Abstract
Background
Fasting and time-restricted eating (TRE) are popular practices that have health benefits, but may also carry a risk of harm. Little is known about the impact of TRE during pregnancy on the long-term health of offspring beyond the immediate post-natal period.
Methods
We conducted a systematic review and narrative synthesis of research on the health impact of time-restricted eating (TRE) during pregnancy and its potential long-term effects on offspring. We searched three electronic databases on 20 January 2023, and updated the search on 6 May 2024, combining search terms for pregnancy and fasting. Risk of bias was assessed using the ROBINS-E tool. We adhered to PRISMA and Synthesis Without Meta-analysis (SWiM) guidelines and the protocol was registered on PROSPERO (CRD42023387174).
Results
We identified 16 studies with data for 1,895,744 total participants mainly set in countries around or close to the equator, published between 2004 and 2023. All studies focused on fasting during Ramadan, a religious custom practiced among Muslims worldwide that consists of refraining from food and drink from sunrise to sunset, that represents the most studied form of TRE. Outcomes included effects on body size, cognitive performance, disability, respiratory health, child mortality and general health.
Conclusions
Results were consistent with the Developmental Origins of Health and Disease (DOHaD) model, showing offspring health risks associated with exposure to TRE during pregnancy. Body size was the most studied outcome and showed a strong correlation to exposure. The association between exposure and adverse effects appears to be stronger in low-income settings and becomes more apparent as the study sample grows older. Precautions should thus be taken by pregnant mothers when deciding whether to fast or not during their pregnancy. More research is needed to find a safe cut-off for time-restricted eating in different climates and socioeconomic settings.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12889-024-20367-2.
Keywords: Fasting, Time-restricted eating, Pregnancy, Ramadan, Child health, Fetal development
Introduction
Intermittent fasting has been recognised throughout history among all religious traditions as a means of acquiring spiritual and mental purification. Research has also shown that fasting and time-restricted eating have health benefits [1].
The most researched form of fasting is related to the practice of an Islamic annual periodic fasting during the month of Ramadan. This specific fast lasts from dawn until sunset during which the one fasting must refrain from eating, drinking, smoking, and sexual activity. According to scientific terminology Ramadan fasting can be categorized as periodic time-restricted eating (TRE); it is a type of diurnal intermittent fasting [2]. A variety of other intermittent fasting regimens are also practiced worldwide, such as complete alternate day fasting, or the 5:2 diet which involves fasting for two days and eating normally for the rest of the week [3].
Ramadan is a religious custom that a large proportion of the human population partake in. It can represent a form of natural experiment and thus be useful in population-based research where controlled studies are less feasible. Although most religious scholars agree that pregnant women ought to be exempt from fasting during Ramadan due to possible health risks for the fetus, women might choose to fast for a variety of reasons, thereby exposing their children to TRE in utero [4].
Observations from famines have firmly established that starving during pregnancy has negative effects on the fetus [5]. However, contrary to starvation, TRE presents a milder reduction in nutrient intake. Nevertheless, metabolic changes have been observed during Ramadan fasting, leading to a lack of essential nutrients and to temporary dehydration [6, 7]. Although previous studies have reported effects on both pregnant women and newborn babies with regards to Ramadan, limited research exists on long-term effects on the offspring beyond the immediate postnatal period.
This systematic review aims to explore the long-term effects on offspring of TRE during pregnancy analyzed according to the Developmental Origins of Health and Disease (DOHaD) model.
Methods
We conducted the review in accordance with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines 2020 [4]. The protocol was registered on PROSPERO on 2 January 2023 (CRD42023387174).
Our inclusion criteria were:
Reports published after the year 2000.
English language only.
Any quantitative study design matching population, exposure, and outcome.
Population: children, adolescents, and adults.
Exposure: time-restricted eating in utero.
Human studies only.
The outcomes were iteratively identified during data extraction as we did not know in advance which of these had been studied.
We searched three electronic databases on 20 January 2023, and updated the search on 6 May 2024: Embase, MEDLINE, and The Cochrane Central Register of Controlled Trials (CENTRAL). We used Google Scholar for an initial scoping overview and to search grey literature. The full search strategy is available in Additional file 1.
After automated removal of duplicates, two reviewers screened each record independently using Covidence review management software. Initial screening composed of reading titles and abstracts of each record. Any conflicts were resolved through discussion between these two reviewers. Thereafter, two reviewers independently screened full-text articles, with disagreements resolved through consultation with a third reviewer.
