Maternal hybrid immunity and risk of infant COVID-19 hospitalizations: national case-control study in Israel.

Hybrid immunity, acquired through vaccination followed or preceded by a COVID-19 infection, elicits robust antibody augmentation. We hypothesize that maternal hybrid immunity will provide greater infant protection than other forms of COVID-19 immunity in the first 6 months of life. We conducted a case-control study in Israel, enrolling 661 infants up to 6 months of age, hospitalized with COVID-19 (cases) and 59,460 age-matched non-hospitalized infants (controls) between August 24, 2021, and March 15, 2022. Infants were grouped by maternal immunity status at delivery: Naïve (never vaccinated or tested positive, reference group), Hybrid-immunity (vaccinated and tested positive), Natural-immunity (tested positive before or during the study period), Full-vaccination (two-shot regimen plus 1 booster), and Partial-vaccination (less than full three shot regimen). Applying Cox proportional hazards models to estimate the hazard ratios, which was then converted to percent vaccine effectiveness, and using the Naïve group as the reference, maternal hybrid-immunity provided the highest protection (84% [95% CI 75-90]), followed by full-vaccination (66% [95% CI 56-74]), natural-immunity (56% [95% CI 39-68]), and partial-vaccination (29% [95% CI 15-41]). Maternal hybrid-immunity was associated with a reduced risk of infant hospitalization for Covid-19, as compared to natural-immunity, regardless of exposure timing or sequence. These findings emphasize the benefits of vaccinating previously infected individuals during pregnancy to reduce COVID-19 hospitalizations in early infancy.

Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Assessing the Clinical Significance of Third-Trimester Post-Coital Bleeding.

Introduction - This study aims to evaluate the impact of third-trimester post-coital bleeding (PCB) on pregnancy outcomes. Methods - A retrospective cohort study was conducted at two tertiary medical centers, including all pregnant women between 24-34 weeks of gestation referred due to vaginal bleeding over an eleven-year period. The study population includes all singleton deliveries; within this population, women were further classified into three groups: those admitted due to vaginal bleeding related to PCB, those admitted due to vaginal bleeding not related to PCB, and those who did not report vaginal bleeding. The primary outcome measure was delivery prior to 37 weeks of gestation, while secondary outcome measures included maternal and neonatal complications. Baseline characteristics of the two groups were compared. Results - During the study period, there were a total of 51,698 deliveries. Among these, 230 cases involved bleeding between 24-34 weeks of gestation, 34 (14.8%) were identified as PCB, and 196 as bleeding unrelated to intercourse. In addition, 51,468 pregnancies without bleeding were analyzed as the general population for comparison. The incidence of preterm labor before 37 weeks of gestation was notably higher in both women with post-coital bleeding (14.7%) and those with bleeding unrelated to coitus (20.9%) compared to the general population (5.6%); however, there was no statistically significant difference between the two bleeding groups (p=0.403) while both were significantly different from the general population (p<0.001). The odds ratio for preterm birth before 37 weeks of gestation after post-coital bleeding was 3.29 (95% CI: 1.26 to 8.56, p=0.0149). There were no significant differences between the PCB and bleeding unrelated to intercourse groups in terms of maternal and neonatal complications. Conclusion - This study found that third-trimester PCB is a risk factor for preterm delivery, with rates similar to other causes of third-trimester bleeding but significantly higher than the general population without bleeding. These findings challenge the assumption that PCB is benign.

Validating staging criteria for sonographic and physical examination for cervical changes at <24 weeks' gestation to predict preterm birth.

