Finding simple solutions to complex problems
Physiology is complicated. The more we learn about physiology, the more complicated we realise it is. As healthcare students and practitioners, we don’t do well with complexity. We want simple mental shortcuts that make it easy for us to get from point A to point B, while providing safe care for most people, most of the time.
For the duration of my time as a learner in healthcare (coming up for forty years…) the same shortcut story about fetal hypoxia has been used. In essence, the story goes – when oxygen levels fall below a critical point, cells switch over to metabolic processes that generate energy without needing oxygen. Acid, and in particular lactic acid or lactate, is a byproduct of this process. So if you want to know whether a fetus is or was getting enough oxygen, measure either the pH (acid level) or the concentration of lactate in their blood. Easy peasy.
But it’s not that simple
We maternity professionals tend to live in a little world all of our own. When changes in knowledge happen in other fields, we don’t always keep up with it. Physiologists shifted their stance on the lactate story about twenty years ago, recognising that, well, it’s not that simple. Gladden, an actual real-life physiologist, summarised the change in thinking in 2004. Increased lactate levels can occur in hypoxia, but this is now seen as the exception rather than the rule. Yes, lactate is produced in anaerobic metabolic processes, but it is also produced when oxygen levels are adequate. Lactate plays an important role as an energy source for metabolically active muscle tissues (like the uterus in labour). Lactate appears to have roles in mediating wound repair and tissue regeneration. Lactate production is stimulated by high levels of adrenaline (which happens in labour) and this, rather than low oxygen levels, is thought to be responsible for rises in lactate in sepsis and after haemorrhage.
Part of the reason that I believe that CTG monitoring has not been able to have a significant impact on outcomes thought to be due to hypoxia in labour is that maternity professional’s assumptions about fetal physiology are stuck back in the 1960s, and are, well, wrong. There is increasing research that should prompt us to rethink, and admit that things are a whole lot more complicated than we thought they were.
Some physiology to think about
I’m not an actual physiologist, though I have taught physiology. Here are a few tips to get us started before I start getting into the research. Lactate is an acid (it releases protons – H- atoms). It is a wee tiny molecule, and wee tiny molecules pass from one cell to another easily. Lactate plays an important role as an intermediary in metabolic processes that require energy, so being able to nip across cell membranes to find a job that needs doing is a handy thing.
Lactate turns up pretty much everywhere we might look for it in reproductive health care. Not only is it in fetal blood, it is in women’s blood too. And bacteria in the vagina (lactobacilli) love to make lactic acid, where it is considered an important part of our first line defence against vaginal infection. Lactate is in amniotic fluid, and semen, and even tears. While I think this idea is a bit “out there” it has been proposed that lactate molecules might play a role in pair-bonding (Sri Kantha, et al., 2021). Maybe that pheromone that women are sniffing on their newborn baby as they fall in love is lactate?
Being a small molecule that is found in blood, lactate can duck across the placenta easily in either direction. If the woman is making a lot of it, it will turn up in fetal blood. If the fetus is making a lot, it will diffuse into the maternal blood volume, diluting it, and making use of the woman’s mechanisms for dealing with changes in blood pH to even things out again. Lactate also shifts into and out of amniotic fluid, where it is pretty easy to measure (at least once the membranes are open) without needing to stab anyone.
Some research thoughts
So what are some of the research goings on that might have us rethinking the fetal hypoxia – lactate story as we know it?
- Lactate levels in women’s blood are higher during pregnancy than the non-pregnant population, and are even higher during labour (Bauer, et al., 2019; Dockree, et al., 2022). Levels are higher in women who given birth vaginally than by caesarean section.
- Maternal lactate levels increase as labour progresses, peaking in the second stage of labour (Nordström, et al., 2001). There is also a close correlation between fetal and maternal lactate concentrations in labour.
- Drinking juice in labour blunts the rise in lactate concentration (Andriani, et al., 2018).
- Lactate levels in amniotic fluid also correlate with longer labour duration (Wiberg-Itzel, 2021).
- Administering bicarbonate to women in labour lowers amniotic fluid lactate concentration and increases the vaginal birth rate without changing perinatal outcomes (Wiberg-Itzel, et al., 2018).
Not surprisingly, research seems to support the idea that lactate moves freely between maternal blood, amniotic fluid, and fetal blood. It is possible to tell a different story about fetal lactate levels than the one I was taught in the 1980s. Fetal lactate concentration might reflect changes in maternal lactate levels as it is produced to meet the metabolic requirements of uterine muscle during labour – rather than reflecting fetal oxygenation. Treating or preventing fetal lactic acidosis might involve adequate carbohydrate intake during labour, or enhancing women’s ability to buffer pH by giving them bicarbonate, rather than immediate recourse to caesarean section. Or none of this might be true – we just don’t have enough research to be confident.
Fetal blood sampling for lactate estimation
We really have no idea what we are doing when it comes to fetal blood sampling during labour. It entered practice before CTG monitoring did, but soon fell into a supplementary role, used only when the CTG was abnormal. There has been very little research to help us to understand whether measuring fetal pH or lactate can help us ensure better outcomes for women or their babies. Because we THINK we know the physiology, it seems logical to keep doing it. But – what if we have it all wrong? There is starting to be indirect evidence that shows that we don’t actually know what is going on with fetal lactate concentrations. Surely now is a good time to pause fetal blood sampling, go back to basics, and really understand the physiology of it all before we move on.
Andriani, R., Safari, M., Hidayat, Y., Husin, F., Nugraha, G., Susiarno, H., & Cahyadi, W. (2018). Mixed juice consumption during labour to the mother’s blood lactate levels. Global Medical & Health Communication, 6(3), 169 – 175. https://doi.org/10.29313/gmhc.v6i3.2907
Bauer, M., Balistreri, M., MacEachern, M., Cassidy, R., Schoenfeld, R., Sankar, K., Clauw, D., & Langen, E. Normal range for maternal lactic acid during labor: A systematic review and meta-analysis of observational studies. American Journal of Perinatology, 36(9), 898 – 906. https://www.scirp.org/journal/paperinformation.aspx?paperid=76732
Dockree, S., O’Sullivan, J., Shine, B., James, T., & Vatish, M. (2022). How should we interpret lactate in labour? A reference study. British Journal of Obstetrics & Gynaecology, in press. https://doi.org/10.1111/1471-0528.17264
Gladden, L.B. (2004), Lactate metabolism: a new paradigm for the third millennium. Journal of Physiology, 558, 5-30. https://doi.org/10.1113/jphysiol.2003.058701
Nordström, L., Achanna, S., Naka, K., & Arulkumaran, S. (2001). Fetal and maternal lactate increase during active second stage of labour. British Journal of Obstetrics & Gynaecology, 108(3), 263 – 268. https://doi.org/10.1016/S0306-5456(00)00034-6
Sri Kantha, S., Kobayashi, A., Saito, S., Sakai, S., & Matsui, Y. (2021). Is lactic acid a primary chemosignal molecule for pair bonding in humans? International Medical Journal, 28(2), 208-212.
Wiberg-Itzel, E., Wray, S., & Åkerud, H. (2018, Sep). A randomized controlled trial of a new treatment for labor dystocia. Journal of Maternal-Fetal & Neonatal Medicine, 31(17), 2237-2244. https://doi.org/10.1080/14767058.2017.1339268
Wiberg-Itzel, E. (2021). Amniotic fluid lactate (AFL): a new predictor of labor outcome in dystocic deliveries. Journal of Maternal-Fetal & Neonatal Medicine, in press. 10.1080/14767058.2021.1946790