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In gestational diabetes, tighter glycemic targets could influence outcomes for mother and child

Results of the TARGET trial provide insight into the effects of tight glycemic targets versus less tight targets on maternal and perinatal outcomes among women with gestational diabetes.

New research from investigators in New Zealand is providing new insight into the effects of inadequate glycemic control among mothers with gestational diabetes during pregnancy on maternal and perinatal morbidity.

Named the TARGET Trial, results of the stepped-wedge, cluster-randomized trial, which randomized patients from 10 hospitals in New Zealand, suggest reaching glycemic targets was not associated with a reduction in the risk of a large for gestational age infant, but investigators pointed out reaching target was associated with a reduction in serious infant morbidity and an increase in serious maternal morbidity.

“This unique trial allowed for the sequential implementation of the newly, recommended tighter treatment targets for women with gestational diabetes and assessed if there are true benefits, without harm, to use of tighter treatment targets,” said lead investigator Caroline Crowther, of the University of Auckland, New Zealand.

Launched with the intent of further examining the effects of glycemic control thresholds on outcomes for both mother and child, Crowther and a team of colleagues designed the TARGET trial as a stepped-wedge, cluster-randomized trial to be conducted at 10 maternity hospitals in New Zealand. With the primary inclusion criteria being a diagnosis of gestational diabetes, investigators identified 1100 women with gestational diabetes between May 2015 and November 2017 for inclusion in the trial.

Per study protocol, all sites used less stringent targets (fasting plasma glucose [FPG] <5.5 mmol/L, 1-hour <8.0 mmol/L, 2 hour postprandial <7.0 mmol/L) and, every 4 months, 2 hospitals moved to use tighter targets (FPG <5.0 mmol/L, 1-hour <7.4 mmol/L, 2 hour postprandial<6.7 mmol/L).The primary outcome of interest for the trial was giving birth to a large for gestational age infant and secondary outcomes of interest pertained to maternal and infant outcomes, which were assessed in intention-to-treat analyses. The 1100 women included in the trial birthed 1108 infants. Among the 1100, 598 women who birthed 602 infants used the tighter glycemic targets and 502 women who birthed 506 infants used less tight targets.

Upon analysis, results indicated the rate of large for gestational age infants was similar among both groups, occurring among 14.7% of mothers using the tighter targets and 15.1% of mothers using the less tight targets (aRR, 0.96 [95% CI, 0.66-1.40]; P=.839). In analyses adjusted for gestational age at diagnosis of gestational diabetes, BMI, ethnicity, and history of gestational diabetes, investigators found incidence of a composite outcome for infant health that included perinatal death, birth trauma, or shoulder dystocia was lower among those with tighter glycemic targets (aRR, 0.23 [95% CI, 0.06-0.88]; P=.032), but no differences were observed for other infant secondary outcomes apart from shorter stays in intensive care (P=.041).

Additional analysis suggested tighter glycemic control was associated with an apparent increase for the composite serious health outcome that included major hemorrhage, coagulopathy, embolism, and obstetric complications (aRR 2.29 [95% CI, 1.14-4.59]; P=.020). Investigators also pointed out there were no differences observed between trial groups for preeclampsia, induction of labor, or cesarean birth, but more women using tighter targets required pharmacological treatment (aRR, 1.20 [95% CI, 1.00-1.44]; P=.047).

This study, “Tighter or less tight glycaemic targets for women with gestational diabetes mellitus for reducing maternal and perinatal morbidity: A stepped-wedge, cluster-randomised trial,” was published in PLOS Medicine.

This article was published by our sister publication Endocrinology Network.