BACKGROUND: Preterm birth represents a significant clinical challenge, and the ability to predict it effectively is a priority in obstetrics. The cervix undergoes specific changes during pregnancy, and staging these changes may offer a valuable predictive model for preterm birth, particularly among women with a midtrimester short cervical length. OBJECTIVE: The study aimed to validate a proposed staging model for asymptomatic women with midtrimester short cervical length and to evaluate its potential for predicting preterm birth. The integration of cervical examination and inspection with cervical length measurement was a novel approach to be assessed. STUDY DESIGN: This was a multicenter, retrospective cohort study that included 925 pregnant women with a singleton fetus and a midtrimester cervical length measurement of ≤25 mm. Cervical conditions were assessed using ultrasonography, a speculum, and a physical examination and were classified into 1 of 5 cervical stages to correlate with the likelihood of preterm birth. Statistical analyses included Kaplan-Meier survival analysis to illustrate the time-to-event characteristics across the 5 stages and density plot evaluation to visualize the distribution of the gestational ages within the stages. RESULTS: The staging model included 5 stages based on cervical length, appearance, and dilatation. Among the 925 participants, 649 were classified as being stage 1, 245 as stage 2, 18 as stage 3, 10 as stage 4, and 3 as stage 5. The observed rates of preterm birth before 37 weeks for individuals classified in stages 1, 2, 3, 4, and 5 were 22.3%, 26.5%, 44.4%, 60%, and 66.7%, respectively (P=.005). The overall observed rates of preterm birth before 28, 32, 34, and 37 weeks' gestation were 5.5%, 9.9%, 12.2%, and 24.1%, respectively (P=.005). CONCLUSION: This study validated the proposed staging criteria as an effective predictor of preterm birth caused by cervical insufficiency. The results demonstrate a significant increase in the preterm birth rate with advancing stage classification, indicating that the staging effectively stratified women based on their risk for preterm birth and highlighting the potential use for targeted interventions. Implementing these staging criteria can potentially improve the counseling and management of pregnant women at risk for preterm birth.

The Impact of Advanced Maternal Age on Pregnancy Outcomes: A Retrospective Multicenter Study.

The aim of this multicenter retrospective cohort study was to examine the impact of maternal age on perinatal outcomes in multiparas, stratified according to maternal age in one- and two-year increments. The analysis involved 302,484 multiparas who delivered between the years 2003 and 2021 in four university-affiliated obstetrics departments. Maternal age was considered both as a continuous variable and in two-year intervals, as compared with a comparison group of parturients aged 25-30 years. The study focused on cesarean delivery and neonatal intensive care unit (NICU) admission as primary outcomes. The findings revealed that cesarean delivery rates increased as maternal age advanced, with rates ranging from 6.7% among 25-30 year olds, rising continuously from 13.5% to 19.9% between the age strata of 31 and 42, to exceeding 20% among those aged ≥ 43 years (p < 0.01 for each stratum when compared to 25-30 year old group). Similarly, NICU admission rates rose from 2.7% in the comparison group to 6% in parturients aged 45-46 years (p < 0.01 for each stratum when compared to 25-30 year old group). The study highlights the association between incrementally advanced maternal age and increased rates of maternal and neonatal complications, necessitating global awareness of these implications for family planning decisions and maternal care.

Failed vacuum and preterm delivery risk in the subsequent pregnancy: a multicenter retrospective cohort study.

BACKGROUND: Second-stage cesarean delivery is associated with subsequent preterm delivery. Failed vacuum-assisted delivery is a subgroup of second-stage cesarean delivery in which the fetal head is engaged deeper in the pelvis and, thus, is associated with an increased risk of short-term maternal complications. OBJECTIVE: This study aimed to investigate the maternal and neonatal outcomes of women at their subsequent delivery after a second-stage cesarean delivery with failed vacuum-assisted extraction vs after a second-stage cesarean delivery without a trial of vacuum-assisted extraction. STUDY DESIGN: This was a multicenter retrospective cohort study. The study population included all women in their subsequent pregnancy after a second-stage cesarean delivery who delivered in all university-affiliated obstetrical centers (n=4) in a single geographic area between 2003 and 2021. Maternal and neonatal outcomes of women who had second-stage cesarean delivery after a failed vacuum-assisted delivery were compared with women who had second-stage cesarean delivery without a trial of vacuum-assisted delivery. The primary outcome of this study was preterm delivery at <37 weeks of gestation. The secondary outcomes were vaginal birth rate and other adverse maternal and neonatal outcomes. Univariate analysis was followed by multiple logistic regression modeling. RESULTS: During the study period, 1313 women met the inclusion criteria, of whom 215 (16.4%) had a history of failed vacuum-assisted delivery at the previous delivery and 1098 (83.6%) did not. In univariate analysis, women with previously failed vacuum-assisted delivery had similar preterm delivery rates (<37, <34, <32, and <28 weeks of gestation), a successful trial of labor after cesarean delivery rates, uterine rupture, and hysterectomy. However, multivariable analyses controlling for confounders showed that a history of failed vacuum-assisted delivery is associated with a higher risk of preterm delivery at <37 weeks of gestation (adjusted odds ratio, 2.05; 95% confidence interval, 1.11-3.79; P=.02), but not with preterm delivery at <34 or <32 weeks of gestation. CONCLUSION: Among women with a previous second-stage cesarean delivery, previously failed vacuum-assisted delivery was associated with an increased risk of preterm delivery at <37 weeks of gestation in the subsequent birth.

