Gestational Diabetes: beyond the label

This post explores blood glucose levels (BGLs) in pregnancy, and attempts to make some sense of the fairly nonsense diagnosis and management of 'gestational diabetes' (GDM). This post is not about Type 1 or Type 2 diabetes, and I am assuming you already know about the relationship between blood glucose (sugar) and insulin, if not do some googling.

Blood glucose and insulin in a healthy pregnancy

Babies need glucose to grow, and the demand for glucose increases as pregnancy progresses and the baby develops. From around 20 weeks, placental hormones cause insulin resistance in the mother’s cells. Insulin-resistant cells are less able to convert glucose into energy, resulting in a peak of blood glucose after eating a meal which goes through the placenta to 'feed' the baby. In response to this peak, the woman’s pancreas increases the production of insulin to bring BGLs back down to a healthy pre-meal range. So, during pregnancy, a woman's body needs to bump up insulin production to counteract the effect of insulin-resistant cells. Once the baby is born, the placental hormones stop entering the woman's circulation and her insulin metabolism returns to her pre-pregnant state.

High blood glucose in pregnancy

[NOTE: the clear as mud definition of 'high' is discussed below in 'parameters of normal']

Some women's bodies are unable to produce the additional insulin required during pregnancy. This results in high levels of glucose remaining in the blood instead of being converted into energy by insulin. The exact cause of this situation is not clear. However, pregnancy places additional demands on the body's metabolism, and pre-existing health issues influence the ability of the body to meet these demands. High BGLs in pregnancy are associated with an increased chance of health problems during pregnancy (eg. pre-eclampsia) and later in life (eg. cardiovascular disease and Type 2 diabetes). Therefore, pregnancy may offer a glimpse into the general health of a woman, and her ability to meet physical challenges. Rather than causing ill health, abnormal BGLs may reflect underlying ill health.

What is known is that high maternal BGLs influence the development of the baby. In early pregnancy (before 14 weeks) high BGLs are associated with an increased chance of miscarriage, congenital abnormality and subsequent stillbirth [1]. This is because the structural development of the major organs is taking place at this time, and any toxin, including excessive glucose, can cause damage. However, BGLs are only high in early pregnancy in poorly controlled, pre-existing diabetes.

In contrast, pregnancy-induced high BGLs do not occur until after 20 weeks when insulin resistance kicks in. By 20 weeks all of the baby's major organs have formed, and the baby grows mostly in size rather than in complexity. Therefore, pregnancy-induced high BGLs primarily influence the weight/shape of the baby. In response to high maternal BGLs passing through the placenta, the baby increases their insulin production. This insulin converts the excess blood glucose into additional fat stores resulting in a heavier baby. This extra fat is concentrated around the baby's upper body, in particular around the shoulders. Chunky shoulders increase the chance of shoulder dystocia and perineal tearing during birth. Insulin can also delay the production of surfactant, which prepares the lungs for breathing. This can cause breathing issues at birth, particularly if the baby is born early (eg. by early induction or c-section, which are more common when GDM is diagnosed).

Once the baby is born, they no longer need to produce high insulin. However, adjusting and re-balancing insulin and BGLs can be a bit of a bumpy ride for the baby. The withdrawal of high BGLs is sudden (as soon as the placenta stops functioning), but it can take some hours before the baby's insulin levels drop. During this time the high insulin can convert too much of the baby's blood glucose into energy resulting in low BGLs (hypoglycaemia).

The baby's high insulin levels during pregnancy also increase their red blood cells. After birth, the baby needs to break down and excrete these additional red blood cells. A by-product of breaking down red blood cells is bilirubin. If there is a lag between breaking down the red blood cells and excreting them out of the body, bilirubin builds up causing jaundice. Jaundice is common in babies who produced high insulin in the uterus.

The effects of high BGLs and high insulin in utero may also cause long-term epigenetic changes to the baby's metabolism. These babies have an increased chance of developing obesity and Type 2 diabetes later in life.

If you want a more in-depth explanation watch this movie:

In summary, high BGLs in pregnancy are not ideal and can alter the growth and development of the baby.