We designed a data extraction template using Covidence to extract data. We used an open template for collecting the outcomes since they were not defined in advance. The iteratively identified outcomes included disability, cognitive performance, body size, cardiovascular fitness, offspring fetal growth, general health, child mortality, respiratory conditions, and coronary heart disease. Two reviewers independently extracted data, resolving disagreements by discussion and consultation with a third reviewer. Any assumptions made about missing or unclear information were addressed in the quality assessment and discussed between the reviewers.
The Risk of Bias in Non-randomized Studies - of Exposures (ROBINS-E) tool was used to assess risk of bias for each included study, using a template on Covidence [8]. Two reviewers assessed each study independently categorising each domain as low risk, some concerns, high risk, or very high risk of bias. Differences between reviewers were resolved through discussion and consultation with a third reviewer.
The synthesis process was conducted as a narrative Synthesis Without Meta-analysis (SWiM), following a 9-step extension of the PRISMA guidelines, as there was insufficient data and outcomes were too disparate for a meaningful statistical synthesis [9]. Results were categorised by outcomes grouped under intuitive themes. Data on significant outcome measures was extracted and presented separately for better overview and comparability. Vote counting was the main synthesis method used due to the disparate outcomes in the included studies. The certainty of evidence was not graded through a framework such as GRADE since it is difficult to do so when vote counting.
Results
Search results
Database searching returned 3,728 reports, of which 3,305 were screened after removal of duplicates. 3,255 reports were excluded at the title/abstract stage, leaving 50 reports for full-text review. 16 reports met criteria for inclusion in the review. The most common reason for exclusion was studies having no long-term offspring outcomes. Figure 1 presents the PRISMA diagram.
Fig. 1.
PRISMA diagram showing search and study selection process
Study characteristics
14 reports were full articles, and two were conference proceedings. Among the included studies one was set in a rural area, five in urban areas, and ten in mixed settings. 11 were set in a low- or middle-income country, three in high-income countries, and two reports collected information from more than one country. Data were included for 1,895,744 total participants and sample size ranged from 191 to 759,799 participants. Table 1 presents a summary of characteristics of included studies.
Table 1.
Characteristics of included studies
| Author | Year | Country | Setting | Participants | Study design | Fasting definition | Outcomes |
|---|---|---|---|---|---|---|---|
| Van Ewijk | 2013 | UK | Mixed | 222,000 children | Cohort study (conference abstract) | Intention-to-treat | cognitive performance |
| Loney | 2014 | United Arab Emirates | Urban | 881 adolescents | Cohort study (conference abstract) | Intention-to-treat | body size, cardiovascular fitness |
| Azizi | 2004 | Iran | Urban | 191 children | Cohort study | Self-reported | cognitive performance |
| Alwasel | 2011 | Saudi Arabia | Urban | 967 babies | Cross sectional study | Intention-to-treat | offspring fetal growth |
| Van Ewijk | 2011 | Indonesia | Mixed | 29,695 people | Cohort study | Intention-to-treat | general physical health, diabetes, coronary heart disease, body size |
| Van Ewijk | 2013 | Indonesia | Mixed | 14,120 people | Cohort study | Intention-to-treat | body size |
| Alwasel | 2013 | Tunisia | Urban | 1321 babies | Cross sectional study | Intention-to-treat | offspring fetal growth |
| Schoeps | 2018 | Burkina Faso | Rural | 41,025 children | Cohort study | Intention-to-treat | child mortality |
| Pradella | 2018 | Indonesia | Mixed | 28,489 people | Cohort study | Intention-to-treat | respiratory condition |
| Karimi | 2018 | 37 countries | Mixed | 308,879 children | Cohort study | Intention-to-treat | body size |
| Kunto | 2019 | Indonesia | Mixed | 21,723 children | Cohort study | Intention-to-treat | body size |
| Chaudhry | 2021 | Pakistan | Mixed | 179,943 children | Cohort study | Intention-to-treat | body size |
| Karimi | 2021 | Iran | Urban | 4931 children | Cohort study | Intention-to-treat | body size |
| Majid | 2019 | Indonesia | Mixed | Birth weight 559 observations (females) and 624 (males) Ravens CPM scores 1693 (females) and 1821 (males) for 8–15 year olds math test scores 1696 (females) and 1825 (males) for 8–15 year olds hours worked 3181 (females) and 4599 (males) for 18–65 year olds earnings 2419 (females) and 4019 (males) for 18–65 year olds | Cohort study | Intention-to-treat | cognitive performance |
| Chu | 2023 | 56 countries | Mixed | 759,799 children | Cohort study | Intention-to-treat | body size |
| Chaudry | 2022 | Pakistan | Mixed | 277,000 adults | Cohort study | Intention-to-treat | disability |
Defining time-restricted eating
All sixteen reports examined fasting during Ramadan; an annually recurring intermittent, periodic fast categorised as TRE.
