Despite universal recommendations for COVID-19 mRNA vaccination in pregnancy, uptake has been lower than desired. There have been limited studies of the direct impact of COVID-19 mRNA vaccine exposure in human placental tissue. Using a primary human placental explants model, we investigated the uptake of two common mRNA vaccines (BNT162b2 Pfizer-BioNTech or mRNA-1273 Moderna), and whether exposure altered villous cytokine responses. Explants derived from second or third trimester chorionic villi were incubated with vaccines at supraphysiologic concentrations and analyzed at two time points. We observed minimal uptake of mRNA vaccines in placental explants by in situ hybridization and quantitative RT-PCR. No specific or global cytokine response was elicited by either of the mRNA vaccines in multiplexed immunoassays. Our results suggest that the human placenta does not readily absorb the COVID-19 mRNA vaccines nor generate a significant inflammatory response after exposure.

Objective

To describe a single U.S. perinatal center's ongoing experience with evaluating pregnant patients with potential exposure to Zika virus infection.

Methods

This is an institutional review board-approved longitudinal observational study from January to August 2016 from a single perinatal referral center. Patients who had traveled to or had sexual contact with a person who traveled to a region with documented local Zika virus transmission were included in the study. The aim of the study was to identify the rate of confirmed infection among pregnant women referred to our center with established risk factors for Zika virus acquisition. We also sought to characterize travel patterns that constituted risk, to identify rates of symptoms suggesting infection, and to potentially describe findings suggestive of congenital Zika virus infection in prenatal ultrasound evaluations.

Results

We evaluated 185 pregnant women with potential Zika virus exposure. Testing was offered in accordance with the version of the Centers for Disease Control and Prevention guidelines in place at the time of the consultation visit. Geographic exposure data showed Mexico (44%), the Caribbean (17%), North America (16%), South America (13%), and Central America (9%) to be the most common areas in which potential exposure occurred. One hundred twenty-three (67%) patients reported insect bites and 19 (10%) patients reported symptoms. Overall, five (3% of all) patients had prenatal ultrasound findings suggestive of possible fetal Zika virus infection; all their Zika virus test results returned negative. These findings included microcephaly, echogenic intracardiac foci, and ventricular calcifications. Of the 153 Zika virus screening tests ordered, eight (5%) immunoglobulin M results returned positive or equivocal with only one positive through confirmatory testing. Overall, 1 of 185 (0.5%) of all those consulted and 1 of 153 (0.7%) of those tested had a confirmed Zika virus infection with no confirmed fetal or neonatal infections.

Conclusion

We identified low rates of confirmed maternal Zika virus infection in our cohort, but the number of patients described here demonstrates the magnitude of concern existing among both patients and physicians regarding possible perinatal Zika virus infection. It also underscores the need for health care providers to be prepared to answer questions, explain laboratory and ultrasound results, and describe testing options for concerned patients and their families.

Background

COVID-19 during pregnancy can have serious effects on pregnancy outcomes. The placenta acts as an infection barrier to the fetus and may mediate adverse outcomes. Increased frequency of maternal vascular malperfusion has been detected in the placentas of patients with COVID-19 compared with controls, but little is known about how the timing and severity of infection affect placental pathology.

Objective

This study aimed to examine the effects of SARS-CoV-2 infection on placental pathology, specifically whether the timing and severity of COVID-19 affect pathologic findings and associations with perinatal outcomes.

Study design

This was a descriptive retrospective cohort study of pregnant people diagnosed with COVID-19 who delivered between April 2020 and September 2021 at 3 university hospitals. Demographic, placental, delivery, and neonatal outcomes were collected through medical record review. The timing of SARS-CoV-2 infection was noted, and the severity of COVID-19 was categorized on the basis of the National Institutes of Health guidelines. The placentas of all patients with positive nasopharyngeal reverse transcription-polymerase chain reaction COVID-19 testing were sent for gross and microscopic histopathologic examinations at the time of delivery. Nonblinded pathologists categorized histopathologic lesions according to the Amsterdam criteria. Univariate linear regression and chi-square analyses were used to assess how the timing and severity of SARS-CoV-2 infection affected placental pathologic findings.

Results

This study included 131 pregnant patients and 138 placentas, with most patients delivered at the University of California, Los Angeles (n=65), followed by the University of California, San Francisco (n=38) and Zuckerberg San Francisco General Hospital (n=28). Most patients were diagnosed with COVID-19 in the third trimester of pregnancy (69%), and most infections were mild (60%). There was no specific placental pathologic feature based on the timing or severity of COVID-19. There was a higher frequency of placental features associated with response to infection in the placentas from infections before 20 weeks of gestation than that from infections after 20 weeks of gestation (P=.001). There was no difference in maternal vascular malperfusion by the timing of infection; however, features of severe maternal vascular malperfusion were only found in the placentas of patients with SARS-CoV-2 infection in the second and third trimesters of pregnancy, not in the placentas of patients with COVID-19 in the first trimester of pregnancy.

