Placental Histopathological Lesions and Adverse Neonatal Outcomes in Patients with Inflammatory Bowel Diseases- A retrospective Cohort Study.

Inflammatory bowel diseases (IBD) are significantly associated with adverse pregnancy and neonatal outcomes, though the pathomechanism is yet unknown. To investigate the relationship between IBD and adverse pregnancy outcomes by comparing neonatal outcomes and placental histopathology in two matched groups of patients with and without IBD. In this retrospective study, data of all patients who gave birth between 2008-2021 and were diagnosed with IBD were reviewed and compared to a control group matching two control cases for every IBD case. Neonatal outcomes and placental pathology were compared between the groups. Compared to the control group (n=76), the placentas of patients with IBD (n=36) were characterized by significantly lower placental weight (p < 0.001), and higher rates of maternal vascular malperfusion lesions (MVM, p < 0.001) and maternal and fetal inflammatory response lesions (p < 0.001). Neonates of patients with IBD were more frequently small for gestational age (SGA) (p=0.01), with increased rates of need for phototherapy (p = 0.03), respiratory morbidity and NICU admission (p < 0.001 for both outcomes). Multivariate logistic regression analyses adjusting for possible confounders (including maternal age, gestational age, chronic hypertension, smoking, and thrombophilia) confirmed the independent association between IBD and composite MVM lesions (aOR 4.31, p < 0.001), maternal inflammatory responses (aOR 40.22, p < 0.001) and SGA infants (aOR 4.31, p = 0.013). IBD is associated with increased rates of placental histopathological lesions and adverse pregnancy outcomes, including SGA infants. These novel findings imply the role of placental malperfusion and inflammatory processes in pregnancy complications of IBD patients, which should be followed accordingly. Approval of local ethics committee # WOMC-0219-20.

Improved neonatal outcomes in pregnancies with coexisting gestational diabetes and preeclampsia in normal birthweight neonates- insights from a retrospective cohort study.

INTRODUCTION: We aimed to assess neonatal and maternal outcomes in appropriate-for-gestational-weight (AGA) neonates of mothers with both gestational diabetes mellitus (GDM) and preeclampsia (PET). METHODS: Medical records of women diagnosed with GDM or PET were reviewed. Women with AGA neonates were divided into three groups- GDM, PET, and GDM + PET and maternal neonatal and placental outcomes were compared. The primary outcome was a composite of adverse neonatal outcomes, including intensive care unit admission (NICU), neurological morbidity, hypoglycemia, ventilation, respiratory distress syndrome (RDS), phototherapy, sepsis, blood transfusion, and neonatal death. Post-hoc analysis was performed to determine between-group significance. RESULTS: Composite adverse neonatal outcomes are significantly lower in women with multiple morbidities compared to women with confined PET (p = 0.015), and a similar trend is observed when comparing neonatal outcomes between women with GDM to those with GDM + PET, yet these results are underpowered (18.9 % vs. 12.8 % respectively, p = 0.243). Placentas of women with GDM + PET were larger, with a lower rate of placentas below the 10th percentile as compared to placentas of women with isolated PET (p < 0.001), but with similar rates of MVM lesions. DISCUSSION: While maternal and placental outcomes in patients of the GDM + PET group resemble the characteristics of the PET group, surprisingly, the neonatal outcomes in this group are significantly better compared to isolated morbidities. The paradoxical benefit attributed to the coexistence of GDM + PET may be explained by a balance of the opposing trends characterizing these morbidities-the reduced blood and nutrient supply characterizing PET vs. chronic overflow and abundance typical of GDM. CLINICAL TRIAL REGISTRATION: approval of local ethics committee WOMC-19-0152.

Fluorescein mapping for identification of residual satellite vulvar Paget's lesion.

