Michal Kovo - Academia.edu (original) (raw)

Papers by Michal Kovo

Research paper thumbnail of Can placental histopathology lesions predict recurrence of fetal growth restriction?

Research paper thumbnail of Insulin Detemir Versus Glibenclamide in Gestational Diabetes Mellitus: A Retrospective Cohort Study

PubMed, Jun 1, 2023

Background: Treatment of gestational diabetes mellitus (GDM) has been shown to improve both mater... more Background: Treatment of gestational diabetes mellitus (GDM) has been shown to improve both maternal and neonatal outcomes. For women with GDM who require glucose-lowering medication, insulin is regarded as the drug of choice by most medical societies. Oral therapy, with metformin or glibenclamide, is a reasonable alternative in certain medical circumstances. Objectives: To compare the efficacy and safety of insulin detemir (IDet) vs. glibenclamide for GDM when glycemic control cannot be achieved through lifestyle modification and diet. Methods: We conducted a retrospective cohort analysis of 115 women with singleton pregnancy and GDM treated with IDet or glibenclamide. GDM was diagnosed via the two-step oral glucose tolerance test (OGTT) of 50 grams glucose, followed by 100 grams. Maternal characteristics and outcomes (preeclampsia and weight gain) and neonatal outcomes (birth weight and percentile, hypoglycemia, jaundice, and respiratory morbidity) were compared between groups. Results: In total, 67 women received IDet and 48 glibenclamide. Maternal characteristics, weight gain, and the incidence of preeclampsia were similar in both groups. Neonatal outcomes were also similar. The proportion of large for gestational age (LGA) infants was 20.8% in the glibenclamide group compared to 14.9% in the IDet group (P = 0.04). Conclusions: In pregnant women with GDM, glucose control on IDet yielded comparable results as on glibenclamide, except for a significantly lower rate of LGA neonates.

Research paper thumbnail of Postpartum antihypertensive treatment: Is there a correlation to placental lesions?

Archives of Gynecology and Obstetrics

Research paper thumbnail of Hypertensive disorders and diabetic pregnancy

Research paper thumbnail of Is there a difference in placental pathology in pregnancies complicated with gestational diabetes A2 versus gestational diabetes A1, versus one abnormal value, on 100 gr glucose tolerance test?

Placenta, Mar 1, 2022

INTRODUCTION The objective of the study was to investigate pregnancy outcome and placental pathol... more INTRODUCTION The objective of the study was to investigate pregnancy outcome and placental pathology lesions among patients with gestational diabetes mellitus (GDM) versus patients with one abnormal value (OAV), in the oral glucose tolerance test (OGTT). METHODS A prospective study was performed from 2016 to 2019. All participants performed an OGTT between 24 and 28 weeks. Included patients who delivered at term (>37 weeks) with the diagnosis of GDMA2 (treated with insulin), GDMA1 (controlled with diet) and those with OAV. Maternal characteristics, pregnancy outcomes, and placental histopathology reports were compared between the GDMA2, GDMA1, and OAV groups. Placental lesions were classified according to "Amsterdam" criteria to maternal and fetal vascular malperfusion (MVM, FVM) lesions, and inflammatory lesions. RESULTS The GDMA2 group (n = 59) was characterized by higher maternal BMI (p < 0.001), increased rate of chronic hypertension (p < 0.01), cesarean delivery (CD) (p < 0.001), adverse neonatal outcomes (p < 0.001) and prolonged hospitalization (p < 0.001) as compared to the GDMA1 (n = 73) and the OAV group (n = 124). Average placental weight in the GDMA2 group were higher (p = 0.004). There were no between groups differences in the rate of placental MVM or inflammatory lesions. The OAV and GDMA1 groups were characterized by an increased rate of FVM lesions, as compared to the GDMA2 group (p = 0.02). DISCUSSION GDMA2 is associated with increased rate of CD and adverse neonatal outcome. The similar rate of placental MVM lesions among the study groups, and the increased rate of FVM lesions observed among the OAV group, implies of impaired placental function among the OAV group as in GDM pregnancies.

Research paper thumbnail of 169: Is advanced maternal age associated with placental vascular malperfusion? A prospective study

American Journal of Obstetrics and Gynecology, 2020

There were no differences between groups in measures of sleep knowledge or quality. CONCLUSION: T... more There were no differences between groups in measures of sleep knowledge or quality. CONCLUSION: This pilot study demonstrates that implementation of a sleep education program specific to pregnancy for women with GDM is feasible in the context of typical prenatal care. However, our pilot study did not suggest that a clinic-based sleep intervention in women with GDM results in improved glycemic control.

