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.

Medical treatment for early pregnancy loss following in vitro fertilization compared to spontaneous pregnancies.

BACKGROUND: Misoprostol is a well-studied medical treatment for early pregnancy loss (EPL), with success rates ranging between 70 and 90%. However, treatment failure is associated with major patient discomfort, including the need for surgical intervention to evacuate the uterus. It was previously reported that medical treatment was especially successful among women who conceived after in vitro fertilization (IVF). We aimed to study if there is a difference in rates of medical treatment failures for EPL between pregnancies conceived by IVF and spontaneous pregnancies. METHODS: In this retrospective cohort study, we included all women who underwent medical treatment for EPL at our institute between 07/2015 and 12/2020. Treatment outcome was compared between IVF and spontaneous pregnancies. Treatment failure was defined as a need for surgical intervention, namely, dilation & curettage (D&C) and/or hysteroscopy, due to retained products of conception, which was defined as a gestational sac or endometrial thickness greater than 15 mm in a TVS scan. RESULTS: Overall, 775 patients were included, of which 195 (169/775 = 25.1%) ultimately required surgical intervention. There was no difference between the study groups in the rate of treatment failure. However, among IVF pregnancies, the rate of emergency D&C was lower (3.6% vs. 9.8%, p = 0.001), compared to spontaneous group. CONCLUSION: In cases of medical treatment for EPL, IVF pregnancies had no differences in rates of treatment failure compared to spontaneous pregnancies. That being said, IVF pregnancies have lower chances to undergo emergency D&C, compared to spontaneous pregnancies.

D&C has the best concordance between preoperative and postoperative grades among morbidly obese endometrial cancer patients.

AIM: Endometrial cancer is diagnosed by obtaining uterine biopsies by pipelle, dilatation and curettage (D&C), or hysteroscopy. In 15%-25% of the cases, the preoperative and postoperative grades do not match. This discrepancy may carry significant clinical and prognostic consequences. We aimed to assess how body mass index (BMI) affects preoperative and postoperative grade mismatches and whether biopsy methods mitigate this effect. METHODS: We conducted a retrospective review of patients with endometrial cancer who underwent surgery at our center between 2014 and 2022. We stratified patients into six classes of BMI based on the WHO classification. Preoperative and postoperative grades were compared for concordance with regards to patient BMI and sampling method. RESULTS: A total of 158 patients were included, diagnosed by pipelle (n = 99), hysteroscopy (n = 15), or D&C (n = 44). For all methods, every unit increase in BMI increased the odds of having a gap between histology grades by 5.2%. In the pipelle group, the odds of a larger gap between the histology grades was 62% higher than that of women in the other groups. Among the D&C group, the odds of having a bigger difference between histology grades were 91.8% lower compared to the other groups. Patients with BMI over 30 had nearly 50% discrepancy when diagnosed with pipelle or hysteroscopy, but less than 10% with D&C. CONCLUSIONS: Increasing BMI is associated with decreasing concordance between preoperative and postoperative grades in endometrial cancer, especially when it exceeds 30. This effect is much less pronounced, however, when the diagnostic method is D&C.

Failure Rate of Medical Treatment for Miscarriage Correlated with the Difference between Gestational Age According to Last Menstrual Period and Gestational Size Calculated via Ultrasound.

Objective: To study whether the interval between gestational age calculated using the last menstrual period (GA-LMP) and gestational age calculated via ultrasound (GA-US) is correlated with the success rate of medical treatment in cases of miscarriages. Methods: This was a retrospective cohort study conducted in a gynecology unit in a tertiary medical center. Women who underwent medical treatment with Misoprostol for miscarriage at the Edith Wolfson Medical Center between 07/2015 and 12/2020 were included. Incomplete or septic miscarriages, multiple pregnancies, patients with irregular periods, and cases of missing data were excluded. Failure of medical treatment was defined as the need for surgical intervention due to a retained gestational sac, severe bleeding or retained products of conception. The cohort study was divided into two groups: patients with successful treatment and patients for whom surgical intervention was eventually needed. We performed both a univariate and multivariate analysis in order to identify whether a correlation between GA-LMP and GA-US interval is indeed a factor in the success rate of a medical abortion. Results: Overall, 778 patients were included in the study. From this cohort 582 (74.9%) had undergone a successful medical treatment, while 196 (25.1%) required surgical intervention due to the failure of medical treatment, as defined above. The GA-LMP to GA-US interval (in weeks) was 2.6 ± 1.4 in the success group, while the GA in the failure group was 3.1 ± 1.6 (p < 0.001). After performing a multivariant regression analysis, we were able to show that the GA-LMP to GA-US interval was found to be independently correlated with an increase in the treatment failure rate (aOR = 1.24, CI 95% (1.01-1.51), p = 0.03). Conclusions: In cases of miscarriage, longer GA-LMP to GA-US interval has been shown to be an independently correlated factor to lower success rate of the medical treatment option.