Background: Vulvar Paget disease (VPD) is a rare neoplastic condition exhibiting extensive multifocal involvement. It is clinically difficult to distinguish the margins of VPD from normal skin resulting in involved surgical margins leading to frequent lesion persistence and repeated excisions. Recently, fluorescein mapping has shown promise in providing accurate surgical margins in VPD. However, utilization of this technique after previous resection has not been explored. Case: A 63-year-old female underwent wide local excision of a large microinvasive VPD with involved resection margins. Two months later, the patient underwent additional surgery to excise the involved margins and for sentinel inguinal lymph nodes evaluation. With gross visualization, the vulvar skin appeared normal. However, after intravenous fluorescein sodium injection and Wood's lamp illumination, residual satellite pathological area was observed and resected, revealing more microinvasive tumor. Conclusion: Fluorescein mapping directly highlights sites of involvement in VPD and provides an improved estimation of disease extent which is otherwise not clinically visible.

Postpartum antihypertensive treatment: Is there a correlation to placental lesions?

OBJECTIVE: We aimed to examine the association of clinical risk factors and placental lesions, in gestations complicated with preeclampsia, with the need for antihypertensive treatment in the early postpartum period. METHODS: The computerized files and placental reports of all singleton deliveries at 24.0-42.0 weeks complicated by preeclampsia were reviewed between January 2013 and October 2020. Obstetric characteristics and placental lesions were compared between patients who required antihypertensive treatment in the early postpartum period and those who did not (control group). Placentas were classified into maternal and fetal malperfusion lesions and inflammatory responses. RESULTS: As compared to controls (n = 200), the anti-hypertensive treatment group (n = 95) was characterized by increased rates of preterm birth, preeclampsia with severe features, and cesarean delivery (p < 0.001 for all). More placental hematomas (p = 0.01) and placental maternal vascular lesions (p = 0.03) were observed in the antihypertensive treatment group as compared to controls. In adjusted logistic regression analysis, gestational age (OR 0.86, 95% CI 0.79-0.93, p = 0.001) and preeclampsia with severe features (OR 8.89, 95% CI 3.18-14.93 p < 0.001) were found to be independently associated with the need for postpartum antihypertensive treatment. CONCLUSION: Placental vascular lesions are more common in preeclamptic patients who need postpartum antihypertensive treatment, yet only early onset of preeclampsia with severe features was found to be independently associated with antihypertensive treatment in the early postpartum period.

Fetal growth restriction, neonatal morbidity and placental pathology in dichorionic twins-a comparison of twin-specific versus singleton growth charts .

INTRODUCTION: Fetal growth restriction (FGR) in dichorionic diamniotic (DCDA) twin gestations is a known complication associated with adverse neonatal outcomes. The international guidelines have no consensus on whether to use singleton or twin-specific growth charts. Thus, we aimed to compare growth charts in correlation with pregnancy outcomes and placental histopathology. METHODS: The medical files of all DCDA twin deliveries between 2010 and 2020 were reviewed. Birthweight percentile for gestational age (GA) for each individual neonate was assigned using the updated local singleton and twin-specific growth chart. We then divided the study population into two groups, neonates that were FGR based on the local singleton charts (FGR-singleton group) versus FGR on both twin-specific and singleton charts (FGR-twin group). Placental lesions were classified as lesions related to maternal or fetal malperfusion lesions (MVM, FVM), vascular and villous changes, and inflammatory lesions. RESULTS: Overall, 185 neonates met the inclusion criteria. The FGR-twin group (59/185) had a higher rate of PE, lower GA at delivery, lower birthweight, and a higher rate of neonatal composite adverse outcomes compared to the FGR-singleton group. Moreover, placental pathology of the FGR-twin group demonstrated a higher rate of MVM lesions (p = 0.035). DISCUSSION: In our cohort, neonates considered FGR based on twin-specific charts had worse neonatal outcomes with underlying placental insufficiency demonstrated by a higher rate of placental malperfusion vascular lesions. Our findings support using a twin-specific chart to diagnose FGR that is more clinically relevant.

Pregnancy and placental outcomes according to maternal BMI in women with preeclampsia: a retrospective cohort study.