Only one study tried to identify mothers that had actually fasted during Ramadan, by distributing questionnaires among students of fifteen Islamic primary schools in Tehran asking the mothers about fasting habits throughout all their pregnancies [10].
The rest of the studies used an intent-to-treat (ITT) approach, in which all study subjects were included by labeling Ramadan as a natural experiment and implicitly assuming that all Muslim mothers who are pregnant during Ramadan, do fast.
Two studies were intergenerational examining both in-utero exposure of the mother and the child [11, 12].
The effects of seasonality
Since Muslims follow the lunar calendar, Ramadan moves back 11 days in the Gregorian calendar each year with a full circulation being fulfilled after 33 years. This affects which season Ramadan occurs in, except for countries on the equator. The amount of daylight hours, and thus fasting length, is therefore strongly dependent on both latitude and seasonality.
To distinguish the effects of Ramadan from those of the season of the year the two intergenerational reports conducted a regression analysis after determining the quarters of the year during which each mother was exposed to Ramadan in utero [11, 12]. Another report also used regression analysis to determine seasonal effects [13]. Five studies were conducted in Indonesia, located at the equator where daylight hours and thus length of fasting is about the same each year: approximately 13.5 h [14–18]. One report was from Burkina Faso, a country located close to the equator [19]. In the two Iranian studies daylight hours and thus exposure to fasting was calculated [10, 20]. In another study that included 37 countries, the latitude was used to calculate hours of daylight corresponding to the amount of exposure [21]. One study relied on a long enough time-series to be able to distinguish the impact of Ramadan from seasonal-calendar effects [22]. Among the two conference abstracts, one had no mention of seasonality, while the other used seasonal patterns among non-Muslim ethnic groups, who have the same season-of-birth patterns but cannot have been exposed to Ramadan in a ‘‘difference-in-differences’’ estimation [23, 24].
Only one report failed to take seasonality into account in its analysis altogether [25].
In-utero exposure
All studies considered an average pregnancy to last 266 days, except for two studies using 270 days [20, 21].
Three cohort studies included in the case group only those that had been exposed to a full month of fasting, i.e. a full Ramadan [14, 15, 20]. In another cohort study the mothers had to fast for at least 27 days during the pregnancy to be included, which was met by 12% of the 2000 mothers answering the initial questionnaire [10]. One study did not specify inclusion criteria regarding length of exposure [13]. The two intergenerational cross-sectional studies examined whether the mothers had been in utero during Ramadan. The mother’s date of birth was used to identify the trimester of exposure; those born and conceived during Ramadan were included. Both the reports also examined whether the children were exposed in utero [11, 12].
A total of eleven studies, including the two cross-sectional studies, assigned Ramadan exposure in utero based on a calculation of whether there was any overlap between Ramadan and gestation. In other words, those partially exposed; conceived and born during Ramadan, were also included in these reports [16–19, 21–25].
How the partially exposed were treated in the analyses differed between studies. One report used a dichotomous approach of exposed or not [15]. Four studies used in their analysis four categories: the three trimesters, and a control group. Two of these studies excluded those conceived and born during Ramadan [14, 20]. while the other two incorporated the partially exposed into the first and third trimesters respectively [11, 12]. Two studies divided the sample into five categories: conceived during Ramadan, the three trimesters, and a control group [23]. Three studies divided the sample into six categories: conceived, born, the three trimesters, and a control [16–18]. One study used seven categories: certainly not exposed, probably not exposed, conceived during Ramadan, the three trimesters, and born during Ramadan [19]. Two studies classified exposed samples by month of gestation from zero to nine [13, 25].
Pre-term and post term safe margins
Six studies applied a safe margin for post term births by dropping from the data all those that were conceived three weeks after Ramadan [14–19]. Five of the studies applied exactly 21 days as their safe margin while one chose to apply 20 days [19]. One report considered potential misassignment due to pre-term birth. Children whose estimated conception month coincided with Ramadan were excluded as well as those partially exposed to Ramadan during their birth month [20]. Nine reports either applied no safe margin or did not mention it for either pre- or post term births [10–13, 21–25].
Outcomes
Outcomes are presented below in a narrative-synthesis format. Table 2 presents a summary of offspring health outcomes across the included studies, categorised by stage of exposure. Table 3 presents quantitative outcome data extracted from the included studies, categorised by outcome type.
