Study Design: Multicentred randomised controlled trial.
Inclusion Criteria: Women with a singleton, live gestation between 10+0-20+0 weeks who are obese or overweight (defined as a body mass index greater than or equal to 25 kg/m2), at their first antenatal visit.
Exclusion Criteria: Women with a multiple pregnancy, or type 1 or 2 diabetes diagnosed prior to pregnancy.
Trial Entry: Eligible women will be identified in the antenatal clinic, given the trial information sheet and counselled by the researcher, before obtaining informed written consent. Randomisation will occur between 10+0 and 20+0 weeks gestation by telephoning the central randomisation service. The randomisation schedule will use balanced variable blocks, and will be prepared by an investigator not involved with recruitment or clinical care. There will be stratification of women according to parity (parity 0 versus parity 1 or more), body mass index at booking visit (BMI 25-29.9 kg/m2 versus BMI ≥ 30 kg/m2), and collaborating centre.
Treatment Schedules: Eligible women will be randomised and allocated a study number corresponding to either the 'Dietary and Lifestyle Advice Group' or the 'Standard Care Group'.
Women randomised to the Dietary and Lifestyle Advice Group
will receive a comprehensive intervention to limit weight gain in pregnancy that includes a combination of dietary, exercise and behavioural strategies, delivered by a research dietician and trained research assistants. Women will be provided with dietary advice consistent with current Australian dietary standards,[31
] that maintains a balance of carbohydrates, fat and protein. Women will be encouraged to reduce their intake of foods high in refined carbohydrates and saturated fats, while increasing their intake of fibre, and promoting consumption of two serves of fruit and five serves of vegetables each day [31
]. Exercise advice will focus on encouraging women to adopt a more active lifestyle, primarily by increasing the amount of walking [32
]. Tailoring of the intervention will be informed by stage theories of health decision making that propose that individuals progress through a series of cognitive phases when undertaking behavioural change [33
Initially, there will be a planning session with a research dietician, in which women are provided with written dietary and activity information, an individual diet and physical activity plan, a food and activity diary, recipe book and example menu plans. Women will be encouraged to set achievable goals for dietary and exercise change, supported to make these lifestyle changes and to self-monitor their progress. Additionally, women will be encouraged to identify potential barriers and enablers to facilitate the implementation of their goals. This information will be reinforced during subsequent inputs at regular intervals during pregnancy, provided by the research dietician (at 28 weeks' gestation) and trained research assistants (via telephone call at 22, 24, and 32 weeks' gestation and a face-face visit at 36 weeks' gestation).
Women randomised to the Standard Care Group will continue to receive their pregnancy care according to local hospital guidelines, which does not currently include routine provision of dietary, lifestyle and behavioural advice.
Follow-up of women in both treatment groups: All women will continue to have their clinical care provided by clinicians at their planned hospital of birth. After birth, information will be obtained relating to birth and infant outcomes from the case notes by a research assistant not involved in the provision of the intervention, and blinded to treatment allocation. Similarly, the postnatal and neonatal forms will be completed for each live born infant after discharge from hospital. Outcomes will be determined at the time of primary hospital discharge or at 6 weeks post-partum, whichever is greater.
Study Endpoints: The primary study outcome is:
• Infant large for gestational age (defined as birth weight ≥ 90th centile for gestational age).
The secondary study outcomes are
1) Adverse outcomes for the infant including preterm birth (defined as birth at less than 37 weeks gestation); mortality (defined as either a stillbirth (intrauterine fetal death after trial entry and prior to birth), or infant death (death of a live born infant prior to hospital discharge, and excluding lethal congenital anomalies)); congenital anomalies; infant birth weight ≥ 4000 grams; hypoglycaemia requiring intravenous treatment; admission to neonatal intensive care unit, or special care baby unit; hyperbilirubinaemia requiring phototherapy; nerve palsy; fracture; birth trauma; shoulder dystocia.
2) Adverse outcomes for the woman
including maternal hypertension and pre-eclampsia (in accordance with recognised Australasian Society for the Study of Hypertension in Pregnancy criteria)[34
]; maternal gestational diabetes (defined as a positive oral glucose tolerance test with fasting blood glucose level ≥ 5.5 mmol/L, or 2 hour blood glucose level ≥ 7.8 mmol/L); need for and length of antenatal hospital stay; antepartum haemorrhage requiring hospitalisation; preterm prelabour ruptured membranes; chorioamnionitis requiring antibiotic use during labour; need and reason for induction of labour; any antibiotic use during labour; caesarean section; postpartum haemorrhage (defined as blood loss ≥ 600 mL); perineal trauma; wound infection; endometritis; use of postnatal antibiotics; length of postnatal hospital stay; thromboembolic disease; maternal death.
Sample Size: The clinical endpoint of infant large for gestational age has been chosen as the primary outcome for this trial. Population studies consistently identify high infant birth weight as a significant, independent factor associated with a 2-3 fold increased odds of obesity at age 4 yrs,[35
] and more accurately assesses size at birth than weight above a particular cut-off value. We estimate the incidence of infant large for gestational age in women eligible for this trial to be 14.4% [37
]. To reduce this by 30% to 10.1% (alpha 0.05; power 80%; two-tailed test), and allowing for 15% loss to follow-up, we will need to recruit a total of 2,180 women.
Analysis and Reporting of Results: The initial analysis will examine baseline characteristics of all randomised women, as an indication of comparable treatment groups. Outcome comparisons for women and infants will be analysed for the primary and secondary outcomes on an "intention to treat" basis, according to treatment allocation at randomisation to either dietary and lifestyle group or standard care group. The relative risks and 95% confidence intervals will be reported for the major outcomes, and the number needed to treat to prevent one adverse outcome will be calculated. Regression techniques will be used to examine the influence of prognostic factors on the major outcomes. Pre-specified secondary analyses will explore the effect of maternal BMI, gestational weight gain and parity on clinical outcomes.
Approval to conduct this study has been obtained from the following research and ethics committees: Women's and Children's Hospital (Adelaide, South Australia); Flinders Medical Centre (Adelaide, South Australia); Lyell McEwin Health Service (Adelaide, South Australia); The Queen Elizabeth Hospital (Adelaide, South Australia).