In a world where women’s pain in healthcare settings is underestimated, perinatal care can be overlooked – but it doesn’t have to be.
Author: Mudra Ko
Artist: Yasmin Yong
Editor: Hannah Walter
A 2007 study revealed that women with hyperemesis gravidarum (prolonged vomiting during pregnancy), who underwent elective terminations, were three times more likely to express that their medical providers were uncaring. Moreover, conditions such as acute fatty liver of pregnancy can also be difficult to diagnose early due to having varying severities. Understanding the mechanisms that drive these rarer disorders of pregnancy is imperative to provide better care for women.
These disorders are slightly more overlooked and less known than other gestational syndromes. Therefore, this article will explore hyperemesis gravidarum and acute fatty liver of pregnancy, highlighting their causes and drawing upon relevant studies from UCL.
What is Hyperemesis Gravidarum (HG)?
Have you heard of “morning sickness” in pregnancy? Well, this is a severe form of that and not just in the morning.
HG is a rare disorder that causes severe nausea and vomiting in pregnancy. It can present with many complications in the mother including Wernicke’s encephalopathy (vitamin B1 deficiency-related brain damage), esophageal injury, negative psychological impacts, and even acute liver and kidney failure. HG can be very debilitating, limiting daily activities, and even forcing some women to terminate their pregnancy.
The exact causes of HG are yet to be fully understood, though there appears to be a genetic component. A study by Fejzo et al. demonstrated that 28% of women reported a family history of the mother also having HG. In fact, a genetic factor (GDF15) was shown to be significantly elevated in HG patients, which suggests that abnormal expression may drive disease.
The Link between HG and Spontaneous Preterm Birth (sPTB)
To fully understand the complications associated with HG, it is important to consider its potential correlation with spontaneous preterm birth (sPTB), given that it is one of the most serious complications in pregnancy. While it is not fully established, fear for the baby’s life and adverse complications may contribute to the emotional distress and anxiety experienced by women with HG.
Preterm birth is defined as delivery of the foetus before 37 weeks of pregnancy, with sPTB including preterm labour as well as other preterm conditions. A group of researchers affiliated with UCL conducted a study hypothesising that a HG diagnosis would be less likely in women who had an elevated sPTB or spontaneous late miscarriage risk, based on progesterone levels. Progesterone is a hormone produced by the ovaries and placenta which inhibits uterine contractions. Women with elevated sPTB risk have lower progesterone levels while HG pathogenesis may involve high levels. The examined records from University College London Hospital revealed that there was lower incidence of HG in women with an elevated risk of sPTB risk, compared to women with no apparent risk factors.
However, a consensus still has not been reached on the relationship between HG and sPTB; some studies show that HG has no effect on sPTB, while others suggest otherwise. Further research is needed on the pathogenesis of HG, as it may also benefit our understanding of sPTB, the leading cause of perinatal mortality.
What is Acute Fatty Liver of Pregnancy (AFLP)?
AFLP is a rare life-threatening syndrome that occurs in the third trimester and is characterised by acute liver failure through the accumulation of fat in the mother’s liver. Symptoms include jaundice (yellow skin and eyes), nausea, vomiting, and abdominal pain. Extreme cases may give rise to acute kidney failure, encephalopathy (altered brain function), and gastrointestinal bleeding. Patients can also develop pre-eclampsia — a pregnancy complication associated with high blood pressure and protein in the urine, which can lead to severe headache, vomiting, vision problems, and more.
It has been hypothesised that AFLP is due to a defect in fatty acid oxidation —the metabolism of fatty acids to generate energy. This pathway produces Acetyl-CoA, which is later converted into ketone bodies. Ketones serve as an energy source when the body’s glucose supply is limited. Additionally, AFLP has been linked to deficiency in a number of enzymes involved in fatty acid oxidation. However, not all patients with AFLP have these deficiencies, suggesting that there may be other factors involved in its pathogenesis.
AFLP as a consequence of defective fatty acid oxidation
Dr. Mandeep Kaur Kaler’s award-winning PhD in 2019 revealed groundbreaking information on AFLP. Her phenotype study showed that women with AFLP did not have ketonuria (high ketone levels in the urine) even with persistent nausea and vomiting. A defect in metabolising fat into ketones explains the lack of ketonuria and the possibility of AFLP being a ‘disorder of energy metabolism.’
Dr. Kaler also conducted a fasting and fat-burning exercise study and found that ketone levels were similar between women who previously had AFLP and women who have never had AFLP. This indicates that women who experienced AFLP during pregnancy could produce ketones normally outside of pregnancy, highlighting that AFLP is specific to pregnancy.
Concluding remarks
With the detrimental effects of both HG and AFLP, there is a pressing need for a deeper understanding of their pathogenesis and aetiology. This holds the promise of improved pregnancy outcomes and quality of life for women in the future.
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