Conclusion

Placentas from patients with COVID-19 showed no specific pathologic feature, regardless of the timing or severity of the disease. There was a higher proportion of placentas from patients with COVID-19-positive tests in earlier gestations with evidence of placental infection-associated features. Future studies should focus on understanding how these placental features in SARS-CoV-2 infections go on to affect pregnancy outcomes.

Climate change is accelerating the intensity and frequency of wildfires globally. Understanding how wildfire smoke (WS) may lead to adverse pregnancy outcomes and alterations in placental function via biological mechanisms is critical to mitigate the harms of exposure. We aim to review the literature surrounding WS, placental biology, biological mechanisms underlying adverse pregnancy outcomes as well as interventions and strategies to avoid WS exposure in pregnancy. This review includes epidemiologic and experimental laboratory-based studies of WS, air pollution, particulate matter (PM), and other chemicals related to combustion in relation to obstetric outcomes and placental biology. We summarized the available clinical, animal, and placental studies with WS and other combustion products such as tobacco, diesel, and wood smoke. Additionally, we reviewed current recommendations for prevention of WS exposure. We found that there is limited data specific to WS; however, studies on air pollution and other combustion sources suggest a link to inflammation, oxidative stress, endocrine disruption, DNA damage, telomere shortening, epigenetic changes, as well as metabolic, vascular, and endothelial dysregulation in the maternal-fetal unit. These alterations in placental biology contribute to adverse obstetric outcomes that disproportionally affect the most vulnerable. Limiting time outdoors, wearing N95 respirator face masks and using high quality indoor air filters during wildfire events reduces exposure to related environmental exposures and may mitigate morbidities attributable to WS.

Purpose

To study maternal retinal changes in pregnancies that resulted in a small for gestational age (SGA) infant.

Methods

Pregnant women with SGA infants at birth and age-matched pregnant women with appropriate for gestational age (AGA) infants at birth (controls) were enrolled. All subjects underwent spectral domain optical coherent tomography angiography (OCTA) imaging using a 10° × 10° scan pattern centered on the fovea. Vessel density (VD) and vessel length density (VLD) of the superficial capillary plexus (SCP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were analyzed and compared between the two groups.

Results

Twelve eyes of eight subjects with SGA infants and 64 eyes of 44 age-matched subjects with AGA infants were included in this study. There was no significant difference in chronic hypertension (P = 1.0), gestational hypertension (P = 1.0), type 1/2 diabetes (P = 1.0), gestational diabetes (P = 0.97), or preeclampsia (P = 0.50) between the SGA group and AGA group. There were significant increases in both VD and VLD in the SCP and ICP layers when comparing the SGA group with the AGA group (P < 0.05).

Conclusions

In this pilot study, subjects with SGA infants had increases in selective retinal vasculature layers that may represent systemic perfusion changes compensating for placental insufficiency.

Translational relevance

Additional assessment of maternal retinal changes in pregnancy using OCTA could prove the technology useful as a biomarker of fetal morbidity.

Despite the occurrence of wildfires quadrupling over the past four decades, the health effects associated with wildfire smoke exposures during pregnancy remains unknown. Particulate matter less than 2.5 μms (PM_2.5) is among the major pollutants emitted in wildfire smoke. Previous studies found PM_2.5 associated with lower birthweight, however, the relationship between wildfire-specific PM_2.5 and birthweight is uncertain. Our study of 7923 singleton births in San Francisco between January 1, 2017 and March 12, 2020 examines associations between wildfire smoke exposure during pregnancy and birthweight. We linked daily estimates of wildfire-specific PM_2.5 to maternal residence at the ZIP code level. We used linear and log-binomial regression to examine the relationship between wildfire smoke exposure by trimester and birthweight and adjusted for gestational age, maternal age, race/ethnicity, and educational attainment. We stratified by infant sex to examine potential effect modification. Exposure to wildfire-specific PM_2.5 during the second trimester of pregnancy was positively associated with increased risk of large for gestational age (OR = 1.13; 95% CI: 1.03, 1.24), as was the number of days of wildfire-specific PM_2.5 above 5 μg m^-3 in the second trimester (OR = 1.03; 95% CI: 1.01, 1.06). We found consistent results with wildfire smoke exposure in the second trimester and increased continuous birthweight-for-gestational age z-score. Differences by infant sex were not consistent. Counter to our hypothesis, results suggest that wildfire smoke exposures are associated with increased risk for higher birthweight. We observed strongest associations during the second trimester. These investigations should be expanded to other populations exposed to wildfire smoke and aim to identify vulnerable communities. Additional research is needed to clarify the biological mechanisms in this relationship between wildfire smoke exposure and adverse birth outcomes.