Perinatal outcomes in nulliparous women with a history of multiple pregnancy losses according to number of previous pregnancy losses.

BACKGROUND: While it is widely acknowledged that pregnancy losses can lead to negative outcomes for both mothers and fetuses, there is limited information available on the specific levels of risk associated with each additional pregnancy loss. OBJECTIVE: This study aimed to investigate the effect of number of previous pregnancy losses among nulliparous women on maternal and neonatal adverse outcomes. STUDY DESIGN: This was a multicenter retrospective cohort study. The study population included all nulliparous women with singleton pregnancies who delivered in all university-affiliated obstetrical centers in a single geographic area between 2003 and 2021. Maternal and neonatal outcomes of women who delivered at our medical centers and had varying numbers of previous pregnancy losses were compared with women who had no previous pregnancy loss. The primary outcome of this study was preterm delivery rate at <37 weeks of gestation. The secondary outcomes were adverse maternal and neonatal outcomes. Univariate analysis was performed using multiple logistic regression modeling. RESULTS: During the study period, 97,904 nulliparous women met the inclusion and exclusion criteria. Of those women, 84,245 (86%) had no previous pregnancy losses (reference group), 10,724 (11%) had 1 previous pregnancy loss, 2150 (2.2%) had 2 previous pregnancy losses, 516 (0.5%) had 3 previous pregnancy losses, 160 (0.2%) had 4 previous pregnancy losses, and 99 (0.1%) had ≥5 previous pregnancy losses. Women who had previous pregnancy losses had significantly higher rates of preterm delivery, hypertensive disorders of pregnancy, diabetes mellitus (pregestational and gestational), unplanned cesarean delivery, perinatal death, neonatal intensive care unit admissions, and neonatal hypoglycemia. The risks of preterm delivery and most other adverse obstetrical outcomes correlated with the number of previous pregnancy losses. Multivariate analyses showed that each previous pregnancy loss was associated with an additional, significant, increased risk of preterm delivery of 14% at <37 weeks of gestation, 37% at <34 weeks of gestation, 45% at <32 weeks of gestation, and 77% at <28 weeks of gestation. CONCLUSION: A history of previous pregnancy losses increased the risk of preterm delivery and other perinatal outcomes in a dose-dependent manner. To minimize perinatal complications, obstetricians should be aware of the risks and complications in this unique population, consider close monitoring of the cervical length, and maintain high vigilance in case of complications with special attention to other potentially modifiable risks.

Maternal third dose of BNT162b2 mRNA vaccine and risk of infant COVID-19 hospitalization.

Infants are at a higher risk of Coronavirus Disease 2019 (COVID-19)-related hospitalizations compared to older children. In this study, we investigated the effect of the recommended third maternal dose of BNT162b2 COVID-19 vaccine during pregnancy on rates of infant COVID-19-related hospitalizations. We conducted a nationwide cohort study of all live-born infants delivered in Israel between 24 August 2021 and 15 March 2022 to estimate the effectiveness of the third booster dose versus the second dose against infant COVID-19-related hospitalizations. Data were analyzed for the overall study period, and the Delta and Omicron periods were analyzed separately. Cox proportional hazard regression models estimated hazard ratios and 95% confidence intervals (CIs) for infant hospitalizations according to maternal vaccination status at delivery. Among 48,868 live-born infants included in the analysis, rates of COVID-19 hospitalization were 0.4%, 0.6% and 0.7% in the third-dose, second-dose and unvaccinated groups, respectively. Compared to the second dose, the third dose was associated with reduced infant hospitalization with estimated effectiveness of 53% (95% CI: 36-65%). Greater protection was associated with a shorter interval between vaccination and delivery. A third maternal dose during pregnancy reduced the risk of infant hospitalization for COVID-19 during the first 4 months of life, supporting clinical and public health guidance for maternal booster vaccination to prevent infant COVID-19 hospitalization.

