Antenatal steroids: are there links with mental and behaviour problems later on?

In Episode 8 of Series 3 of the DIAL Podcast, Katri Räikkönen from Helsinki University and a member of DIAL’s PremLife project, talks about her research investigating whether the babies of mothers who whilst pregnant are prescribed steroid drugs, because of concerns around premature births, are more likely to develop behavioural and mental disorders later on.

Associations Between Maternal Antenatal Corticosteroid Treatment and Mental and Behavioural Disorders in Children is research published in the Journal of the American Medical Association. 

Transcript

Christine Garrington  0:00  

Welcome to DIAL a podcast where we tune in to evidence on inequality over the life course. In this series, we discuss emerging findings from DIAL research. Our guest today is Katri Räikkönen from the University of Helsinki, who has been looking into babies whose mothers are treated with steroid drugs during pregnancy, to see if they're more likely to suffer from mental and behavioural disorders later on. I started by asking her why a mum to be might be prescribed steroids, as part of her prenatal care?

Katri Räikkönen  0:28  

Maternal antenatal steroid treatment is a standard treatment to accelerate fetal maturation, if there is a risk of delivery before 34 gestational weeks within seven days. This a treatment that has been given, since 1990s, as a routine care for this purpose. And the reason why these corticosteroids or steroid treatment is given is that it really accelerates fetal maturation, and if the baby is born preterm, it reduces the risk of the infant to have multiple morbidities that are related to preterm birth, and it also decreases the risk of death. So, this is a really effective treatment in those babies being born preterm if there has been a threat of preterm delivery.

Christine Garrington  1:27  

Okay, understood. So what was it about the prescription of these medications then, that you wanted to look into specifically and why?

Katri Räikkönen  1:33  

This treatment, it has a short-term benefits for infant morbidity and mortality. But the debate is about whether it carries long-term harms and the long-term harms relates specifically to foetal neurodevelopment, because this, this treatment readily processed the placenta. And it's also able to cross the blood brain barrier. And while corticosteroids are very important for brain development. If the fetus becomes overexposed to unnecessarily high levels of corticosteroids steroids, it carries opposite effects, and may harm fetal neurodevelopment because it affects multiple neurodevelopmental processes, and this has a rise and rise the concern that because it crosses readily to the fetal side and may carry harms on fetal inner development, it can then increase risk of mental and behavioural disorders later in life.

Christine Garrington  2:42  

And where did you get your information from to carry out the study?

Katri Räikkönen  2:45

Hmmm, we exploited the Finnish nationwide registers. In Finland since 1969 all residents have been given a personal identification number. This identification number can be used to link data from different registers. And since 1987, Finland, established the Finnish medical birth register, and we linked data from this birth register to a register called the Care Register for Health Care, which carries all hospital treatment diagnoses and all treatment diagnoses, even in public specialised medical care, and we use data from, from all births in Finland between 2006 and 2017. And the reason for that was that we were able to take into account many confounding factors in this study to just verify whether antenatal corticosteroid treatments really increased risk of mental and behavioural disorders in children.

Christine Garrington  4:01  

So what exactly then did you do with that fantastic array of data that you had available to you?

Katri Räikkönen  4:08  

So after merging, data from the medical birth register and this Care Register for Health Care. We then studied if those children are almost 700,000 children born between 2006 and 17, we identified those children who were exposed to maternal antenatal corticosteroid treatment and compared them to those children who were not. And then we compare whether these two groups of children differed in their risk of developing mental and behavioural disorders, up to 12 years of age.

Christine Garrington  4:50  

So of the children in your study whose mother had received the treatment, what proportion had gone on to be diagnosed with a mental or behavioural disorder?

Katri Räikkönen  4:58

Well I mean there was a very dramatic difference between the rates of that diagnoses in those who were exposed, and in those who were not exposed. So of the children who were not exposed 6.5 per cent had received a diagnosis, and of the children who were exposed 12 per cent had received a diagnosis. So this difference was very apparent. And it was statistically significant. And when we made adjustments in in our statistical models, for multiple factors might compound, the association or this difference increment, it still remained significant, and this was especially true when we compare children who were born at term after the antenatal corticosteroid treatment exposure.

Christine Garrington  5:53

And how did the risk of having a mental or behavioural disorder compare with those children in the study whose mothers did not receive the treatment? 

Katri Räikkönen  6:00 

Well, we compare these in terms of hazard ratios, and the hazard ratio was one point thirty three times higher, for those children who were exposed than were not exposed, and the absolute difference in percentages was almost 6 per cent. So there was, they had a, a 6 per cent higher rate of receiving a mental and behavioural disorder diagnosis.

Christine Garrington  6:29  

Okay, so some really interesting, really important findings here, capturing what does this lead you to conclude and I wonder if there are some key messages for those responsible for the health of moms to be, you know, particularly where a birth looks like it might be preterm?

Katri Räikkönen  6:45  

I mean, preterm birth is very difficult to predict. So for instance, in our study, we found that even though these mothers had had a threat of preterm delivery before 34 weeks of gestation, nearly half continue delivering a term baby. So, it is very difficult to give recommendations that these corticosteroids ought not to be used because we know that it reduces significantly risk of morbidity and mortality and those children who then end up being born preterm. But in some countries, the treatment recommendations go by your own 34 weeks of gestation. For instance in the USA, this treatment is recommended, also in delayed preterm window. And in my opinion, these findings, then rise concerns whether this treatment, ought to be extended to wider window above and beyond 34 weeks of gestation, like, like the European guidelines suggests. It benefits in the end, delayed preterm window, are no longer as life threatening, as they are, when the baby is being born preterm.

Christine Garrington  8:11  

In light of all of that, I wonder if there are any specific recommendations you would make or whether you hold back a bit from that?

Katri Räikkönen  8:19

These findings may help inform decisions about maternal antenatal corticosteroid treatment. Especially when administered in the late preterm window when the threats to the fetus are decreased. So it's, it's less likely to increase mortality in the in the late preterm window. This also means that if a baby is born at term after being exposed to antenatal corticosteroid treatment, preventive interventions are in place. So these children ought to be followed up more closely, we all ought to offer them targeted preventive interventions. I mean this group of children is not that large. In our study, nearly 15,000 children during, during the years of birth were exposed to antenatal corticosteroid treatment but only 50% ended up being born at term. So, even though it's a large number during these years of follow up. It is still annually, a fairly small number of children who would benefit from targeted prevention intervention.

Christine Garrington  9:38  

So in summary, it's not possible to give a cut and dry answer to whether or not this type of treatment is a good or bad thing.

Katri Räikkönen  9:44  

So it does carry, it does carry benefits for those children who were born preterm. But these benefits do not extend to those children, born at term.

Christine Garrington  9:57  

Associations Between Maternal Antenatal Corticosteroid Treatment and Mental and Behavioural Disorders in Children  is research by Katri Räikkönen and colleagues and is published in the Journal of the American Medical Association. It is part of DIAL’s PremLife project which is looking at the outcomes of preterm and low birth weight babies across the life course. Thanks for listening to this episode of our podcast which is presented and produced by me Chris Garrington and edited by Elina Kilpi-Jakonen.