Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that have mutations associated with increased transmission and antibody escape have arisen over the course of the ...current pandemic. Although the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.1.529) spike protein appear to diminish the protection conferred by preexisting immunity. Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wild-type (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses, whereas responses may have been reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.
Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of ...antibodies. Here, we evaluate the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during late pregnancy. We find no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we find time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persists during early infancy. Additionally, using phage immunoprecipitation sequencing, we find a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. Timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy.
Nirmatrelvir-ritonavir (Paxlovid) is recommended to reduce the risk of hospitalization from coronavirus disease 2019 (COVID-19) in pregnancy. Data on use in pregnancy, including prescribing patterns ...and patient experience (adverse effects, incidence of rebound), are limited. We performed a cross-sectional study in which we surveyed a cohort of vaccinated pregnant or lactating individuals with breakthrough COVID-19. Of 35 pregnant respondents, 51.4% were prescribed and 34.3% took nirmatrelvir-ritonavir; of these, 91.7% experienced dysgeusia and 50.0% had rebound (50.0% positive test result, 33.3% return of symptoms). Three of five lactating respondents were prescribed and two took nirmatrelvir-ritonavir. There were no significant adverse outcomes. Unknown risk was the most common reason for declining nirmatrelvir-ritonavir. More research is needed to establish the safety of nirmatrelvir-ritonavir in pregnancy and lactation, to improve public health messaging, and to increase uptake of this treatment.
Data regarding symptoms in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines.
From a prospective ...cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires. Anti-SARS-CoV-2 antibody levels in blood and milk were measured by Pylon 3D automated immunoassay and ELISA. In addition, vaccine-related PEGylated proteins in milk were measured by ELISA. Blood samples were collected from a subset of infants whose mothers received the vaccine during lactation (4-15 weeks after mothers' 2nd dose).
No severe maternal or infant adverse events were reported in this cohort. Two mothers and two infants were diagnosed with COVID-19 during the study period before achieving full immune response. PEGylated proteins were not found at significant levels in milk after vaccination. After vaccination, levels of anti-SARS-CoV-2 IgG and IgM significantly increased in maternal plasma and there was significant transfer of anti-SARS-CoV-2-Receptor Binding Domain (anti-RBD) IgA and IgG antibodies to milk. Milk IgA levels after the 2nd dose were negatively associated with infant age. Anti-SARS-CoV-2 IgG antibodies were not detected in the plasma of infants whose mothers were vaccinated during lactation.
COVID-19 mRNA vaccines generate robust immune responses in plasma and milk of lactating individuals without severe adverse events reported.
Unplanned pregnancies in women with maternal cardiac disease (MCD) are associated with increased morbidity and mortality, but the majority of these individuals do not use highly reliable ...contraception on postpartum hospital discharge. Contraceptive counseling in this population outside of pregnancy is incomplete and counseling during pregnancy remains poorly characterized. Our objective was to evaluate the provision and quality of contraceptive counseling for individuals with MCD during pregnancy.
All individuals with MCD who delivered between 2008 and 2021 at a tertiary care institution with a multidisciplinary cardio-obstetrics team were sent a 27-question survey. A subset of questions were derived from the validated Interpersonal Quality in Family Planning (IQFP) survey, which emphasizes interpersonal connection, adequate information, and decision support for the individual. Each participant received a $15 gift card for survey completion. We performed chart review for clinical and demographic details, including cardiac risk score.
Of 522 individuals to whom the survey was sent, 133 responded and met inclusion criteria. Overall, 67% discussed contraception with their general obstetrician, 36% with their maternal-fetal medicine (MFM) specialist, and 24% with their cardiologist. Compared to individuals with low cardiac risk scores, those with high cardiac risk scores had a nonsignificant trend toward being more likely to discuss contraception with a MFM provider (52% vs 33%, p = .08). 65% reported that their provider was 'excellent' or 'good' in all IQFP domains. Respondents valued providers who respected their autonomy and offered thorough counseling. Respondents disliked feeling pressured or uninformed about the safety of contraceptive options.
