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.

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..

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.

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.

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.

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.

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.

Associations between diet, the gut microbiome and short chain fatty acids in youth with islet autoimmunity and type 1 diabetes.

AIM: We aimed to characterize associations between diet and the gut microbiome and short chain fatty acid (SCFA) products in youth with islet autoimmunity or type 1 diabetes (IA/T1D) in comparison with controls. RESEARCH DESIGN AND METHODS: Eighty participants (25 diagnosed with T1D, 17 with confirmed IA, 38 sibling or unrelated controls) from the Australian T1D Gut Study cohort were studied (median [IQR] age 11.7 [8.9, 14.0] years, 43% female). A Food Frequency Questionnaire characterized daily macronutrient intake over the preceding 6 months. Plasma and fecal SCFA were measured by gas chromatography; gut microbiome composition and diversity by 16S rRNA gene sequencing. RESULTS: A 10 g increase in daily carbohydrate intake associated with higher plasma acetate in IA/T1D (adjusted estimate +5.2 (95% CI 1.1, 9.2) µmol/L p = 0.01) and controls (adjusted estimate +4.1 [95% CI 1.7, 8.5] µmol/L p = 0.04). A 5 g increase in total fat intake associated with lower plasma acetate in IA/T1D and controls. A 5% increase in noncore (junk) food intake associated with reduced richness (adjusted estimate -4.09 [95%CI -7.83, -0.35] p = .03) and evenness (-1.25 [95% CI -2.00, -0.49] p < 0.01) of the gut microbiome in IA/T1D. Fiber intake associated with community structure of the microbiome in IA/T1D. CONCLUSIONS: Modest increments in carbohydrate and fat intake associated with plasma acetate in all youth. Increased junk food intake associated with reduced diversity of the gut microbiome in IA/T1D alone. These associations with the gut microbiome in IA/T1D support future efforts to promote SCFA by using dietary interventions.

A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial.

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.

Effects of an antenatal dietary intervention in women with obesity or overweight on child outcomes at 3-5 years of age: LIMIT randomised trial follow-up.

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.

Effect of metformin in addition to an antenatal diet and lifestyle intervention on fetal growth and adiposity: the GRoW randomised trial.

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 ).

Skin and subcutaneous fascia closure at caesarean section to reduce wound complications: the closure randomised trial.

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.

In overweight and obese women, fetal ultrasound biometry accurately predicts newborn measures.

INTRODUCTION: The aim of this study was to evaluate the association between fetal ultrasound and newborn biometry and adiposity measures in the setting of maternal obesity. MATERIAL AND METHODS: The study population involved 845 overweight or obese pregnant women, who participated in the Standard Care Group of the LIMIT randomised trial (ACTRN12607000161426, 9/03/2007). At 36 weeks gestation, fetal biometry, estimated fetal weight (EFW) and adiposity measures including mid-thigh fat mass (MTFM), subscapular fat mass (SSFM), and abdominal fat mass (AFM) were undertaken using ultrasound. Neonatal anthropometric measurements obtained after birth included birthweight, head circumference (HC), abdominal circumference (AC) and skinfold thickness measurements (SFTM) of the subscapular region and abdomen. RESULTS: At 36 weeks gestation, every 1 g increase in EFW was associated with a 0.94 g increase in birthweight (95% CI 0.88-0.99; P < 0.001). For every 1 mm increase in the fetal ultrasound measure, there was a 0.69 mm increase in birth HC (95% CI 0.63-0.75, P < 0.001) and 0.69 mm increase in birth AC (95% CI 0.60-0.79, P < 0.001). Subscapular fat mass in the fetus and the newborn (0.29 mm, 95% CI 0.20-0.39, P < 0.001) were moderately associated, but AFM measurements were not (0.06 mm, -0.03 to 0.15, P = 0.203). There is no evidence that these relationships differed by maternal body mass index. CONCLUSION: In women who are overweight or obese, fetal ultrasound accurately predicts neonatal HC and AC along with birthweight.

Maternal cardiometabolic markers are associated with fetal growth: a secondary exploratory analysis of the LIMIT randomised trial.

