key: cord-0937881-828tv9uy
authors: Cauldwell, Matthew; van‐de‐L’Isle, Yolande; Watt Coote, Ingrid; Steer, Philip J
title: Seasonal and SARS‐CoV‐2 pandemic changes in the incidence of gestational diabetes
date: 2021-05-28
journal: BJOG
DOI: 10.1111/1471-0528.16779
sha: ac2197d172ac7a12dc409f0452d3f6d7bcc118bf
doc_id: 937881
cord_uid: 828tv9uy

OBJECTIVE: To test the hypothesis that there is seasonal variation in the rates of gestational diabetes (GDM) diagnosed using a 2 hour oral glucose tolerance test. DESIGN: Monthly assessment of the percentage of women screened from 1(st) April 2016 to the 31(st) December 2020 who were diagnosed as having gestational diabetes SETTING: London Teaching Hospital POPULATION: 28,128 women receiving antenatal care between April 1(st) 2016 and 31 December 2020. METHODS: Retrospective study of prospectively collected data. MAIN OUTCOME MEASURES: Proportion of women screened diagnosed as having gestational diabetes. RESULTS: The mean (SD) percentage of women diagnosed with GDM was 14.78 (2.24) in summer (June, July, August) compared with 11.23 (1.62) in winter (p < 0.001), 12.13 (1.94) in spring (p = 0.002), and 11.88 (2.67) in autumn (p = 0.003). There was a highly significant positive correlation of the percentage testing positive for GDM with the mean maximum monthly temperature (R(2) = 0.248, p < 0.001). There was a statistically significant 33.8% increase in the proportion of GDM diagnoses from June 2020 onwards, possibly related to a reduction in exercise secondary to the Covid‐19 pandemic. CONCLUSIONS: There is a 23.3% higher rate of GDM diagnoses in the warmer summer months. There has been a 33.8% rise in GDM diagnoses associated with the Covid‐19 pandemic.

Gestational diabetes (GDM) is a relatively common disorder which typically affects about one in eight pregnancies in the United Kingdom(UK) (1) . A meta-analysis published in 2017 focusing on GDM diagnosed in European countries reported a prevalence of 5.4% (2) . However, it should be acknowledged that many studies included in in this meta-analysis are over 20 years old (3, 4) .

During this time maternity demographics have changed with women delaying pregnancy until they are older, there are greater rates of obesity (5) and more multiple pregnancies(6) as a result of assisted conception. All of these are known to be risk factors for gestational diabetes. At present screening for gestational diabetes in the UK is largely based on a risk factor-based approach system with guidance set out by the National Institute for Healthcare and Excellence (NICE)(7). In their guidance the gold standard for testing is a 75g oral glucose tolerance (OGTT) performed between 24-28 weeks (although testing maybe done earlier, particularly if there was GDM in a prior pregnancy). A positive result is determined by either a fasting reading of >5.3mmol/l or a two-hour blood level of 7.8mmol/l. Retesting for GDM in pregnancy maybe done if there is high level of clinical suspicion despite the finding of a normal OGTT. Data from the landmark Hyperglycaemia and Adverse Pregnancy Events (HAPO) Trial only tested women using a OGTT up until 32 completed weeks of pregnancy (8) , beyond this point there are concerns regarding the validity of using a OGTT to diagnose GDM and so home blood glucose monitoring is typically used.

There is increasing evidence to suggest that rates of GDM vary by season. (9) . A single centre cohort study from Australia showed the prevalence of GDM was 28% higher in summer and 31% lower in winter (9) . Similar findings have been replicated in several other populations.

Retnakaran et al investigated beta cell function and insulin sensitivity in almost 1500 women who were screened for GDM (10) . Their data showed that rising environmental temperature in the 3-4 weeks prior to testing appeared to be associated with beta cell dysfunction and therefore greater rates of GDM (10) . To date there have been few studies in the UK population analysing seasonal variation in the rates of GDM(11). We there conducted a single centre study examining rates of GDM diagnosed in our institution over a 4 year period, examining the hypothesis that the rate of GDM diagnosis would be higher in the summer than in the other seasons. We also

This article is protected by copyright. All rights reserved took the opportunity of investigating the hypothesis that there had been a change in the rate of GDM diagnosis following the onset of the Covid-19 (SARS-CoV-2) pandemic.