Boosting maternal and neonatal anti-SARS-CoV-2 humoral immunity using a third mRNA vaccine dose.

BACKGROUND: To minimize COVID-19 pandemic burden and spread, 3-dose vaccination campaigns commenced worldwide. Since patients who are pregnant are at increased risk for severe disease, they were recently included in that policy, despite the lack of available evidence regarding the impact of a third boosting dose during pregnancy, underscoring the urgent need for relevant data. We aimed to characterize the effect of the third boosting dose of mRNA Pfizer BNT162b2 vaccine in pregnancy. METHODS: We performed a prospective cohort study of anti-SARS-CoV-2 antibody titers (n = 213) upon delivery in maternal and cord blood of naive fully vaccinated parturients who received a third dose (n = 86) as compared with 2-dose recipients (n = 127). RESULTS: We found a robust surge in maternal and cord blood levels of anti-SARS-CoV-2 titers at the time of delivery, when comparing pregnancies in which the mother received a third boosting dose with 2-dose recipients. The effect of the third boosting dose remained significant when controlling for the trimester of last exposure, suggesting additive immunity extends beyond that obtained after the second dose. Milder side effects were reported following the third dose, as compared with the second vaccine dose, among the fully vaccinated group. CONCLUSION: The third boosting dose of mRNA Pfizer BNT162b2 vaccine augmented maternal and neonatal immunity with mild side effects. These data provide evidence to bolster clinical and public health guidance, reassure patients, and increase vaccine uptake among patients who are pregnant. FUNDING: Israel Science Foundation KillCorona grant 3777/19; Research grant from the "Ofek" Program of the Hadassah Medical Center.

Partogram of Grandmultiparous Parturients: A Multicenter Cohort Study.

Sparse and conflicting data exist regarding the normal partogram of grand-multiparous (GMP, defined as parity of 6+) parturients. Customized partograms may potentially lower cesarean delivery rates for protraction disorders in this population. In this study, we aim to construct a normal labor curve of GMP women and compare it to the multiparous (MP, defined as parity of 2-5) partogram. We conducted a multicenter retrospective cohort analysis of deliveries between the years 2003 and 2019. Eligible parturients were the trials of labor of singletons ≥37 + 0 weeks in cephalic presentation with ≥2 documented cervical examinations during labor. Exclusion criteria were elective cesarean delivery without a trial of labor, preterm labor, major fetal anomalies, and fetal demise. GMP comprised the study group while the MP counterparts were the control group. A total of 78,292 deliveries met the inclusion criteria, comprising 10,532 GMP and 67,760 MP parturients. Our data revealed that during the first stage of labor, cervical dilation progressed at similar rates in MPs and GMPs, while head descent was a few minutes faster in GMPs compared to MPs, regardless of epidural anesthesia. The second stage of labor was faster in GMPs compared to MPs; the 95th percentile of the second stage duration of GMPs (48 min duration) was 43 min less than that of MPs (91 min duration). These findings remained similar among deliveries with and without epidural analgesia or labor induction. We conclude that GMPs' and MPs' cervical dilation progression in the active phase of labor was similar, and the second stage of labor was shorter in GMPs, regardless of epidural use. Thus, GMPs' uterus function during labor corresponds, and possibly surpasses, that of MPs. These findings indicate that health providers can use the standard partogram of the active phase of labor when caring for GMP parturients.

Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study.

BACKGROUND: In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. METHODS: INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. FINDINGS: We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0-38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03-1·31]) and SPMMI (RR 1·21 [95% CI 1·00-1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88-1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12-1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84-3·43]), perinatal complications (RR 1·84 [95% CI 1·02-3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67-20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02-4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44-41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22-65) and 76% (47-89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48-87) and 91% (65-98) after a booster dose. INTERPRETATION: COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority. FUNDING: None.

Trial of labor after 2 previous cesareans: a multicenter study.