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

European Journal of Obstetrics & Gynecology and Reproductive Biology, Jul 1, 2022

Research paper thumbnail of Boosting maternal and neonatal anti SARS-CoV-2 humoral immunity using a third mRNA vaccine dose

Research Square (Research Square), Mar 22, 2022

Importance: To minimize COVID-19 pandemic burden and spread, third booster dose vaccination campa... more Importance: To minimize COVID-19 pandemic burden and spread, third booster dose vaccination campaigns commenced worldwide. Since pregnant patients 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. Objective: We aimed to characterize the effect on anti-SARS-CoV-2 antibody titers of the third, boosting dose of mRNA P zer BNT162b2 vaccine in pregnancy, and pro le its most common side effects. Design: Prospective cohort study of anti-SARS-CoV-2 antibody titers measured at the time of delivery in maternal and cord blood, and dedicated side effect questionnaire. Setting: Labor and delivery ward and virology laboratory of a large, urban, university-a liated medical center. Participants: Gravidae (N=216) without history of COVID-19 disease, presenting for delivery were divided to two groups by vaccination status: parturients who received a third boosting dose of P zer BNT162b2 mRNA vaccine, were compared to those vaccinated with the 2-dose regimen. Main Outcomes: Anti-SARS-CoV-2 antibody titers measured in maternal and cord blood samples collected at delivery and side effect pro le. Results: We found a robust surge in maternal and cord blood levels of anti-SARS-CoV-2 titers at the time of delivery: parturients that received a third boosting dose had titers 4.7-fold higher as compared to 2dose vaccinated parturients. The effect of the third boosting dose remained signi cant when controlling for the trimester of most recent vaccine dose, suggesting additive immunity extends beyond that obtained after the second dose. E cient transplacental transfer was observed. Neonatal (cord blood) anti-SARS-CoV-2 antibody titers positively correlated with (r= 0.745; P< .0001) and were signi cantly higher than maternal levels (p<0.0001). Overall, fewer side effects were reported following the third dose as compared to the second vaccine dose among the 2-dose group, with lower rates of injection site pain and swelling, myalgia, and general malaise. Conclusions and relevance: The third, boosting dose of mRNA P zer BNT162b2 vaccine augmented maternal and neonatal immunity with mild side effects. These data provide essential evidence to bolster clinical and public health guidance, reassure patients, and increase vaccine uptake among pregnant patients. Key Points Question: What is the effect of a third, boosting dose of P zer BNT162b2 mRNA vaccine in pregnancy on anti-SARS-CoV-2 antibody titers at delivery, in parturients and cord blood, compared to vaccinated parturients who received the 2-dose regimen? Findings: A third vaccine dose yielded signi cantly higher anti-SARS-CoV-2 antibody levels in maternal and cord blood, with mild reported side effects. Effect remained signi cant when controlling for trimester of exposure to last vaccine dose. Meaning: A third, boosting dose of mRNA P zer BNT162b2 vaccine signi cantly augments maternal and neonatal humoral immunity, beyond that achieved with the 2-dose regimen, with mild side effects.

Research paper thumbnail of 1085: Fetal growth restriction in hypertensive vs. smoking women- pregnancy outcomes, ultrasound findings, and placental pathology

American Journal of Obstetrics and Gynecology, 2020

as well as history of prior cesarean delivery (aOR¼16.761, 95% CI 8.684-32.353) and presence of p... more as well as history of prior cesarean delivery (aOR¼16.761, 95% CI 8.684-32.353) and presence of placenta previa (aOR¼58.550, 95% CI 15.864-216.094). When adjusted for the number of prior cesarean deliveries, the correlation persisted for IVF (aOR¼6.108 95% CI 2.396-15.569). CONCLUSION: IVF significantly increases the odds of developing PAS independent of placenta previa and history of cesarean delivery. The pathophysiology behind this relationship remains to be investigated.

Research paper thumbnail of Reduced fetal movements at term in singleton low risk pregnancies—Is there an association with placental histopathological findings?

