A randomized feasibility trial of time-restricted eating during pregnancy in people with increased risk of gestational diabetes

This study was the first experimental investigation of adherence rates to a TRE intervention during pregnancy. Our results largely support our main hypothesis that 5 weeks of TRE is feasible during pregnancy, as the participants adhered to a ≤ 10 h/day eating window on ~ 5 days/week throughout the intervention period. The average eating window was just under 10 h/day in the intervention period, representing a 2-h reduction from baseline. Despite this reduced eating window, we failed to detect any beneficial effects of TRE on glycemic control or other metabolic outcomes.

The adherence rate to TRE in our study was 67%, which is somewhat lower than the rates reported in other studies of TRE involving non-pregnant individuals and with a daily eating window of maximum 10 h^13,16. We have previously showed that reproductive-aged women with overweight/obesity managed to adhere to an identical TRE intervention on 6.2 days/week (89%) for 7 weeks¹³, while Anton and colleagues reported an adherence rate of 84% to a similar 4-week intervention among overweight, sedentary adults aged 65 years or older¹⁶. All these studies had a relatively short intervention period, but Lin et al.¹⁷ reported 87% adherence to an 8-h TRE protocol over the course of a 12-month study in participants with obesity. The main reason for lower adherence in the present study is likely the pregnant state of our participants. In pregnancy, nausea and preference of specific foods (cravings) are common, especially in the first trimester. These factors may affect the ability to consume energy only at specific periods during the day as required for TRE. Indeed, a qualitative study on attitudes towards TRE among people who were pregnant or had recently given birth, reported that some were concerned about the baby’s health, nausea, and hunger¹⁴. However, 47% of the participants in that study perceived TRE as safe during pregnancy, but only 24% of them said they would be willing to try a TRE regimen during pregnancy¹⁴.

We report no serious adverse effects of adhering to a 10-h TRE window for 5 weeks and neither do previous studies^{11,13,16,17,18,19,20}. The most commonly reported adverse effects of TRE are nausea, headaches, dizziness, diarrhea, and dry mouth. However, these effects will either diminish over time, or are resolved by increasing water intake^11,16,18. Despite that a 10-h TRE window was found to be feasible in the current study, including participants earlier in pregnancy could yield different results. The mean gestational age in the intervention group in our study was 18.6 weeks (ranging from 12 to 30 weeks) at baseline, whereas nausea is most common in early pregnancy²¹. The on-going BEFORE THE BEGINNING trial will determine the feasibility and effectiveness of TRE also in early pregnancy²².

There was no effect of TRE on any of the measured cardiometabolic outcomes in our study. A reason for this could be that 5 weeks may be insufficient to induce any significant glycemic changes in pregnant individuals²³. However, in non-pregnant individuals, TRE interventions do improve glycemic control after interventions of similar duration^13,18,24. In one study, restricting the window for energy intake to between 08:00 and 16:00 h improved skeletal muscle insulin sensitivity among healthy males after 2 weeks²⁴. Similar results were also seen in a crossover trial involving men with prediabetes, in which 5 weeks of TRE with a 6-h eating window early in the day reduced the concentrations of insulin both in the fasting state and during a 3-h OGTT¹⁸. In both these studies, the window of energy intake was substantially shorter than in the present study, which may explain the different findings. In our previous study involving reproductive-aged women with overweight/obesity, we showed lower nocturnal glucose after 7 weeks of TRE with a 10-h window for energy intake¹³. In contrast to our previous trial, the participants in the present study did not reduce their energy intake during the intervention period.

Concurrent with no change in energy intake or expenditure, 5 weeks of TRE did not affect body weight. Weight loss is often the goal of TRE interventions^11,25,26,27, with improvements in glycemic measures frequently occurring after weight loss¹³. Even if most TRE regimens allow unrestricted intake of energy within the stipulated eating window, people typically reduce their daily energy intake unintentionally, which likely underpins most of the cardiometabolic benefits of TRE²⁸. The weight loss observed after TRE interventions makes it difficult to determine whether there is a weight loss-independent effect of TRE. However, in the study by Sutton and colleagues, in which the participants were provided with standardized meals to maintain energy balance and weight, they observed several improvements in glycemic outcomes¹⁸. Conversely, others have reported reductions in body weight after a TRE intervention without concomitant improvements in measures of glycemic control²⁷. Additionally, we found no change in blood pressure or resting heart rate after the intervention, which is in concordance with findings in similar trials^11,13,27. Conversely, some trials have reported reduced blood pressure following TRE interventions^18,29,30,31.

We placed no restrictions on the timing of the eating window, but we recommended that the participants started their daily energy intake by 09:00 h. On average, participants commenced their daily eating window at 08:43 h and ended it at 18:50 h during the intervention. Placing the eating window early in the day has been shown to improve glycemic outcomes in animals and humans^18,32,33, and it is suggested to be beneficial for glucose metabolism and insulin sensitivity to synchronize meal timing with the circadian rhythm. Implementing an eating schedule synchronized with the body’s natural activity-rest cycles has been shown to lower blood glucose and insulin concentrations^33,34. In pregnant individuals, it was recently shown that consuming > 50% of total daily energy intake between 19:00 and 07:00 h was associated with less desirable glycemic outcomes, including increased fasting glucose and higher 24-h glucose levels³⁵. A previous study by the same research group also indicated that increased maternal night-fasting intervals were associated with decreased fasting glucose in the late-second trimester of pregnancy³⁶. Furthermore, in non-pregnant individuals with overweight or obesity, early TRE has superior effects compared with later TRE in improving glycemic control³⁷.

The participants in our study had increased risk of developing GDM, but none had signs of abnormal glucose metabolism at baseline. A more pronounced effect of TRE on glycemic outcomes would be more likely if the participants’ glucose metabolism was compromised²³. As such, TRE has demonstrated improved cardiometabolic outcomes in people with impaired glucose metabolism, including individuals with the metabolic syndrome, pre-diabetes, or type 2 diabetes^{18,19,31,38,39}.

There are several limitations to this study and the interpretation of results. We had relatively few participants and the intervention period was only 5 weeks. We did not adjust the p-values for multiple comparisons and, therefore, there is a risk of type 1 error. However, several of the between-group changes we observed in ratings of hunger were highly significant, with p-values < 0.001. The participants who volunteered for our study were probably less bothered by nausea than the general population of pregnant people with increased risk of GDM. We recruited participants in either the second or third semester of pregnancy (mean gestational week 19, range 12–30 weeks). While it would have been ideal to recruit all participants at the same stage of pregnancy to investigate the effect of TRE on glycemic outcomes and body weight changes, this was not practical given the constraints of the study. However, our main aim was to assess the adherence to TRE during pregnancy as a measure of its feasibility among pregnant individuals. Due to the randomized design of the study, there was no systematic difference between the groups in gestational length or any other baseline characteristics at the time of inclusion. Furthermore, even if all the participants in our study had increased risk of GDM, not all had a BMI above the healthy range. Since the physiological responses to a dietary intervention may differ according to baseline BMI, future studies should investigate whether TRE can limit gestational weight gain in people with elevated BMI.

It is also possible that the intervention period was too short, that duration of the daily eating window was too long, or that the eating window was placed too late in the day, to impact glycemic control and other cardiometabolic outcomes. Considering the unique physiological state of pregnancy, our results are difficult to compare with studies in non-pregnant populations. Pregnant individuals require special considerations and adjustments, and the metabolic response in pregnant people could differ significantly from that of non-pregnant individuals.