BACKGROUND: Trial of labor after cesarean after 2 cesarean deliveries is linked to a lower success rate of vaginal delivery and higher rates of adverse obstetrical outcomes than trial of labor after cesarean after 1 previous cesarean delivery. OBJECTIVE: This study aimed to investigate the factors associated with failed trial of labor after cesarean among women with 2 previous cesarean deliveries. STUDY DESIGN: This was a multicenter retrospective cohort study, which included all women with singleton pregnancies attempting trial of labor after cesarean after 2 previous cesarean deliveries between 2003 and 2021. This study compared labor, maternal, and neonatal characteristics between women with failed trial of labor after cesarean and those with successful trial of labor after cesarean. Univariate analysis was initially performed, followed by multivariable analysis (adjusted odds ratios with 95% confidence intervals). RESULTS: The study included a total of 1181 women attempting trial of labor after cesarean after 2 previous cesarean deliveries. Among these cases, vaginal birth after cesarean was achieved in 973 women (82.4%). Women with failed trial of labor after cesarean had higher rates of maternal and neonatal morbidities. Several factors were found to be associated with failed trial of labor after cesarean, including longer interpregnancy and interdelivery intervals, lower gravidity and parity, lower rates of previous successful vaginal delivery, smoking, earlier gestational age at delivery (38.3±2.1 vs 39.5±1.3 weeks), late preterm delivery (34-37 weeks of gestation), lower cervical dilation on admission, no use of epidural, and smaller neonatal birthweight. Our multivariable model revealed that late preterm delivery (adjusted odds ratio, 3.79; 95% confidence interval, 1.37-10.47) and cervical dilation on admission for labor <3 cm (adjusted odds ratio, 2.58; 95% confidence interval, 1.47-4.54) were associated with higher odds of failed trial of labor after cesarean. CONCLUSION: In the investigated population of women with 2 previous cesarean deliveries undergoing trial of labor after cesarean, admission at the late preterm period with a cervical dilation of <3 cm, which reflects the latent phase, may elevate the risk of failed trial of labor after cesarean and a repeated intrapartum cesarean delivery.

Effectiveness of a third BNT162b2 mRNA COVID-19 vaccination during pregnancy: a national observational study in Israel.

The Centers for Disease Control (CDC) recommend a third dose of COVID-19 vaccine for pregnant women, although data regarding effectiveness during pregnancy are lacking. This national, population-based, historical cohort study of pregnant women in Israel, delivering between August 1, 2021 and March 22, 2022, aims to analyze and compare the third and second doses' vaccine effectiveness in preventing COVID-19-related hospitalizations during pregnancy during two COVID-19 waves (Delta variant in the summer of 2021 and Omicron, BA.1, variant in the winter of 2022). Time-dependent Cox proportional-hazards regression models estimate the hazard ratios (HR) and 95% confidence intervals (CI) for COVID-related outcomes according to vaccine dose, and vaccine effectiveness as 1-HR. Study includes 82,659 and 33,303 pregnant women from the Delta and Omicron waves, respectively. Compared with the second dose, the third dose effectively prevents overall hospitalizations with SARS-CoV-2 infections, with estimated effectiveness of 92% (95% CI 83-96%) during Delta, and enhances protection against significant disease during Omicron, with effectiveness of 92% (95% CI 26-99%), and 48% (95% CI 37-57%) effectiveness against hospitalization overall. A third dose of the BNT162b2 mRNA COVID-19 vaccine during pregnancy, given at least 5 months after the second vaccine dose, enhances protection against adverse COVID-19-related outcomes.

Birthweight difference between deliveries and the risk of obstetric anal sphincter injury in parous women.

INTRODUCTION AND HYPOTHESIS: While obstetric anal sphincter injury (OASI) is less frequent in parous compared to nulliparous women, it remains a major concern affecting quality of life of women worldwide. The aim of this study was to evaluate the association between birthweight (BW) difference between deliveries and risk of OASI in parous women. METHODS: We performed a retrospective case-control study including parous women with at least one previous vaginal delivery who were diagnosed with OASI. The control group consisted of parous women who did not have OASI during vaginal delivery. Controls were matched in a 1:2 ratio by year of birth, maternal age, and parity. Medical history, obstetric background, and current labor-related data were compared. Further univariate and multivariable analyses were performed, assessing for risk factors for OASI. RESULTS: One hundred eight parous women who had a diagnosis of OASI and a control group of 216 parturients who delivered without OASI were included in the final analysis. Differences between the current BW and the preceding and maximal previous BW were evaluated. There were significantly higher rates of women who had a larger neonate with > 500 g difference between the current and previous BW in the OASI group than in those with no OASI (28.7% vs. 12.30%, respectively; p < 0.001). Following a multivariable analysis for the dependent parameter of OASI, the following parameters were found to be independently associated with OASI outcome: previous operative vaginal delivery, BW ≥ 90th percentile, and current BW ≥ 500 g compared to previous maximal BW. CONCLUSIONS: In parous women, neonatal BW increase between deliveries of > 500 g is associated with OASI.