Acta Obstetricia et Gynecologica Scandinavica, Feb 14, 2020

Introduction: Maternal perception of fetal movements has long been considered an indicator of fet... more Introduction: Maternal perception of fetal movements has long been considered an indicator of fetal well-being. A sudden decrease in the number of fetal movements is suggestive of fetal compromise. We aimed to determine whether the maternal perception of reduced fetal movements (RFM) is associated with placental pathological lesions in a low-risk term population. Material and methods: Our study was a case-control study that was performed in a single university center. Placental histopathology, maternal demographics, labor characteristics, and neonatal outcomes of term, singleton pregnancies with maternal perception of RFM during the 2 weeks prior to delivery were collected. To isolate the effect of RFM on placental pathology, we excluded cases complicated by preterm birth, hypertensive disorders, diabetes mellitus, small-for-gestational-age and congenital/genetic anomalies. We compared pregnancy outcomes and placental pathology between the RFM group and a control group matched for gestational age and mode of delivery. Placental lesions were classified according to the "Amsterdam" criteria. Composite adverse neonatal outcome was defined as one or more of the following: sepsis, transfusion, hypoglycemia, phototherapy, respiratory morbidity, cerebral morbidity, necrotizing enterocolitis and fetal/neonatal death. Multivariable regression analysis was performed to identify independent associations with adverse neonatal outcome.

Research paper thumbnail of Velocity Time Integral: A Novel Method for Assessing Fetal Anemia

Children

The velocity time integral (VTI) is a clinical Doppler ultrasound measurement of blood flow, meas... more The velocity time integral (VTI) is a clinical Doppler ultrasound measurement of blood flow, measured by the area under the wave curve and equivalent to the distance traveled by the blood. This retrospective study assessed the middle cerebral artery (MCA) VTI of fetuses in pregnancies complicated by maternal alloimmunization. Doppler indices of the MCA were retrieved from electronic medical records. Systolic deceleration-diastolic time, systolic acceleration time, VTI, and peak systolic velocity (PSV) were measured at 16–40 weeks gestation. Cases with PSV indicating fetal anemia (cutoff 1.5 MoM) and normal PSV were compared. The study included 255 Doppler ultrasound examinations. Of these, 41 were at 16–24 weeks (group A), 100 were at 25–32 weeks (group B), and 114 were at 33–40 weeks (group C). VTI increased throughout gestation (5.5 cm, 8.6 cm, and 12.1 cm in groups A, B, and C, respectively, p = 0.003). VTI was higher in waveforms calculated to have MCA-PSV ≥ 1.5 MoM compared to ...

Research paper thumbnail of 670: Can placental histopathology lesions predict recurrence of spontaneous preterm birth?

American Journal of Obstetrics and Gynecology

Research paper thumbnail of The Impact of Total Deceleration Area and Fetal Growth on Neonatal Acidemia in Vacuum Extraction Deliveries

Children

We aimed to investigate the correlation between total deceleration area (TDA), neonatal birthweig... more We aimed to investigate the correlation between total deceleration area (TDA), neonatal birthweight and neonatal acidemia in vacuum extractions (VEs). This is a retrospective study in a tertiary hospital, including VE performed due to non-reassuring fetal heart rate (NRFHR). Electronic fetal monitoring during the 120 min preceding delivery was interpreted by two obstetricians who were blinded to neonatal outcomes. TDA was calculated as the sum of the area under the curve for each deceleration. Neonatal birthweights were classified as low (<2500 g), normal (2500–3999 g) or macrosomic (>4000 g). A total of 85 VEs were analyzed. Multivariable linear regression, adjusted for gestational age, nulliparity and diabetes mellitus, revealed a negative correlation between TDA in the 60 min preceding delivery and umbilical cord pH. For every 10 K increase in TDA, the cord pH decreased by 0.02 (p = 0.038; 95%CI, −0.05–0.00). The use of the Ventouse-Mityvac cup was associated with a 0.08 de...

Research paper thumbnail of Impact of Thin Meconium on Delivery and Early Neonatal Outcomes

Children

Several reports regarding the effects of thin meconium on maternal and neonatal outcomes are cont... more Several reports regarding the effects of thin meconium on maternal and neonatal outcomes are contradictory. This study evaluated the risk factors and obstetrical outcomes during deliveries complicated with thin meconium. This retrospective cohort study included all women with a singleton pregnancy, who underwent trial of labor >24 weeks of gestation, in a single tertiary center, over a six-year period. Obstetrical, delivery, and neonatal outcomes were compared between deliveries with thin meconium (thin meconium group) to deliveries with clear amniotic fluid (control group). Included in the study were 31,536 deliveries. Among them 1946 (6.2%) were in the thin meconium group and 29,590 (93.8%) were controls. Meconium aspiration syndrome was diagnosed in eight neonates in the thin meconium group and in none of the controls (0.41%, p < 0.001). In multivariate logistic regression analysis, the following adverse outcomes were found to be independently associated with increased odds...