'Gestational diabetes'

In an attempt to identify and manage women with high BGLs, the maternity system has defined a disease and created a label that clinical guidelines can be based around. When high BGLs are identified for the first time during a pregnancy it is referred to as ‘gestational diabetes’ or ‘gestational diabetes mellitus’ (GDM). Most cases of GDM are pregnancy-induced ie. caused by an inability to meet the additional insulin needs of pregnancy as described above. Occasionally, Type 2 diabetes was already present but only identified in pregnancy. Either way, high BGLs will be termed GDM until proven otherwise ie. after pregnancy when BGLs fail to return to normal in the case of undiagnosed Type 2.

However, due to inconsistencies in who is tested, and how and what parameters are applied, there is a huge variation in whether an individual woman gets diagnosed and labelled with GDM or not. For example, the incidence of GDM varies globally from 2% to 26% depending on the definition used, the approach to screening, and the population of women tested.

Applying the label

There are two main approaches to screening for GDM. Universal screening (every woman is offered a test) and risk factor-based (only women with an increased chance of developing GDM are offered a test). There is no evidence to demonstrate that either approach improves outcomes for mothers and babies. A Cochrane Review [2] concluded: There is not enough evidence to guide us on effects of screening for GDM based on different risk profiles or settings on outcomes for women and their babies… Low-quality evidence suggests universal screening compared with risk factor-based screening leads to more women being diagnosed with GDM.

Types of testing

The Oral Glucose Tolerance Test (OGTT) is offered between 24 and 28 weeks gestation, or earlier for women considered 'at risk' of GDM. It is the standard recommended test for GDM diagnosis in most clinical guidelines worldwide. It involves fasting overnight, then drinking a glucose solution, followed by a blood test to assess BGLs. The dose of glucose can vary from 50g to 75g to 100g; and the timing of the blood test varies from 1 hour, 2 hours or 3 hours afterwards. There is no evidence to support any of these variations, however, most guidelines recommend 75g of glucose and a 2-hour blood test. The OGTT assesses how well a woman’s body responds to a huge bolus of glucose (and chemicals, read the label).

The Glucose Challenge Test (GCT) was previously recommended as a screening assessment (24-28 weeks) to determine which women went on the have the OGTT. The test involves drinking a 50g glucose solution and having a blood test 1 hour later. However, the test lacks both sensitivity and specificity and is no longer recommended (except in the US).

The Glycated Haemoglobin (HbA1c) is only recommended for identifying pre-existing diabetes during the first trimester of pregnancy. The results of the blood test indicate what the average BGLs have been over a 2-3 month period. This test cannot effectively identify pregnancy-induced diabetes, only previously undiagnosed Type 2 diabetes.

Self-testing is not recommended in any guidelines however, some women choose to do this rather than an OGTT. The woman tests her BGLs over a few days to get an idea about what her BGLs are doing when she is following her usual diet and lifestyle.

Parameters of normal

It is generally agreed that the normal range of blood glucose for non-pregnant people is 4.0 to 6.0 mmol/L (millimoles per litre) when fasting, and up to 7.8 mmol/L two hours after eating. Diagnosis of non-pregnant diabetes occurs when an OGTT identifies fasting BGLs ≥ 7 mmol/L or BGLs ≥ 11.1 two hours after 75g glucose.

However, when it comes to pregnancy, definitions and parameters of normal are not so clear. Various organisations advocate differing diagnostic parameters [3]. However, I'll stick to the most commonly used criteria initiated by the International Association of Diabetes and Pregnancy Study Group (IADPSG). In 2010, the IADPSG Consensus Panel lowered the threshold for GDM diagnosis [4]. This move was based on the findings of one study, the HAPO study [5], an observational study looking at the risk of 'adverse outcomes' in relation to BGLs. The study excluded women with GDM, and participants were grouped into categories of seven non-diabetic BGL ranges.

There were two significant study findings. Firstly, BGLs were associated with birth weight. Women with BGL in the highest category had a 26.3% incidence of a baby above the 90th percentile, compared to women in the lowest category, who had an incidence of 5.3%. However, 73.7% of women with the highest BGLs had a baby smaller than the 90th centile. Secondly, BGLs were associated with umbilical C-peptide (reflecting the baby's insulin production). The babies of mothers with the highest BGL had a 32.4% incidence of C-peptide levels above the 90th centile compared to 3.7% in the lowest BGL category. This is no surprise, considering the physiology described above. What is important to note is that there was no significant increase in hypoglycaemia for babies with higher C-peptide levels. In summary, they found that the higher the maternal BGL was during pregnancy, the higher the chance that the baby would grow bigger and have higher insulin levels.