BACKGROUND: To determine the association between maternal cardiometabolic and inflammatory markers with measures of fetal biometry and adiposity. METHODS: Women included in this exploratory analysis were randomised to the 'Standard Care' group (N = 911) from the LIMIT randomised trial involving a total of 2212 pregnant women who were overweight or obese (ACTRN12607000161426, Date of registration 9/03/2007, prospectively registered). Fetal biometry including abdominal circumference (AC), estimated fetal weight (EFW), and adiposity measurements (mid-thigh fat mass, subscapular fat mass, abdominal fat mass) were obtained from ultrasound assessments at 28 and 36 weeks' gestation. Maternal markers included C reactive protein (CRP), leptin and adiponectin concentrations, measured at 28 and 36 weeks' gestation and fasting triglycerides and glucose concentrations measured at 28 weeks' gestation. RESULTS: There were negative associations identified between maternal serum adiponectin and fetal ultrasound markers of biometry and adiposity. After adjusting for confounders, a 1-unit increase in log Adiponectin was associated with a reduction in the mean AC z score [- 0.21 (- 0.35, - 0.07), P = 0.004] and EFW [- 0.23 (- 0.37, - 0.10), P < 0.001] at 28 weeks gestation. Similarly, a 1-unit increase in log Adiponectin was association with a reduction in the mean AC z score [- 0.30 (- 0.46, - 0.13), P < 0.001] and EFW [- 0.24 (- 0.38, - 0.10), P < 0.001] at 36 weeks gestation. There were no consistent associations between maternal cardiometabolic and inflammatory markers with measurements of fetal adiposity. CONCLUSION: Adiponectin concentrations are associated with measures of fetal growth. Our findings contribute to further understanding of fetal growth in the setting of women who are overweight or obesity.

Can the Bayley Scales of Infant Development at 18 months predict child behaviour at 7 years?

AIM: Infants born preterm (<37 weeks' gestation) are at risk of poor neurodevelopmental outcomes; hence, many neonatal centres routinely follow up infants using the Bayley Scales of Infant Development (BSID), although the predictive validity of the BSID for children born preterm is questionable. Our objective is to evaluate the predictive capacity of the BSID for behavioural functioning at school age of children born preterm. METHODS: Children (n = 657 children born <33 weeks' gestation) were enrolled at birth from five neonatal centres around Australia. A psychologist assessed child development at 18 months using the BSID-II. When children were 7 years (corrected age) of age, parents completed the Strengths and Difficulties Questionnaire, the Behavior Rating Inventory of Executive Function and the Conners 3rd Edition Attention Deficit Hyperactivity Disorder Index. We explored associations between BSID-II at 18 months and behaviour scores at 7 years and examined the interaction effect of the use of an allied health service between the BSID-II and behaviour assessments. RESULTS: For every one-point increase on the BSID-II Mental Development Index, behaviour scores decreased by 0.07 points for the Strengths and Difficulties Questionnaire Total Difficulties (95% confidence interval (CI) -0.10, -0.03), 0.12 points for the Behavior Rating Inventory of Executive Function Global Executive Composite (95% CI -0.21, -0.04) and 0.16 points for the Conners 3rd Edition Attention Deficit Hyperactivity Disorder Index (95% CI -0.26, -0.05). CONCLUSION: The BSID-II at 18 months was weakly associated with parent-reported behaviour at 7 years in children born preterm.

Effects of an antenatal dietary intervention in overweight and obese women on 6 month infant outcomes: follow-up from the LIMIT randomised trial.

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).

Evaluation of a smartphone nutrition and physical activity application to provide lifestyle advice to pregnant women: The SNAPP randomised trial.

Our objective was to evaluate the impact of a smartphone application as an adjunct to face-to-face consultations in facilitating dietary and physical activity change among pregnant women. This multicentre, nested randomised trial involved pregnant women with a body mass index ≥18.5 kg/m2 , with a singleton pregnancy between 10 and 20 weeks' gestation, and participating in 2 pregnancy nutrition-based randomised trials across metropolitan Adelaide, South Australia. All women participating in the SNAPP trial received a comprehensive dietary, physical activity, and behavioural intervention, as part of the GRoW or OPTIMISE randomised trials. Women were subsequently randomised to either the "Lifestyle Advice Only Group," where women received the above intervention, or the "Lifestyle Advice plus Smartphone Application Group," where women were additionally provided access to the smartphone application. The primary outcome was healthy eating index (HEI) assessed by maternal food frequency questionnaire completed at trial entry, and 28 and 36 weeks' gestation. Analyses were performed using intention-to-treat principles, with statistical significance at p = .05. One hundred sixty-two women participated: 77 allocated to the Lifestyle Advice plus Smartphone Application Group and 85 to the Lifestyle Advice Only Group. Mean difference in HEI score at 28 weeks of pregnancy was 0.01 (CI [-2.29, 2.62]) and at 36 weeks of pregnancy -1.16 (CI [-4.60, 2.28]). There was no significant additional benefit from the provision of the smartphone application in improving HEI score (p = .452). Although all women improved dietary quality across pregnancy, use of the smartphone application was poor. Our findings do not support addition of the smartphone application.