The Effect of Preemptive Local Infiltration on Postoperative Pain After Vaginal Hysterectomy: A Retrospective Study.

STUDY OBJECTIVE: To investigate the effect of preemptive infiltration on postoperative pain and the use of analgesics after vaginal hysterectomy (VH). DESIGN: A retrospective study. SETTING: An urogynecology unit in a tertiary medical center. PATIENTS: A total of 120 patients who had undergone VH. INTERVENTIONS: The study group contained 60 patients who participated in a former randomized control study, in which preemptive local infiltration of bupivacaine (n = 30) or sodium chloride 0.9% (n = 30) was performed. The control group included 60 consecutive patients who underwent a VH, for whom no local infiltration was performed. MEASUREMENTS AND MAIN RESULTS: Postoperative pain at rest was assessed using the 10 cm visual analog scale at 3, 8, and 24 hours after surgery. The levels of pain, as well as the use of analgesics, postoperatively, were compared between the groups. The mean surgery length in the infiltration group was shorter (86.4±29 vs 118.6±30, p <.001) and the rate of posterior colporrhaphy was lower (73.1% vs 91.3%, p = .010) than the control group. There were no differences in levels of pain at all points of time. However, the infiltration group required a lower morphine dose in the recovery unit (3.7 ± 2.3 mg vs 5.3 ± 2.4 mg, p <.001) and less use of analgesia (all kinds) 24 hours after surgery (54.2% vs 79.6%, p <.001) compared with the control group. On multivariant analysis, preemptive infiltration was found to be independently inversely associated with the dose of morphine used in recovery, as well as analgesics used 24 hours after surgery. CONCLUSION: Preemptive local infiltration of either bupivacaine or sodium chloride 0.9% reduced the use of morphine in the recovery unit, as well as the use of analgesics 24 hours after VH, compared with no infiltration at all.

High-risk HPV testing vs liquid-based cytology for cervical cancer screening among 25- to 30-year-old women: A historical cohort study.

INTRODUCTION: High-risk human papilloma virus (hrHPV) DNA testing is more sensitive than cytology screening, achieving greater protection against cervical cancer. Controversy exists regarding the preferred screening method for women 25-30 years of age. At this age, infection with HPV is common and usually transient. Consequently, hrHPV screening in this age group is fraught with high false-positive screening results, leading to more colposcopies and unnecessary treatments with the potential for harm. In the present study, we aimed to compare the results of two screening methods in relation to high-grade cervical intraepithelial lesion detection rate in the young age group of 25-30 years. MATERIAL AND METHODS: Retrospective information on cervical cytology, hrHPV testing, colposcopy referrals and histologic results, from one screening round, were retrieved from the Maccabi HealthCare Health Maintenance Organization centralized database during the study period from March 1, 2017 to April 1, 2019 for 25- to 30-year-old women. Screening with hrHPV testing for types 16, 18 and 12 other hrHPV types was compared with the conventional PAP liquid-based cytology (LBC) test. Odds ratio (OR) of detection with 95% confidence interval (CI) was calculated for cervical intraepithelial neoplasia (CIN) grade 3 or higher (CIN 3+). RESULTS: During the study period, 42 244 women 25-30 years old underwent cervical cancer screening; of them, 20 997 were screened with LBC between March 1, 2017 and March 1, 2018 and compared with 21 247 who were screened with hrHPV between April 1, 2018 and April 1, 2019. Testing for hrHPV resulted in a higher colposcopy referral rate compared with primary LBC screening: 9.8% vs 7.8%, respectively; (OR 1.28; 95% CI 1.2-1.37; p < 0.001). Screening with hrHPV led to significantly higher detection of CIN 3+ lesions (OR 1.4; 95% CI 1.2-1.6; p < 0.001) compared with LBC. HPV infections with non-16/18 hrHPV (other hrHPV) were the most prevalent (84.8%). CONCLUSIONS: In women 25-30 years old, primary hrHPV screening was associated with a higher detection rate of CIN 3+ compared with cytology screening and should be considered for primary screening in this age group.

