Tag: nausea and vomiting of pregnancy

Hyperemesis Gravida Linked to Pregnancy, Birth Complications

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Pregnant women with a severe form of nausea face increased risks for several pregnancy and birth complications, according to a new Stanford Medicine study of 2.5 million California births.

The research, published in the American Journal of Epidemiology, is the first large, US population-based study of the dangers of severe pregnancy nausea and vomiting, a condition formally known as hyperemesis gravidarum, or HG.

While most pregnant women – 70% to 80% – experience some nausea, it usually leaves no lasting effects. In contrast, as the new research shows, HG puts a major strain on the 1% to 3% of the pregnancies affected.

“Hyperemesis gravidarum is not just bad morning sickness; it’s severe enough to cause dehydration and significant weight loss,” said lead study author Rebecca Gardner, a Stanford Medicine graduate student in epidemiology and clinical research.

The study’s senior authors are Julia Fridman Simard, ScD, associate professor of epidemiology and population health and of immunology and rheumatology, and Gary Shaw, DrPH, the Rosemarie Hess Professor and a professor of pediatrics.

The research team looked at complications in pregnancies in which the mother was hospitalised for HG, compared with pregnancies without such hospitalisations.

“We found hyperemesis gravidarum was linked to higher risk for preterm birth, anaemia, smaller-than-expected babies, preeclampsia, gestational hypertension and placental abruption,” Gardner said. “Hospitalization for HG really does flag a pregnancy as being at higher risk for a range of serious complications.”

Struggling to get nourishment

Pregnant women with HG experience severe, sustained nausea and vomiting, often continuing throughout their pregnancies. They struggle to eat; stay hydrated; and absorb enough nutrients that play key roles in early pregnancy, such as folate. (Adequate folate intake reduces the risk of certain birth defects.) Women with HG can lose a lot of weight at a time when they should be gaining; one study found that about a quarter of HG patients lost more than 15% of their pre-pregnancy weight.

“We know from other studies that women with HG don’t get as many nutrients,” Gardner said. “This could impair placental development, which we think leads to higher risk for some of the outcomes we looked for, such as preeclampsia and babies being smaller than expected at birth.”

But previous studies examining potential links between HG and poor pregnancy outcomes had weaknesses, Gardner said: Many were small, and nearly all used data from European countries with populations that are less diverse than the U.S. population and that have medical systems structured differently from the U.S. system.

The study examined records for single-baby California births from 2007 to 2011. The researchers had access to demographic information about mothers, pre-pregnancy body mass index and census tract data that was used to calculate each patient’s level of social vulnerability. The researchers also had access to diagnostic codes from patients’ pregnancy and birth medical records.

Of the 2 476 492 births included in the final analysis, 53,681, or 2.2%, were to mothers with HG, meaning they received emergency department or hospital inpatient care for hyperemesis gravidarum.  

Compared with those who were never hospitalised for HG, women with HG had higher risk for preeclampsia, a pregnancy complication that can cause seizures if untreated; gestational hypertension, or high blood pressure in pregnancy; preterm birth, meaning delivery three or more weeks before the due date; babies that were small for their gestational age, meaning they had grown less than expected during foetal development, anaemia, and placental abruption, in which the placenta becomes partly or completely detached from the uterus before delivery.

The increase in relative risk for each complication varied. For instance, after adjusting for possible confounding factors, women with HG were about 18% more likely to have preeclampsia, about 25% more likely to deliver early, about 37% more likely to be anaemic and about 14% more likely to experience a placental abruption than women without HG.

Women who were first hospitalised for HG during the second trimester of pregnancy were more likely to experience complications than those hospitalised during the first trimester, the study found.

A flag for closer monitoring

Guidelines from the American College of Obstetricians and Gynecologists for treating HG changed in 2018, after the data used for this study was collected, Gardner noted. The guidelines now encourage treating pregnancy nausea faster and more aggressively, and two medications are now approved by the US Food and Drug Administration for nausea and vomiting in pregnancy. More research could help clarify the effects of these newer guidelines, Gardner said.

More research could also show whether HG should prompt physicians to offer additional preventive care, such as low-dose aspirin, which is already used to prevent preeclampsia in patients who are at risk for other reasons.

The research team hopes that its findings will motivate physicians and pregnant women to pay closer attention to HG.

“For physicians, I think this data means that pregnancies with HG hospitalisation may warrant closer monitoring for certain complications,” Gardner said.