The effect of an antenatal lifestyle intervention in overweight and obese women on circulating cardiometabolic and inflammatory biomarkers: secondary analyses from the LIMIT randomised trial.

BACKGROUND: Maternal overweight and obesity during pregnancy is associated with insulin resistance, hyperglycaemia, hyperlipidaemia and a low-grade state of chronic inflammation. The aim of this pre-specified analysis of secondary outcome measures was to evaluate the effect of providing antenatal dietary and lifestyle advice on cardiometabolic and inflammatory biomarkers. METHODS: We conducted a multicentre trial in which pregnant women who were overweight or obese were randomised to receive either Lifestyle Advice or Standard Care. We report a range of pre-specified secondary maternal and newborn cardiometabolic and inflammatory biomarker outcomes. Maternal whole venous blood was collected at trial entry (mean 14 weeks gestation; non-fasting), at 28 weeks gestation (fasting), and at 36 weeks gestation (non-fasting). Cord blood was collected after birth and prior to the delivery of the placenta. A range of cardiometabolic and inflammatory markers were analysed (total cholesterol, triglycerides, non-esterified fatty acids, high-density lipoprotein cholesterol, insulin, glucose, leptin, adiponectin, C-reactive protein, granulocyte macrophage-colony stimulating factor, interferon gamma, TNF-α, and interleukins 1ß, 2, 4, 5, 6, 8, and 10). Participants were analysed in the groups to which they were randomised, and were included in the analyses if they had a measure at any time point. RESULTS: One or more biological specimens were available from 1951 women (989 Lifestyle Advice and 962 Standard Care), with cord blood from 1174 infants (596 Lifestyle Advice and 578 Standard Care). There were no statistically significant differences in mean cardiometabolic and inflammatory marker concentrations across pregnancy and in infant cord blood between treatment groups. Estimated treatment group differences were close to zero, with 95% confidence intervals spanning a range of differences that were short of clinical relevance. There was no evidence to suggest that the intervention effect was modified by maternal BMI category. CONCLUSIONS: Despite our findings, it will be worth considering potential relationships between cardiometabolic and inflammatory markers and clinical outcomes, including longer-term infant health and adiposity. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ( ACTRN12607000161426 ; Date Registered 09/03/2007).

Metformin and dietary advice to improve insulin sensitivity and promote gestational restriction of weight among pregnant women who are overweight or obese: the GRoW Randomised Trial.

BACKGROUND: Obesity is a significant global health problem, with approximately 50% of women entering pregnancy having a body mass index greater than or equal to 25 kg/m2. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant. Currently available data from large scale randomised trials and systematic reviews highlight only modest effects of antenatal dietary and lifestyle interventions in limiting gestational weight gain, with little impact on clinically relevant pregnancy outcomes. Further information evaluating alternative strategies is required. The aims of this randomised controlled trial are to assess whether the use of metformin as an adjunct therapy to dietary and lifestyle advice for overweight and obese women during pregnancy is effective in improving maternal, fetal and infant health outcomes. METHODS: Design: Multicentre randomised, controlled trial. INCLUSION CRITERIA: Women with a singleton, live gestation between 10+0-20+0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m2), at the first antenatal visit. Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10+0 and 20+0 weeks gestation using an online computer randomisation system, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth. Treatment Schedules: Women randomised to the Metformin Group will receive a supply of 500 mg oral metformin tablets. Women randomised to the Placebo Group will receive a supply of identical appearing and tasting placebo tablets. Women will be instructed to commence taking one tablet daily for a period of one week, increasing to a maximum of two tablets twice daily over four weeks and then continuing until birth. Women, clinicians, researchers and outcome assessors will be blinded to the allocated treatment group. All women will receive three face-to-face sessions (two with a research dietitian and one with a trained research assistant), and three telephone calls over the course of their pregnancy, in which they will be provided with dietary and lifestyle advice, and encouraged to make change utilising a SMART goals approach. Primary Study Outcome: infant birth weight >4000 grams. SAMPLE SIZE: 524 women to detect a difference from 15.5% to 7.35% reduction in infants with birth weight >4000 grams (p = 0.05, 80% power, two-tailed). DISCUSSION: This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12612001277831 , prospectively registered 10th of December, 2012.