This was a single centre study undertaken in a tertiary London hospital where there are approximately 5000 deliveries per year. Within our institution we have offered screening for GDM using a 2hr OGTT since 2010, based upon the NICE guidelines (which include ethnic/racial origin) as well as additional risk factors including a maternal age of 35 or more, multiple pregnancy, and previous late pregnancy loss. The diagnosis of GDM was initially made on either an elevated fasting plasma blood glucose level of 5.6 mmol/litre or above or a plasma glucose level of 7.8 mmol/litre or above in a blood sample taken 2 hours after a polycal drink which contains the equivalent of 75g of glucose. Data have been collected on the number of women tested and diagnosed with GDM by OGTT prospectively each month. . An update to NICE guidance in September 2015 recommended a reduction in the fasting threshold for the diagnosis of GDM to 5.3mmol/litre(7); this was implemented in our institution from 1 st April 2016. We offer screening with OGTT up until 32+6 weeks' gestation; beyond this gestation we use home glucose testing. The technique used in our laboratory to measure plasma glucose is the Glucose HK Gen.3 produced by COBAS ® (Roche Diagnostics). The coefficient of variation of the measurement is 0.5 -0.7%. We have no reason to consider that the laboratory techniques used vary in their sensitivity by season.

To test the hypothesis that there is a seasonal variation in the rate of positive GDM diagnoses we examined the prevalence of GDM diagnosed by screening using OGTT only before 33 weeks' gestation to test whether there is a monthly and seasonal variation in the proportion of women tested who receive a positive result.

Because of the changes in diagnostic threshold, we have analysed only those women attending for antenatal care from 1 st April 2016 until 31 st December 2020. We also analysed the

This article is protected by copyright. All rights reserved demographics of women presenting for antenatal care to assess whether they showed any variation which would explain a seasonal effect.

Data were analysed using SPSS version 26. Initially we plotted the monthly proportion of screened women testing positive using an individual moving range control chart. We then plotted the distribution of that proportion against the average monthly maximum temperature at Heathrow Airport (17 miles from our institution) for which data are publically available (12) .

We then assessed the mean proportions diagnosed with GDM (+/-SD) by season, where winter is December to February, spring is March to May, summer is June to August and autumn (fall) is September to November inclusive. We assessed the demographics of women having their antenatal care at our institution, on the same seasonal basis. Gaussian (normally distributed) data were analysed using the Student-t test. Core outcome sets and patient involvement were not involved in this study

The average proportion of women testing positive for GDM was 12.7% (SD 2.60), median 12.78 (IQR 10.68 to 13.98). Demographic data for women booked at are institution is displayed in There was a highly significant correlation of the percentage testing positive for GDM with the mean maximum monthly temperature at Heathrow Airport (figure 3), R = 0.498, R 2 = 0.248, p < 0.001. This effect is not associated with any significant variation in the demographics of women presenting for antenatal care by season (table 1) , with the exception of the autumn, which has a

This article is protected by copyright. All rights reserved slightly younger mean age and a slightly higher proportion of South Asians compared with the other three seasons. The demographics of the summer population are not significantly different from spring or winter.

An unexpected finding was that, apart a single high proportion in July 2016, there was a consistently higher proportion of GDM positives from June 2020 onwards, following the onset of the COVID-19 pandemic. We therefore compared the six months from June to December 2020 inclusive (period 2, since the beginning of the Covid-19 pandemic) with the previous 65 months 

Our study demonstrates there is a significant seasonal variation with regards to women receiving a positive screening result for gestational diabetes through the OGTT, with more women being diagnosed in summer months compared to winter months. The proportion of women testing Accepted Article positive is strongly correlated with the mean maximum monthly temperature. Furthermore, since the beginning of the Covid-19 pandemic there has been a significant increase in the proportion of women screened for GDM receiving a positive result.

The findings from our study in England agree with others who have examined how seasonality influences rates of GDM in (9, (14) (15) (16) . In their review paper Pace and colleagues (16) report higher rates of GDM in the warmer months in Italy, Greece, Sweden, Brazil, Canada and Taiwan, although two of three studies in Australia did not (perhaps because of limited seasonal differences). The only previous study we have identified in the UK reported a GDM prevalence of 2.9% in June compared with 1.1% in November (11), but they concluded that there was no significant seasonal effect, probably because of small numbers of positive diagnoses (they only studied 4,942 women who were all white European).

Pace et al outline several different mechanistic ways in which this effect of temperature may be explained (17) . One possible pathway is through brown adipose tissue metabolism. Data suggests that exposure to cold temperatures improves insulin sensitivity in those with Type 2 diabetes (18). Conversely with rising temperatures, brown adipose tissue is rather less activated (19) ; this may partially explain the higher rates of GDM witnessed in warmer months.

Interestingly our data did not show quite such a striking variation in rates of GDM as the Australian study by Moses et al ((9) . They found that the prevalence of GDM was 29% higher in summer as compared to winter. The variation witnessed in our study was 23.3%. Whilst average seasonal temperature differences are similar in both cohorts, the mean summer temperatures they reported were much higher. There are compelling data that GDM is an important indicator that women are likely to develop Type 2 diabetes later in life, with rates being ten times greater for those with a prior history of GDM compared with healthy controls (20) . Our data confirm that the rate of diagnosis of GDM is higher in the summer months, but it is not known whether this is associated with long term changes in beta cell function, or temporary changes in beta cell function and/or insulin sensitivity. It will therefore be important in future long term follow-up studies to document the season in which the GDM diagnosis was made. If diagnosis in the Accepted Article summer is associated with a lower rate of long term type II diabetes, this would be in favour of the elevated rate of GDM diagnosis being due to temporary changes in insulin sensitivity rather than a permanent effect on beta cell function. Future studies should also investigate whether the season at diagnosis alters the significance of the diagnosis in relation to the clinical outcome of the affected pregnancy.