Most individuals with MCD reported excellent contraceptive counseling during pregnancy. Additional work is needed to understand barriers to and enablers for effective, patient-centered contraceptive counseling and use in this population.
Little is known about the persistence of human milk anti-SARS-CoV-2 antibodies after 2nd and 3rd vaccine doses and infection following 3rd dose. In this study, human milk, saliva, and blood samples ...were collected from 33 lactating individuals before and after vaccination and infection. Antibody levels were measured using ELISA and symptoms were assessed using questionnaires. We found that after vaccination, milk anti-SARS-CoV-2 antibodies persisted for up to 8 months. In addition, distinct patterns of human milk IgA and IgG production and higher milk RBD-blocking activity was observed after infection compared to 3-dose vaccination. Infected mothers reported more symptoms than vaccinated mothers. We examined the persistence of milk antibodies in infant saliva after breastfeeding and found that IgA was more abundant compared to IgG. Our results emphasize the importance of improving the secretion of IgA antibodies to human milk after vaccination to improve the protection of breastfeeding infants.
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•Milk anti-SARS-CoV-2 antibodies persist 6–8 months following vaccination•Distinct patterns of milk IgA and IgG are produced after infection versus vaccination•Infant saliva IgA is more abundant and persists compared to IgG after breastfeeding
Health sciences; Pediatrics; Immunology; Virology
Rates of maternal sepsis are increasing, and prior studies of maternal sepsis have focused on immediate maternal morbidity and mortality associated with sepsis during delivery admission. There are no ...data on pregnancy outcomes among individuals who recover from their infections prior to delivery.
To describe perinatal outcomes among patients with antepartum sepsis who did not deliver during their infection hospitalization.
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.
Antepartum admission for infection with clinical concern for sepsis and hospital discharge prior to delivery.
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 (mean SD age at delivery, 33.1 5.2 years), 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 (mean SD age at delivery, 30.6 5.7 years vs 33.1 5.2 years; P < .001), were more likely to have pregestational diabetes (5 individuals 8.5% vs 233 individuals 1.6%; P = .003), and had higher mean (SD) pregestational body mass index scores (26.1 6.1 vs 24.4 5.9; P = .03). In the sepsis group, the most common infections were urinary tract infections (24 patients 40.7%) and pulmonary infections (22 patients 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 (interquartile range) 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%; odds ratio, 1.77; 95% CI, 1.04-3.02; P = .04). On multivariable logistic regression analysis, antepartum sepsis was an independent factor associated with placental dysfunction (adjusted odds ratio, 1.88; 95% CI, 1.10-3.23; P = .02) after adjusting for possible confounders.
This study found that pregnancies complicated by antepartum sepsis were associated with higher odds of placental dysfunction. These findings suggest that increased antenatal surveillance should be considered for these patients.
To assess the impact of an evidence-informed protocol for management of placenta accreta spectrum (PAS).
This was a retrospective cohort study of patients who underwent cesarean hysterectomy (c-hyst) ...for suspected PAS from 2012 to 2022 at a single tertiary care center. Perioperative outcomes were compared pre- and post-implementation of a standardized Multidisciplinary Approach to the Placenta Service (MAPS) protocol, which incorporates evidence-informed perioperative interventions including preoperative imaging and group case review. Intraoperatively, the MAPS protocol includes placement of ureteral stents, possible placental mapping with ultrasound, and uterine artery embolization by interventional radiology. Patients suspected to have PAS on prenatal imaging who underwent c-hyst were included in the analysis. Primary outcomes were intraoperative complications and postoperative complications. Secondary outcomes were blood loss, need for ICU, and length of stay. Proportions were compared using Fisher's exact test, and continuous variables were compared used
-tests and Mood's Median test.