The IADPSG Consensus Panel concluded that: because associations were continuous with no obvious thresholds at which risks increased... a consensus was required to translate these results into clinical practice. So, the new GDM diagnostic threshold was created: OGTT results of BGL ≥ 5.1 mmol/l fasting or ≥ 8.5 mmol/l two hours after 75g glucose load. These levels are significantly lower than the thresholds for non-pregnant people, and the threshold is based on the average BGL values that increased the odds of a big baby by 1.75 times. Whilst this threshold may reduce the rates of babies over 4kg, there is no evidence that it will reduce the rate of birth/newborn complications [3].

The World Health Organization changed their recommendations to align with IADPSG's [6]. WHO even state in their recommendation that the quality of evidence to support this new threshold is 'very low', and the strength of the recommendation is 'weak'. In 2014 Kevat et al. raised several concerns about the impact of the lower threshold for Australian women, which can be applied to other populations [7]. However, despite an initial wave of concern from care providers, consumers, maternity organisations and researchers, these new thresholds made it into clinical guidelines and practice worldwide. The graph below shows the impact of the implementation of lower thresholds for GDM in Australia up until 2017 [8]. The latest available Australian data (2021-2022) [9] reports that 19.3% of pregnant women were diagnosed with GDM.

Research carried out after the implementation of a lower BGL threshold demonstrates no improvements to outcomes, quite the opposite. A Cochrane review looked at ‘different intensities of glycaemic control’ for women with GDM [10]. They found that with lower BGL targets there was no difference in the rates of c-section, induction of labour or body fat percentage of the baby. However, there was an increased risk of the women developing high blood pressure and protein in the urine. The review concludes that:

There remains limited evidence regarding the benefit of different glycaemic targets for women with GDM to minimise adverse effects on maternal and infant health. Glycaemic target recommendations from international professional organisations vary widely and are currently reliant on consensus given the lack of high-certainty evidence.

Two Australian studies investigated the benefits and harms of lower BGL thresholds for GDM. The first study [11] examined the impact of introducing the new thresholds and found that:

There was an increase in annual incidence of GDM of 74% without overall improvements in primary health outcomes. This incurred a net cost increase of AUD$560 093. Babies of women with GDM had lower rates of neonatal hypoglycaemia and special care nursery admissions after the change, suggesting a milder spectrum of disease.

The latest Australian study [12] compared two large retrospective cohorts, one before the BGL threshold changed (2011-2013) and one after the change (2016-2018). The rate of GDM diagnosis increased from 7.8% to 14.3% between the cohorts. For the cohort with lower BGL thresholds, there was no improvement in the rate of shoulder dystocia, c-sections or hypertensive disorders. Instead, there was an increased rate of planned birth (induction or c-section with no labour) from 62.9% to 71.8% and planned early birth (before 39 weeks) from 35% to 45%. These rates were even higher for women prescribed insulin. Early planned birth is important to consider in relation to short and long-term newborn health and breastfeeding. For women diagnosed with GDM, the chance of going into spontaneous labour and giving birth vaginally (SLVB) went from 30.01% to 23.6% between the two cohorts. Note that I can’t work out from the article if ‘vaginal birth’ includes an instrumental birth or if this 'spontaneous labour' includes augmentation. However, I think it is safe to say that physiological birth is likely to be very uncommon for women diagnosed with GDM. The researchers conclude that:

Outcomes were not apparently improved with increased GDM diagnosis. The merits of increased IOL or decreased IOL or decreased SLVB depend on the views of individual women, but categorising more pregnancies as abnormal, and exposing more babies to the potential effects of early birth, medication effects and growth limitation may be harmful.

Increasing calls for a review of the diagnostic criteria (from medicine) [13,14] are being ignored as the new threshold norm continues.