PURPOSE: Obesity and preeclampsia share similar patho-mechanisms and can both affect placental pathology. We aimed to investigate pregnancy outcomes in correlation with placental pathology among pregnancies complicated by preeclampsia in three different maternal body mass index (BMI, kg/m2) groups. METHODS: In this retrospective cohort study, medical and pathological records of patients with preeclampsia and a singleton pregnancy delivered between 2008 and 2021 at a single tertiary medical center were reviewed. Study population was divided into three BMI groups: BMI < 22.6 kg/m2 (low BMI group), 22.7 ≤ BMI ≤ 28.0 kg/m2 (middle-range BMI group), and BMI > 28.0 kg/m2 (high BMI group). Data regarding maternal characteristics, neonatal outcomes, and placental histopathological lesions were compared. RESULTS: The study groups included a total of 295 patients diagnosed with preeclampsia-98, 99, and 98 in the low, middle-range, and high BMI groups respectively. Neonatal birth weight was significantly decreased in the low maternal BMI group compared to both middle and high BMI groups (p = 0.04) with a similar trend seen in placental weight (p = 0.03). Villous changes related to maternal malperfusion were more prevalent in the low and high BMI groups compared to middle-range BMI group (p < 0.01) and composite maternal vascular malperfusion lesions were also more prevalent in the groups of BMI extremities compared to the middle-range BMI group (p < 0.01). CONCLUSION: Maternal BMI might influence neonatal outcomes and placental pathology in pregnancies complicated by preeclampsia. Both extremes of BMI were associated with higher rates of placental maternal vascular malperfusion. Balanced BMI in women at risk for preeclampsia may reduce the incidence of placental lesions.

Placenta previa in in vitro fertilization and unassisted pregnancies-is there a difference in perinatal outcomes and placental histology?

INTRODUCTION: In-vitro-fertilization (IVF) is an independent risk factor for placenta previa (PP). Our aim was to study this link by comparing the clinical characteristics and placental histology of pregnancies complicated by PP in IVF versus unassisted pregnancies. METHODS: A retrospective-cohort study of deliveries with PP between 2008 and 2021. Placental histology, obstetric and neonatal outcomes were compared between IVF and unassisted pregnancies. Included, were singleton deliveries complicated by PP at gestational weeks (GA) >24. RESULTS: A total of 182 pregnancies were included - 23 IVF pregnancies (IVF group) and 159 unassisted pregnancies (Control group). The control group was characterized by higher gravidity (p = .007) and parity (p < .001) and a trend of more past cesarean deliveries, whereas the IVF group- by a higher rate of nulliparity (p < .001) and diabetes mellitus (p = .04). The control group was characterized by a higher rate of placental weight below the 10th percentile (47.8 versus 13.9%, p = .001) and by a trend of a lower overall placental weight. No differences were noted in maternal and fetal vascular lesions. DISCUSSION: While PP in non-assisted pregnancies is probably associated with previous CDs, in IVF it is more "sporadic," and may complicate any index pregnancy. A lower placental weight was more prevalent in the control group, supporting the concept that pregnancies complicated by PP following IVF can be attributed to initial abnormal location of placentation, rather than an underlying pathological uterine segment of implantation. Nevertheless, IVF and unassisted pregnancies entail similar perinatal outcomes in cases of PP.

Placental pathology in pregnancies with late fetal growth restriction and abnormal cerebroplacental ratio.