Research paper thumbnail of Effects of ‘rescue’ dose of antenatal corticosteroids on placental histopathology in preterm births

Placenta

INTRODUCTION Antenatal corticosteroids (ACS) are frequently used to reduce neonatal morbidity in ... more INTRODUCTION Antenatal corticosteroids (ACS) are frequently used to reduce neonatal morbidity in preterm births (PTBs). A 'rescue' dose of ACS can be administer, if the risk of PTB remains. Some reports indicated that repeated doses of ACS might impact placental histology and possibly its function. We aimed to study whether repeated doses of ACS effect placental histopathology and pregnancy outcome. METHODS The medical files and placental reports of all PTB, at 24-336/7 weeks, between Nov 2008-Dec 2019, were reviewed. The study population was divided into three groups; no-ACS (PTBs without ACS treatment), one-ACS (PTBs after a full or partial ACS course), and rescue-ACS (PTBs after a 'rescue' course of ACS). Placental lesions were classified according to "Amsterdam" criteria into maternal and fetal vascular malperfusion lesions, maternal and fetal inflammatory responses and chronic villitis. Placental lesions and pregnancy outcome were compared between the study groups. RESULTS The no-ACS group (n = 58) was characterized by increased rates of PTB<28 weeks (p = 0.003), perinatal death (p < 0.001) and composite neonatal infectious morbidity (p = 0.022), as compared to the one-ACS group (n = 331) and the rescue-ACS group (n = 53). Placental MIR lesions were more common among the rescue-ACS group, compared to the one- and no-ACS groups (p = 0.022). Other placental lesions did not differ between the groups. On multivariate logistic regression analysis, MIR lesions were independently associated with rescue-ACS treatment (aOR 3.00, 95% CI 1.10-8/17, p = 0.031). DISCUSSION Rescue course of ACS is associated with increased rate of placental maternal inflammatory response. These findings probably result from maternal stress stimuli without an adverse impact on early neonatal outcome.

Research paper thumbnail of The differential regulation of placenta trophoblast bisphosphoglycerate mutase in fetal growth restriction: preclinical study in mice and observational histological study of human placenta

BackgroundFetal growth restriction (FGR) is a pregnancy complication in which a newborn fails to ... more BackgroundFetal growth restriction (FGR) is a pregnancy complication in which a newborn fails to achieve its growth potential, increasing the risk of perinatal morbidity and mortality. Chronic maternal gestational hypoxia, as well as placental insufficiency are associated with increased FGR incidence; however, the molecular mechanisms underlying FGR remain unknown.MethodsIn a case control study of murine and human control and FGR placentae, we implied MR imaging, IHC and metabolomics to assess the levels of BPGM and 2,3 BPG to elucidate the impact of maternal gestational hypoxia, and the molecular mechanisms underlying human FGR.ResultsWe show that murine acute and chronic gestational hypoxia recapitulates FGR phenotype and affects placental structure and morphology. Gestational hypoxia decreased labyrinth area, increased the incidence of red blood cells (RBCs) in the labyrinth while expanding the placental spiral arteries (SpA) diameter. Hypoxic placentae exhibited higher hemoglobi...

Research paper thumbnail of Is there an association between the length of the second stage of labour and urinary incontinence in multiparous women?

European Journal of Obstetrics & Gynecology and Reproductive Biology

Research paper thumbnail of MP63-11 DOES Iatrogenic Bladder Injury During Cesarean Section Has an Impact on Lower Urinary Tract Symptoms in the Future?

Research paper thumbnail of Boosting maternal and neonatal humoral immunity following SARS-CoV-2 infection using a single messenger RNA vaccine dose

American Journal of Obstetrics and Gynecology

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Research paper thumbnail of Gestational diabetes mellitus in in-vitro fertilization pregnancies – Clinical and placental histological characteristics

Placenta, 2022

We aimed to investigate obstetric and neonatal outcomes and placental histological findings in in... more 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. 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. 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. 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.