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.

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.

The effect of preemptive local anesthesia on postoperative pain following vaginal hysterectomy: A randomized controlled trial.

OBJECTIVE: We aimed to study the effect of preemptive local anesthetic without adrenaline on postoperative pain following vaginal hysterectomy and concomitant trans obturator tape (TOT). STUDY DESIGN: This was a double-blinded, randomized, controlled trial. Women who undergone elective vaginal hysterectomy were included. Solutions of either Bupivacaine-Hydrochloride 0.5%, or Sodium-Chloride 0.9% as a placebo, were prepared prior to surgery, according to randomization. The chosen solution was injected before incision, in a circumferential manner, to the cervix. The amount of fluid administered was 10 ml. When colporrhaphy was also performed, an additional 5 ml of solution were injected in the midline of the vaginal wall prior to each incision line. We conformed to the CONSORT recommendations. By utilizing the 10 cm Visual-analogue-scale (VAS) we assessed post-operative pain at rest at 3, 8, and 24 h, and during ambulation at 8 and 24 h. We estimated that the intervention would cause a 25% reduction in the primary outcome. The required total sample size was calculated to be 30 patients women for each group. We used ANOVA for continuous variables and the Chi-square or Fisher exact tests for categorical variables. RESULTS: A total of 30 women were included in each group. The level of postoperative pain, as assessed by VAS, was not significantly different between the groups, in all points of time. In addition, there was no difference between the groups in opioid based analgesics during recovery, nor in postoperative analgesic use. CONCLUSION: Preemptive local anesthesia was not shown to be efficient in reducing postoperative pain after vaginal hysterectomy and TOT.

The effect of subcutaneous and intraperitoneal anesthesia on post laparoscopic pain: a randomized controlled trial.

A few modes of perioperative local analgesia have been studied in order to reduce postoperative pain after laparoscopy, including preemptive local anesthetics in the trocar sites and intraperitoneal anesthetics administration at the end of the surgery. However, the evidence regarding their efficacy are conflicting. In addition, the combination of both aforementioned methods has been rarely studied. Our aim was to evaluate whether subcutaneous trocar site and/or intraperitoneal analgesia reduce pain after gynecologic operative laparoscopy. This was a single-centered, randomized, controlled, double-blinded trial. The patients were randomly assigned to one of four equally sized groups: group 1-subcutaneous and intraperitoneal analgesia; group 2-subcutaneous analgesia and intraperitoneal placebo; group 3-subcutaneous placebo and intraperitoneal analgesia; Group 4-subcutaneous and intraperitoneal placebo. The patients, the surgeons, and the pain evaluators were all blinded to the patient's allocation. Included were patients who underwent elective operative laparoscopy. Exclusion criteria were: active infection, pregnancy, known sensitivity to Bupivacaine-Hydrochloride, chronic pelvic pain, surgeries with additional vaginal procedures, conversion to laparotomy, and malignancy. A total of 9 ml of Bupivacaine-Hydrochloride (Marcaine) 0.5%, or Sodium-Chloride 0.9%, as a placebo, were injected subcutaneously to the trocar sites (3 ml to each trocar site), prior to skin incision. In addition, 10 ml of Bupivacaine-Hydrochloride 0.5%, diluted with 40 ml of Sodium-Chloride 0.9% (a total of 50 ml solution), or 50 ml of Sodium-Chloride 0.9%, as a placebo, were injected intraperitoneally at the end of the surgery. By utilizing the 10 cm Visual-analogue-scale (VAS) we assessed post-operative pain at rest at 3, 8, and 24 h, and during ambulation at 8 and 24 h. The study was approved by the local Institutional Review Board and has been registered at clinicaltrials.gov. We conformed to the CONSORT recommendations. Between December 2016 and July 2019, a total of 119 patients were included in the study. Demographic and interventional characteristics were similar among the groups. The level of postoperative pain, either at rest or with change of position, was not significantly different between the groups, at all-time points. Application of subcutaneous and/or intraperitoneal analgesia is not effective in reducing pain after gynecologic operative laparoscopy.Clinical trial identification number: NCT02976571. Date of trial registration 11/29/2016. URL of the registration site: https://clinicaltrials.gov .

