While associations between maternal diabetes and birth defects in the offspring have been recognised for some time, relationships with neurodevelopmental outcomes are less well understood. This well conducted population-based data linkage study evaluated the effects of pregestational and gestational diabetes on a range of neurodevelopmental outcomes in a Taiwanese birth cohort of 877,233 singletons born between 2004 and 2008. The risks of adverse outcomes which included autism spectrum disorder, intellectual disability, cerebral palsy, epilepsy, ADHD and developmental delay, were generally greatest for mothers with pregestational type 1 diabetes, followed by pregestational type 2 diabetes and less so for gestational diabetes. However, many of the conditions studied would be co-occurring in the same individual e.g. autism and intellectual disability and the authors didn’t explain how they dealt with this.

The results of the study are significant because of the current growing epidemic of type 1 and type 2 diabetes which will affect more and more women of child-bearing age across the world, particularly those from under-resourced and disadvantaged populations.  However, given its much higher prevalence it is fortunate that the risks for gestational diabetes were shown to be lower than for pregestational diabetes.

Type II diabetes and to a large extent gestational diabetes are diseases caused by unhealthy behaviours principally low levels of physical activity and exercise and poor diet. This results in overweight and obesity, low muscle mass, metabolic dysregulation, systemic inflammation, causing type II diabetes and greater risk of gestational diabetes. All this is of course a huge concern for the mother’s health and impacts the gestational environment of the developing foetus. This latest research establishes an association with “increased risk of autism spectrum disorder, ADHD, developmental delay, intellectual disability, cerebral palsy, and epilepsy” in the offspring which has devastating consequences for their entire life with implications for their family and community.

Unfortunately, overweight and obesity and sedentary lifestyle are increasing in Australian women and occurring at a younger age and the impact on their children is accumulating. The authors of this latest paper specifically acknowledge the impact of maternal obesity on increased risk of neurodevelopmental disorders. It is now established that the health, physical activity and fitness, body composition and nutrition of both mother AND father from conception through gestation, birth and the first few years of life impact the genetic and epigenetic characteristics of their child. This determines the health and behaviour of their offspring for the rest of life, including the risk of the quite debilitating neurologigal disorders listed above impacting not only quality of life but how long the person lives.

This is a large and well conducted study. Being retrospective in nature, it cannot establish causation, only an association. The correct interpretation is that mothers with diabetes of any kind are more likely to have children who develop various neurodevelopmental disorders (NDD), such as ADHD and Autism Spectrum Disorder (ASD), compared to mothers without diabetes.

This does not mean that maternal diabetes is responsible for the increased risk, there could be other factors that increase the risk of developing these conditions by the offspring and being affected by maternal diabetes at the same time, such as obesity. The increased risk is most evident for Type 1 Diabetes (T1DM), to a lesser extent for Type 2 Diabetes (T2DM), and the smallest risk was observed for Gestational Diabetes (GDM). While a number of important factors were incorporated into the statistical analysis, such as maternal and paternal age, child sex and socioeconomic status, some very important factors were not accounted for: maternal BMI, weight gain during pregnancy and the adequacy of glucose control preconception and in pregnancy. These factors are likely to be important and may be significant risk factors for the development of NDDs.

What conclusions and recommendations can be made based on this study? Women with T1DM have the highest risk of having a child with NDDs. It is possible that strict glycaemic control immediately before conception and throughout pregnancy may decrease this risk, since most other complications of T1DM are reduced by this strategy. It is also important to recognise that early appropriate diagnosis and treatment of NDDs improve future neurodevelopmental outcome. Therefore, it may be of benefit to screen children of T1DM mothers for these conditions in early childhood and to institute treatment without delay if required. T2DM and GDM have numerous modifiable risk factors, the most significant of which is obesity.

Addressing this important risk factor periconceptually reduces the risk and severity of both T2DM and GDM. In some women weight loss may reverse T2DM and prevent the development of GDM. Should this strategy be ineffective, it is possible that strict glycaemic control during pregnancy may reduce the risk of NDDs in the offspring, but this conclusion cannot be made based on this study.