An unexpected finding was the significant increase in the proportion of women testing positive for GDM since the onset of the Covid pandemic. We hypothesise that this may be related to restricted activity during the various lockdowns(21, 22) without a commensurate reduction in dietary intake (23) . A review of 11 studies of the effect of the pandemic in India (24) found that restriction of travel outside the home and workplace has led to an increase in snacking and meal frequency, paralleled by a reduction in physical activity and exercise duration, resulting in weight gain. Another study of 307 diabetics in India found an increment in mean HBA1c levels of 0.51% from a mean of 7.92% pre-lockdown to a mean of 8.43% and concluded that lockdown had produced a significant derangement of glycaemic control (25) . A similar finding has been reported from Italy (26) , and was attributed to "a dysfunctional adaptive reaction to lockdowninduced stress".

One of the key strengths of our study is that data regarding the incidence of GDM in women screened has been collected prospectively. Although we did not record the maternal demographics specifically of those tested, we do have them for the total population, and there have been no significant temporal changes in the characteristics of the population served. We have longitudinal data spanning more than 4.5 years, with large numbers making our findings highly statistically significant. While our data are limited to a single centre and may not be generalisable to other maternity units, our cohort includes over 25,000 women; furthermore, our population is highly diverse with just over half the women booking describing their ethnicity as being something other than White European.

This article is protected by copyright. All rights reserved

The diagnosis of GDM is significantly temperature sensitive, with the incidence being 23.3% higher in the summer months. This may affect its significance in relation to outcome, which would have management implications. There has been a significant 33.8% increase in the proportion of GDM diagnoses since the onset of the COVID-19 pandemic, which may be due to reduced exercise levels during lock down, or alternatively may be secondary to stress-induced hyperglycaemia. 

Prevalence of gestational diabetes mellitus in Europe: A meta-analysis

Relation of birthweight to maternal plasma glucose and insulin concentrations during normal pregnancy

Universal vs. risk factor-based screening for gestational diabetes mellitus: detection rates, gestation at diagnosis and outcome

Trends in maternal obesity in a large university hospital 2009-2013

National Institute for Health and Care Excellence: Clinical Guidelines. Diabetes in pregnancy: management from preconception to the postnatal period

Hyperglycemia and adverse pregnancy outcomes

Seasonal Changes in the Prevalence of Gestational Diabetes Mellitus

Impact of daily incremental change in environmental temperature on beta cell function and the risk of gestational diabetes in pregnant women

Accepted Article This article is protected by copyright. All rights reserved 11

Gestational diabetes mellitus in

prevalence, seasonal variation and associated factors

Impact of changes to national UK Guidance on testing for gestational diabetes screening during a pandemic: a single-centre observational study

Impact of Seasonality on Gestational Diabetes Mellitus

The impact of environmental temperature on the diagnosis of gestational diabetes mellitus

Influence of environmental temperature on risk of gestational diabetes

Gestational diabetes, environmental temperature and climate factors -From epidemiological evidence to physiological mechanisms

Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus

Brown adipose tissue and glucose homeostasis -the link between climate change and the global rise in obesity and diabetes

Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and metaanalysis

Prenatal exercise for the prevention of gestational diabetes mellitus and hypertensive disorders of pregnancy: a systematic review and meta-analysis

COVID-19 Lockdown and Changes of the Dietary Pattern and Physical Activity Habits in a Cohort of Patients with Type 2 Diabetes Mellitus

Gestational diabetes is associated with high energy and saturated fat intakes and with low plasma visfatin and adiponectin levels independent of prepregnancy BMI

Impact of COVID-19 outbreak on lifestyle behaviour: A review of studies published in India

Observational study on effect of lock down due to COVID 19 on HBA1c levels in patients with diabetes: Experience from Central India. Prim Care Diabetes

Effects of work status changes and perceived stress on glycaemic control in individuals with type 1 diabetes during COVID-19 lockdown in Italy

We would like to acknowledge the staff working in the diabetes service who worked tirelessly to arrange retesting of women for GDM.

They authors have no disclosures of interest to report Author Roles:YDVL Abstraction of data and study design.PJS analysed data and edited the manuscript IWC -study design MC wrote manuscript.

This article is protected by copyright. All rights reserved As this study analysed routinely collated data as part of a service evaluation ethical approval was not required.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

This article is protected by copyright. All rights reserved