The effect of concomitant histologic chorioamnionitis in pregnancies complicated by fetal growth restriction.

INTRODUCTION: We aimed to investigate the effect of placental histologic chorioamnionitis (HC) on neonatal outcomes in pregnancies complicated by fetal growth restriction (FGR). METHODS: - The computerized medical files of all pregnancies diagnosed with FGR (birthweight <10th percentile) at 24-42 weeks of gestation between 2008 and 2019 were reviewed. Maternal and neonatal outcomes were compared between FGR with and without evidence of placental HC. Placental lesions were classified according to "Amsterdam" criteria. Composite adverse neonatal outcome-included any of the following complications: neurological morbidity, neonatal respiratory assistance, RDS, NEC, sepsis, blood transfusion, phototherapy, hypoglycemia, or neonatal death. Composite severe adverse neonatal outcome included any of the following complications - neurological morbidity, blood transfusion, NEC, sepsis, RDS, neonatal death. RESULTS: - Compared to FGR without HC (n = 446), FGR with HC (n = 57) was characterized by more advanced gestational age at delivery 39.2 (38.3-39.9) vs. 38.2 (36.9-39.2), weeks respectively, p < 0.001), higher rate of nulliparity (73.7% vs. 45.1%, p < 0.001), less vascular lesions of MVM (1.8% vs.11.2%, p = 0.02), higher rate of Apgar scores at 5 min <7 (10.5% vs. 2%, p = 0.004), increased neonatal death (7.0% vs. 0.9%, p = 0.007), higher rates of both composite adverse neonatal outcome (31.1% vs. 17.3% p = 0.02), and composite severe adverse neonatal outcome (16.3% vs. 8.2% p = 0.04). By multivariate regression analysis HC was found to be independently associated with composite adverse neonatal outcome (aOR = 1.21, 95% CI 1.08-2.38) and with severe composite adverse neonatal outcome (aOR = 1.39, 95% CI 1.16-3.76). CONCLUSIONS: Pregnancies complicated by FGR with concomitant HC were associated with higher rates of adverse neonatal outcomes.

Preeclampsia in Different Maternal Age Groups-Is There an Association with Pregnancy Outcomes and Placental Pathology?

We aimed to compare maternal characteristics, pregnancy outcomes, and placental pathology in pregnancies complicated by preeclampsia at three different maternal age groups. Medical records and pathological reports of patients diagnosed with preeclampsia and delivered between 2008 and 2018 in a single tertiary center, were reviewed. Preeclampsia was diagnosed according to the current ACOG guidelines. Study population was divided into 3 groups of maternal age: group 1-< 27 years; group 2-27-35 years; and group 3-> 35 years (advanced maternal age = AMA). Data regarding maternal characteristics, neonatal outcomes, and placental histopathological lesions were compared between the groups. Composite adverse neonatal outcome was defined as ≥ 1 early neonatal complication. The AMA group (n = 145) was associated with a higher BMI, and higher rates of diabetes mellitus (DM), chronic hypertension (CHTN), and Cesarean deliveries compared with group 1 (n = 107) and group 2 (n = 255). The AMA group also had lower neonatal birthweights and a higher rate of composite adverse neonatal outcome compared with the other age groups. None of the placental lesions differed between the groups. By multivariable analysis, we found that maternal age (aOR 1.36, 95% CI 1.17-3.93), GA at delivery (aOR 0.80, 95% CI 0.61-0.90), DM (aOR 1.19, 95% CI 1.07-3.05), and CHTN (aOR 1.23, 95% CI 1.08-2.01) were independently associated with composite adverse neonatal outcome. Pregnancies at AMA were associated with higher complication rates, but without any differences in placental pathology, suggesting that the worse outcomes associated with AMA in preeclampsia are attributed to maternal chronic morbidities and not to differences observed in placental pathology.