Research paper thumbnail of Can placental histopathology lesions predict recurrence of fetal growth restriction?

Research paper thumbnail of Insulin Detemir Versus Glibenclamide in Gestational Diabetes Mellitus: A Retrospective Cohort Study

PubMed, Jun 1, 2023

Background: Treatment of gestational diabetes mellitus (GDM) has been shown to improve both mater... more Background: Treatment of gestational diabetes mellitus (GDM) has been shown to improve both maternal and neonatal outcomes. For women with GDM who require glucose-lowering medication, insulin is regarded as the drug of choice by most medical societies. Oral therapy, with metformin or glibenclamide, is a reasonable alternative in certain medical circumstances. Objectives: To compare the efficacy and safety of insulin detemir (IDet) vs. glibenclamide for GDM when glycemic control cannot be achieved through lifestyle modification and diet. Methods: We conducted a retrospective cohort analysis of 115 women with singleton pregnancy and GDM treated with IDet or glibenclamide. GDM was diagnosed via the two-step oral glucose tolerance test (OGTT) of 50 grams glucose, followed by 100 grams. Maternal characteristics and outcomes (preeclampsia and weight gain) and neonatal outcomes (birth weight and percentile, hypoglycemia, jaundice, and respiratory morbidity) were compared between groups. Results: In total, 67 women received IDet and 48 glibenclamide. Maternal characteristics, weight gain, and the incidence of preeclampsia were similar in both groups. Neonatal outcomes were also similar. The proportion of large for gestational age (LGA) infants was 20.8% in the glibenclamide group compared to 14.9% in the IDet group (P = 0.04). Conclusions: In pregnant women with GDM, glucose control on IDet yielded comparable results as on glibenclamide, except for a significantly lower rate of LGA neonates.

Research paper thumbnail of Postpartum antihypertensive treatment: Is there a correlation to placental lesions?

Archives of Gynecology and Obstetrics

Research paper thumbnail of Hypertensive disorders and diabetic pregnancy

Research paper thumbnail of Is there a difference in placental pathology in pregnancies complicated with gestational diabetes A2 versus gestational diabetes A1, versus one abnormal value, on 100 gr glucose tolerance test?

Placenta, Mar 1, 2022

INTRODUCTION The objective of the study was to investigate pregnancy outcome and placental pathol... more INTRODUCTION The objective of the study was to investigate pregnancy outcome and placental pathology lesions among patients with gestational diabetes mellitus (GDM) versus patients with one abnormal value (OAV), in the oral glucose tolerance test (OGTT). METHODS A prospective study was performed from 2016 to 2019. All participants performed an OGTT between 24 and 28 weeks. Included patients who delivered at term (>37 weeks) with the diagnosis of GDMA2 (treated with insulin), GDMA1 (controlled with diet) and those with OAV. Maternal characteristics, pregnancy outcomes, and placental histopathology reports were compared between the GDMA2, GDMA1, and OAV groups. Placental lesions were classified according to "Amsterdam" criteria to maternal and fetal vascular malperfusion (MVM, FVM) lesions, and inflammatory lesions. RESULTS The GDMA2 group (n = 59) was characterized by higher maternal BMI (p < 0.001), increased rate of chronic hypertension (p < 0.01), cesarean delivery (CD) (p < 0.001), adverse neonatal outcomes (p < 0.001) and prolonged hospitalization (p < 0.001) as compared to the GDMA1 (n = 73) and the OAV group (n = 124). Average placental weight in the GDMA2 group were higher (p = 0.004). There were no between groups differences in the rate of placental MVM or inflammatory lesions. The OAV and GDMA1 groups were characterized by an increased rate of FVM lesions, as compared to the GDMA2 group (p = 0.02). DISCUSSION GDMA2 is associated with increased rate of CD and adverse neonatal outcome. The similar rate of placental MVM lesions among the study groups, and the increased rate of FVM lesions observed among the OAV group, implies of impaired placental function among the OAV group as in GDM pregnancies.

Research paper thumbnail of 169: Is advanced maternal age associated with placental vascular malperfusion? A prospective study

American Journal of Obstetrics and Gynecology, 2020

There were no differences between groups in measures of sleep knowledge or quality. CONCLUSION: T... more There were no differences between groups in measures of sleep knowledge or quality. CONCLUSION: This pilot study demonstrates that implementation of a sleep education program specific to pregnancy for women with GDM is feasible in the context of typical prenatal care. However, our pilot study did not suggest that a clinic-based sleep intervention in women with GDM results in improved glycemic control.

