Mother and child health 4.5 years after gestational diabetes mellitus managed using tight or less tight targets for glycaemic control: Post-hoc follow-up study of the TARGET trial

Background Optimal glycaemic targets for women with gestational diabetes mellitus (GDM) are unclear. The aim of this study was to compare maternal and child health 4.5 years after women with GDM had been randomised to use tight or less tight targets for glycaemic control during their pregnancy. Methods and findings The TARGET trial was a stepped-wedge, cluster-randomised trial conducted between May 29, 2015 and November 7, 2017 at 10 hospitals in New Zealand. All hospitals were initially allocated to use less tight glycaemic treatment targets (fasting plasma glucose (FPG) <5.5 mmol/L (<99 mg/dL), 1-hour <8.0 mmol/L (<144 mg/dL), 2 hour postprandial <7.0 mmol/L (<126 mg/dL)) for women with GDM and every 4 months two hospitals were randomised to use tighter targets (FPG ≤ 5.0 mmol/L (≤90 mg/dL), 1-hour ≤7.4 mmol/L (≤133 mg/dL), 2 hour postprandial ≤6.7 mmol/L) (≤121 mg/dL). Women with GDM, blinded to the targets in use, were eligible. The primary outcome was large for gestational age. This is a post-hoc follow-up study of the TARGET randomised trial, conducted from October 2020 to June 2022. We assessed 315/427 (74%) eligible mothers and 313/427 (73%) of their children. Primary outcomes were maternal glycated haemoglobin (HbA1c) and child body mass index (BMI) z-score. Secondary outcomes included maternal cardiometabolic risk, body size, and healthcare utilisation, and for the child, body size, vision, hearing, motor function, and behavioural outcomes. Data were collected from maternal and child health questionnaires, and their health records. Maternal HbA1c results were similar between tight and less tight glycaemic groups (40 mmol/mol standard deviation (SD) 12.6 versus 38 mmol/mol SD 8.8; adjusted mean difference (adjMD) 2.17 (95% confidence interval (CI) −0.26, 4.60; P = 0.080)). Child BMI z-scores were similar between groups (mean z-score 0.83 SD 1.72 versus 0.75 SD 1.48; adjMD 0.12 (95% CI −0.24, 0.48; P = 0.498)), although children in the tight glycaemic group were taller (107.8 cm SD 5.5 versus 106.0 cm SD 5.5; adjMD 1.83 (95% CI 0.58, 3.08; P = 0.004)). Worse child outcomes were seen in the tight glycaemic group for coordination difficulties (31/109, 28.4% versus 21/118, 17.8%; adjusted relative risk (adjRR) 1.66 (95% CI 1.01, 2.73; P = 0.044)), behaviour (likely on the autism spectrum 10/108, 9.3% versus 3/117, 2.6%; adjRR 3.67 (95% CI 1.02, 13.23; P = 0.047)) and total difficulties scores from the strengths and difficulties questionnaire (mean score 8.4 SD 5.1 versus 6.8 SD 4.5; adjMD 1.75 (95% CI 0.51, 3.00; P = 0.006)). The main limitation was the use of questionnaires rather than health professional assessments for some of the outcomes. Conclusions Tight compared to less tight glycaemic targets in women with GDM during pregnancy did not result in lower maternal HbA1c or lower child BMI z-scores 4.5 years later, and may be associated with adverse child motor and behavioural outcomes.