Here at County, we are lucky enough to have an open labor and delivery unit and on-site OB/GYN consultants. Unfortunately, 217 obstetric units have closed from 2011 to 2023 according to the health care consulting firm Chartis. With decreasing access to obstetrical care, you, in your future practice, may be in a position where patients depend on you for high-quality care related to reproductive health. Here, we discuss some recent randomized trials investigating low-cost, high-value interventions related to gynecologic and obstetrical processes.
In an institution whose formulary only includes levonorgestrel for emergency contraception, is there anything else I can do to increase the efficacy of this medication?
Levonorgestrel, the current emergency contraceptive on formulary at Cook County, is a medication taken as a single dose within 72 hours of sexual intercourse for emergency contraception. Mechanistically, it prevents pregnancy by blocking or posting the luteinizing hormone (LH) surge (1). If your patient has ovulated, this medication has no further method of preventing pregnancy. Prostaglandins are involved in multiple phases of reproduction, from ovulation to implantation.
With this physiology in mind, a 2023 study published in The Lancet by Li RHW et al. (1) investigated whether a single dose of 1.5 mg of levonorgestrel plus a single dose of 40 mg piroxicam (a long-acting NSAID dosed at 20 mg once daily for osteoarthritis) had greater efficacy in preventing pregnancy compared to levonorgestrel plus placebo. They recruited 860 women in Hong Kong and randomized 430 to each treatment arm. They then estimated the rate of pregnancy that should occur should none of the patients have received any emergency contraceptive and found that levonorgestrel alone reduced pregnancies compared to expected by 63.4%. In comparison, the levonorgestrel plus NSAID group reduced pregnancies by 94.7%. Notably, the study population consisted of primarily thin, east Asian females, limiting the generalizability. Although not studied in a population similar to that at Cook County, the low-risk nature of this intervention, combined with our understanding of the physiology of prostaglandins in pregnancy, makes this a worthy intervention.
Answer: You can consider adding a single dose of a long-acting NSAID at two times the dose recommended for osteoarthritis to a single dose of levonorgestrel to increase the potential for pregnancy prevention in patients seeking emergency contraception.
In patients who will be delivering a baby in my emergency department or who will require transfer while in labor, is there an intervention I could provide to prevent the risk of developing sepsis?
Maternal sepsis occurs more frequently in patients with limited prenatal care and patients who are transferred from an outside hospital (2). With decreasing access to prenatal care and a greater likelihood of being employed in a hospital without obstetrical services, emergency physicians should be knowledgeable of interventions that may prevent maternal sepsis. A recent multi-national, randomized, placebo-controlled trial published in 2023 in the New England Journal of Medicine by Tita ATN et al. (3) investigated whether a single dose of 2 g oral azithromycin intrapartum could decrease maternal sepsis. They randomized 14,590 patients to the treatment group and 14,688 to the placebo group and found that sepsis occurred at a rate of 1.6% compared to 2.4%, respectively. This resulted in a relative risk reduction of 1/3rd.
Answer: In an instance where you are transferring a patient who is in labor or have a patient who you expect to deliver imminently in your emergency department, a 2 g dose of oral azithromycin may decrease the risk of maternal sepsis with a limited likelihood of adverse events.
After delivering a newborn who requires resuscitation, are there alternatives to delayed cord clamping that safely provide the benefits of delayed cord clamping with greater speed?
Per ACOG, delayed umbilical cord clamping at 30 to 180 seconds results in improved circulating blood volume and improved iron stores, decreasing the likelihood of need for transfusion (4). A significant portion of obstetricians in the U.S. utilize this practice in the full-term neonate. In the case of a sick neonate requiring rapid resuscitation, delayed cord clamping may not be feasible. Umbilical cord milking, comprised of grasping an unclamped umbilical cord and pushing blood toward the newborn neonate 3-4 times, has been suggested to increase the risk of intraventricular hemorrhage secondary to a rapid change in circulating blood volume (5). In a 2023 randomized trial published in Pediatrics by Kahteria A et al. (5), a group of researchers aimed to investigate whether umbilical cord milking was inferior to delayed cord clamping in regards to the incidence of neonatal death and severe intraventricular hemorrhage. In this trial of 1019 premature infants birthed at gestational ages between 28 weeks to 32 weeks, the authors found no difference in severe intraventricular hemorrhage or death. Additionally, no difference was found in the mean hemoglobin of patients receiving either intervention, suggesting equal benefit with each intervention. Notably, previous data did find an increased risk of intraventricular hemorrhage in preterm infants born at 23 to 27 weeks gestational age (6), and, therefore, this does not apply to neonates born before 28 weeks gestational age.
Answer: After delivering a 28-week gestational age or greater neonate, umbilical cord milking can safely be conducted to expedite resuscitative measures and initial circulating blood volume.
Authored by Jose Reyes, MD
References:
Li RHW, Lo SST, Gemzell-Danielsson K, Fong CHY, Ho PC, Ng EHY. Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trial [published correction appears in Lancet. 2023 Sep 9;402(10405):850]. Lancet. 2023;402(10405):851-858. doi:10.1016/S0140-6736(23)01240-0
Lin L, Ren LW, Li XY, et al. Evaluation of the etiology and risk factors for maternal sepsis: A single center study in Guangzhou, China. World J Clin Cases. 2021;9(26):7704-7716. doi:10.12998/wjcc.v9.i26.7704
Tita ATN, Carlo WA, McClure EM, et al. Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth. N Engl J Med. 2023;388(13):1161-1170. doi:10.1056/NEJMoa2212111
Delayed Umbilical Cord Clamping After Birth: ACOG Committee Opinion Summary, Number 814. Obstet Gynecol. 2020;136(6):1238-1239. doi:10.1097/AOG.0000000000004168
Katheria A, Szychowski J, Carlo WA, et al. Umbilical Cord Milking Versus Delayed Cord Clamping in Infants 28 to 32 Weeks: A Randomized Trial. Pediatrics. 2023;152(6):e2023063113. doi:10.1542/peds.2023-063113
Katheria A, Reister F, Essers J, et al. Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants. JAMA. 2019;322(19):1877–1886. doi:10.1001/jama.2019.16004
References:
Li RHW, Lo SST, Gemzell-Danielsson K, Fong CHY, Ho PC, Ng EHY. Oral emergency contraception with levonorgestrel plus piroxicam: a randomised double-blind placebo-controlled trial [published correction appears in Lancet. 2023 Sep 9;402(10405):850]. Lancet. 2023;402(10405):851-858. doi:10.1016/S0140-6736(23)01240-0
Lin L, Ren LW, Li XY, et al. Evaluation of the etiology and risk factors for maternal sepsis: A single center study in Guangzhou, China. World J Clin Cases. 2021;9(26):7704-7716. doi:10.12998/wjcc.v9.i26.7704
Tita ATN, Carlo WA, McClure EM, et al. Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth. N Engl J Med. 2023;388(13):1161-1170. doi:10.1056/NEJMoa2212111
Delayed Umbilical Cord Clamping After Birth: ACOG Committee Opinion Summary, Number 814. Obstet Gynecol. 2020;136(6):1238-1239. doi:10.1097/AOG.0000000000004168
Katheria A, Szychowski J, Carlo WA, et al. Umbilical Cord Milking Versus Delayed Cord Clamping in Infants 28 to 32 Weeks: A Randomized Trial. Pediatrics. 2023;152(6):e2023063113. doi:10.1542/peds.2023-063113
Katheria A, Reister F, Essers J, et al. Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants. JAMA. 2019;322(19):1877–1886. doi:10.1001/jama.2019.16004