“Pregnant women need to know that most HG pregnancies still result in healthy outcomes for the mom and baby, but HG does need to be taken seriously,” she said. It’s important to advocate for yourself by asking your doctor if you need more monitoring or anti-nausea medication, Gardner said, adding, “This is not just something to push through.”

Source: Stanford Medicine

Nausea and Vomiting of Pregnancy Caused by a Complex Inflammatory Response

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UCLA researchers have uncovered a link between “morning sickness” symptoms and the body’s natural, but complex, inflammatory response to biological and bodily changes during pregnancy.

According to the National Institutes of Health, up to 80% of early-stage pregnant mothers experience some nausea, vomiting and aversions to certain foods and smells. While uncomfortable, these symptoms are not typically a sign that anything is wrong with the health of the mother or the developing fetus, but rather an indication of a delicate balance unique to pregnant women. 

“During pregnancy, a mother’s immune system faces a tricky challenge: it has to protect both her and the foetus from infection, but without accidentally attacking the foetus, whose genetic identity is half-foreign because it is half derived from the father. Normally, the immune system attacks anything that seems foreign, so in pregnancy, it has to carefully adjust to keep the foetus safe while still defending against infection,” said UCLA anthropology professor Molly Fox, corresponding author of the study published in Evolution, Medicine and Public Health.

The researchers believe that this delicate balance, which protects mother and foetus, is achieved by a unique mix of inflammatory responses. They function to prevent the mother’s body from rejecting the foetus, alongside adaptive behavioural mechanisms, like nausea, that encourage the mother to avoid foods that are potentially harmful, especially in the first and second trimesters when the foetus is most vulnerable.

“Nausea, vomiting or aversions to foods or smells are not indications that something is going wrong for the mother or the foetus. It’s likely an indication that everything is moving along normally, and a reflection of the body’s healthy and helpful immune response,” said UCLA anthropology professor and paper co-author Daniel Fessler.

Methodology and findings

For the study, the UCLA-led team of anthropologists and epidemiologists collected and analysed blood samples to measure immune system molecules called cytokines. Cytokines are proteins that send signals to help the body launch a quick defence against sickness and regulate inflammation. Participants also filled out questionnaires that asked about morning sickness-related symptoms and food and smell aversions during the early stages of pregnancy. The participants were 58 Latina women in Southern California who were followed beginning in early pregnancy through the postpartum.

Sixty-four percent of study participants experienced odour or food aversions, primarily to tobacco smoke and meat. Sixty-seven percent reported nausea and 66% experienced vomiting.

The study team measured pro-inflammatory cytokines as well as anti-inflammatory cytokines. They found that women who experienced an aversion to tobacco smoke showed a noticeable shift toward a more inflammatory response. Food aversions, nausea and vomiting were also associated with a more pro-inflammatory immune balance.

An evolutionary process?

The correlation is consistent with researchers’ theory that these symptoms may be part of an evolutionary adaptation that helps pregnant mothers’ bodies minimize exposure to harmful substances, though the study’s authors caution that the evidence is not definitive and more research is needed. 

They emphasised that the study allowed the team to look at both human biological and behavioural responses during pregnancy.

“In many mammals, the foetal compartment has barriers separating it from the mother’s blood supply, where her immune cells are. But in humans, we have a unique setup – foetal cells are bathed in maternal blood. Humans have the most invasive of all placentas, burrowing deep into maternal tissue. So humans need unique strategies to prevent the mother’s immune system from attacking the foetus,” said Fox.

These immunological changes may induce nausea, which in turn encourages food avoidance that might act as an additional layer of protection, according to the researchers

“Nowadays, you will see labels on packages of ground beef or soft cheese that warn pregnant women to be cautious about these products because of the risks of foodborne illness during pregnancy. Aversions to certain odours and foods, and nausea and even vomiting, appear to be evolution’s way of achieving that same objective,” said Fessler.

Practical implications

The researchers, including first author Dayoon Kwon, who just completed her PhD in epidemiology at UCLA (and is now a postdoctoral fellow at Stanford), said that the study could help bolster recognition that nausea and vomiting are normal symptoms with biological underpinnings associated with healthy pregnancies. The study’s results could help in paving the way for common-sense workplace accommodations, such as more efficient deployment of health care benefits and other helpful resources to reduce stigma, excessive absences and lost productivity.

They also encourage other researchers to continue to look into the questions raised by the study, to not only explore the evolutionary questions, but to work toward providing clinicians with non- or low-invasive measures of prognoses.

