetal growth, not mediated by treated gestational diabetes. There was no association between increased maternal BMI and fetal adiposity measures, or mediation by treated gestational diabetes. Whether these findings represent 'saturation' in the effect of maternal BMI on fetal growth or the effect of treatment of GDM is unclear. Funding This project was funded by a 4-year project grant from the National Health and Medical Research Council (NHMRC), Australia (ID 519240); The Channel 7 Children's Research Foundation, South Australia; and the US National Institutes of Health (R01 HL094235-01). Tweetable abstract Increased fetal growth associated with maternal obesity is not mediated by gestational diabetes.

BACKGROUND: Multiple pregnancy is a strong risk factor for preterm birth, and more than 50% of women with a twin pregnancy will give birth prior to 37 weeks' gestation. Infants born preterm are recognised to be at increased risk of many adverse health outcomes, contributing to more than half of overall perinatal mortality. Progesterone is produced naturally in the body and has a role in maintaining pregnancy, although it is not clear whether administering progestogens to women with multiple pregnancy at high risk of early birth is effective and safe. Since publication of this new review in Issue 10, 2017, we have now moved one study (El‐Refaie 2016) from included to studies awaiting classification, pending clarification about the study data. OBJECTIVES: To assess the benefits and harms of progesterone administration for the prevention of preterm birth in women with a multiple pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (1 November 2016) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials examining the administration of a progestogen by any route for the prevention of preterm birth in women with multiple pregnancy. We did not include quasi‐randomised or cross‐over studies. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed reports identified by the search for eligibility, extracted data, assessed risk of bias and graded the quality of the evidence. MAIN RESULTS: We included 16 trials, which all compared either vaginal or intramuscular (IM) progesterone with a placebo or no treatment, and involved a total of 4548 women. The risk of bias for the majority of included studies was low, with the exception of three studies that had inadequate blinding, or significant loss to follow‐up or both, or were not reported well enough for us to make a judgement. We graded the evidence low to high quality, with downgrading for statistical heterogeneity, design limitations in some of the studies contributing data, and imprecision of the effect estimate. 1 IM progesterone versus no treatment or placebo More women delivered at less than 34 weeks' gestation in the IM progesterone group compared with placebo (risk ratio (RR) 1.54, 95% confidence interval (CI) 1.06 to 2.26; women = 399; studies = 2; low‐quality evidence). Although the incidence of perinatal death in the progesterone group was higher, there was considerable uncertainty around the effect estimate and high heterogeneity between studies (average RR 1.45, 95% CI 0.60 to 3.51; infants = 3089; studies = 6; I(2) = 71%; low‐quality evidence). No studies reported maternal mortality or major neurodevelopmental disability at childhood follow‐up. There were no clear group differences found in any of the other maternal or infant outcomes (preterm birth less than 37 weeks (RR 1.05, 95% CI 0.98 to 1.13; women = 2010; studies = 5; high‐quality evidence); preterm birth less than 28 weeks (RR 1.08, 95% CI 0.75 to 1.55; women = 1920; studies = 5; moderate‐quality evidence); infant birthweight less than 2500 g (RR 0.99, 95% CI 0.90 to 1.08; infants = 4071; studies = 5; I(2) = 76%, moderate‐quality evidence)). No childhood outcomes were reported in the trials. 2 Vaginal progesterone versus no treatment or placebo by dose There were no clear group differences in incidence of preterm birth before 34 weeks (average RR 0.90, 95% CI 0.66 to 1.23; women = 1503; studies = 5; I(2) = 36%; low‐quality evidence). Although fewer births before 34 weeks appeared to occur in the progesterone group, the CIs crossed the line of no effect. Incidence of perinatal death was higher in the progesterone group, although there was considerable uncertainty in the effect estimate and the quality of the evidence was low for this outcome (RR 1.23, 95% CI 0.74 to 2.06; infants = 2287; studies = 3; low‐quality evidence). No studies reported maternal mortality or major neurodevelopmental disability at childhood follow‐up. There were no clear group differences found in any of the other maternal or infant outcomes (preterm birth less than 37 weeks (average RR 0.97, 95% CI 0.89 to 1.06; women = 1597; studies = 6; moderate‐quality evidence); preterm birth less than 28 weeks (RR 1.53, 95% CI 0.79 to 2.97; women = 1345; studies = 3; low‐quality evidence); infant birthweight less than 2500 g (average RR 0.95, 95% CI 0.84 to 1.07; infants = 2640; studies = 3; I(2) = 66%, moderate‐quality evidence)). No childhood outcomes were reported in the trials. For secondary outcomes, there were no clear group differences found in any of the other maternal outcomes except for caesarean section, where women who received vaginal progesterone did not have as many caesarean sections as those in the placebo group, although the difference between groups was not large (8%) (RR 0.92, 95% CI 0.86 to 0.98; women = 1919; studies = 5; I(2) = 0%). There were no clear group differences found in any of the infant outcomes except for mechanical ventilation, which was required by fewer infants whose mothers had received the vaginal progesterone (RR 0.70, 95% CI 0.52 to 0.94; infants = 2695; studies = 4). AUTHORS' CONCLUSIONS: Overall, for women with a multiple pregnancy, the administration of progesterone (either IM or vaginal) does not appear to be associated with a reduction in risk of preterm birth or improved neonatal outcomes. Future research could focus on a comprehensive individual participant data meta‐analysis including all of the available data relating to both IM and vaginal progesterone administration in women with a multiple pregnancy, before considering the need to conduct trials in subgroups of high‐risk women (for example, women with a multiple pregnancy and a short cervical length identified on ultrasound).

Objective The effect of providing antenatal dietary and lifestyle advice on secondary measures of maternal anthropometry was evaluated and their correlation with both gestational weight gain and infant birth weight was assessed. Methods In a multicenter, randomized controlled trial, pregnant women with BMI of ≥25 kg/m2 received either Lifestyle Advice or Standard Care. Maternal anthropometric outcomes included arm circumference, biceps, triceps, and subscapular skinfold thickness measurements (SFTM), percentage body fat (BF), gestational weight gain, and infant birth weight. The intention to treat principles were utilized by the analyses. Results The measurements were obtained from 807 (74.7%) women in the Lifestyle Advice Group and 775 (72.3%) women in the Standard Care Group. There were no statistically significant differences identified between the treatment groups with regards to arm circumference, biceps, triceps, and subscapular SFTM, or percentage BF at 36-week gestation. Maternal anthropometric measurements were not significantly correlated with either gestational weight gain or infant birth weight. Conclusions Among pregnant women with a BMI of ≥25 kg/m2, maternal SFTM were not modified by an antenatal dietary and lifestyle intervention. Furthermore, maternal SFTM correlate poorly with both gestational weight gain and infant birth weight.