Overall preventions of diabetes by lifestyle modification (for T2DM and GDM) appears to be the best strategy which also decreases other significant risks associated with these conditions in pregnancy. For T1DM, strict glycaemic control periconceptually and during pregnancy appears to be the best option. Childhood surveillance for NDDs with early diagnosis and prompts interventions, especially for children of T1DM mothers, is likely to improve long-term neurodevelopmental outcomes of these children.

Diabetes affecting pregnancy can be pre-existing (for example, type 1 or type 2) or may develop during pregnancy (gestational diabetes). The link between maternal diabetes and neurodevelopmental delays in the offspring is not new, many human and animal studies have shown this association. This retrospective cohort aimed to assess the risk of a wide spectrum of neurodevelopmental disorders in offspring of mothers with diabetes affecting pregnancy in Taiwan.

Although I acknowledge the challenges of accessing and analysing population-based data, it is important to note that the study did not control for several relevant cofounding factors. For example, measures related to birth hypoxia, infection, maternal smoking and alcohol consumption during gestation, obesity, physical activity and body weight gain were not considered. Consequently, we should exercise caution when interpreting the outcomes as these non-reported confounding factors may have influenced the findings.

This topic is relevant for Australians though, as the proportion of mothers with gestational diabetes has been increasing over the past few years (currently about 15%) and we know that kids’ future health can be affected by high blood sugar in utero. So, we need more prospective studies in this area exploring how we can attenuate the short- and long-term effects on the offspring.

It has long been known that maternal diabetes of any form during a pregnancy is associated with a higher risk pregnancy and confers an increased risk of adverse events for both mother and child.
This study further adds to the body of knowledge we already have about these adverse events to include neurodevelopmental disorders such as ADHD, developmental delay intellectual disability, cerebral palsy and epilepsy.

The study confirmed the already known increased risk of physical manifestations of diabetes in pregnancy for the mother such as preterm delivery, maternal high blood pressure and pre-eclampsia as well as the effects on the children. The children born of these mothers are more likely to be large for gestational age and have low Apgar scores. Although larger in size, these babies are more metabolically delicate and require more intensive treatment after delivery.

The study design had a number of issues which should promote caution in interpretation of results.
Although it was a four-year large study, it was retrospective in nature, undertaken in a country with different background rates of all types of diabetes, presumably genetics and importantly, the diagnostic criteria used for the diagnosis of gestational diabetes is different to the ones used in Australia.

The highest rates of complication were found in infants of mothers with type 1 diabetes which is consistent with findings of physical complications from other parts of the world. Those women diagnosed with gestational diabetes had the lowest rate of affected infants and the issue of whether medication used to control sugars in these women had any effect on their babies is unresolved.

The study offers further support to the practice of looking for and diagnosing diabetes, of whichever type prior to and during pregnancy. It also points to the need for ongoing surveillance and research into the effects of diabetes can have. The mechanisms of harm causation from the different types of diabetes (type one, type II, and gestational) may be different but the take-home message is that diabetes is an important contributor to adverse events in both mothers and children. For this reason, it is important that it be looked for, and treated when found.

Whilst it’s clear that we can’t claim that all women with diabetes will have babies with neurodevelopmental delays, what is evident is the importance of early intervention for these mummas. There is a lot that pregnancy dietitians can do for mummas to help reduce the risk of neurodevelopmental delays including helping mummas to optimise their blood glucose levels, optimise micronutrients that are essential for brain development and enhancing the mother’s microbiome. Furthermore, there’s a lot that pregnancy dietitians can do to help reduce the risk of mummas developing gestational diabetes.

This study provides new evidence supporting an association between diabetes in mothers and disorders of brain development in their children, including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), intellectual disability, epilepsy and cerebral palsy. Importantly, this study cannot establish that the diabetes directly caused an increased risk of these brain disorders in offspring, as it may reflect indirect effects such as maternal diet and levels of physical activity. 