Trial of labor of vertex-nonvertex twins following a previous cesarean delivery.

BACKGROUND: Maternal and neonatal outcomes of trial of labor after cesarean delivery of twins are similar to those of singleton trials of labor after cesarean delivery. However, previous studies did not stratify outcomes by second-twin presentation on admission to labor. OBJECTIVE: To examine maternal and neonatal outcomes following trial of labor after cesarean delivery in twins with vertex-nonvertex presentation. STUDY DESIGN: A retrospective multicenter study was conducted including data on deliveries occurring between the years 2005 and 2020. We included trials of labor after a previous cesarean delivery (at ≥320/7 weeks' gestation) of twin gestations with a vertex-presenting first twin on admission to labor. The exposed group was defined as deliveries with a nonvertex second twin at admission to labor, whereas the comparison group included deliveries with a vertex second twin at admission. Only parturients who attempted vaginal delivery were included. Cases of prelabor fetal death of either twin or major fetal anomalies were excluded. The primary outcome was uterine rupture. RESULTS: A total of 236 twin trials of labor after cesarean delivery were included, of which 128 involved nonvertex second twins and 108 a second vertex twin. Uterine rupture rates were comparable between the groups (1/128 [0.9%] vs 1/108 [0.8%]; P=1.000). Successful trial of labor after cesarean delivery of both twins occurred in 76.6% of the exposed group vs 81.5% of the comparison group, whereas cesarean delivery of both twins was performed in 21.9% of the exposed group vs 17.6% of the comparison group (P=.418; odds ratio, 1.32; confidence interval, 0.7-2.5). Two cases of cesarean delivery of the second twin occurred in the exposed group and 1 in the comparison group (1.6% vs 0.9%, respectively, P=1.000). There was no difference between the groups in maternal outcomes, including rates of postpartum hemorrhage, blood transfusion, placental abruption, thromboembolic events, and maternal fever. Neonatal outcomes were also comparable between the groups, including rates of intensive care admission and low (≤7) 5-minute Apgar scores. CONCLUSION: Our data show that trial of labor after cesarean delivery of noncephalic second twins holds favorable maternal and neonatal outcomes, comparable with those of vertex-vertex trials of labor after cesarean delivery. Second-twin noncephalic presentation should not discourage parturients and caregivers from considering trial of labor after cesarean delivery if desired.

Boosting maternal and neonatal humoral immunity following SARS-CoV-2 infection using a single messenger RNA vaccine dose.