Table 2.
An overview of offspring health outcomes categorized by stage of exposure to TRE in pregnancy
| Conceived during Ramadan | 1st trimester | 2nd trimester | 3rd trimester | Born during Ramadan | |
|---|---|---|---|---|---|
| Underweight | X | X | X | X | |
| Stunting | X | X | X | ||
| Cognitive Performance | X | ||||
| Respiratory Health | X | X | X | X | |
| Cardiovascular Health | X | X | |||
| Offspring Fetal Growth | X | ||||
| Child Mortality | X | X | X | ||
| General Health | X | X | X | X | |
| Sight | X | ||||
| Hearing | X | ||||
| Communication | X | ||||
| Memory | X | ||||
| Mobility | X |
The table above provides an overview of the health outcomes based on trimester of exposure. Various adverse effects are present in every trimester. The first and second trimesters correlate with the highest number of adverse outcomes, whereas the children born during Ramadan have the least amount of adverse effects
Table 3.
Quantitative outcome data organised by outcome type
| Outcomes | Results |
|---|---|
| Offspring Fetal Growth, exposed mothers |
Males: 1.2 cm taller (p = 0.005) [11]. Females: 0.4 week shorter gestation period (p = 0.04) [11]. Sex-adjusted mean weight: -93 g (p = 0.003) [12]. Sex-adjusted mean ponderal index: -0.52 kg/m3 (p < 0.001) [12]. Sex-adjusted placental weight: -21 g (p = 0.01) [12]. |
| Disability, exposed males |
Sight: 0. %pts (p < 0.05) [13]. Hearing: 0.4%pts (p < 0.05) [13]. Communication: 0.5%pts (p < 0.01) [13]. Memory: 0.5%pt (p < 0.05) [13]. Mobility: 0.9%pts (p < 0.01) [13]. |
| General Health, exposed males | Age adjusted mean: -0.06 (p < 0.01) [17]. |
| Child Mortality |
Conceived, HR: 1.37 (p = 0.03) [19]. First Trimester, HR: 1.33 (p = 0.01) [19]. Second Trimester, HR: 1.25 (p = 0.05) [19]. |
| Sex Ratio | Male proportion: -0.026 (p < 0.01) [17]. |
| Cognitive Performance |
IQ scores case group: 111 ± 1. Control group: 112 ± 10 [10]. Reduction test scores: -0.05–0.08 SD, 95% CI (p < 0,05) [18]. |
| Respiratory Health | Wheezing: OR: 1.71 (p = 0.156) [16]. |
| Cardiovascular Health |
Pulse pressure (< 45 years), Age-adjusted mean: 0.964 (p < 0.01) [17]. Pulse pressure (all Muslims), Age-adjusted mean: 0.903 (p < 0.01) [17]. Run-time, Conceived: −47.4 s, 95% CI: −77.3, − 17.5 (p < 0.01) [23]. Run-time, Third trimester: −22.2 s, 95% CI: −41.2, − 3.2 (p < 0.05) [23]. |
| Weight |
Adjusted adult BMI: 0.32, 95% CI: −0.57, − 0.06 (p < 0.05) [18]. Waist circumference (female Muslims > 40 years), Age-adjusted mean: -2.164 cm (p < 0.05) [17]. First trimester: underweight OR: 1.203, 95% CI: 1.138, 1.271 (p < 0.001) [22]. Second trimester: underweight OR: 1.125, 95% CI: 1.064, 1.190 (p < 0.001) [22]. |
| Height |
HAZ: −0.105 SD (p < 0.05) [14]. HAZ: −0.091 SD (p < 0.01) [20]. HAZ: −0.073 SD (p = 0.001) [21]. HAZ: OR: 1.225 (p < 0.001) [22]. Conceived: −2.16 cm, 95% CI: −3.96, − 0.35 (p < 0.05) [23]. Exposed: −1.4% points lower probability (p < 0.01) [25]. |
Provides a summary of the outcomes with their associated intervention measures. Abbreviations: %pts: percentage points, HR: hazard ratio, OR : odds ratio, CI: confidence interval, HAZ : height-for-age Z-score, BMI: Body mass index
Effects on body-size
Eight studies revealed associations with exposure to fasting in utero and body size, i.e. stunting or underweight. During the period of conception five reports found correlation with stunting [17, 18, 22, 23, 25]. and two with underweight [17, 18]. During the first trimester five studies found a correlation to stunting [14, 20–22, 25]. while two reports found a correlation to underweight [17, 22]. In the second trimester three studies found associations with stunting [20–22]. and two studies with underweight [18, 22]. Three studies found an association with underweight during third trimester exposure [14, 17, 18, 23]. Three reports explored gender-specific differences and consistently found male offspring stunting to be more pronounced [14, 20, 21].
