Elad Barber

The placental factor in spontaneous preterm birth in twin vs. singleton pregnancies

OBJECTIVE The association between infection and inflammatory response in singleton preterm birth (PTB) is well established, yet, less is known about PTB in twins. We aimed to compare the placental component and pregnancy outcome in pregnancies complicated with PTB of singletons vs. twin deliveries. We hypothesized that due to different underlying mechanisms, placental inflammatory lesions will be more prevalent in placentas derived from singleton pregnancies than twins. STUDY DESIGN Labor characteristics, neonatal outcome and placental histopathology reports of spontaneous PTB at 24-336/7 weeks, from 1/2008-12/2015, were reviewed. RESULTS were compared between dichorionic-diamniotic twin deliveries (twins group) and singleton deliveries (singleton group) matched for gestational age. Excluded from the study medically indicated deliveries, due to preeclampsia or fetal growth restriction, and monochorionic twins. Placental lesions were classified to maternal vascular supply lesions, fetal vascular supply lesions, and maternal (MIR) and fetal (FIR) inflammatory responses. Composite neonatal outcome was defined as one or more of early complications: respiratory distress, necrotizing enterocolitis, sepsis, blood transfusion, ventilation, seizures, intra-ventricular hemorrhage, hypoglycemia, phototherapy, or death. RESULTS The twins group (n=72) was characterized by higher maternal BMI (p=0.009), and higher rates of assisted reproductive techniques (56.2% vs. 17.8%, p<0.001) and cesarean deliveries (75.3% vs. 32.8%, p<0.001) as compared to the singleton group (n=72). Placentas from the singleton group were characterized by higher rate of MIR, 58.9% vs. 19.2%, (p<0.001), FIR, 31.5% vs. 3.4%, (p<0.001), retro-placental hemorrhage, 26% vs. 8.9% (p<0.001), and vascular lesions related to maternal malperfusion, 28.8% vs. 9.6%, (p<0.001), as compared to placentas from the twins group. Higher rate of neonatal sepsis was observed in the singleton group as compared to the twins group, 24.7% vs. 4.1%, p<0.001, respectively. By logistic regression analyses retro-placental hemorrhage, placental maternal vascular malperfusion lesions, MIR, FIR and neonatal sepsis were found to be independently associated with singleton PTB: aOR 3.4, 95% CI 2.1-6.9, p<0.001, aOR=3.1, 95% CI 1.8-7.2, p<0.001, aOR=2.9, 95% CI 1.4-7.8, p<0.001, aOR=4.9, 95% CI 2.3-6.9, p<0.001, and aOR=4.8, 95% CI 2.3-6.7, p<0.001 respectively. CONCLUSION Placentas from singleton PTBs are characterized by higher rate of inflammatory and malperfusion lesions. The lack of these findings in twins PTBs suggests different factors that participate in the development of preterm birth in twins, such as over-distension of the uterus and up regulation of oxytocin receptors.

Placental Component and Pregnancy Outcome in Singleton versus Twin Pregnancies Complicated by Preeclampsia

Objective: To compare placental histopathological lesions and pregnancy outcomes in singleton and twin pregnancies complicated by preeclampsia (PE). Methods: Maternal characteristics, neonatal outcomes, and placental histopathology reports of pregnancies complicated by PE between January 2008 and October 2016 were reviewed. Results were compared between singletons (singleton group) and dichorionic-diamniotic twins (twin group). Placental lesions were classified into maternal and fetal vascular supply lesions. Small for gestational age (SGA) was defined as birth weight ≤10th percentile. Composite adverse neonatal outcome was defined as one or more early neonatal complications. Results: Compared to the twin group (n = 67), the singleton group (n = 275) was characterized by lower maternal age (p = 0.003), higher gestational age (p < 0.001), higher rates of previous PE (p = 0.017), chronic hypertension (p = 0.036), and severe features (p < 0.001). Placentas from the singleton group were characterized by higher rates of maternal vascular malperfusion lesions (p < 0.001) and fetal vascular supply lesions (p = 0.002). Using multivariable regression analysis, composite maternal and fetal vascular malperfusion lesions were independently associated with singletons (aOR = 2.7, 95% CI = 1.2-7.8, p < 0.001, and aOR = 1.2, 95% CI = 1.2-5.6, p = 0.025, respectively). SGA was more common in the singleton group (p = 0.002). Neonatal outcome did not differ between the groups. Conclusion: Placentas from singleton pregnancies complicated by PE were characterized by higher rates of maternal and fetal vascular lesions compared to those from twin pregnancies, suggesting that different mechanisms participate in the development of PE in these two groups.