PURPOSE:To evaluate whether cerclage in twins reduces the rate of spontaneous preterm birth <32 weeks when compared to expectant management. METHODS:This is a retrospective cohort study of twin pregnancies with the following indications for cerclage from two institutions: history of prior preterm birth, ultrasound-identified short cervix ≤2.5 cm, and cervical dilation ≥1.0 cm. The "cerclage" cohort received a cerclage from a single provider at a single institution from 2003-2016. The "no cerclage" group included all patients with similar indications that were expectantly managed from 2010-2015, at a second institution where cerclages are routinely not performed in twin pregnancies. The primary outcome was the rate of spontaneous preterm birth at <32 weeks. Secondary outcomes were the rates of spontaneous and overall (including medically indicated) preterm births at <32 weeks, < 34 weeks, and <36 weeks, chorioamnionitis, birth weight, and neonatal mortality within 30 days of life. We also performed a planned subgroup analysis stratified by cerclage indication. RESULTS:In all, 135 women were included in two cohorts: cerclage (n = 96) or no cerclage (n = 39). The rates of spontaneous preterm birth <32 weeks were 10.4% (n = 10) with cerclage versus 28.2% (n = 11) without cerclage (OR 0.23, CI 0.08-0.70, p = .017). After adjusting for cerclage indication, clinical history, age, chorionicity, insurance type, race, BMI, in-vitro fertilization, and multifetal reduction, there remained a significant reduction in the cerclage group of spontaneous preterm birth <32 weeks (adjusted odds ratio (aOR) 0.24, CI 0.06-0.90, p = .035), spontaneous preterm birth <36 weeks (aOR 0.34, CI 0.04-0.81, p = .013) as well as in overall preterm birth <32 weeks (aOR 0.31, CI 0.1-0.86, p = .018), and overall preterm birth <36 weeks (aOR 0.37, CI 0.10-0.84, p = .030). When stratified by short cervix or cervical dilation in the cerclage versus no cerclage groups, there was a significant decrease in spontaneous preterm birth <32 weeks in the cerclage group with cervical dilation (11.1 versus 41.2%, p = .01) but not in the cerclage group with short cervix only, even for cervical length <1.5 cm. Pregnancy latency was 91 days in the cerclage group versus 57 days in the no cerclage group (p = .001), with a median gestational age at delivery of 35 versus 32 weeks (p = .002). There was no increase in chorioamnionitis in the cerclage group. Furthermore, there was a significant increase in birth weight (median 2278 versus 1665 g, p < .001) and decrease in perinatal death <30 days (1.6 versus 12.9%, p = .001). CONCLUSIONS:Cerclage in twin pregnancies significantly decreased the rate of spontaneous preterm birth <32 weeks compared to expectant management. However, when stratified by cerclage indication, this decrease in primary outcome only remained significant in the group with cervical dilation.

Importance

Epidural analgesia is used by approximately 70% of birthing persons in the US to alleviate labor pain and is a common cause of elevated temperature in the birthing parent during labor, which, in turn, is associated with adverse neonatal outcomes such as hypoxic-ischemic encephalopathy (HIE).

Objective

To determine whether epidural analgesia is associated with increased risk of HIE after adjusting for the birthing person's maximal temperature before epidural placement and for the propensity to get an epidural.

Design, setting, and participants

This retrospective, population-based cohort study was conducted at 15 Kaiser Permanente Northern California hospitals. Participants included singleton neonates born at 35 weeks' or later gestational age between 2012 and 2019. Elective cesarean deliveries and deliveries within 2 hours of hospital admission were excluded. Data analysis was performed from November 2022 to June 2024.

Exposure

The primary exposure was epidural analgesia during labor.

Main outcomes and measures

The primary outcome was HIE, defined as the presence of both neonatal acidosis (ie, pH <7 or base deficit ≥10) and encephalopathy. The presence and timing of epidural analgesia and demographic, pregnancy, and labor characteristics were extracted from electronic medical records. A propensity score for receiving epidural analgesia was created including demographic variables and comorbidities predating epidural placement. Logistic regression was used to evaluate the association between epidural analgesia and HIE, adjusting for maximal birthing parent's temperature before epidural placement and the propensity for receiving an epidural.

Results

Among 233 056 infants born at 35 weeks' or later gestational age by vaginal or unplanned cesarean delivery after at least 2 hours of in-hospital labor, 177 603 (76%) were exposed to epidural analgesia and 439 (0.19%) had HIE. On unadjusted analysis, epidural analgesia was associated with an increased risk of maximal temperature greater than 38 °C during labor (risk ratio [RR], 8.58; 95% CI, 8.06-9.14). Each degree increase in maximal temperature during labor was associated with nearly triple the odds of HIE (odds ratio [OR], 2.82; 95% CI, 2.51-3.17). However, there was no significant association between epidural analgesia and the risk of HIE either on crude (RR, 1.21; 95% CI, 0.96-1.53) or adjusted (adjusted OR, 0.93; 95% CI, 0.73-1.17) analyses.

Conclusions and relevance

In this cohort study including more than 230 000 parent-infant dyads, epidural analgesia was associated with increased maximal temperature during labor, a known risk factor for HIE. However, epidural analgesia was not associated with increased odds of HIE.