Nevertheless, this study, together with prior studies, indicates that maternal health can have major impacts on a baby’s brain development, and hence the risk of various brain disorders. It is unclear whether it is the diabetes itself that is altering brain development, as other relevant factors include the mother’s diet before and during pregnancy, and possibly afterwards, during breastfeeding.

This emphasises the importance of the field of science called ‘developmental origins of health and disease’, or DOHaD, and its particular relevance to intergenerational inheritance associated with disorders of brain development. We urgently need to invest in more research in this area, and understand how shifts in public health (including the highly addictive nature of junk food and growing intergenerational problems of poor diet and physical inactivity) may be putting children at increased risk of specific brain disorders.

By understanding in detail (down to the level of molecules, cells and tissues) how the lifestyle, environmental exposures and experience of parents can affect their children, we can develop new approaches to prevent and treat these increasingly common brain disorders.

The study provides one of the largest investigations of the association of diabetes, including Type 1, Type 2, and gestational diabetes, across neurodevelopmental conditions. The study supports previous work that has shown diabetes in the mother during pregnancy does seem to be associated with neurodevelopmental conditions.

The study is interesting as it sheds light on some of the mechanisms and factors that can contribute to NDDs. It also tells us that these associations are across many NDDs, rather than being restricted to one. I think there is growing awareness that NDDs can often be studied as a larger group as many of the factors that are associated with development are common across conditions or disorders.  

It is important to note, however, that like most of the studies in the field currently, this study is unable to determine whether diabetes is causally related. NDDs are associated with lots of other medical comorbidities and it is just as likely that this association reflects many of the genetic and psychosocial factors that are common to both NDDs and diabetes. It is also clear that, despite the association, many mothers with diabetes do not have children with any form of delay, so mothers should not be too concerned. It is going to be a great and exciting science story to understand this relationship, but we are not there yet.  

It certainly also cannot explain why there has been a significant increase in the rates of autism when for many other conditions like ADHD and Cerebral Palsy, rates have either stayed the same or dropped over many years.

This is an epidemiological study that seeks to identify risk factors for neurodevelopmental disorders, such as autism and ADHD. So far, these studies have not contributed a great deal to our understanding of the causes of these conditions, other than to show that there is much we don't know. This study is another in that tradition. 

While offspring of mothers with a disability had an increased chance of having a child diagnosed with a neurodevelopmental disorder, the increase was very small, and the association could have been caused by very many other things. This is very much a 'correlation doesn't equal causation' story.

The study was well conducted, and the authors should be congratulated. But the findings do not tell us a great deal about possible causal pathways to neurodevelopmental conditions, and should not prompt any clinical advice.

This is an interesting epidemiological paper that establishes an association between various types of maternal diabetes, particularly Type 1 Diabetes, and six neurodevelopmental diseases (NDDs) in children. We already know that maternal diabetes can have long-lasting health effects for children, so it is not surprising that some of these may be related to issues such as epilepsy and developmental delay.

However, it’s also important to note that this study had some quite complicated results. While in general diabetes was associated with an increased risk of NDDs, there were some cases where children had a lower risk of disease if their mother had diabetes while pregnant. For example, children born to mothers with gestational diabetes had a reduced risk of intellectual disability.

As the authors note, this may be a sign that there is some other factor associated with both diabetes and these NDDs that is the causal factor driving them both. Perhaps women who have diabetes are more prone to other maternal complications, and that’s the driving force behind the NDDs, or maybe obesity is causing both diabetes and NDDs in children. That doesn’t mean that these associations aren’t real, but it does provide a note of caution about overinterpreting the results and what they mean.

It is also useful to note that the increased risks were, on the whole, quite small. I could not access the full supplementary data, but even from the Kaplan-Meier curves you can see that the absolute difference between the 'no diabetes' and 'gestational diabetes' groups was on the order of 0.5%. The risks were much bigger for mothers with Type 1 and 2 diabetes, but the populations were much smaller so there’s also much more uncertainty there as well.

All in all, a very useful study with plausible associations that requires more research to understand if diabetes is causing NDDs in children, as the authors themselves note.