Hyperemesis gravidarum and risks of placental dysfunction disorders
Hello. My name's [INAUDIBLE]. I'm going to discuss the paper on hyperemesis gravidarum and the risk of placental dysfunction disorders, a population-based cohort study. For today's outline, we're going to go over the introduction, discuss the paper, do a critique on it, discuss the applicability and recommendations, and a conclusion. Let's start with the definition of hyperemesis gravidarum, described as extreme, excessive, and persistent vomiting in early pregnancy that may lead to dehydration and malnutrition. It's usually associated with the weight loss of more than 5% of a woman's pre-pregnancy weight.
It more commonly affects young women in their first pregnancies and in women carrying multiple fetuses. Hyperemesis gravidarum usually stops by the 20th week of pregnancy. Treatment of mild hyperemesis gravidarum usually involves dietary measures, rest, and use of antacids.
Very severe hyperemesis gravidarum may call for the use of intravenous fluids and nutrition. Hyperemesis gravidarum affects about 0.5% to 3% of all pregnancies. So today's paper is "Hyperemesis Gravidarum and the Risk of Placental Dysfunction Disorders, a Population-Based Cohort Study." It was published in the British Journal of O&G in January of 2013. It is a nationwide study based in Sweden. The hypothesis is based on the fact that hCG is elevated in hyperemesis gravidarum. HCG is also required for trophoblast migration into spiral arteries, which allows for placental implantation.
In the absence of sufficient trophoblast migration in the first trimester, placenta is hypoxic, and we see an increase in the hCG levels in the second trimester. The hypothesis is that there is an association of increased second trimester hCG with placental dysfunction disorders, namely, pre-eclampsia, placental abruption, stillbirth, and small for gestational age. So the study is designed to determine the correlation between hyperemesis due to elevated hCG and subsequent placental dysfunction disorders. So the study is based on the Swedish Medical Birth Register. It was a population-wide study that covered more than 1 million pregnant women with singleton births. The inclusion criteria included all births between January 1, 1997, and December 31, 2009.
Only singleton births were included and required at least one admission for hyperemesis gravidarum. The exclusion criteria included the first admission for hyperemesis gravidarum after 22 weeks, and after analyzing the risk for small for gestational age, stillbirths and births with missing information were excluded. So the study is a population-based cohort study. The outcome variables include placental abruption, pre-eclampsia, small for gestational age, and stillbirth. The control group were women without an inpatient diagnosis of hyperemesis gravidarum. Odds ratio using 95% confidence interval was used to make the comparison. Adjustment for other risk factors, as mentioned on the slide, were made based on the findings of the registry.
This table shows the covariates for the study population findings. Mothers with admission for hyperemesis gravidarum in the first trimester are generally older than mothers admitted in the second trimester. They are also multi-gravida, have a lower BMI, and are nonsmokers.
They're also carrying a female fetus and are from a non-Nordic birth country. As for other results, they will be discussed later in the presentation. So this table shows the associated risk of all four of the placental dysfunction disorders in pregnancy complicated by hyperemesis gravidarum.
Basically, they found that there is no such strong association between first trimester admission for hyperemesis gravidarum and placental dysfunction disorders. For women diagnosed with second trimester hyperemesis gravidarum, they have a two-fold increased risk of pre-eclampsia, threefold increased risk for placental abruption, and a 39% increased risk for small for gestational age. The sample size was too small, and therefore, stillbirths were excluded.
OK, so one of the major strengths of the study is that it is a nationwide population-based design, and data was collected prospectively and precludes recall bias. Also, it has a very large sample size that made it possible to stratify hyperemesis gravidarum by trimester of hospitalization and to study any rare adverse outcomes such as placental abruption. Study of such a scale was only possible due to Sweden's universal standardized care and comprehensive national database. There was attempt to normalize a substantial number of confounding factors like BMI, socioeconomic status, smoking, maternal chronic conditions. This is important, as such maternal characteristics have previously been shown to be associated with adverse fetal outcomes.
The findings of an increased risk of pre-eclampsia and hyperemesis gravidarum is also in agreement with findings of a formal study by Zang, et al, in 1991. There were also a number of weaknesses to the study. One of them is poorly defined exposure variables, such as lack of consensus on the precise definition of severe hyperemesis, onset dates, and so on. There were also no general criterion or guidelines in Sweden for hospital admission of pregnant women with hyperemesis gravidarum. The general criterion is that requirement of IV fluid infusion was used. Another weakness was there were missing covariates. Important covariates such as ethnicity, anemia, history of infections, weight change during pregnancy were not included.
For placental abruption, covariates such as domestic violence, accidents, or everyday injury, trauma, are important factors as well, but they were also not included. For small for gestational age, malnutrition is an important risk factor. Maternal weight information and constitutional reasons were also omitted in the study. Another weakness is in their statistical analyses.
Stillbirths are rare, and thus the sample size is too small for the study. There were only six cases for stillbirths and 22 cases for placental abruption. And their methodology for the adjustment of maternal factors were also not stated explicitly.
So if you look at this table, the numbers are not adjusted for women who were not admitted for hyperemesis gravidarum and for those who were admitted in the second trimester. Now, if you look at this next table, other factors such as education, hyperthyroidism, gestational diabetes, hypertension, are other confounding factors that were not adjusted for in the study. This study is also in discordance with other studies. Some other studies have proved that women with severe hyperemesis gravidarum did not have statistically significant differences in the incidence of pregnancy complications compared to women without hyperemesis gravidarum. Other studies have also shown that adverse infant outcomes associated with hyperemesis gravidarum are consequences of, and mostly limited to, women with poor maternal weight gain. So how does this study apply to a local context? First, we have to adjust for the demographics such as race and co-morbidities prevalent in Singapore. There is also a difference in the management of patients.
Sweden's screening protocol is that there is one scan at 17 weeks, and most women opt for it. In Singapore, the screening protocol is such that there is one scan between 8 to 12 weeks, a growth scan at 20 weeks, and weekly follow-ups after 36 weeks. There is also no treatment for hyperemesis gravidarum. We recommend that there be a more focused study because too many factors could contribute to placental problems, and not all risk factors/covariates were covered in the study. We also recommend that investigations be more concentrated on each disorder and explore the various items that could influence the disease outcome. We also recommend the monitoring of additional parameters, such as first and second trimester hCG levels and fetal DNA concentration in maternal plasma. So in conclusion, placental dysfunction disorders are multi-factorial.
While this study gives us some insight into a causal relationship between hyperemesis gravidarum and a few placental dysfunction disorders, there is inconclusive evidence as to the cause and effect of each event. Elevated levels of hCG is hypothesized to be one of the causers of hyperemesis gravidarum, and the same hormone may also be a direct culprit of a variety of placental dysfunction disorders. To say that hyperemesis gravidarum is a risk factor for placental dysfunction disorders is premature.
Nonetheless, this study has made a good attempt at exploring this complex relationship.
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