Effects on cognitive performance
Two of three studies showed that children exposed to Ramadan had lower academic performances. Exposed girls and boys aged between 8 and 15 had a 3% lower mean score on the Raven’s math test in comparison with the non-exposed children [15]. Test scores from Key Stage 1 assessments in England showed that students exposed to Ramadan in the first trimester had an estimated lower test score of 0.05–0.08 SD compared to unexposed Pakistani and Bangladeshi students [24]. An Iranian report showed no significant differences in the crude full-scale IQ-scores [10].
Effects on respiratory health
An Indonesian study showed that exposure in pregnancy independent of pregnancy phase, except for birth during Ramadan was associated with a higher prevalence of wheezing as a proxy for asthma, chronic obstructive airway disease and emphysema, odds ratio 1.71 (p = 0.156). Associations were the most profound in males aged > 40 years and in those who smoke [16].
Effects on cardiovascular health
Another Indonesian study found high pulse pressure, a risk factor for developing atrial fibrillation, occurring more often among young Muslims under the age of 45 exposed to Ramadan in utero, age adjusted mean difference 0.964, (p < 0.01) [17]. An Emirati report found that those exposed completed a mile run quicker: exposed during conception, -47.4s, 95% CI -77.3, -17.5 (p < 0.01); exposed during third trimester, -22.2s, 95% CI, -41.2, -3.2 (p < 0.05), compared to the unexposed [23].
Effects on offspring fetal growth
Two reports, from Saudi Arabia and Tunisia, examined the intergenerational effects of the mothers’ in-utero exposure. A Saudi Arabian study on intergenerational effects found that exposed male offspring whose mothers were in the second trimester of their own gestation during Ramadan were a mean 1.2 cm taller (p = 0.005) compared to babies whose mothers were not in utero during Ramadan. The female offspring had a 0.4 week shorter gestation period (p = 0.04) [11]. A Tunisian study found in a series of newborn babies that those whose mothers were in utero during Ramadan were smaller and thinner, sex-adjusted mean weight − 93 g (p = 0.003) than those whose mothers were not in utero during Ramadan, and they also had smaller placentas, sex-adjusted placental weight − 21 g (p = 0.01). The study found similar results for boys and girls [12].
Effects on child mortality
Decades of surveillance data from northwestern Burkina Faso showed a strong association between Ramadan exposure in utero and increased mortality among children under the age of five. The association was present from conception to the second trimester only among exposed Muslims. The increased five-year-mortality rate for exposed at conception, first, and second trimesters were 37% (p = 0.03), 33% (p = 0.01), and 25% (p = 0.05), respectively. Those exposed during the third trimester and at birth did not have an increased mortality rate [19]. In another report an altered sex ratio among newborns and adults could be seen. After correction for time trends and month of birth, among the exposed, the share of males was about 2.6% lower. This effect was not observed in offspring from non-Muslim mothers who had been in utero during the same periods [17].
Effects on general health
A study examining general health through both objective and subjective parameters found a highly significant negative effect of having been exposed in utero. The effect was seen among those over 45 years of age from conceived to third trimester. For those conceived during Ramadan the effect was 21.1% (p < 0.05), first trimester 15.8% (p < 0.05), second trimester 25.6% (p < 0.001), and third trimester 19.1% (p < 0.05). Furthermore, the effects were only seen in males and when sex was applied to the analysis, no effects were found for non-Muslims [17].
Regarding subjective health, exposed older people judged their own health more negatively in comparison with the unexposed of the same age and sex. Among younger people, this effect could not be seen. Parents however did evaluate the children conceived during Ramadan as sicker and less healthy. Exposure to Ramadan in utero does not seem to affect the risk of suffering from mild health problems though such as headache, nausea, or various infections such as a cold, an eye infection, or a skin infection [17].
Effects on disability
A Pakistani study investigated the impact of exposure to Ramadan on disability among adults between ages 18 and 64. For exposed males a relative increase in impairment was observed in all areas examined: sight with 0.5% points (p < 0.05), hearing 0.4% points (p < 0.05), communication 0.5% points (p < 0.01), memory 0.5% points (p < 0.05) and mobility 0.9% points (p < 0.01). The authors did not specify how these disabilities were measured [13].