INTRODUCTION: Late fetal growth restriction (FGR) is associated with mild growth restriction and normal or mild abnormal doppler flows. The cerebroplacental ratio (CPR) has been demonstrated as more sensitive to hypoxia than its individual components in these fetuses. We hypothesized that abnormal CPR in late FGR is reflected in specific placental vascular malperfusion lesions. METHODS: Retrospective cohort study of late FGR newborns between 2012 and 2022 in a tertiary hospital. Overall, 361 cases were included: 104 with pathological CPR (study group), and 257 with normal doppler flows (control group). The primary outcome was a composite of maternal vascular malperfusion lesions (MVM) and fetal vascular malperfusion lesions (FVM). Secondary outcomes were macroscopic placental characteristics and various obstetrical and neonatal outcomes. RESULTS: The study group had lower birthweight compared with the normal CPR group (2063.5 ± 470.5 vs. 2351.6 ± 387.4 g. P < 0.0001), higher rates of composite adverse neonatal outcomes (34.2% vs. 22.5%, p < 0.0001), lower mean placental weight (318 ± 71.6 vs. 356.6 ± 76.5 g, p < 0.0001), as well as a higher prevalence of Vascular lesions of MVM (15.3% vs. 5.0%, p = 0.002), villous lesions of FVM (37.5% vs. 24.9%, p = 0.02), and composite FVM lesions (36.5% vs. 25.6%, p = 0.04). On multivariate regression analysis for MVM lesions and composite FVM lesions, abnormal CPR was found as an independent risk factor (aOR 2.17, 95% CI 1.63-4.19, and aOR 1.31, 95% CI 1.09-3.97, respectively). DISCUSSIONS: Abnormal CPR in late FGR is reflected in placental histopathologic vascular malperfusion lesions, and the incidence of these lesions is higher than in FGR placentas with normal CPR.

Acute Kidney Injury and Hair-Straightening Products: A Case Series.

RATIONALE & OBJECTIVE: Keratin-based hair-straightening treatment is a popular hair-styling method. The majority of keratin-based hair-straightening products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible, and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe acute kidney injury (AKI) following use of hair-straightening treatment in Israel during the past several years. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 26 patients from 14 medical centers in Israel who experienced severe AKI and reported prior treatment with hair-straightening products in 2019-2022. FINDINGS: The 26 patients described had a median age of 28.5 (range, 14-58) years and experienced severe AKI following a hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients experienced a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies, which demonstrated intratubular calcium oxalate deposition in 6 and microcalcification in tubular cells in 1. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in 4 cases. Three patients required temporary dialysis. LIMITATIONS: Retrospective uncontrolled study, small number of kidney biopsies. CONCLUSIONS: This series describes cases of AKI with prior exposure to hair-straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential underrecognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.

Is there an association between isolated sonographic abdominal circumference below the 10th percentile and placental vascular lesions?

OBJECTIVE: To study the association between prenatal diagnosis of isolated abdominal circumference (AC) below the 10th percentile (AC <10th) in appropriate for gestational age (AGA) neonates and placental vascular lesions. METHODS: A prospective study was conducted of healthy women who underwent sonographic fetal biometric measurements, up to 7 days before delivery, and delivered AGA neonates. The study cohort was divided into those with and without prenatal isolated AC <10th. Placental histopathology lesions were classified into maternal and fetal vascular malperfusion (MVM, FVM) lesions. RESULTS: Compared to the AC over 10th percentile group (n = 85), the AC <10th group (n = 85) was characterized by lower maternal body mass index, higher rate of smokers, and increased rate of induced labor (P = 0.029, P = 0.029, P = 0.001, respectively). There were no between-group differences regarding maternal age, gestational age, and neonatal outcome. Mean placental weight was lower in the isolated AC <10th (P < 0.001). The rate of MVM or FVM lesions did not differ between the groups. By multivariate logistic regression analysis, isolated AC <10th was not found to be associated with increased risk for placental vascular lesions. CONCLUSION: Isolated AC <10th is associated with increased rate of induction of labor; however, it is not associated with increased placental vascular lesions.

Is there an impact of fetal sex in dichorionic discordant twins on placental histopathological abnormalities?

