Patient's temperament
From November 2019 to July 2023, 428 participants were registered at eight UK centres and randomized under a controlled diet (n = 211; Standard energy content, 2,000 kcal d-1) or intervention diet (n = 214; Energy limit, 1,200 kcal d-1 (Figure 1 and extended data Figure 1). Overall, the two groups were balanced in terms of baseline characteristics (Table 1). Characteristics of participants with missing maternal data (n = 38) or newborn (n = 45) Primary endpoints were similar to endpoints across the trial population (Extended Data Tables 1 and 2).
Participants were randomized into trial groups after complete baseline measurements and complete the number details achieved for maternal and neonatal primary outcomes.
During trial, 59 participants withdrew from the study (29 (13.7%) from the control group and 30 (14.0%) from the intervention group). A further 53 patients stopped receiving diet boxes before birth, but remained in the study (13.3% control group, 11.7% intervention group). This usually occurs 36 weeks later (after collecting maternal endpoint data), with reasons for which participants (less than 1-2 weeks) tired of food in light of imminent delivery. Ta. Especially if hospitalization is required, pregnancy complications such as pre-lamp syndrome or blackmailed premature birth. Hunger; high glucose concentrations and stress concerns (Extended Data Table 3).
Participants received a mean dietary intervention of 6.15 (SD 3.24) weeks in the control arm and 6.35 (3.29) weeks in the intervention group (Extended Data Table 4). When 10-day baseline data collection was allowed, the average number of weeks between registration and delivery was 8.95 (SD 1.80) in the control and 9.27 (1.85) in the intervention group (Extended Data Table 4). 68.9% in the control group and 68.8% in the intervention group. Satisfaction levels were consistent across the trials, with most participants very satisfied or satisfied with food quality (85% control group, 81% intervention group, Supplementary Table 1).
Key Results
There was no evidence of a difference in maternal weight change over 36 weeks. Key maternal outcomes between groups (intervention +0.39 kg (4.23), control +0.54 kg (4.17), baseline-adjusted differential intervention and control; Beta (Adjusted effect size) -0.20 (95% confidence interval (CI) -1.02, 0.61); p = 0.623;Table 2). If participants with preterm birth are included in the adjustment for gestational age, if multiple assignments (Extended Data Tables 5 and 6) were used, and if the analysis was limited to women who ordered diet boxes for 4 weeks or more (gestational age) (if included in adjustments for the results) were not affected. Extended Data Table 7).
No significant differences were observed in standardized birth weight (growth) between the intervention and control groups for primary neonates (0.45 (1.04) vs. 0.44 (0.91). Beta 0.005 (95% CI -0.19, 0.20); p = 0.962; Table 2).
Secondary results
Providing a low-energy diet reduced the requirement for long-acting insulin therapy (39.2% control, 27.5% intervention, odds ratio (OR) 0.36 (95% CI 0.18–0.70); p = 0.003; Necessary (NNT) 8.5) for treatment in 36 weeks (Table 3). The effects of interventions on long-acting insulin requirements were not affected by enrollment, education, ethnicity, deprivation score, maternal age or maternal BMI at the research center (Figure 2). There was no evidence of differences in metformin or short-acting Plandall insulin, delivery modality, blood pressure, or continuous glucose monitoring metric requirements over 36 weeks of the study group (Table 3). Postnatal hemoglobin A1C (HBA1C) was significantly lower in the intervention group after adjusting baseline HBA1C and research centers: median HBA1c (control group)n = 36) Interquartile range (IQR)) 40.0 (36.5–42.0) mmol mol– –1;Intervention group (n = 27) 37.0 (37.0–40.0) mmol mol– –1. Percentage: Control group 5.8 (5.5–6.0)%; Intervention group 5.5 (5.5–5.8)%; Beta -2.36 mmol mol– –1 (95% CI -4.46, -0.26); p = 0.029; -0.22% (95%CI -0.41, -0.02); p = 0.029 (Table 3). Outcomes from core outcomes of diabetes during pregnancy are provided (Table 3 and Supplementary Table 2). Maternal health-related quality of life was stable throughout the study (Supplementary Table 3).
Post hoc subgroup analysis determines the interaction effect of participant traits on the efficacy of interventions against long insulin requirements. Subgroup analyses were conducted for maternal baseline BMI, education, ethnicity, socioeconomic status, maternal age and research centers. Estimated effect sizes were calculated using unadjusted logistic regression and are presented as ORs for each subgroup of 95% CI. Exchange p value(p All subgroup interactions >0.05) show no statistically significant interactions with subgroups. IMD, multiple deprivation index. n This represents the number of participants with that characteristic of the total number of participants in the trial group that requires long-acting insulin.
There was no evidence of a large age (LGA) rate, neonatal intensive care unit (NICU) hospitalization, estimates of gestational age at birth or significant differences in cerebral blood C peptide concentrations between the test groups (Table 3).
Safety Results
There was a similar number of small age (SGA) infants between the test arms, but this was within the expected limits (Table 3). The proportion of LGA, appropriate age (AGA) and SGA infants were 18.4%, 77.9%, and 3.7% in the control group, and 20.3%, 74.5%, and 5.2% in the intervention group, respectively.
Exploratory results
Exploratory analyses were conducted to assess the effects of weight loss. Data were treated as a cohort and were divided into two groups according to weight loss or weight gain during the study. The proportion of participants who lost weight did not differ statistically between the intervention and control groups (Supplementary Table 4).
