2 Minute Medicine Rewind December 5, 2022

Artificial rupture of membranes as a mode for induction of labor in women with a previous cesarean section- a retrospective cohort study

1. Artificial rupture of membranes (AROM) alone is a safe and efficient way to induce labour in women with previous c-section.

Evidence Rating Level: 2 (Good)

Induction of labour (IOL) is an increasing practice and currently can be done by use of oxytocin, prostaglandins, artificial rupture of membranes (AROM) and balloon catheters. Those who have had previous c-section have limited options for IOL as prostaglandins and oxytocin are contraindicated due to increased risk of uterine rupture. Minimal studies have evaluated the use of AROM as a non-pharmacological mode of IOL for those with a history of c-section. This study aimed to examine if AROM was safe and effective in this population. This study also investigated if delayed or early administration of oxytocin is beneficial for those who did not go into active labour after AROM. This retrospective study consisted of 665 women with a history of one prior c-section and were undergoing trial of labor after cesarean (TOLAC). The primary outcome was the rate of successful vaginal delivery. Women had AROM and then were admitted to hospital to await onset of spontaneous labour. 492 of the women did not receive or require oxytocin, 172 did and these were broken into two groups, early (< 12 hour) and late (> 12 hour) oxytocin administration. Those who only received AROM for IOL had a higher rate of successful vaginal delivery (81.3% vs.73.9% p = 0.03), a lower total time of induction of labour (8.7 h vs.16.13 h p < 0.001) and lower risk of chorioamnionitis. Between those who received early versus late oxytocin, no significant differences were seen in rates of successful vaginal delivery or chorioamnionitis. However this study was limited, between the groups who received AROM alone vs AROM + oxytocin, as there were large differences such as higher rates of previous vaginal delivery, prior vaginal birth after c-section, larger cervical dilation and older age. Once these differences were accounted for, there were no differences in rates of successful vaginal delivery after c-section. Despite these limitations, this study demonstrates that AROM is a safe way to begin IOL and can be used alone patients where other treatment options are contraindicated or limited.

Oxytocin receptor single nucleotide polymorphism predicts atony-related postpartum hemorrhage

1. Homozygotes and carriers of allele A of the OXTR gene were found to be at greater of risk and severity of postpartum hemorrhage (PPH) and require second line treatments for PPH

Evidence Rating Level: 2 (Good)

Postpartum hemorrhage (PPH), defined by blood loss causing signs/symptoms of hypovolemia and/or 1000 mL of blood loss in 24 hours after birth, is a primary contributor to maternal morbidity and mortality. The etiology of PPH is multifactorial and includes uterine atony, adherent placenta, trauma, and blood disorders. Current tools that are used to predict PPH still miss 40% of PPH cases. Oxytocin is routinely given after birth to help prevent PPH, as it binds to the myometrial oxytocin receptor (OXTR) and causes uterine contraction. Two identified alleles, A and G, are associated with differential OXTR gene expression and it is believed that genetic differences in the oxytocin system could serve as risk factors for PPH. This case-control study involved 95 patients who underwent vaginal birth at a gestational age of at least 37 weeks. Cases were defined as those who had either 1000mL or more of blood loss or had heavy bleeding where they required additional uterotonic treatment. Controls were matched and genotypes from maternal blood samples were taken during the 2^nd post-partum month. Genotype distributions included 40% of G/G individuals, 50.5% of A/G individuals and 9.5% of A/A individuals. A/A homozygotes were found to be most likely to have PPH (55.6% vs 12.5% for AG and 7.9% of GG, p=0.005). A carriers were also found to have higher amounts of blood loss (p<0.01) even when controlled for factors such as parity, intrapartum oxytocin, self-reported ancestry, active management of third stage or genital tract lacerations. A carriers also had a 79% higher risk of needing one or more second line treatment for PPH. Interestingly however, GG participants were found to have greater blood loss with higher levels oxytocin exposure. This study was limited in sample size as well as examined only one single nucleotide polymorphism, and only focused on atony as an etiology for PPH. It does show however, that genetic variants of the OXTR gene may be associated with greater risk of PPH, and may be used as a predictor for bleeding risk in the postpartum period.

 Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomized controlled trial

1. In a cohort of patients who had symptomatic isolated distal deep vein thrombosis, an additional 6 weeks of rivaroxaban therapy in addition to standard therapy reduced the risk of recurrent venous thromboembolism

2. Additional treatment with rivaroxaban was not associated with increased incidence of hemorrhage

Evidence Rating Level: 1 (Excellent)

Isolated distal deep vein thrombosis (DVT) is generally perceived as more benign than proximal DVT, but can still lead to pulmonary embolism in up to 22% of untreated patients. Guidelines for isolated DVT currently suggest anticoagulant therapy for patients with symptoms or those with risk factors, whereas others are treated with repeated imaging of deep veins. This randomized control trial involved 403 patients who had symptomatic isolated distal DVT, thus qualifying for anticoagulant therapy. Patients were given standard doses of rivaroxaban for 6 weeks, then were randomly assigned to receive 20 mg of rivaroxaban or a placebo for 6 additional weeks, and then followed for 2 years. Five follow-up visits were scheduled including a baseline visit that collected lab tests including: complete blood count, D-dimer, prothrombin, activated partial thromboplastin time, liver and renal function. Following the baseline visit, compression ultrasonography and lab tests were completed at six weeks, 3 months and as needed if there were any future symptoms of DVT. 11% of rivaroxaban patients and 19% of placebo patients had recurrent venous thromboembolism (relative risk 0.59, 95% confidence interval 0.36 to 0.95; P=0.03). Recurrent isolated DVT occurred in 8% of rivaroxaban patients and 15% of placebo patients (P=0.02). No significant differences were seen in rates of proximal DVT or pulmonary embolism (P=0.8), and no major bleeding events occurred in either group. Strengths of this study included the population size and the study design of randomized controlled trial, however it does not help address whether patients with isolated DVT should receive treatment and these guidelines remain unclear. Overall, this study showed that 6 additional weeks of treatment with rivaroxaban reduced the risk of recurrent venous thromboembolism over a two year time period, without increasing the risk of bleeding.

Oxygen administration during surgery and postoperative organ injury: observational cohort study

1. Supraphysiological oxygen administration during surgery is associated with higher incidence of kidney, myocardial and lung injury

Evidence Rating Level: 2 (Good)

Greater than 80% of patients undergoing general anesthesia are exposed to oxygen administration higher than that required to maintain normal blood oxygen levels. There are potentially harmful effects of supplemental oxygen administration, however, due to the consequences of hypoxemia, supplemental oxygen is a common component of anesthesia. This retrospective cohort study included 350, 657 patients who underwent surgical procedures longer than 120 minutes under general anesthesia and measured clinical outcomes based on level of oxygen exposure including acute kidney injury (measured using the Kidney Disease Improving Global Outcomes) myocardial injury (defined as a troponin >0.04 ng/mL within 72 hours of operation) and lung injury (defined using the international classification of diseases hospital discharge diagnosis codes). For each patient, minute to minute FiO2 and SpO2 data were obtained, and the amount of oxygen that was in excess was determined. The incidence of acute kidney injury, myocardial infarction and lung injury were higher in those who received oxygen levels at supraphysiological levels; for example, those at the 75th percentile of oxygen levels had a 26% greater odds of acute kidney injury, 12% greater odds of myocardial injury, and 14% greater odds of lung injury compared to those at the 25^th percentile. The observational nature of this study and discrepancies on general diagnosis of these injuries (for example the use of diagnosis codes to identify lung injury) are a few limitations to this study. Future studies are needed to identify the best intraoperative oxygen administration guidelines, knowing that both hypoxemia and supraphysiological oxygen may be associated with adverse events.

Association of Maternal and Child Anemia With Brain Structure in Early Life in South Africa

1. Anemia during pregnancy associated with altered brain structure in children including smaller volumes of bilateral caudate, putamen and corpus callosum

Evidence Rating Level: 2 (Good)

It is estimated that 38% of pregnant women worldwide are anemic. Anemia is known to be a risk factor for poor maternal and infant health outcomes, however limited studies have been done to determine the association of maternal anemia with child brain structure. This cohort study sought to further investigate this association by examining the subsequent brain structure changes of 147 mother child pairs. Mothers had hemoglobin levels measured during pregnancy and these levels were adjusted for trimester of pregnancy. Children had brain magnetic imaging done at age 2-3 years, hemoglobin was only measured in children if they had hospital visits between birth and MRI. Of the 147 mothers, 31% were found to have anemia in pregnancy. After adjusting for covariates, maternal anemia was not found to be associated with child global brain volumes but significant associations between individual structures were identified including: smaller volumes of bilateral caudate, putamen and corpus callosum (−5.30% [95% CI, −7.01 to −3.59, −4.33% [95% CI, −5.74 to −2.92], −7.75% [95% CI, −11.24 to −4.26] respectively). Not all of the children in the study had hemoglobin measurements taken, however within those who did child anemia was not found to be associated with brain volume changes. Limitations to this study include a high-risk group as many participants had maternal HIV and alcohol use, as well as a small sample size for child anemia. Additionally, this study did not include any longitudinal findings, limiting the ability of the study to further extrapolate subsequent neurodevelopmental outcomes. Overall, this study shows that maternal anemia has an association with brain development in children, and optimizing interventions to manage maternal anemia may have a positive impact on brain development.

Image: PD

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