Risk of bias assessment
We used the ROBINS-E tool to assess risk of bias in the included studies [10–25]. Five studies were rated as low risk of bias, seven with some concern and two with high risk of bias. Some parts of the results should thus be read with caution, however we decided not to exclude these reports from our analysis since they were the only studies on respiratory health and disability respectively, thus these two reports had no impact on syntheses of findings for other outcome categories. Full risk of bias ratings are available in Additional file 2.
Discussion
Body size was the most studied outcome, probably since it is a good marker for health in later life, and all the reports that controlled for body size showed stunting of those exposed.
Based on earlier studies the cut-off point for some of the positive health effects that time-restricted eating produce is 16 h [26, 27]. To find a similar cut-off point for adverse effects on the fetus would be very helpful. All but one of the studies in our review controlled for seasonality and thus in extension for the length of fasting [25]. Finding a reliable cut-off point for the adverse effects related to pregnancy, however is not possible based on the material at hand, and should be the focus of future research.
Previous research suggests harmful exposure in early life may increase the risk of disease later in life. These risks can carry over into future generations, a concept called the fetal developmental origins of health and disease [28]. The concept explains how epigenetic changes likely play an important role in this development and are thought to be involved in a wide range of diseases and disorders. Females exposed to midgestational fasting in utero experienced significant effects on the growth of their offspring, suggesting such an intergenerational impact. For example, children to mothers who had been in utero during a fasting month, were smaller and thinner in a middle-income country. While the opposite was observed in a high-income country where the gestation period was shorter for girls and the boys grew taller [11, 12]. Depending on the nutritional status of the mother fetuses thus seem to be programmed accordingly, even across generations, which is why the above mentioned concept is sometimes called the fetal programming theory. The theory describes fetal adaptations to adverse conditions in utero as beneficial in the short run, but mainly leading to problems after the reproductive age. The results on general health shows a significant effect on exposed offspring, especially in older males who were exposed during conception and second trimester [17]. It has previously been described how male fetuses are more vulnerable to shortage of nutrition due to their faster growth [29].
Limitations of the included reports
Fifteen out of the sixteen included reports were designed as intention-to-treat studies that minimises the risk for bias and increases the statistical power. The intention-to-treat models include all pregnant mothers and therefore removes the risk of confounding factors affecting the child’s health. Conversely, since not all mothers did fast, the outcomes will necessarily be underestimations both of negative health outcomes and of missing potential health benefits.
According to a British report fasting patterns during pregnancy differ between ethnic groups and depend very much on the mother’s health and her educational level [30]. British women with an Asian background only fasted a full month in 14% of cases while 78% of pregnant women living in Bangladesh did [31]. In Singapore 74% of pregnant women fasted for at least 20 days while 90% of pregnant Yemeni women did [32, 33]. This is important to note as most of the studies in our review are from low- and middle-income countries around the equator, limiting the possibility to apply the results elsewhere.
Several reports used proxies for the studied outcome such as wheezing for asthma and school results for cognitive performance [16, 17]. Many of these proxies are more susceptible to error or misclassification than others. Like the intention-to-treat model described above this can lead to an underestimation of the real effect. We decided to remove one outcome from the results due to a very poor proxy; slow wound healing as a proxy for diabetes mellitus type 2 [15].
Two studies were categorized as prone to a high risk of bias, in one of them neither the inclusion criteria, such as the length of exposure, nor the type of measurements used for the outcomes were specified [13, 16]. We decided not to exclude these reports from our analysis since they had no impact on syntheses of findings as they both were the only studies with their respective outcome. Thus, the results on respiratory health and disability should be read with caution.
Finally a cut-off length for when fasting becomes harmful could not be established since necessary data was unavailable in the included material.
Limitations of the review process
We have attempted to ensure rigour by registering the protocol on PROSPERO, following the PRISMA guidelines and using the ROBINS-E tool to evaluate quality of the included reports. Still some limitations remain such as the heterogenity of the statistical measures across studies and the inconsistency across studies limiting the ability to synthesise and compare findings in a fully coherent or statistical manner. Any narrative synthesis carries the risk of subjective interpretation, less rigorous quantifiying and a lesser degree of reproducibility compared to a statistical synthesis. The PRISMA guidelines and SWiM extension were utilised to adress these issues, adding a higher degree of transparency and a more standardised process.
Implications
The access to nutrition seems to affect the degree of adverse outcomes, making exposure in a low-income setting more dangerous. Regardless of socioeconomic setting however, precaution should be taken by pregnant mothers when deciding whether to fast or not during their pregnancy. In low-income settings exposed children are more prone to be stunted and develop various chronic diseases as they age, while in high-income settings exposed children tend to be overweight and develop disease associated with lifestyle.