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

European Journal of Obstetrics & Gynecology and Reproductive Biology, Jul 1, 2022

Research paper thumbnail of Boosting maternal and neonatal anti SARS-CoV-2 humoral immunity using a third mRNA vaccine dose

Research Square (Research Square), Mar 22, 2022

Importance: To minimize COVID-19 pandemic burden and spread, third booster dose vaccination campa... more Importance: To minimize COVID-19 pandemic burden and spread, third booster dose vaccination campaigns commenced worldwide. Since pregnant patients 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. Objective: We aimed to characterize the effect on anti-SARS-CoV-2 antibody titers of the third, boosting dose of mRNA P zer BNT162b2 vaccine in pregnancy, and pro le its most common side effects. Design: Prospective cohort study of anti-SARS-CoV-2 antibody titers measured at the time of delivery in maternal and cord blood, and dedicated side effect questionnaire. Setting: Labor and delivery ward and virology laboratory of a large, urban, university-a liated medical center. Participants: Gravidae (N=216) without history of COVID-19 disease, presenting for delivery were divided to two groups by vaccination status: parturients who received a third boosting dose of P zer BNT162b2 mRNA vaccine, were compared to those vaccinated with the 2-dose regimen. Main Outcomes: Anti-SARS-CoV-2 antibody titers measured in maternal and cord blood samples collected at delivery and side effect pro le. Results: We found a robust surge in maternal and cord blood levels of anti-SARS-CoV-2 titers at the time of delivery: parturients that received a third boosting dose had titers 4.7-fold higher as compared to 2dose vaccinated parturients. The effect of the third boosting dose remained signi cant when controlling for the trimester of most recent vaccine dose, suggesting additive immunity extends beyond that obtained after the second dose. E cient transplacental transfer was observed. Neonatal (cord blood) anti-SARS-CoV-2 antibody titers positively correlated with (r= 0.745; P< .0001) and were signi cantly higher than maternal levels (p<0.0001). Overall, fewer side effects were reported following the third dose as compared to the second vaccine dose among the 2-dose group, with lower rates of injection site pain and swelling, myalgia, and general malaise. Conclusions and relevance: The third, boosting dose of mRNA P zer BNT162b2 vaccine augmented maternal and neonatal immunity with mild side effects. These data provide essential evidence to bolster clinical and public health guidance, reassure patients, and increase vaccine uptake among pregnant patients. Key Points Question: What is the effect of a third, boosting dose of P zer BNT162b2 mRNA vaccine in pregnancy on anti-SARS-CoV-2 antibody titers at delivery, in parturients and cord blood, compared to vaccinated parturients who received the 2-dose regimen? Findings: A third vaccine dose yielded signi cantly higher anti-SARS-CoV-2 antibody levels in maternal and cord blood, with mild reported side effects. Effect remained signi cant when controlling for trimester of exposure to last vaccine dose. Meaning: A third, boosting dose of mRNA P zer BNT162b2 vaccine signi cantly augments maternal and neonatal humoral immunity, beyond that achieved with the 2-dose regimen, with mild side effects.

Research paper thumbnail of 1085: Fetal growth restriction in hypertensive vs. smoking women- pregnancy outcomes, ultrasound findings, and placental pathology

American Journal of Obstetrics and Gynecology, 2020

as well as history of prior cesarean delivery (aOR¼16.761, 95% CI 8.684-32.353) and presence of p... more as well as history of prior cesarean delivery (aOR¼16.761, 95% CI 8.684-32.353) and presence of placenta previa (aOR¼58.550, 95% CI 15.864-216.094). When adjusted for the number of prior cesarean deliveries, the correlation persisted for IVF (aOR¼6.108 95% CI 2.396-15.569). CONCLUSION: IVF significantly increases the odds of developing PAS independent of placenta previa and history of cesarean delivery. The pathophysiology behind this relationship remains to be investigated.

Research paper thumbnail of Reduced fetal movements at term in singleton low risk pregnancies—Is there an association with placental histopathological findings?

