2 Minute Medicine Rewind September 6, 2021

Perinatal Outcomes Among Patients With Sepsis During Pregnancy

1. Pregnancies with antepartum sepsis were associated with placental dysfunctions

2. Increased antenatal surveillance to avoid sepsis during pregnancy may reduce the risk of fetal complications

Evidence Rating Level: 2 (Good)

Maternal sepsis is a prevalent, life threatening condition that evolves rapidly with a fatality rate ranging from 10% to 30% in the United States. Sepsis during pregnancy is often associated with preterm deliveries as well as emergencies such as postpartum hemorrhage. The majority of studies focus on peripartum infection and emergent situations during labour or postpartum intensive care admissions. However, fewer studies have investigated the association between sepsis and long term outcomes in maternal and fetal health. This study aimed to address this gap by examining placental complications among patients who experienced antepartum sepsis hospitalizations and subsequently recovered from their infections. This retrospective cohort study of 14565 patients collected data between 2012-2018 on patients with uncomplicated, singleton pregnancies after 20 weeks’ gestation. Patients were assessed for antenatal sepsis between the first confirmation of pregnancy until the onset of labour.  Perinatal outcomes were also analyzed for placental dysfunctions including fetal growth restriction leading to small for gestational age, stillbirth, preeclampsia, and deficient amniotic fluid levels.  These outcomes were compared between the sepsis group and the reference group. Overall, of the 14565 patients, n= 59 had antenatal sepsis with the most common causes coming from urinary tract and pulmonary infections.  Individuals who had experienced antepartum sepsis hospitalisations had twice the risk of placental dysfunctions (n=21 [35.6%] vs n=3450 [23.8%]; odds ratio, 1.77; 95% CI, 1.04-3.02). Furthermore, sepsis patients were at higher risk of postpartum hemorrhage, maternal ICU admissions, and preeclampsia compared to their non septic counterparts.  As previously mentioned, prior studies have focused primarily on immediate maternal morbidity and mortality. Therefore, a strength of this study was its focus on obstetric and postpartum health as well as neon ration outcomes. On the other hand, a limitation of this study was its lack of analysis for the severity of sepsis. Some patients may have experienced life threatening sepsis while others may have had an acute and rapidly treated infection. Overall, this study is very clinically relevant as it highlights the importance of increasing antenatal surveillance and monitoring for sepsis to avoid placental dysfunction. History of antepartum sepsis significantly increased obstetric complications and postpartum health and therefore should be monitored carefully.


Association between intimate partner violence during pregnancy and risk of preterm birth 

1. Pregnant individuals in Zimbabwe exposed to intimate partner violence during pregnancy were at increased risk of preterm birth  

Evidence Rating Level: 2 (Good)

Preterm birth is becoming growingly prevalent in sub-Saharan Africa, contributing substantially to their infant mortality rate. Complications, such as sepsis, infections and cerebral palsy, have been associated with preterm birth. Thus, further investigation is required to study etiological risk factors associated with preterm birth. Particularly, the issue of intimate partner violence (IPV) has been found to be the most prevalent form of gender-based violence during and/or before pregnancy. IPV may have physical, psychological, or sexual effects on the mother, leading to possible adverse health effects for the fetus. Despite maternal and child mortality rates being high in sub-Saharan Africa, the association between IPV and preterm birth in this region has never been investigated. As such, this study estimated the effects of IPV during pregnancy on preterm birth using the 2015 Zimbabwe Demographic and Health Survey. The study included pregnant women (n=4833), aged 15 to 49 years, who gave birth 5 years prior to the survey. Preterm birth, being the outcome measure under evaluation, was defined as babies born alive before week 37 of gestation. On the other hand, IPV was measured using a series of questions about whether the women were exposed to any physical, sexual or emotional forms of violence. The statistical analysis used for this study included a propensity score analysis, estimated using logistic regression modeling. The analysis allowed for the comparison between those who did and did not report experiencing IPV, and the respective risk associated with each group. Conclusively, over 21% of the cohort reported experiencing IPV during pregnancy. Of the women who did and did not experience IPV, 8.9% and 3.0% delivered preterm, respectively. Additionally, a risk factor associated with IPV included women residing in urban areas, leading to a five-fold increased risk of preterm birth. A limitation of this study was the reliance upon self reporting which may be subject to recall bias. Furthermore, as IPV is a sensitive topic, many women may not have felt comfortable or safe disclosing information regarding their domestic situation. However, the study did have many strengths including its comprehensive propensity score analyses which accounted for baseline characteristics of participants as well as risk stratification for preterm subgroups. Overall, this study highlights the importance of identifying risk factors, such as low economic status, unemployment, and living in an urban area, which can lead to higher likelihood of IPV. Furthermore, it highlights the gravity of the situation and the need to prevent IPV not only for the women’s health and safety, but that of their children. Safety resources, health policies and education are required to remove individuals from harm, especially in their own homes.