We hope that this review will lead to increased equality in healthcare through awareness and policy changes related to a sometimes-overlooked area that involves a large part of the global population. More research is needed to find a safe cut-off for time-restricted eating in pregnant women in different climates and socioeconomic settings.
Conclusions
According to the current systematic review time-restricted eating during pregnancy is associated with adverse long-term effects. Body size was the most studied outcome and showed a strong correlation to exposure. In exposed offspring intergenerational long-term effects were observed. The effects are also more pronounced in males as they grow older which is consistent with the fetal programming theory, also known as DOHaD. Thus, the results are in accordance with previous and well-established research.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Acknowledgements
Not applicable.
Abbreviations
- DOHaD
Developmental Origins of Health and Disease
- ITT
Intention-To-Treat
- PRISMA
Preferred Reporting Items for Systematic Review and Meta-Analyses
- ROBINS-E
Risk of Bias in Non-randomized Studies - of Exposures
- SWiM
Synthesis Without Meta-analysis
- TRE
Time-Restricted Eating
Author contributions
MA conceptualised the study. TJ advised on methodology. MA and DK conducted the search. MA, DK, and TJ conducted the screening. MA and DK conducted the data extraction and risk of bias assessment. MA and DK wrote the original draft with editing by TJ. All authors contributed to and approved of the final manuscript.
Funding
TJ is funded by an NIHR Academic Clinical Fellowship (ACF-2021-17-009). The funders had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Mujahed Abassi and Dilan Karim are joint first authors.
References
- 1.Soliman GA. Intermittent fasting and time-restricted eating role in dietary interventions and precision nutrition. Front Public Health. 2022;10:1017254. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Almeneessier AS, BaHammam AS. How does diurnal intermittent fasting impact sleep, daytime sleepiness, and markers of the biological clock? Current insights. Nat Sci Sleep. 2018;10:439–52. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Patterson RE, et al. Intermittent Fasting and Human Metabolic Health. J Acad Nutr Diet. 2015;115(8):1203–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Ghazal K et al. Ramadan fasting during pregnancy: characteristics and outcomes. Int J Reprod Contracept Obstet Gynecol, 2020. 9(10).
- 5.Roseboom T, de Rooij S, Painter R. The Dutch famine and its long-term consequences for adult health. Early Hum Dev. 2006;82(8):485–91. [DOI] [PubMed] [Google Scholar]
- 6.Leiper JB, Molla AM, Molla AM. Effects on health of fluid restriction during fasting in Ramadan. Eur J Clin Nutr. 2003;57(2):S30–8. [DOI] [PubMed] [Google Scholar]
- 7.Petridou A, et al. Effects of Periodic Religious Fasting for decades on nutrient intakes and the blood biochemical Profile. Nutrients. 2021;13. 10.3390/nu13113963. [DOI] [PMC free article] [PubMed]
- 8.(ROBINS-E Development Group, Higgins J, Rooney MR, Taylor A, Thayer K, Silva K, Lemeris R, Akl C, Arroyave A, Bateson W, Berkman T, Demers N, Forastiere P, Glenn F, Hróbjartsson B, Kirrane A, LaKind E, Luben J, Lunn T, McAleenan R, McGuinness A, Meerpohl L, Mehta J, Nachman S, Obbagy R, O’Connor J, Radke A, Savović E, Schubauer-Berigan J, Schwingl M, Schunemann P, Shea H, Steenland B, Stewart K, Straif T, Tilling K, Verbeek K, Vermeulen V, Viswanathan R, Zahm M, Sterne S. J), Risk Of Bias In Non-randomized Studies - of Exposure (ROBINS-E). Launch version 2022 June.