INTRODUCTION: Growth discordancy in dichorionic diamniotic (DCDA) twin gestations is a known complication associated with adverse neonatal outcomes. We aimed to study the differences in placental pathology, in relation to fetal sex, in DCDA twin gestations complicated with growth discordancy. METHODS: The medical files of all DCDA twin deliveries complicated by growth discordancy between 2010 and 2020 were reviewed. Growth discordance was defined as a gap between twin birthweights > 20%. A comparison was made between female vs. male growth discordant twins. Placental lesions were classified as lesions related to maternal or fetal malperfusion lesions (MVM, FVM), vascular and villous changes, and inflammatory lesions. RESULTS: Included 174 DCDA twins. Eighty-eight were in the discordant female group and eighty-six in the discordant male group. The groups did not differ in maternal demographics, pregnancy characteristics, and neonatal outcome. The discordant male group had a higher rate of placental MVM lesions as compared to the discordant female group (p = 0.003). The increased rate of placental MVM lesions in the discordant male group compared to the discordant female group did not change whether its co-twin was of similar or opposite sex. DISCUSSION: Higher rate of MVM lesions characterizes growth discordant male neonates in DCDA twin gestations. This finding could represent a different adaptation of male fetuses to a hostile intrauterine environment.

Perinatal outcomes and placental histology in small-for-gestational-age pregnancies-A comparison of population-based and universal growth charts.

OBJECTIVE: To assess obstetric, perinatal, and placental histologic findings in small-for-gestational-age (SGA) neonates according to different growth charts. METHODS: A retrospective cohort of singleton deliveries from 2008 to 2019 were divided into SGA neonates according to the local population-based chart, SGA according to universal standard growth charts (but appropriate for gestational age [AGA] according to local charts) and AGA deliveries according to both charts. RESULTS: A total of 626 local population SGA deliveries, 132 universal SGA and 468 AGA deliveries were compared. The local population SGA group had a significantly higher rate of preterm and cesarean deliveries. An adverse neonatal outcome occurred in 27.2% of the local population SGA group, 9.8% of the universal SGA group and 6.7% of the AGA group (P < 0.001). In the local population SGA group, placental weight was lower, birth weight to placental weight ratio was highest, and the rate of maternal malperfusion lesions was highest-55.4% versus 45.4% in the universal SGA group and 39.1% in the AGA group (P < 0.001). Villitis of unknown etiology was significantly more common and histologic chorioamnionitis was significantly less common in the local population SGA group. CONCLUSIONS: Our findings support the use of a local population-based growth chart for the diagnosis of fetal growth restriction.

The association of placental histopathological lesions and adverse obstetric outcomes in patients with Müllerian anomalies.

INTRODUCTION: An increased risk of an unfavorable obstetric outcome has been reported in relation with Müllerian anomalies (MA). We evaluated whether placental lesions are more frequent among patients with MA and correlates with adverse pregnancy outcomes. METHODS: The medical records and placental histopathologyy of consecutive patients with MA between 2007 and 2020 were reviewed. A control group matched for maternal age and pregnancy complications was selected in a 1:1 ratio. Characteristics were then compared between the MA and control groups. RESULTS: The study group included 110 patients with MA. Patients in the MA group gave birth at earlier gestational age as (35.8 ± 3.3 vs 39.1 ± 1.3 weeks, respectively, P < 0.001). Placental weight <10th percentile was significantly more frequent in the MA cohort compared with controls (31% vs. 6%, respectively, p < 0.001). Higher rates of vascular and villous lesions of maternal vascular malperfusion (MVM) were also detected in the MA group (P = 0.04, P = 0.01, respectively). On multivariable analysis the presence of MA was an independent predictor of composite placental MVM lesions (OR 3.9, 95% CI 2.2, 6, p = 0.04). Using multivariate logistic regression models, the presence of MA was also found to be an independent predictor of small for gestational age (SGA), (OR 4.2, 95% CI 2.7, 11.7, p = 0.01). DISCUSSION: MA are associated with placental MVM lesions and SGA independent of background confounders including gestational age - suggesting a placental involvement in the association between MA and adverse pregnancy outcomes. Prospective studies among larger cohorts are needed to corroborate our results.

Gestational diabetes mellitus in in-vitro fertilization pregnancies - Clinical and placental histological characteristics.

