Pregnancies complicated by antepartum sepsis linked to placental dysfunction: JAMA

Pregnancies complicated by sepsis are associated with increased rates of adverse obstetric outcomes, including cesarean delivery, postpartum hemorrhage, and preterm delivery. Much of current understanding of sepsis in pregnancy is based on studies of peripartum infections occurring during labor or the postpartum period, such as septic abortion, intra-amniotic infection, and endometritis.

There is abundant evidence regarding placental dysfunction after maternal infection with pathogens capable of causing placental or fetal infection.

Antenatal risk stratification for placental disorders is of paramount importance, given that impaired placental development and function are important factors associated with multiple pregnancy complications, including preeclampsia, placental abruption, preterm birth, infants born small for their gestational age, and stillbirth.

The objective of this study carried out by Christine A. Blauvelt and team was to describe perinatal outcomes among patients with an antepartum sepsis hospitalization who recovered from their infection and did not deliver prior to hospital discharge.

This retrospective cohort study was conducted using data from August 1, 2012, to August 1, 2018, at an academic referral center in San Francisco, California. Included patients were all individuals with nonanomalous, singleton pregnancies who delivered after 20 weeks' gestation during the study period. Data were analyzed from March 2020 through March 2021. The primary outcome was a composite of perinatal outcomes associated with placental dysfunction and consisted of 1 or more of the following: fetal growth restriction, oligohydramnios, hypertensive disease of pregnancy, cesarean delivery for fetal indication, child who is small for gestational age, or stillbirth.

• Among 14,565 patients with nonanomalous singleton pregnancies, 59 individuals (0.4%) were in the sepsis group and 14,506 individuals (99.6%) were in the nonsepsis group; 8533 individuals (59.0%) were nulliparous.

• Patients with sepsis, compared with patients in the reference group, were younger (P < .001), were more likely to have pregestational diabetes (P = .003), and had higher mean (SD) pregestational body mass index scores (P = .03).

• In the sepsis group, the most common infections were urinary tract infections (40.7%) and pulmonary infections (37.3%).

• Among patients with sepsis, 5 individuals (8.5%) were admitted to the intensive care unit, the mean (SD) gestational age at infection was 24.6 (9.0) weeks, and the median time from infection to delivery was 82 (42-147) days.

• Antepartum sepsis was associated with higher odds of placental dysfunction (21 patients [35.6%] vs 3450 patients [23.8%]; P = .04).

• On multivariable logistic regression analysis, antepartum sepsis was an independent factor associated with placental dysfunction (P = .02) after adjusting for possible confounders.

This cohort study found that patients with a history of antepartum sepsis had statistically significantly higher odds of obstetric complications associated with placental dysfunction. When adjusting for possible confounders, including maternal age, parity, BMI score, and medical comorbidities, patients with antepartum sepsis had nearly 2-fold higher odds of placental dysfunction compared with patients without antepartum sepsis. The timing of infection during pregnancy also had important associations with perinatal outcomes. Early infection (ie, at less than 24 weeks' gestational age) was associated with the greatest increase in odds of composite placental dysfunction, hypertensive disease of pregnancy, and newborns who were small for gestational age.

Authors hypothesized that the dysregulated host response to maternal infection that occurs during sepsis may disrupt placental development and function, leading to poor perinatal outcomes among these patients.

The recognition that antepartum sepsis may be associated with placental dysfunction has important implications for pregnancy management. Ultrasonographic screening for fetal growth restriction may be considered for patients with a history of antepartum sepsis. Of 7 patients in our study who delivered infants who were small for their gestational age, 4 patients (57.1%) had growth ultrasonography screenings in the third trimester and 1 patient (14.3%) was diagnosed with fetal growth restriction prenatally.

Fetal growth restriction is known to be associated with increased risk of stillbirth, neonatal morbidity, and mortality, underscoring the potential need for increased antepartum surveillance for pregnancies complicated by antepartum sepsis. Authors also observed increased rates of hypertensive disease of pregnancy in the sepsis group, occurring in approximately 24% of patients. Of note, most of these individuals (9 patients [64.3%]) exhibited mild hypertensive disease at the time of delivery. These findings suggest that patients with antepartum sepsis should be counseled on signs and symptoms of preeclampsia and receive close monitoring of their blood pressure.

"This study found that antepartum sepsis was associated with increased odds of placental dysfunction. Earlier gestational age at the time of infection was associated with higher odds of placental dysfunction, including hypertensive disease of pregnancy and lower birth weight. Our study provides new information to inform patient counseling regarding expected perinatal outcomes after antepartum sepsis and the potential need for increased pregnancy surveillance. This study may also open up new avenues for research regarding pathophysiologic mechanisms of placental dysfunction after antepartum sepsis and potential interventions including anti-inflammatory medications to mediate the association of sepsis with adverse pregnancy outcomes."

Source: Christine A. Blauvelt; Kiana C. Nguyen; Arianna G. Cassidy; Stephanie L. Gaw; JAMA Network Open. 2021;4(9):e2124109.

doi:10.1001/jamanetworkopen.2021.24109