The placental component and neonatal outcome in singleton vs. twin pregnancies complicated by gestational diabetes mellitus

OBJECTIVE We aimed to compare placental histopathological lesions and neonatal outcome in singleton vs. twin pregnancies complicated by gestational diabetes mellitus (GDM). METHODS Maternal characteristics, neonatal outcomes, and placental histopathology reports of pregnancies complicated by GDM, between 1/2008-10/2016, were reviewed. Results were compared between singletons (singleton group) and dichorionic-diamniotic twins (twin group). Placental lesions were classified as placental weight abnormalities, maternal and fetal vascular malperfusion lesions (MVM, FVM), inflammatory lesions, and lesions associated with chronic villitis. LGA was defined as birth-weight ≥90th percentile. Composite adverse neonatal outcome was defined as one or more early neonatal complications. RESULTS Compared with the twin group (n = 57), the singleton group (n = 228) was characterized by higher gestational-age (38.6 ± 0.9 vs. 35.1 ± 1.8 weeks, p < 0.001) and a higher rate of insulin treatment (32.9% vs. 17.5%, p = 0.023). Placentas from the singleton group were characterized by higher rates of MVM lesions (54.4% vs. 30.7%, p < 0.001), villitis of unknown etiology (VUE, 5.7% vs. 0.9%, p = 0.040), villous immaturity (10.1% vs. 0.9%, p = 0.001), and placental weight <10th percentile (16.7% vs. 8.8%, respectively, p = 0.049). Using multivariable regression analysis, MVM (aOR = 2.2, 95% CI = 1.6-4.1), VUE (aOR = 1.2, 95% CI = 1.1-2.1), villous immaturity (aOR = 2.3, 95% CI 1.8-7.6), and placental weight <10th percentile (aOR = 1.1, 95% CI = 1.02-1.6), were the only lesions associated with singleton pregnancies. Composite adverse neonatal outcome was more common in the twin group (54.3% vs. 14.0%, p < 0.001) and it was associated only with lower GA (aOR = 3.7, 95% CI 2.1-7.3). CONCLUSION Higher rate of placental weight <10th percentile, MVM lesions, villous immaturity, and VUE characterize GDM singleton pregnancy as compared to twins GDM gestation, suggesting different placental alterations in the diabetic environment.

Placental Histopathology Differences and Neonatal Outcome in Dichorionic–Diamniotic as Compared to Monochorionic–Diamniotic Twin Pregnancies:

Objective: We aimed to compare the differences in placental histopathology lesions and pregnancy outcome in dichorionic–diamniotic (DCDA) versus uncomplicated monochorionic–diamniotic (MCDA) twin gestations. Study Design: Maternal characteristics, neonatal outcome, and placental histopathology reports of all twin deliveries between 24 and 41 weeks were reviewed. Excluded were pregnancies complicated by twin-to-twin transfusion syndrome, twin anemia–polycythemia sequence, selective intrauterine growth restriction, placenta previa, intrauterine fetal death, and malformation. Placental lesions were classified to maternal/fetal vascular malperfusion lesions. Umbilical cord abnormalities included hypo-/hypercoiling and abnormal insertion. Composite adverse neonatal outcome was defined as 1 or more early complications. Small for gestational age (SGA) was defined as birth weight ≤10th percentile. Results: The DCDA group (n = 362) was characterized by higher rates of assisted reproductive techniques (P < .001) and nulliparity (P = .03) as compared to the MCDA group (n = 65). Gestational age at delivery was similar between groups. Placental maternal vascular malperfusion lesions were more common in placentas from DCDA group (38.2% vs 23.1%; P = .016), while fetal vascular malperfusion lesions and abnormal cord insertion were more common in placentas from MCDA group (P = .027; P< .001). The SGA and composite adverse neonatal outcome were more common in the MCDA group (P = .031 and P = .038, respectively). By multivariate regression analysis, composite adverse neonatal outcome was found to be independently associated with the MCDA group, adjusted odds ratio (aOR) = 1.2, 95% confidence interval (CI) = 1.04 to 1.89, P = .041, and with placental fetal malperfusion lesions aOR = 1.3, 95% CI = 1.1 to 2.09, P = .038. Conclusion: Placental pathology differs between MCDA and DCDA twin pregnancies. Adverse neonatal outcome in uncomplicated MCDA twins, as compared to DCDA twins, could be related to increased placental fetal malperfusion lesions and abnormal cord insertion.

