Study design
One hundred-seventeen pregnant women with false-positive early GDM were selected from the TTIGDM study, and 1774 pregnant women with NGT were selected among pregnant women who delivered neonates after 22 weeks of gestation. These populations were then compared. The protocol for this research project has been approved by a suitably constituted Ethics Committee of the institution and it conforms to the provisions of the Declaration of Helsinki. Committee of the Yokohama City University Medical Center, Approval No. F211000053.
Participants
The participants of this study consisted of 117 individuals selected from the TTIGDM study with false-positive early GDM, as defined below, who delivered single neonates after 22 weeks of gestation at the Yokohama City University Medical Center. The TTIGDM study was a prospective cohort trial conducted between January 2018 and December 2019 at five secondary and tertiary medical facilities in Japan. Among patients with high-risk GDM, we targeted pregnant women who underwent a 75 g OGTT prior to 20 weeks of gestation and diagnosed women with GDM if they exceeded IADPSG thresholds defined by one or more of the following: FPG level ≥ 92 mg/dL, 1 h post-prandial glucose ≥ 180 mg/dL, and/or 2 h post-prandial glucose ≥ 153 mg/dL. The definition of high-risk GDM has previously been described in detail. [10]
As shown in Figure 1, the enrolled study participants did not receive any therapeutic intervention until the repetition of the 75 g OGTT at 24–28 weeks of gestation. Pregnant women who met the IADPSG criteria at 24-28 weeks gestation were designated as true GDM patients and initiated therapy. Women diagnosed with GDM in early pregnancy who did not meet the diagnostic criteria during the second OGTT were defined as having false-positive early GDM. Women with false-positive early GDM did not receive any therapeutic intervention during gestation.
Control
The control group comprised 1774 pregnant women diagnosed with NGT by a two-step screening process performed during early and mid-pregnancy and who delivered single neonates after 22 weeks of gestation between January 2018 and December 2019 at the Yokohama City University Medical Center. For the two-step screening process, a 75 g OGTT was performed, with cutoff values of 95 mg/dL during early pregnancy or 140 mg/dL after 50 g glucose challenge test (GCT) during mid-pregnancy.
Study outcomes
We examined maternal characteristics, such as maternal age, pre-pregnancy BMI, and nulliparity rate (%). Pregnancy outcomes included gestational age (weeks), cesarean delivery rate, emergency cesarean delivery rate, gestational weight gain (GWG), birth weight (g), large for gestational age (LGA) rate, small for gestational age (SGA) rate, and rates of hypertensive disorders of pregnancy (HDP). We examined pregnancy and neonatal outcomes, such as the neonatal intensive care unit (NICU) admission rate, neonatal hypoglycemia, respiratory distress syndrome (RDS), and neonatal hyperbilirubinemia, using both univariate and multivariate analyses.
The amount of GWG was defined as the difference between the body weight at delivery and pre-pregnancy body weight. LGA neonates were defined as those with a birth weight greater than or equal to the 90th percentile. On the other hand, SGA neonates were defined as those with birth weights below the 10th percentile. Neonatal hypoglycemia was defined as a blood glucose level of <40 mg/dL. In the false-positive early GDM group, blood glucose level was measured in all neonates after birth. In the NGT group, neonatal blood glucose level was measured only if neonates were SGA or LGA, if NICU admission was required, or if judged necessary by the neonatologist. The presence or absence of hyperbilirubinemia, defined as the need for phototherapy in neonates, was confirmed in all patients of both groups.
RDS was defined by characteristic findings on chest radiographic examination and oxygen requirement within 24 h after birth. Macrosomia was defined as a birth weight exceeding 4000 g. Shoulder dystocia was defined clinically as the presence of difficulty in delivering the shoulder after delivery of the neonate's head and the necessity for some form of treatment or procedure.
Statistical analyses
JMP pro 15 (SAS Institute Inc., North Carolina, USA) was used for statistical analyses. The medians and proportions were compared using the Mann–Whitney U-test and Fisher’s exact test, respectively. The level of statistical significance (p) was set at <0.05. In multivariate analyses, the adjusted regression coefficient (aRC), adjusted odds ratio (aOR), and 95% confidence intervals (CIs) were used.