- 9.Campbell M, et al. Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ. 2020;368:l6890. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Azizi F, et al. Intellectual development of children born of mothers who fasted in Ramadan during pregnancy. International journal for vitamin and nutrition research. Internationale Zeitschrift fur vitamin- und Ernahrungsforschung. J Int de Vitaminologie et de Nutr. 2004;74(5):374–80. [DOI] [PubMed] [Google Scholar]
- 11.Alwasel SH, et al. Sex differences in birth size and intergenerational effects of intrauterine exposure to Ramadan in Saudi Arabia. Am J Hum Biology: Official J Hum Biology Council. 2011;23(5):651–4. [DOI] [PubMed] [Google Scholar]
- 12.Alwasel SH, et al. Intergenerational effects of in utero exposure to Ramadan in Tunisia. Am J Hum Biology: Official J Hum Biology Council. 2013;25(3):341–3. [DOI] [PubMed] [Google Scholar]
- 13.Chaudhry TT. Impact of prenatal exposure to Ramadan on disability in Pakistan among adults age 18–64. Dialogues Health. 2022;1:100062. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Kunto YS, Mandemakers JJ. The effects of prenatal exposure to Ramadan on stature during childhood and adolescence: evidence from the Indonesian Family Life Survey. Econ Hum Biol. 2019;33(101166135):29–39. [DOI] [PubMed] [Google Scholar]
- 15.Majid F, Behrman J, Mani S. Short-term and long-term distributional consequences of prenatal malnutrition and stress: using Ramadan as a natural experiment. BMJ Global Health. 2019;4(3):e001185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Pradella F, van Ewijk R. As Long as the Breath lasts: in Utero exposure to Ramadan and the occurrence of wheezing in Adulthood. Am J Epidemiol. 2018;187(10):2100–8. [DOI] [PubMed] [Google Scholar]
- 17.van Ewijk R. Long-term health effects on the next generation of Ramadan fasting during pregnancy. J Health Econ. 2011;30(6):1246–60. [DOI] [PubMed] [Google Scholar]
- 18.van Ewijk RJG, Painter RC, Roseboom TJ. Associations of prenatal exposure to Ramadan with small stature and thinness in adulthood: results from a large Indonesian population-based study. Am J Epidemiol. 2013;177(8):729–36. [DOI] [PubMed] [Google Scholar]
- 19.Schoeps A, et al. Ramadan exposure in Utero and Child Mortality in Burkina Faso: analysis of a Population-based cohort including 41,025 children. Am J Epidemiol. 2018;187(10):2085–92. [DOI] [PubMed] [Google Scholar]
- 20.Karimi SM, Little BB, Mokhtari M. Short-term fetal nutritional stress and long-term health: child height. Am J Hum Biology: Official J Hum Biology Council. 2021;33(6):e23531. [DOI] [PubMed] [Google Scholar]
- 21.Karimi SM, Basu A. The effect of prenatal exposure to Ramadan on children’s height. Econ Hum Biol. 2018;30(101166135):69–83. [DOI] [PubMed] [Google Scholar]
- 22.Chaudhry TT, Mir A. The impact of prenatal exposure to Ramadan on Child Anthropomorphic outcomes in Pakistan. Matern Child Health J. 2021;25(7):1136–46. [DOI] [PubMed] [Google Scholar]
- 23.Loney T, et al. Associations of prenatal exposure to Ramadan with smaller body size and greater cardiovascular fitness in male adolescents in the United Arab Emirates. Obes Rev. 2014;15(SUPPL 2):123. [Google Scholar]
- 24.Van Ewijk R, Mazumder B, Almond D. In utero Ramadan exposure and children’s academic performance. Eur J Epidemiol. 2013;28(1 SUPPL 1):pS17. [Google Scholar]
- 25.Chu H, Goli S, Rammohan A. Utero Ramadan exposure and child nutrition. J Dev Origins Health Disease. 2023;14(1):96–109. [DOI] [PubMed] [Google Scholar]
- 26.Stote KS et al. A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults. Am J Clin Nutr. 2007;85(4):981–8 (0002-9165 (Print)). [DOI] [PMC free article] [PubMed]
- 27.Moro TA-O et al. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males. J Transl Med. 2016;14(1):290 (1479–5876 (Electronic)). [DOI] [PMC free article] [PubMed]
- 28.Godfrey KM, Barker DJ. Fetal nutrition and adult disease. Am J Clin Nutr. 2000;71(5):S1344–52. [DOI] [PubMed] [Google Scholar]
- 29.Godfrey KM, Barker DJ. Fetal programming and adult health. Public Health Nutr. 2001;4(2b):611–24. [DOI] [PubMed] [Google Scholar]
- 30.Petherick ES, Tuffnell D, Wright J. Experiences and outcomes of maternal Ramadan fasting during pregnancy: results from a sub-cohort of the Born in Bradford birth cohort study. BMC Pregnancy Childbirth. 2014;14(1):1–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Seiermann AU, et al. Women’s fasting habits and dietary diversity during Ramadan in rural Bangladesh. Matern Child Nutr. 2021;17(3):e13135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Joosoph J, Abu J, Yu S. A survey of fasting during pregnancy. Singap Med J. 2004;45(12):583–6. [PubMed] [Google Scholar]
- 33.Makki AM. Impact of Ramadan fasting on birth weight in 4 hospitals in Sana’a city. Yemen Saudi Med J. 2002;23(11):1419–20. [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