Use of pharmacotherapy for alcohol use disorder in Manitoba, Canada: A whole-population cohort study

  1. Pharmacotherapy prescriptions for naltrexone, acamprosate, and disulfiram have been proven safe and effective treatments for alcohol use disorder (AUD)
  2. Despite this evidence, pharmacotherapy remains underutilized in Manitoba as a treatment plan for AUD. 

Evidence Rating Level: 2 (Good)

Alcohol use disorder (AUD) is a potentially devastating condition leading to significant morbidity and mortality rates in North America. The disorder is characterized by compulsive alcohol use and can lead to various physical diseases, adverse psychosocial and mental health outcomes, and death. Previous studies have found that medications such as naltrexone have been proven to be safe and effective pharmacotherapies for AUD. However, despite the clinical and societal health burden caused by AUD and the existence of these evidence-based medications, the rates of prescription for pharmacotherapy remains low. This population based, longitudinal cohort study examined the use of pharmacotherapy, specifically naltrexone, acamprosate, and disulfiram among individuals with AUD. In order to do so, data was collected between 1996 and 2014 through the Manitoba Population Research Data Repository databases. These databases supplied information on all residents of Manitoba diagnosed with an alcohol use disorder. Next, individuals with AUD were compared between those who received and filled a pharmacotherapy prescription compared to those individuals with AUD who did not. Overall, 2.9% (n=37,388) of the Manitoban population were diagnosed with AUD between 1996 and 2015. Of this cohort, 1.3 % (n=493) of individuals diagnosed with AUD filled a prescription for an AUD medication. The majority of these individuals were males, in urban settings,  receiving their prescriptions from family doctors (53.6%) or psychiatrists (22.3%). The most common medication prescribed for AUD was naltrexone (58%) followed by acamprosate (36.3%) and disulfiram (5.7%). Each of these evidence-based medications were underutilized in Manitoba over the 20-year study period for individuals with AUD. However, a limitation of this study is that it focused solely on pharmacotherapy as a treatment for AUD. In reality, there are many other resources, holistic treatments, support programs, and rehabilitation therapy which may be beneficial to individuals with AUD. When looking specifically at medications, it may appear as though anyone not receiving a prescription is not seeking or receiving aid when in fact, this data was not collected in this study. On the other hand, a strength of this study was its additional analyses of comorbidities such as anxiety disorders or depression. This allowed for a better understanding of the medication’s efficacy in combination with other drugs as well as any contraindications which may decrease prescription rates. Overall, pharmacotherapy drugs such as naltrexone, acamprosate, and disulfiram have been deemed a safe and effective treatment plan for alcohol use disorder. Despite this evidence, individuals living with alcohol use disorder in Manitoba underutilize this treatment option. Alcohol use disorder can have devastating impacts on individuals, their families, and their communities and therefore, more resources, treatment plans, and support is required. Finally, the study highlighted the need for further education for physicians to ensure informed prescribing in order to take an interdisciplinary approach in order to reduce AUD.