BACKGROUND: Post-COVID-19 vaccine boosting is a potent tool in the ongoing pandemic. Relevant data regarding this approach during pregnancy are lacking, which affects vaccination policy guidance, public acceptance, and vaccine uptake during pregnancy. We aimed to investigate the dynamics of anti-SARS-CoV-2 antibody levels following SARS-CoV-2 infection during pregnancy and to characterize the effect of a single postinfection vaccine booster dose on the anti-SARS-CoV-2 antibody levels in parturients in comparison with the levels in naïve vaccinated and convalescent, nonboosted parturients. STUDY DESIGN: Serum samples prospectively collected from parturients and umbilical cords at delivery at our university-affiliated urban medical center in Jerusalem, Israel, from May to October 2021, were selected and analyzed in a case-control manner. Study groups comprised the following participants: a consecutive sample of parturients with a polymerase chain reaction-confirmed history of COVID-19 during any stage of pregnancy; and comparison groups selected according to time of exposure comprising (1) convalescent, nonboosted parturients with polymerase chain reaction-confirmed COVID-19; (2) convalescent parturients with polymerase chain reaction-confirmed COVID-19 who received a single booster dose of the BNT162b2 messenger RNA vaccine; and (3) infection-naïve, fully vaccinated parturients who received 2 doses of the BNT162b2 messenger RNA vaccine. Outcomes that were determined included maternal and umbilical cord blood anti-SARS-CoV-2 antibody levels detected at delivery, the reported side effects, and pregnancy outcomes. RESULTS: A total of 228 parturients aged 18 to 45 years were included. Of those, samples from 64 were studied to characterize the titer dynamics following COVID-19 at all stages of pregnancy. The boosting effect was determined by comparing (1) convalescent (n=54), (2) boosted convalescent (n=60), and (3) naïve, fully vaccinated (n=114) parturients. Anti-SARS-CoV-2 antibody levels detected on delivery showed a gradual and significant decline over time from infection to delivery (r=0.4371; P=.0003). Of the gravidae infected during the first trimester, 34.6% (9/26) tested negative at delivery, compared with 9.1% (3/33) of those infected during the second trimester (P=.023). Significantly higher anti-SARS-CoV-2 antibody levels were observed among boosted convalescent than among nonboosted convalescent (17.6-fold; P<.001) and naïve vaccinated parturients (3.2-fold; P<.001). Similar patterns were observed in umbilical cord blood. Side effects in convalescent gravidae resembled those in previous reports of mild symptoms following COVID-19 vaccination during pregnancy. CONCLUSION: Postinfection maternal humoral immunity wanes during pregnancy, leading to low or undetectable protective titers for a marked proportion of patients. A single boosting dose of the BNT162b2 messenger RNA vaccine induced a robust increase in protective titers for both the mother and newborn with moderate reported side effects.

Improving Patient Safety in General Hospitals Using Structured Handoffs: Outcomes From a National Project.

Background: Promoting quality and patient safety is one of the health policy pillars of Israel's Ministry of Health. Communication among healthcare professionals is of utmost importance and can be improved using a standardized, well-known handoff tool such as the Introduction, Situation, Background, Assessment, and Recommendations (ISBAR). This study aims to present implementation process and participants' satisfaction of a national project that used a standardized tool for team communication. Methods: This national intervention project included process implementation teams from 17 Israeli general hospitals evaluating the ISBAR implementation process for transferring patients from intensive care units to medical/surgical wards. The project, conducted between January 2017 and March 2018, used Fischer's test and logistic regression. The project evaluation was based on the participants' assessment of and satisfaction with the handoff process. Results: Eighty-seven process implementers completed the questionnaire. A statistically significant increase in satisfaction scores in terms of four variables (p < 0.001) was observed following the implementation of the project. Nurses reported higher satisfaction at the end of the process (0.036). Participants who perceived less missing information during handoffs were more satisfied with the process of information flow between wards (84.9%) than those who perceived more missing information (15.6%). Participants who responded that there was no need to improve information flow were more satisfied with the project information flow (95.6%) compared to the group which responded that it was necessary to improve information flow (58.2%). Three out of four variables predicted satisfaction with the process. Being a nurse also predicted satisfaction with information flow with a point estimate of 2.4. The C value of the total model was 0.87. Conclusions: Implementation of a safety project at a national level requires careful planning and the close involvement of the participating teams. A standardized instrument, a well-defined process, and external controls to monitor and manage the project are essential for success. Disparities found in the responses of nurses vs. physicians suggest the need for a different approach for each profession in planning and executing a similar project in the future.

Chorioamnionitis and its association with neonatal and maternal adverse outcomes in women with and without epidural analgesia administration.