Source: University of California – Los Angeles

Cause of Pregnancy Sickness – and Potential Treatment

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A Cambridge-led study has shown why many women experience nausea and vomiting during pregnancy – and why some women, including the Duchess of Cambridge, become so sick they need to be admitted to hospital.

The culprit is a hormone produced by the foetus – a protein known as GDF15. But how sick the mother feels depends on a combination of how much of the hormone is produced by the foetus

The discovery, published today in Nature, points to a potential way to prevent pregnancy sickness by exposing mothers to GDF15 ahead of pregnancy to build up their resilience.

As many as seven in ten pregnancies are affected by nausea and vomiting. In some women – thought to be between one and three in 100 pregnancies – it can be severe, even threatening the life of the foetus and the mother and requiring intravenous fluid replacement to prevent dangerous levels of dehydration. So-called hyperemesis gravidarum is the commonest cause of admission to hospital of women in the first three months of pregnancy.

Although some therapies exist to treat pregnancy sickness and are at least partially effective, widespread ignorance of the disorder compounded by fear of using medication in pregnancy mean that many women with this condition are inadequately treated.

Until recently, the cause of pregnancy sickness was entirely unknown. Recently, some evidence, from biochemical and genetic studies has suggested that it might relate to the production by the placenta of the hormone GDF15, which acts on the mother’s brain to cause her to feel nauseous and vomit.

Now, an international study, involving scientists at the University of Cambridge and researchers in Scotland, the USA and Sri Lanka, has made a major advance in understanding the role of GDF15 in pregnancy sickness, including hyperemesis gravidarum.

The team studied data from women recruited to a number of studies, including at the Rosie Maternity Hospital, part of Cambridge University Hospitals NHS Foundation Trust and Peterborough City Hospital, North West Anglia NHS Foundation Trust. They used a combination of approaches including human genetics, new ways of measuring hormones in pregnant women’s blood, and studies in cells and mice.

The researchers showed that the degree of nausea and vomiting that a woman experiences in pregnancy is directly related to both the amount of GDF15 made by the foetal part of placenta and sent into her bloodstream, and how sensitive she is to the nauseating effect of this hormone.

GDF15 is made at low levels in all tissues outside of pregnancy. How sensitive the mother is to the hormone during pregnancy is influenced by how much of it she was exposed to prior to pregnancy – women with normally low levels of GDF15 in blood have a higher risk of developing severe nausea and vomiting in pregnancy..

The team found that a rare genetic variant that puts women at a much greater risk of hyperemesis gravidarum was associated with lower levels of the hormone in the blood and tissues outside of pregnancy. Similarly, women with the inherited blood disorder beta thalassemia, which causes them to have naturally very high levels of GDF15 prior to pregnancy, experience little or no nausea or vomiting.

Professor Sir Stephen O’Rahilly, Co-Director of the Wellcome-Medical Research Council Institute of Metabolic Science at the University of Cambridge, who led the collaboration, said: “Most women who become pregnant will experience nausea and sickness at some point, and while this is not pleasant, for some women it can be much worse – they’ll become so sick they require treatment and even hospitalisation.

“We now know why: the baby growing in the womb is producing a hormone at levels the mother is not used to. The more sensitive she is to this hormone, the sicker she will become. Knowing this gives us a clue as to how we might prevent this from happening. It also makes us more confident that preventing GDF15 from accessing its highly specific receptor in the mother’s brain will ultimately form the basis for an effective and safe way of treating this disorder.”

Mice exposed to acute, high levels of GDF15 showed signs of loss of appetite, suggesting that they were experiencing nausea, but mice treated with a long-acting form of GDF15 did not show similar behaviour when exposed to acute levels of the hormone. The researchers believe that building up woman’s tolerance to the hormone prior to pregnancy could hold the key to preventing sickness.

Co-author Dr Marlena Fejzo from the Department of Population and Public Health Sciences at the University of Southern California whose team had previously identified the genetic association between GDF15 and hyperemesis gravidarum, has first-hand experience with the condition. “When I was pregnant, I became so ill that I could barely move without being sick. When I tried to find out why, I realised how little was known about my condition, despite pregnancy nausea being very common.

“Hopefully, now that we understand the cause of hyperemesis gravidarum, we’re a step closer to developing effective treatments to stop other mothers going through what I and many other women have experienced.”

The work involved collaboration between scientists at the University of Cambridge, University of Southern California, University of Edinburgh, University of Glasgow and Kelaniya University, Colombo, Sri Lanka. The principal UK funders of the study were the Medical Research Council and Wellcome, with support from the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

The original text of this story is licensed under a Creative Commons License

Source: University of Cambridge