Treating the label

Once a woman has been labelled with GDM she is usually diverted into 'GDM-centred' antenatal care. There is often a stigma attached to having GDM, and there is additional medical surveillance and restricted choices regarding birth setting. Management of GDM centres on keeping the BGLs within a certain range via diet and exercise, and/or insulin medication. The issues around dietary recommendations are a whole other issue that I can't fit into this blog post. Long story short, the usual GDM recommendations involve a high-carb (ie. sugar) diet. Alternatively, Lily Nichols has written a couple of great books about diet in pregnancy and for GDM.

Although there are varying opinions about what BGLs should be maintained by women diagnosed with GD [3]. In general, the fasting BGL target is around 5.0-5.5 mmol/l fasting and the 2-hour post meal BGL is 6.7-7.1 mmol/l (by capillary blood, ie. finger prick test). Not surprisingly, hypoglycaemia (low BGLs) is a common problem for women trying to keep their BGLs within this range.

The World Health Organization [6] summarised the evidence of the effectiveness of GDM treatment. The only outcome categorised as 'high quality' is that treatment for GDM reduces the chance of having a baby 4kg+ (number needed to treat NNT = 11.4 to prevent 1 large baby). However, the evidence indicating a reduction in shoulder dystocia is of 'low quality' (NNT = 48.8 to prevent one shoulder dystocia). There is 'moderate quality' evidence that treatment reduces the chance of hypertension (NNT 18.1) and pre-eclampsia (NNT 21). For all other outcomes, evidence was 'moderate' to 'low' quality. Bear in mind the research in the WHO summary was carried out before the new lower GD thresholds were introduced. A more recent Cochrane Review [15] compared lifestyle interventions (diet and exercise) with 'usual' care or another intervention and found no difference in any outcomes except the size of the baby.

It is also important to note that only 14-22% of women diagnosed with GDM will have a baby over 4kg [16] and ultrasound assessment of size is ineffective.

Labour and birth care for women labelled GDM

The IADPSG Consensus Panel [4] acknowledged that the bias of caregivers toward expectation of adverse outcomes may increase morbidity due to increased intervention for women diagnosed with GDM. Women are often coerced into early induction of labour or even c-section because they have been diagnosed with GDM. By coerced, I mean they are advised to have an intervention, rather than discussing the risks and benefits of various options in relation to their individual situation, and then making their own decision.

Large-scale research exploring birth outcomes for GDM tends to focus on the label rather than on BGLs. This results in 3 groups of women being mixed into the research sample:

Women with pre-existing diabetes only diagnosed during pregnancy
Women diagnosed with GDM who had high BGLs during pregnancy
Women diagnosed with GDM who maintained normal BGLs during pregnancy

For this mixed-up group of GDM women, a Cochrane Review [17] concluded:

There is insufficient evidence to clearly identify if there are differences in health outcomes for women with gestational diabetes and their babies when elective birth is undertaken compared to waiting for labour to start spontaneously or until 41 weeks gestation if all is well. (the '41 weeks' is because induction at this gestation tends to be standard for all women).

However, things look different when we consider women based on what their BGLs have been during pregnancy rather than their GDM label. In this case, there are 2 distinct groups:

1. Women with normal BGLs (and a GDM label)

These women do not have babies affected by high BGLs because they didn't have consistently high BGLs during pregnancy. Their babies are as likely to be over 4kg as women without GDM. They should be cared for in the same way as women without a GDM label because their 'risk profile' is the same. For this group of women, induction is not supported by evidence or clinical guidelines. ACOG (US) [18] states that women with GDM with good glycemic control and no other complications are commonly managed expectantly until term. Queensland Health (Australia) [19] recommend that if blood glucose is well managed, there is no indication for induction for gestational diabetes. Despite this clear guidance, women are often booked in for an induction by their care provider based simply on their GDM label.

2. Women with abnormal BGLs (and a GDM label)

This group of women has an increased chance of experiencing complications associated with high BGLs (see above). However, even for this group of women, there is a lack of evidence to support induction. A paper by Berger and Melamed [20] discusses the research relating to the timing of birth for women with GDM, including the risks of induction for women and babies with GDM. Like the Cochrane review above, they found inadequate evidence to support induction of labour for women with GDM and concluded that until such data are available, the clinician should consider the maternal, fetal and neonatal implications of induction of labour versus expectant management, involve the patient in the decision process and as usual follow the maxim of ‘‘first do no harm.