There were no differences in baseline demographics between the pre- (
= 38) and post-MAPS (
= 34) groups. The pre-MAPS group had more placenta previa (95% pre- vs. 74% post-MAPS,
= 0.013) and prior cesarean sections (2 prior pre- vs. 1 prior post-MAPS,
= 0.012). The post-MAPS group had more severe pathology (PAS Grade 3 8% pre- vs. 47% post-MAPS,
= 0.001). There were fewer intraoperative complications (39% pre- vs.3% post-MAPS,
< 0.001), postoperative complications (32% pre- vs.12% post-MAPS,
= 0.043), hemorrhages >1l (95% pre- vs.65% post-MAPS,
= 0.001), ICU admissions (59% pre- vs.35% post-MAPS,
= 0.04) and shorter hospital stays (10 days pre- vs.7 days post-MAPS,
= 0.02) in the post-MAPS compared to pre-MAPS patients. Neonatal length of stay was 8 days longer in the post-MAPS group (9 days pre- vs. 17 days post-MAPS,
= 0.03). Subgroup analyses demonstrated that ureteral stent placement and uterine artery embolization (UAE) may be important steps to reduce complications and ICU admissions. When comparing just those who underwent UAE, patients in the post-MAPS group experienced fewer hemorrhages greater five liters (EBL >5l 43% pre- vs.4% post-MAPS,
= 0.007).
An evidence-informed approach to management of PAS was associated with decreased complication rate, EBL >1l, ICU admission and length of hospitalization, particularly for patients with severe pathology.
Preterm birth is the leading cause of neonatal morbidity and death in the United States. Although many risk factors for spontaneous preterm birth have been elucidated, some women with a previous term ...delivery experience spontaneous preterm birth in the absence of any identifiable risk factors. Cervical trauma during a prolonged second stage of labor has been postulated as a potential contributor to subsequent spontaneous preterm birth.
This study was designed to examine the relationship between the length of the second stage of labor in the first pregnancy and the risk of spontaneous preterm birth in the subsequent pregnancy.
This was a retrospective cohort study of all women with 2 consecutive singleton deliveries at a single institution between July 2012 and June 2018, with the first delivery occurring ≥37 weeks of gestation. Multiparous women and those women who did not reach the second stage of labor in the first pregnancy were excluded. Prolonged second stage of labor was defined as ≥4 hours, based on the 75th percentile for this cohort and on recommendations from the National Institute of Child Health and Human Development. Very prolonged second stage of labor was defined as ≥7 hours, based on the 95th percentile for this cohort. The primary outcome was spontaneous preterm birth <37 weeks of gestation in the subsequent pregnancy. The Kruskal-Wallis test compared median values for nonparametric continuous variables; Fisher’s exact tests compared proportions for categoric variables, and logistic regression generated odds ratios.
A total of 1032 women met criteria for study inclusion, with an overall subsequent spontaneous preterm birth rate of 3.1%. Prolonged second stage of labor of ≥4 hours was identified in 24.4% (252/1032 women) of the cohort, with 70.6% (178/252 women) of this group delivering vaginally. There was no statistically significant difference in rate of spontaneous preterm birth in those with and without prolonged second stage of labor (4.4% 11/252 women with prolonged labor vs 2.7% 21/780 women without prolonged labor; P=.21; odds ratio, 1.6; 95% confidence interval, 0.8–3.5). Very prolonged second stage of labor of ≥7 hours was identified in 4.3% (44/1032 women) of the cohort, with 45.4% (20/44 women) of this group delivering vaginally. There was a significantly higher rate of spontaneous preterm birth in those with very prolonged second stage of labor compared with those without prolonged labor (9.1% 4/44 women with prolonged labor vs 2.8% 28/988 women without prolonged labor; P=.04; odds ratio, 3.4; 95% confidence interval, 1.1–10.2), although this finding did not persist after we controlled for the mode of first delivery (adjusted odds ratio, 1.55; 95% confidence interval, 0.65–3.73). Spontaneous preterm birth after very prolonged second stage of labor was identified in only 4 patients, all of whom had a cesarean delivery with the first pregnancy.
A second stage of labor of ≥4 hours in the first pregnancy was not associated with an increased risk of subsequent spontaneous preterm birth and was associated with a high rate (>70%) of vaginal birth. A second stage of labor of ≥7 hours did not appear to be associated with an increased risk of preterm birth, when we adjusted for mode of first delivery. There was a nonsignificant increase in the risk of preterm birth in those who delivered via cesarean section after a second stage of labor of ≥7 hours.
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