Acta Obstetricia et Gynecologica Scandinavica, Feb 14, 2020

Introduction: Maternal perception of fetal movements has long been considered an indicator of fet... more Introduction: Maternal perception of fetal movements has long been considered an indicator of fetal well-being. A sudden decrease in the number of fetal movements is suggestive of fetal compromise. We aimed to determine whether the maternal perception of reduced fetal movements (RFM) is associated with placental pathological lesions in a low-risk term population. Material and methods: Our study was a case-control study that was performed in a single university center. Placental histopathology, maternal demographics, labor characteristics, and neonatal outcomes of term, singleton pregnancies with maternal perception of RFM during the 2 weeks prior to delivery were collected. To isolate the effect of RFM on placental pathology, we excluded cases complicated by preterm birth, hypertensive disorders, diabetes mellitus, small-for-gestational-age and congenital/genetic anomalies. We compared pregnancy outcomes and placental pathology between the RFM group and a control group matched for gestational age and mode of delivery. Placental lesions were classified according to the "Amsterdam" criteria. Composite adverse neonatal outcome was defined as one or more of the following: sepsis, transfusion, hypoglycemia, phototherapy, respiratory morbidity, cerebral morbidity, necrotizing enterocolitis and fetal/neonatal death. Multivariable regression analysis was performed to identify independent associations with adverse neonatal outcome.

Research paper thumbnail of Velocity Time Integral: A Novel Method for Assessing Fetal Anemia

Children

The velocity time integral (VTI) is a clinical Doppler ultrasound measurement of blood flow, meas... more The velocity time integral (VTI) is a clinical Doppler ultrasound measurement of blood flow, measured by the area under the wave curve and equivalent to the distance traveled by the blood. This retrospective study assessed the middle cerebral artery (MCA) VTI of fetuses in pregnancies complicated by maternal alloimmunization. Doppler indices of the MCA were retrieved from electronic medical records. Systolic deceleration-diastolic time, systolic acceleration time, VTI, and peak systolic velocity (PSV) were measured at 16–40 weeks gestation. Cases with PSV indicating fetal anemia (cutoff 1.5 MoM) and normal PSV were compared. The study included 255 Doppler ultrasound examinations. Of these, 41 were at 16–24 weeks (group A), 100 were at 25–32 weeks (group B), and 114 were at 33–40 weeks (group C). VTI increased throughout gestation (5.5 cm, 8.6 cm, and 12.1 cm in groups A, B, and C, respectively, p = 0.003). VTI was higher in waveforms calculated to have MCA-PSV ≥ 1.5 MoM compared to ...

Research paper thumbnail of 670: Can placental histopathology lesions predict recurrence of spontaneous preterm birth?

American Journal of Obstetrics and Gynecology

Research paper thumbnail of The Impact of Total Deceleration Area and Fetal Growth on Neonatal Acidemia in Vacuum Extraction Deliveries

Children

We aimed to investigate the correlation between total deceleration area (TDA), neonatal birthweig... more We aimed to investigate the correlation between total deceleration area (TDA), neonatal birthweight and neonatal acidemia in vacuum extractions (VEs). This is a retrospective study in a tertiary hospital, including VE performed due to non-reassuring fetal heart rate (NRFHR). Electronic fetal monitoring during the 120 min preceding delivery was interpreted by two obstetricians who were blinded to neonatal outcomes. TDA was calculated as the sum of the area under the curve for each deceleration. Neonatal birthweights were classified as low (<2500 g), normal (2500–3999 g) or macrosomic (>4000 g). A total of 85 VEs were analyzed. Multivariable linear regression, adjusted for gestational age, nulliparity and diabetes mellitus, revealed a negative correlation between TDA in the 60 min preceding delivery and umbilical cord pH. For every 10 K increase in TDA, the cord pH decreased by 0.02 (p = 0.038; 95%CI, −0.05–0.00). The use of the Ventouse-Mityvac cup was associated with a 0.08 de...

Research paper thumbnail of Impact of Thin Meconium on Delivery and Early Neonatal Outcomes

Children

Several reports regarding the effects of thin meconium on maternal and neonatal outcomes are cont... more Several reports regarding the effects of thin meconium on maternal and neonatal outcomes are contradictory. This study evaluated the risk factors and obstetrical outcomes during deliveries complicated with thin meconium. This retrospective cohort study included all women with a singleton pregnancy, who underwent trial of labor >24 weeks of gestation, in a single tertiary center, over a six-year period. Obstetrical, delivery, and neonatal outcomes were compared between deliveries with thin meconium (thin meconium group) to deliveries with clear amniotic fluid (control group). Included in the study were 31,536 deliveries. Among them 1946 (6.2%) were in the thin meconium group and 29,590 (93.8%) were controls. Meconium aspiration syndrome was diagnosed in eight neonates in the thin meconium group and in none of the controls (0.41%, p < 0.001). In multivariate logistic regression analysis, the following adverse outcomes were found to be independently associated with increased odds...