The main concern regarding high BGLs in pregnancy is the size of the baby (see above). This is often used as the reason for recommending induction. Babies with big shoulders are more likely to experience shoulder dystocia. For example, in non-GDM pregnancies, shoulder dystocia occurs in around 1% of babies weighing less than 4kg compared to 5-9% of babies weighing over 4kg [21]. These figures may be higher for babies subjected to high BGL in pregnancy because of the distribution of their additional weight (ie. upper body and shoulders). However, increased shoulder dystocia rates may also be partially due to the interventions women with suspected big babies experience. For example, if a care provider suspects a 'big baby' the woman is more likely to experience interventions (syntocinon, c-section, instrumental birth, etc) and complications regardless of whether her baby is actually big [22, 23]. For more information about 'big babies' and research about induction for a 'big baby', see this post.

Women with high BGLs in pregnancy need to consider the risks of possible shoulder dystocia with the risks of induction and their individual situation and preferences. Many women with abnormal BGLs can, and do have physiological births, however, most follow care provider recommendations and have their labour induced. The following are some suggestions for reducing/managing complications associated with birth for women who had high BGLs in pregnancy. Most of these suggestions can be applied to physiological labour or induced labour.

Maximise the size of the pelvis and avoid positions that restrict the movement of pelvic bones (eg. don't sit on the back of the pelvis)
Maximise the ability of the baby to rotate. A mobile mother offers lots of opportunities for her baby to move. Water immersion is good for this. Resting space between contractions also allows the baby to move when the uterus is relaxed. If syntocinon is regulating contractions, make sure there is a good 'resting space' between the contractions (no more than 4 contractions in 10 mins). If the woman has an epidural her care providers/support people will need to assist her to move her pelvis (eg. pelvic rocking using the drawsheet or towel).
BG management – if the woman is insulin dependent it may be necessary to check BGLs during labour.
Avoid interventions that cause wounds eg. c-section or episiotomy. High BGLs can interfere with healing and increase the chance of infections.
Avoid any interventions that interfere with instinctive behaviour as the woman pushes her baby out. If she has an epidural then avoid directed pushing until the baby's head is on the perineum, and then keep it gentle with spaces in between for re-oxygenation of mother/baby and a chance for the baby to rotate and move. Do not pull on the baby's head immediately after it has birthed, this can wedge the shoulders into the pelvis before they have had a chance to rotate. If there is no change with the next contraction (no rotation or descent), then suspect shoulder dystocia. and manage accordingly.
After birth do not remove the baby from their mother - this will result in a stress response that will burn up the baby's glycogen (glucose stores). These stores will be needed as the baby re-balances their metabolism. Any resuscitation should be done with the mother and baby together.
Prolonged skin-to-skin with the mother will stabilise the baby's heart rate and temperature; reduce stress; and encourage early breastfeeding, all great for maintaining BGLs.
Ensure the baby feeds early and often. Colostrum provides a nutrient-dense package of glucose to help the baby keep their BGLs within a normal range. Even a few drops can increase the baby's BGLs significantly. The mother can express and store colostrum at the end of pregnancy to provide additional colostrum for the first hours after birth.
The baby may have their BGLs monitored as they adjust to the withdrawal of high maternal BGLs. Any monitoring and/or management can be done with mother and baby together. Separating mother and baby is detrimental for all kinds of reasons, including BGL stabilisation.
Observe the baby during the first week for jaundice. As discussed above, significant jaundice is fairly common for a baby who produced high insulin during pregnancy. The baby may need light therapy to resolve their jaundice.

Breastfeeding is the best way to reduce the chance of hypoglycaemia (low BGLs)

Summary

High BGLs in pregnancy alter the growth and development of the baby, increasing the chance of particular complications occurring. However, the label 'gestational diabetes' is problematic because it is poorly defined, and there is a lack of evidence to demonstrate that diagnosis and treatment improves outcomes. Expected blood glucose parameters in pregnancy are now lower than non-pregnant parameters, resulting in increased GDM diagnosis. Guidelines do not support induction of labour for GDM unless BGLs are high. Inducing women with high BGL before 40 weeks may reduce the chance of a large baby and shoulder dystocia, but it increases the chance of other complications. Labour and birth care for women with high BGLs should centre on minimising the possibility of shoulder dystocia and supporting the baby to regulate their BGLs after birth.