Placental-related disorders of pregnancy and IVF: does placental histological examination explain the excess risk?

RESEARCH QUESTION: What are the clinical characteristics of pregnancies complicated by fetal growth restriction (FGR) and preeclampsia in patients who have undergone IVF, and what is the correlation between these complications and histopathological placental findings in such pregnancies. DESIGN: A retrospective cohort of patients who had delivered their babies at our institution who had been diagnosed with preeclampsia, whose babies had been diagnosed with FGR, or both. Deliveries in which the placenta was sent for histopathological examination were included. Computerized files and pathological reports were reviewed, and maternal, obstetric, neonatal outcomes and placental histopathological reports were compared between pregnancies conceived by IVF and controls. Placental lesions were classified according to the Amsterdam criteria. RESULTS: Between December 2008 and December 2018, the placentas of 1114 singleton babies who had received a diagnosis of FGR, whose mothers had received a diagnosis of preeclampisa, or both, were examined. A total of 105 patients conceived with IVF and 1009 were conceived spontaneously. The IVF group was older, of lower parity and had a higher rate of diabetes and chronic hypertension. Deliveries occurred at an earlier gestational age, although birth weight was not significantly different between the groups. The rate of neonatal adverse composite outcome among IVF deliveries was significantly lower (59.0% versus 76.7%; P < 0.001). On placental examination, placental weight, maternal and fetal vascular malperfusion lesions were similar between the groups, whereas villitis of unknown etiology was significantly more common among the IVF group (16.2% versus 8.3%; P = 0.007). CONCLUSION: Neonatal outcome is relatively favourable in IVF patients with placental-related diseases. Placental chronic villitis is more common in IVF patients, pointing to an additive immunological cause.

None, One, or Both Placentas Involved with Malperfusion Lesions in Twin Pregnancies Complicated by Preeclampsia-Does It Matter?

We aimed to study the association between the number of placentas with vascular malperfusion lesions in dichorionic twin pregnancies complicated by preeclampsia and the severity of the disease and pregnancy outcomes. Dichorionic twin pregnancies with preeclampsia (n = 125), from January 2007-June 2018, were reviewed. Affected placenta was defined as the presence of maternal/fetal vascular malperfusion lesions. Maternal demographics, pregnancy characteristics, and neonatal outcomes were compared between three groups: no pathological placentas, one pathological placenta, and two pathological placentas. Composite adverse neonatal outcome was defined as ≥ 1 early neonatal complication. Regression analysis models were used to recognize independent associations with the number of involved placentas. The two pathological placenta group (n = 57 pregnancies), the one pathological placenta group (n = 40 pregnancies), and the no pathological placenta group (n = 28 pregnancies) differed in terms of gestational age (GA) at delivery (p < 0.001, p = 0.008) and the rates of severe features (p = 0.028, p = 0.047). Neonates born to the two pathological placenta group (n = 114), the one pathological placenta group (n = 80), and the no pathological placenta group (n = 56) were characterized by lower birth weights (p < 0.001, p = 0.031), higher rates of small for gestational age (SGA) (p = 0.017, p = 0.748), neonatal intensive care unit admission (p = 0.004, p = 0.013), and composite adverse neonatal outcome (p < 0.001, p = 0.025). By regression analyses, the presence of two pathological placentas was found to be independently associated with severe features (aOR = 5.1), GA at delivery < 32 weeks (aOR = 2.0), SGA (aOR = 2.5), and composite adverse neonatal outcome (aOR = 2.7). In dichorionic twin pregnancies, there is an association between the presences of placental vascular malperfusion lesions in none, one, or both placentas and the development of early and severe preeclampsia, as well as with SGA and adverse neonatal outcome.

The association between abnormal coagulation testing in preeclampsia, adverse pregnancy outcomes, and placental histopathology.

Objective: We aimed to determine whether abnormal coagulation laboratory testing results in preeclampsia, are associated with adverse pregnancy outcomes and placental histopathology lesions. Methods: Demographic, labor, laboratory-testing, and placental histopathology reports of pregnancies complicated by preeclampsia were compared between those with and without abnormal coagulation profile (ACP). Results: Of 348 cases of preeclampsia 16.1% had ACP. There were no differences between the groups in GA at delivery, severe features, placental-abruption, SGA, composite adverse neonatal outcome and placental histopathology lesions. Conclusion: ACP in pregnancies complicated by preeclampsia was not associated with any of the studied outcomes. Our data question the usefulness of routine coagulation tests in the initial assessment of women presenting with preeclampsia.