Research paper thumbnail of Effects of ‘rescue’ dose of antenatal corticosteroids on placental histopathology in preterm births

Placenta

INTRODUCTION Antenatal corticosteroids (ACS) are frequently used to reduce neonatal morbidity in ... more INTRODUCTION Antenatal corticosteroids (ACS) are frequently used to reduce neonatal morbidity in preterm births (PTBs). A 'rescue' dose of ACS can be administer, if the risk of PTB remains. Some reports indicated that repeated doses of ACS might impact placental histology and possibly its function. We aimed to study whether repeated doses of ACS effect placental histopathology and pregnancy outcome. METHODS The medical files and placental reports of all PTB, at 24-336/7 weeks, between Nov 2008-Dec 2019, were reviewed. The study population was divided into three groups; no-ACS (PTBs without ACS treatment), one-ACS (PTBs after a full or partial ACS course), and rescue-ACS (PTBs after a 'rescue' course of ACS). Placental lesions were classified according to "Amsterdam" criteria into maternal and fetal vascular malperfusion lesions, maternal and fetal inflammatory responses and chronic villitis. Placental lesions and pregnancy outcome were compared between the study groups. RESULTS The no-ACS group (n = 58) was characterized by increased rates of PTB<28 weeks (p = 0.003), perinatal death (p < 0.001) and composite neonatal infectious morbidity (p = 0.022), as compared to the one-ACS group (n = 331) and the rescue-ACS group (n = 53). Placental MIR lesions were more common among the rescue-ACS group, compared to the one- and no-ACS groups (p = 0.022). Other placental lesions did not differ between the groups. On multivariate logistic regression analysis, MIR lesions were independently associated with rescue-ACS treatment (aOR 3.00, 95% CI 1.10-8/17, p = 0.031). DISCUSSION Rescue course of ACS is associated with increased rate of placental maternal inflammatory response. These findings probably result from maternal stress stimuli without an adverse impact on early neonatal outcome.

Research paper thumbnail of The differential regulation of placenta trophoblast bisphosphoglycerate mutase in fetal growth restriction: preclinical study in mice and observational histological study of human placenta

BackgroundFetal growth restriction (FGR) is a pregnancy complication in which a newborn fails to ... more BackgroundFetal growth restriction (FGR) is a pregnancy complication in which a newborn fails to achieve its growth potential, increasing the risk of perinatal morbidity and mortality. Chronic maternal gestational hypoxia, as well as placental insufficiency are associated with increased FGR incidence; however, the molecular mechanisms underlying FGR remain unknown.MethodsIn a case control study of murine and human control and FGR placentae, we implied MR imaging, IHC and metabolomics to assess the levels of BPGM and 2,3 BPG to elucidate the impact of maternal gestational hypoxia, and the molecular mechanisms underlying human FGR.ResultsWe show that murine acute and chronic gestational hypoxia recapitulates FGR phenotype and affects placental structure and morphology. Gestational hypoxia decreased labyrinth area, increased the incidence of red blood cells (RBCs) in the labyrinth while expanding the placental spiral arteries (SpA) diameter. Hypoxic placentae exhibited higher hemoglobi...

Research paper thumbnail of Is there an association between the length of the second stage of labour and urinary incontinence in multiparous women?

European Journal of Obstetrics & Gynecology and Reproductive Biology

Research paper thumbnail of MP63-11 DOES Iatrogenic Bladder Injury During Cesarean Section Has an Impact on Lower Urinary Tract Symptoms in the Future?

Research paper thumbnail of Boosting maternal and neonatal humoral immunity following SARS-CoV-2 infection using a single messenger RNA vaccine dose

American Journal of Obstetrics and Gynecology

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Research paper thumbnail of Gestational diabetes mellitus in in-vitro fertilization pregnancies – Clinical and placental histological characteristics

Placenta, 2022

We aimed to investigate obstetric and neonatal outcomes and placental histological findings in in... more 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. 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. 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. 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.