OBJECTIVE: To evaluate neonatal fever and adverse maternal and neonatal outcomes in febrile laboring women and assess whether the time interval between epidural analgesia (EA) administration and chorioamnionitis is associated with these complications. METHODS: A retrospective cohort study at a university affiliated medical center between 2003 and 2015. Included were women who underwent term vaginal delivery attempt and diagnosed with chorioamnionitis. The primary outcomes compared between febrile women with and without EA were neonatal fever and adverse neonatal and maternal outcomes. The association between time from EA to fever (<6, 6-12, >12 h) and maternal and neonatal complications was also assessed. RESULTS: During the study period, 1,933 women with chorioamnionitis were assessed. Of them, 1,810 (93.6%) received EA prior to fever and 123 (6.4%) febrile parturients did not receive EA. Neonatal fever and other neonatal adverse outcomes were similar in the EA vs. non-EA group (2.2% vs. 0.8% and 2.7% vs. 4.9% (NS)), except for transient tachypnea of the newborn rates which were lower in the EA group (1.4% vs. 4.1%, p = 0.043). Maternal complications were similar, besides for higher rates of instrumental deliveries found in the EA group (24.0% vs. 5.7%, p < 0.001). Time between EA and fever onset was not associated with neonatal complications in logistic regression analysis. CONCLUSION: Neonatal and maternal outcomes are similar in febrile laboring women with and without EA. The time interval between EA and onset of fever is not associated with increased rates of neonatal fever or adverse outcomes and should not affect the management of labor.

Uterine rupture risk in a trial of labor after cesarean section with and without previous vaginal births.

PURPOSE: Previous cesarean delivery (CD) is the main risk factor for uterine rupture when attempting a trial of labor. Previous vaginal delivery (PVD) is a predictor for the trial of labor after cesarean (TOLAC) success and a protective factor against uterine rupture. We aimed to assess the magnitude of PVD as a protective factor from uterine rupture. METHODS: A retrospective cohort study was conducted, including women who underwent TOLACs from 2003 to 2015. Women with and without PVD were compared. Inclusion criteria were one previous CD, trial of labor at ≥ 24 weeks' gestation, and cephalic presentation. We excluded pre-labor intrauterine fetal death and fetal anomalies. The primary outcome was a uterine rupture. Secondary outcomes were maternal and fetal complications. Logistic regression modeling was applied to analyze the association between PVD and uterine rupture while controlling for confounders. RESULTS: A total of 11,235 women were included, 6795 of which had a PVD. Women with PVD had significantly lower rates of uterine rupture (0.18% vs. 1.1%; OR 0.19, p < 0.001), were less likely to be delivered by an emergency CD (13.2% vs. 39.4%, OR 0.17, p < 0.0001), were more likely to undergo labor induction (OR 1.56, p < 0.0001), and were less likely to undergo an instrumental delivery (OR 0.14, p < 0.001). Logistic regression modeling revealed that PVD was the only independent protective factor, with an aOR of 0.22. CONCLUSION: PVD is the most important protective factor from uterine rupture in patients undergoing TOLAC. A trial of labor following one CD should therefore be encouraged in these patients.

Prediction of neonatal subgaleal hemorrhage using first stage of labor data: A machine-learning based model.

BACKGROUND: Subgaleal hemorrhage (SGH) is a rare neonatal condition, mainly associated with instrumental delivery, mainly vacuum extractor (VE). The aim of this study was to develop a machine learning model that would allow a personalized prediction algorithm for Subgaleal hemorrhage (SGH) following vacuum extraction (VE), based on maternal and fetal variables collected during the first stage of labor. MATERIALS AND METHODS: A retrospective cohort study on data from a university affiliated hospital, recorded between January 2013 and February 2017. Balanced random forest algorithm was used to develop a machine learning model to predict personalized risk of the neonate developing SGH, in the eventuality that vacuum extraction was used during delivery. RESULTS: During the study period, 35,552 term, singleton spontaneous or induced trials of labor deliveries were included in this study. Neonatal SGH following vacuum extraction (SGH-VE) occurred in 109 cases (0.3%). Two machine learning models were developed: a proof of concept model (model A), based on a cohort limited to the (n=2955) instances of vacuum extraction, and the clinical support model (model B), based on all spontaneous or induced trials of labor (n=35,552). The models stratified parturients into high- and low-risk groups for development of SGH-VE. Model A showed a 2-fold increase in the high-risk group of parturients compared to the low risk group (OR=2.76, CI 95% 1.85-4.11). In model B, a 4-fold increase in the odds of SGH was observed in the high-risk group of parturients compared to the low risk group (OR=4.2, CI 2.2-8.1), while identifying 90.8% (99/109) of the SGH cases. CONCLUSIONS: Our machine learning-based model stratified births to high or low risk for SGH, making it an applicable tool for personalized decision-making during labor regarding the application of VE. This model may contribute to improved neonatal outcomes.