Cumulative Risk of the Oxytocin Receptor Gene Interacts with Prenatal Exposure to Oxytocin Receptor Antagonist to Predict Children's Social Communication Development.

Compelling evidence for the far-reaching role of oxytocin (OT) in social cognition and affiliative behaviors set the basis for examining the association between genetic variation in the OT receptor (OXTR) gene and risk for autism spectrum disorder (ASD). In the current study, gene-environment interaction between OXTR and prenatal exposure to either OT or OXTR antagonist (OXTRA) in predicting early social communication development was examined. One hundred and fifty-three children (age: M = 4.32, SD = 1.07) were assigned to four groups based on prenatal history: children whose mothers prenatally received OXTRA and Nifedipine to delay preterm labor (n = 27); children whose mothers received Nifedipine only to delay preterm labor (n = 35); children whose mothers received OT for labor augmentation (n = 56), and a no intervention group (n = 35). Participants completed a developmental assessment of intelligence quotient (IQ), adaptive behavior, and social communication abilities. DNA was extracted via buccal swab. A genetic risk score was calculated based on four OXTR single nucleotide polymorphisms (rs53576, rs237887, rs1042778, and rs2254298) previously reported to be associated with ASD symptomatology. OXTRrisk-allele dosage was associated with more severe autism diagnostics observation schedule (ADOS) scores only in the OXTRA group. In contrast, in the Nifedipine, OT, and no intervention groups, OXTRrisk-allele dosage was not associated with children's ADOS scores. These findings highlight the importance of both genetic and environmental pathways of OT in signaling early social development and raise the need for further research in this field. Autism Res 2019, 12: 1087-1100. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In the current study, we examined if the association between prenatal exposure to an oxytocin receptor antagonist (OXTRA) and autism spectrum disorder (ASD) related impairments are dependent on an individual's genetic background for the oxytocin receptor gene (OXTR). Children who carried a greater number of risk alleles for the OXTR gene and whose mothers received OXTRA to delay preterm labor showed more ASD-related impairments. The results highlight the importance of both genetic and environmental pathways of oxytocin in shaping early social development.

The differences in placental pathology and neonatal outcome in singleton vs. twin gestation complicated by small for gestational age.

OBJECTIVE: We aimed to compare placental histopathology and neonatal outcome between dichorionic diamniotic (DCDA) twins and singleton pregnancies complicated by small for gestational age (SGA). METHODS: Medical files and placental pathology reports from all deliveries between 2008 and 2017 of SGA neonates, (birthweight < 10th percentile), were reviewed. Comparison was made between singleton pregnancies complicated with SGA (singletons SGA group) and DCDA twin pregnancies (Twins SGA group), in which only one of the neonates was SGA. Placental diameters were compared between the groups. Placental lesions were classified into maternal and fetal vascular malperfusion lesions (MVM and FVM), maternal (MIR) and fetal (FIR) inflammatory responses, and chronic villitis. Neonatal outcome parameters included composite of early neonatal complications. RESULTS: The twins SGA group (n = 66) was characterized by a higher maternal age (p = 0.011), lower gestational age at delivery (34.9 ± 3.1 vs. 37.7 ± 2.6 weeks, p < 0.001), and a higher rate of preeclampsia (p = 0.010), compared to the singletons SGA group (n = 500). Adverse composite neonatal outcome was more common in the twins SGA group (p < 0.001). Placental villous lesions related to MVM (p < 0.001) and composite MVM lesions (p = 0.04) were more common in the singletons SGA group. On multivariate logistic regression analysis, the singletons SGA group was independently associated with placental villous lesions (aOR 3.6, 95% CI 1.9-7.0, p < 0.001) and placental MVM lesions (aOR 2.44, 95% CI 1.29-4.61, p = 0.006). CONCLUSION: Placentas from SGA singleton pregnancies have more MVM lesions as compared to placentas from SGA twin pregnancies, suggesting different mechanisms involved in abnormal fetal growth in singleton and twin gestations.

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.