Placental histopathological lesions in correlation with neonatal outcome in preeclampsia with and without severe features

OBJECTIVE We aimed to compare pregnancy outcome and placental histopathology in women with preeclampsia (PE) with and without severe features. METHODS The medical records and placental pathology reports of all pregnancies complicated by PE during 2008-2016, were reviewed. Results were compared between those with and without severe features (severe PE vs. mild PE groups), according to current ACOG guidelines. Placental lesions were classified to maternal/fetal vascular supply lesions, and maternal/fetal inflammatory responses. Small for gestational age (SGA) was defined as neonatal birth-weight ≤10th%. Composite adverse neonatal outcome was defined as one or more of the following: sepsis, transfusion, phototherapy, respiratory morbidity, cerebral morbidity, NEC, or death. RESULTS The severe PE group (n = 284) was characterized by lower gestational age at delivery (p < 0.001), and higher rates of antenatal corticosteroid use (p = 0.003), and cesarean deliveries (p < 0.001) as compared to the mild PE group (n = 151). More placentas <10th% and more composite maternal vascular malperfusion (MVM) lesions were observed in the severe PE group as compared to the mild PE group (p < 0.001 for both). In multivariate analysis, composite placental MVM lesions were independently associated with severe PE (aOR = 1.75, 95%CI 1.4-4.9). Higher rates of SGA (p = 0.016), and composite adverse neonatal outcome (p = 0.002) characterized the severe PE group. In multivariate analysis, adverse neonatal outcome was independently associated with gestational age (aOR = 0.54, 95%CI 0.49-0.68), SGA (aOR = 1.75, 95%CI = 1.15-3.59), severe PE (aOR = 1.8, 95%CI = 1.13-3.54) and placental MVM lesions (aOR = 2.13, 95%CI = 1.05-4.39). CONCLUSION More pronounced placental pathology and higher rate of adverse neonatal outcome characterize preeclampsia with severe features as compared with the milder form of the disease.

Placental pathology and neonatal outcome in small for gestational age pregnancies with and without abnormal umbilical artery Doppler flow

OBJECTIVE To compare neonatal outcome and placental pathology in cases of small for gestational age (SGA) according to umbilical artery (UA) Doppler flow. STUDY DESIGN Pregnancy and placental reports of SGA neonates (birth-weight <10th), born between 2008 and 2017 were compared between cases with normal and abnormal UA Doppler indices. Placental lesions were classified to malperfusion lesions and inflammatory responses. RESULTS The abnormal Doppler group (n = 66) delivered at an earlier gestational age, compared to the normal Doppler group (n = 92). Placentas from the abnormal Doppler group were characterized by a higher rate of maternal malperfusion lesions, while placentas from the normal Doppler group exhibited a higher rate of chronic villitis. Neonatal outcome was independently associated with abnormal Doppler, gestational age and birth weight <5th percentile. CONCLUSION SGA may involve a vascular mechanism, associated with abnormal Doppler flow and placental malperfusion, and an inflammatory mechanism, with normal Doppler flow and chronic villitis.