INTRODUCTION: We aimed to investigate obstetric and neonatal outcomes and placental histological findings in in vitro fertilization (IVF) pregnancies complicated by gestational diabetes mellitus (GDM) as compared to unassisted pregnancies. METHODS: This was a retrospective cohort of deliveries at a single university affiliated center between 12/2008 and 01/2020. Included were singleton pregnancies complicated by GDM, for which placental histopathological examination was performed. Obstetric, neonatal and placental outcomes were compared between pregnancies following IVF and unassisted pregnancies. Placental lesions were categorized according to the "Amsterdam" criteria. RESULTS: Included were 688 deliveries with a diagnosis of GDM with placental examination - 69 IVF pregnancies (IVF group) and 619 unassisted pregnancies (control group). The IVF group was characterized by a significantly higher maternal age and higher rate of nulliparous women - 60.8% vs. 32.9%, p < 0.001. There were no differences in GDM type between the study groups - about two thirds of cases were GDMA1 and on third GDMA2. A higher incidence of preeclampsia was noted in the IVF group - 17.3% vs. 9.3%, p = 0.03, with no difference in cesarean deliveries and birthweight. IVF deliveries were characterized by a significantly higher rate of adverse neonatal outcomes - 18.8% vs. 8.8%, p = 0.008, although this did not attain significance after adjustment to gestational age. No differences were noted in placental histology between the groups. DISCUSSION: GDM in IVF is associated with a significantly higher rate of adverse neonatal outcomes, as compared with non-assisted pregnancies complicated by GDM. Placental histology does not shed light on these clinical associations.

Placental vascular lesions differ between male and female fetuses in early-onset preeclampsia.

PURPOSE: A growing body of evidence accumulate pointing to sex-specific differences in placental adaptation to pregnancy complications. We aimed to study if there is a difference in placental histopathology lesions, between female and male fetuses in pregnancies complicated with preeclampsia. METHODS: The medical files of all patients with preeclampsia, were reviewed. Placental lesions were classified to lesions related to maternal or fetal malperfusion lesions (MVM, FVM), vascular and villous changes, and inflammatory lesions. Comparison was performed between the male and the female groups. RESULTS: The study included 441 preeclamptic patients. Women in the male preeclampsia group (n = 225) had higher rate of chronic hypertension (p = 0.05) and diabetes mellitus (p < 0.005), while women in the female preeclampsia group (n = 216) had higher rate of thrombophilia. There were no between groups differences in neonatal outcome or placental histopathology lesions. The early preeclampsia cohort included 91 patients. Placentas from the female early preeclampsia group (n = 44) had more vascular changes related to MVM lesions (decidual arteriopathy), as compared to the male early preeclampsia group (n = 47), 50% vs. 25%, p = 0.01. CONCLUSIONS: Higher rate of placental MVM lesions in the female as compared to male group correspond with sex-specific difference of placental pathophysiological adaptation, in early preeclampsia.

Placental abnormalities differ in small for gestational age neonates in relation to their prenatal sonographic abdominal circumference measurements.

BACKGROUND: Antenatal detection of abdominal circumference (AC) <10th percentile, among small for gestational age (SGA) neonates, probably reflects the severity of their growth restriction. We aimed to study neonatal outcome and placental pathology among SGA neonates in correlation to their AC measurements. METHODS: Maternal and neonatal computerized medical records and placental histopathology reports of all SGA neonates, (neonatal birth-weight ≤10th percentile), born between 24 and 42 weeks, during 2015-2018 were reviewed. Included cases with fetal biometric measurements conducted up to 7 days prior labor. Results were compared between cases with sonographic antenatal AC <10th percentile and neonates with sonographic antenatal AC ≥10th percentile. Placental lesions were classified according to "Amsterdam" Placental workshop criteria. RESULTS: The AC <10th percentile group (n = 148) was characterized by higher rate of nulliparity (p = .003), and induction of labor (p = .009), as compared to the AC ≥10th percentile group (n = 41). There were no between groups differences in the rate of maternal BMI (kg/m2), hypertensive disorders, diabetes or smoking. Neonatal hypoglycemia was more common in the AC <10th percentile group as compared to the AC ≥10th percentile group (p = .04). Placentas from the AC <10th percentile group were smaller (p < .001), with more MVM lesions (p = .02) and chronic villitis (p = .04). By multivariate regression analysis, AC <10th percentile and maternal hypertensive disorders, were found to be independently associated with placental MVM lesions, aOR = 2.43 (95% CI 1.04, 5.88) and aOR = 3.15 (95% CI 1.06, 9.31), respectively. CONCLUSIONS: Higher rate of placental maternal malperfusion lesions, chronic villitis, and more neonatal hypoglycemia characterize SGA neonates with AC <10th percentile, pointing to the importance of AC measurement as an indicator for placental insufficiency.