Systematically developing a family-based health promotion intervention for women with prior gestational diabetes based on evidence, theory and co-production: the Face-it study

1. The Face-it, four-stage health promotion intervention reduced the risk of diabetes among women with prior gestational diabetes

2. Conducting qualitative research, reviewing prior evidence, intervention implementation, pilot testing, and outcome evaluation were essential steps in optimizing the prevention of Type 2 diabetes after gestational diabetes

Evidence Rating Level: 2 (Good)  

Gestational diabetes mellitus (GDM), being one of the most common gestational medical conditions, leaves women at an increased risk of developing early onset type 2 diabetes mellitus (T2DM) and cardiovascular disease following their pregnancy. Additionally, the offspring of the women diagnosed with GDM were found to be eight times more likely to develop T2DM and prediabetes later in life. For women who have a history of GDM, research has found that lifestyle changes can have a positive impact on their long-term risk of developing T2DM. In order to promote these lifestyle changes, the Face-it study adopted elements from two frameworks by MRC and Hawkins et al, using the Medical Research Council UK Development of complex interventions in primary care framework. This study systematically developed a health promotion intervention designed to reduce the risk of diabetes among women with prior GDM and their children. The study used a four stage process, over the course of two years, to analyze and compare the effectiveness of this intervention. The first stage included researching the existing interventions and their limitations. Stage two consisted of discussing and receiving feedback from women with prior GDM and her family to model interventions. Next, stage 3 introduced prototyping, pilot testing, and intervention delivery. Finally stage 4 addressed evaluation of core outcomes while communicating with stakeholders.The complexity of the Face-it study can present both a strength and limitation. The use of multiple stages, stakeholders, and interventions speaks to the dedication and time-consuming process that went into optimizing this framework. However, Face-it may be difficult to apply in certain contexts. For example, low income, rural communities where resources are scarce may not have the infrastructure required to properly implement the Face-it approach. Overall, this study highlighted the clinical burden of GDM as well as the potentially dangerous progression to T2DM. The development of the Face-it intervention presents a comprehensive, systematic approach to prevention of diabetes after pregnancy. This four-step approach offers a template that may be applied to other health burdens in the future and can be transferable into other health sectors as a preventative tool.


Safety and tolerability of transdermal cannabidiol gel in children with developmental and epileptic encephalopathies

Evidence Rating Level: 2 (Good)

1. Transdermal cannabidiol gel was found to be a safe and effective treatment for children and adolescents with developmental and epileptic encephalopathies 

2. Treatment with transdermal cannabidiol was associated with a reduction in focal impaired awareness seizures and tonic-clonic seizures.

Developmental and epileptics encephalopathies (DEEs) are severe, epileptiform, drug resistant seizures with early onset among infants and children. The co-morbidity rates are high among patients with DEEs and they often present with behaviour and intellectual disabilities as well as reduced motor function, respiratory infections, sleep disturbances, and increased mortality risk. DEE patients are often treated with oral anti-seizure medications (ASM) which can be challenging when taking into consideration the physical, behavioural, and cognitive barriers for these children leading to the inability to tolerate oral administration. This study aimed to address this barrier by assessing the safety and efficacy of a transdermal gel medication. Specifically, Cannabidiol (CBD) which has been shown to reduce neuronal excitability and therefore reduces epileptic seizures. Health centers in Melbourne, Australia and Wellington, New Zealand participated in the study with DEE patients aged 3-18. CBD transdermal gel was used for 6.5 months in this nonrandomized, controlled, clinical trial. A total of n=46 patients received the treatment which consisted of 4.2% CBD transdermal gel administered daily in the amount of 125mg CBD each. This dosage increased each month and was adjusted for the child’s weight. Patients were assessed for daily seizure frequency which was recorded and subsequently reported by caregivers at each visit (occurring at weeks 2, 4, 6, 14, and 26). Over the course of the 6.5 month study period, the cohort saw an overall seizure reduction of 12.3% with the highest reduction in focal impaired awareness seizures (FIAS) by 44.5%. A strength of this study was that in addition to its quantitative nature, researchers included a qualitative interview at 6.5 months with caregivers. This allowed for the collection of information regarding overall quality of life and the impact of treatment on daily activities. Caregivers reported improvements with regards to alertness (40%), increased engagement (35%), cognition (33%), and reduced fatigue (28%).  The most common adverse events were related to reactions at the application site (19%) and these side effects were relatively mild. A limitation of this study was the nonrandomized nature of the clinical trial. Future studies may wish to conduct a randomized controlled trial to confirm the safety and efficacy of CBD transdermal gel. Overall, in the nonrandomized clinical trial, CBD transdermal gel was associated with a reduction in FIAS and tonic-clonic seizures (TCS) frequency.

Image: PD

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