Women who lost weight (154 of 389; 39.6%) had higher BMI at the time of enrollment (37.05 kg m– –2 34.58 kg m versus (6.29)– –2 (6.22); Beta 2.19 kg (95% CI 0.93, 3.50; p = 0.001) and was more likely to take metformin (or 2.25 (95% CI 1.16, 4.38). p = 0.017) 36 weeks (Table 4). Women who lost weight showed an average weight change of -3.01 kg (3.60) from enrollment to 36 weeks of pregnancy compared to +2.75 kg (2.74) of women who gained weight (Table 4) .
Weight loss was associated with significantly improved range time (80.40% (15.76) vs. 71.08% (19.27). Beta6.53% (95%CI 2.06, 11.02); p= 0.004), continuous glucose monitoring (CGM) average glucose (5.63 mmol l– –1 (0.68) vs. 5.94 mmol l– –1 (0.86); Beta-0.22 mmol l– –1 (95%CI -0.41, -0.02); p= 0.028); 101.46 mg dl– –1 (12.16) vs. 106.89 mg dl– –1 (15.41); Beta-3.92 mg dl– –1 (95%CI -7.41, -0.43); p= 0.028). Systolic blood pressure was significantly reduced even in women who lost weight (116.58 mmHg (12.61) compared to 119.34 mmHg (13.49). Beta-2.87 mmHg (95% CI -5.49, -0.25); p= 0.032) (Table 4).
Late pregnancy weight loss was associated with a lower proportion of LGA infants (OR 0.52 (95% CI 0.29, 0.93). p= 0.027;Table 4). The proportions of LGA, AGA, and SGA were 22.2%, 72.6%, and 5.2% in the weight gain group, and 15.4%, 81.9%, and 2.7% in the weight loss group, respectively. The number of SGA infants was within the expected limits for both groups. The effect of weight loss on LGA appeared to be mediated through improvement of cytoemia at 36 weeks. When the model was adjusted for maternal range at 36 weeks, the association between LGA and weight loss was no longer significant (or 0.90 (95% CI 0.41, 1.97). p= 0.787).
Late pregnancy weight loss is maintained after birth and is associated with weight loss (Beta-3.34 kg (95% CI -4.85, -1.82); p<0.001) and BMI (Beta-1.25 kg m– –2 (95% CI -1.80, -0.70); p<0.001) 3 months postpartum (Table 4). Late pregnancy weight loss was associated with improved postnatal metabolic health, including improvements in HBA1c (Beta-3.64 mmol mol– –1 (95% CI -5.70, -1.57); p= 0.001; Beta-0.33% (-0.52, -0.14); p= 0.001).
Relationship between weight loss and CGM time in the CGM range (TIR) (3.5-6.7 mmol l– –1), LGA and postnatal HBA1C were not affected by maternal BMI at enrollment, education, ethnicity, deprivation score, maternal age or research center (Extended Data Figure 2).
Participants taking metformin at 36 weeks of pregnancy were more likely to lose weight (or 2.01 (1.19–3.40; p= After adjustment of the trial arm and research center). However, results from weight loss analysis were consistent in size and orientation, even after additional adjustments for metformin use. After adjustment for metformin use in 36 weeks of pregnancy in addition to the research center and study group, participants in the weight loss group had evidence of a decrease in infant LGA (OR 0.48 (95% CI 0.24, 0.95) . p= 0.034), lower maternal systolic blood pressure (Beta-3.00 mmHg (95% CI -5.75, -0.25); p= 0.033), decrease in maternal mean CGM glucose (Mg DL)– –1: Beta-3.94 mg dl– –1 (95%CI -7.63– -0.25); p= 0.037; mmol l– –1: Beta-0.22 mmol l– –1 (95%CI -0.42, -0.01; p= 0.037), increased maternal TIR over 36 weeks (Beta6.22% (95%CI 1.47, 10.97); p= 0.011) and reduction in postnatal HBA1c (mmol mol– –1: Beta-3.78 mmol mol– –1 (95% CI -6.54, -1.010; p= 0.009).
The timescales of weight changes, CGM TIR and mean glucose, and postnatal HBA1C in each study are shown in the expanded data at time points between weight loss and weight gained women. Figure 3.
Sensitivity analysis
Adjustments for gestational age at birth, multiple attribution, and maternal dietary adherence did not alter primary outcomes in neonates (Extended Data Tables 5-7).
Post-hoc analysis
We evaluated whether this subset represents a larger cohort, as enrollment and postnatal HBA1C is only available in a subset of participants due to COVID-19 restrictions (Supplementary Table 5). Participants with HBA1C at both time points were involved in maternal age, BMI, ethnicity, parity, baseline HBA1C (where available), oral glucose tolerance test (OGTT) results or baseline CGM Metric. It was not statistically different from those. However, it is less likely to be a degree (56% vs. 46%), smokers (3% vs. 12%), and more likely to be diagnosed previously (average 20.5 vs. 23.3 weeks), and long-acting insulin at enrollment is taking (40% vs. 21%).
Comparing groups categorized according to the presence of weight gain (>1 kg body weight change), body stability (±1 kg of body weight change), and weight loss (>1 kg body weight loss), I'm now 36 weeks pregnant (Supplementary Table 6). Weight loss was associated with improved postnatal and postnatal cytoemia and a lower likelihood in LGA infants, compared to the weight-stable group.