Passively inhaled tobacco smoke - pregnancy and neonatal outcomes in correlation with placental histopathology.

INTRODUCTION: We aimed to investigate the effect of maternal passive smoking (MPS) during pregnancy-on placental pathology and pregnancy outcomes. METHODS: A prospective case-control study. We recruited low-risk laboring women at 37+0-41 + 0 weeks between 9/2019-7/2020. MPS was defined as exposure to in-house spouse tobacco smoking of >20 cigarettes/day in the absence of maternal active-smoking. In attempt to "purify" the effect of MPS on placental pathology-we excluded cases with preeclampsia, diabetes, suspected fetal growth restriction (FGR), preterm labor, and illicit drug use. Maternal characteristics, pregnancy outcomes, and placental pathology were compared between the MPS group and a control group matched for gestational age, maternal age, and delivery date. Placental lesions were classified according to the "Amsterdam" criteria. The study was powered to detect a 33% difference in placental malperfusion lesions. Multivariable regression was performed to identify independent associations with placental malperfusion lesions. RESULTS: In labor, the MPS group (n = 115) had higher rates of meconium stained amniotic fluid (MSAF, p < 0.001) and non-reassuring fetal heart-rate (NRFHR,p = 0.006), compared to controls (n = 115). Neonates in the MPS group had higher rates of undiagnosed FGR (p = 0.01) and NICU admissions (p = 0.004). The MPS group had higher rates of placental-hypoplasia (p = 0.02) and fetal vascular malperfusion (FVM) lesions (p = 0.04). In regression analysis MPS was associated with FVM lesions independent of background confounders (aOR = 1.24 95% CI 1.10-2.65). DISCUSSION: In otherwise low-risk pregnancies, MPS was associated with higher rates of MSAF, NRFHR, undiagnosed FGR, and NICU admissions, probably mediated via placental FVM. These worrisome findings mandate patient counseling and further investigation in larger population-based studies.

Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine.

BACKGROUNDThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODSA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTSThe BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSIONAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDINGIsrael Science Foundation and the Weizmann Institute Fondazione Henry Krenter.

Placental Lesions and Pregnancy Outcome in Anterior as Compared to Posterior Placenta Previa.

The uterine location of placenta previa (PP), anterior vs. posterior has an impact on pregnancy outcome. We aimed to study maternal and neonatal outcome and placental histopathology lesions in anterior vs. posterior PP. The medical records and histopathology reports of all singleton cesarean deliveries (CD) performed due to PP, from 24 to 41 weeks, between 12.2008 and 10.2018, were reviewed. Placental lesions were classified into maternal and fetal vascular malperfusion lesions (MVM, FVM), maternal and fetal inflammatory responses (MIR, FIR). Gestational age (GA) at delivery was similar between the anterior PP (n = 67) and posterior PP (n = 105) groups. As compared to the posterior PP group, the anterior PP group had higher rate of previous CD (p < 0.001), placental accreta spectrum (p = 0.04), lower neonatal Hb at birth (p = 0.03), higher rate of neonatal blood transfusion (p = 0.007) and prolonged maternal hospitalization (p = 0.02). Placentas from the anterior PP group had lower weights (p = 0.035), with increased rate of MVM lesions (p = 0.017). The anterior PP location is associated with increased adverse maternal and neonatal outcome, lower placental weights and increased rate of malperfusion lesions. Abnormal placentation in the scarred uterine wall probably has an impact on placental function.